Surgery - Articles in Press

Fatty pancreas and increased body mass index are risk factors of pancreatic fistula after pancreaticoduodenectomy - Corrected Proof

2010-02-08

Background: Pancreatic fistula (PF) after pancreatoduodenectomy (PD) remains a challenging problem. The only commonly accepted risk factor is the soft consistency of the pancreatic remnant.Methods: In all, 100 consecutive patients underwent PD. All data, including commonly accepted risk factors for PF and PF defined according to the International Study Group of Pancreatic Fistula, were collected prospectively. On the pancreatic margin, a score of fibrosis and a score of fatty infiltration were assessed by a pathologist blinded to the postoperative course.Results: PF occurred in 31% of patients. In univariate analysis, male sex, age greater than 58 years, body mass index (BMI) ≥25 kg/m2, pre-operative high blood pressure, operation for nonintraductal papillary and mucinous neoplasm (IPMN) disease and for ampullary carcinoma, operative time, blood loss, soft consistency of the pancreatic remnant, absence of pancreatic fibrosis, and presence of fatty infiltration of the pancreas were associated with a greater risk of PF. In a multivariate analysis, only BMI ≥25kg/m2, absence of pancreatic fibrosis, and presence of fatty pancreas were significant predictors of PF. A score based on the number of risk factors present divided the patient population into 4 subgroups carrying a risk of PF that ranged from 7% (no risk factor) to 78% (3 risk factors) and from 0% to 81%, taking into account only symptomatic PF (grade B and C).Conclusion: The presence of an increased BMI, the presence of fatty pancreas, and the absence of pancreatic fibrosis as risk factors of PF allows a more precise and objective prediction of PF than the consistency of pancreatic remnant alone. A predictive score based on these 3 factors could help to tailor preventive measures.

Repair of complex incisional hernias using double prosthetic repair: Single-surgeon experience with 50 cases - Corrected Proof

2010-02-08

Background: The treatment of complex incisional hernias is still difficult and controversial. With technologic developments we can modify and update the operative techniques described for treating complex abdominal wall hernias.Methods: This is a prospective study of 50 patients with complex incisional hernias undergoing complex abdominal wall herniorrhaphy at a university hospital. All patients were evaluated in a multidisciplinary clinic dedicated to abdominal wall reconstruction. All patients underwent pre-operative computed tomography. Complex incisional hernias were regarded as those with multiple recurrences (>3 times), a previous mesh complicated by fistula and chronic infection, giant diffuse lumbar hernias, an associated parastomal hernia, or hernias developing after bariatric surgery. The operative technique was a double reconstruction prosthetic mesh. The type of repair as well as clinical, operative, and follow-up data were analyzed.Results: Eight patients had considerable loss of tissue, 5 had trophic skin lesions, and 2 had chronic suppurative infection. The mean size of the defects was 18.2 cm. Morbidity included 5 cases of seroma, 2 neuralgias, and 2 cutaneous necroses. The mean duration of hospital stay was 5 days (range, 2–9). Complete follow-up (mean, 48 months; range, 12–108) showed no recurrent hernias.Conclusion: While awaiting a longer follow-up to confirm the results, we conclude that complex incisional hernias can be repaired safely and with a low morbidity and recurrence rate by means of a double prosthetic repair technique.

Postischemic poly (ADP-ribose) polymerase (PARP) inhibition reduces ischemia reperfusion injury in a hind-limb ischemia model - Corrected Proof

2010-02-04

Background: Several experiments were designed to determine whether the systemic, postischemic administration of PJ34,which is a poly-adenosine diphosphate (ADP)-ribose polymerase inhibitor, decreased tissue injury and inflammation after hind-limb ischemia reperfusion (I/R).Methods: C57BL6 mouse limbs were subjected to 1.5 h ischemia followed by 24-h reperfusion. The treatment group (PJ) received intraperitoneal PJ34 (30 mg/kg) immediately before reperfusion, as well as 15 min and 2 h into reperfusion. The control group (CG) received lactated Ringer's alone at the same time intervals as PJ34 administration. The skeletal muscle levels of adenosine triphosphate (ATP), macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC), and myeloperoxidase (MPO) were measured. Quantitative measurement of skeletal muscle tissue injury was assessed by microscopic analysis of fiber injury.Results: ATP levels were higher in limbs of PJ versus CG mice (absolute ATP: 4.7 ± 0.35 vs 2.3 ± 0.15-ng/mg tissue, P = .002). The levels of MIP-2, KC, and MPO were lower in PJ versus CG mice (MIP-2: 1.4 ± 0.34 vs 3.67 ± 0.67-pg/mg protein, P = .014; KC: 4.97 ± 0.97 vs 12.65 ± 3.05-pg/mg protein, P = .037; MPO: 46.27 ± 10.53 vs 107.34 ± 13.58-ng/mg protein, P = .008). Muscle fiber injury was markedly reduced in PJ versus CG mice (4.25 ± 1.9% vs 22.68 ± 3.0% total fibers, P = .0004).Conclusion: Systemic postischemic administration of PJ34 preserved skeletal muscle energy levels, decreased inflammatory markers, and preserved tissue viability post-I/R. These results support PARP inhibition as a viable treatment for skeletal muscle I/R in a clinically relevant post hoc scenario.

Predictors of occult nodal metastasis in colon cancer: Results from a prospective multicenter trial - Corrected Proof

2010-02-01

Background: The relationship between primary colon cancer and occult nodal metastases (OMs) detected by cytokeratin immunohistochemistry (CK-IHC) is unknown. We sought to investigate the correlation of clinicopathologic features of colon cancer with OMs and to identify predictors of OM.Methods: Patients with colon cancer from 5 tertiary referral cancer centers enrolled in a prospective trial of staging had standard pathologic analysis performed on all resected lymph nodes (using hematoxylin and eosin staining [H&E]). Nodes negative on H&E underwent CK-IHC to detect OMs, which were defined as micrometastases (N1mic) or isolated tumor cells (N0i+). Patients who were negative on both H&E and CK-IHC were defined as node negative (NN), and those positive on H&E were node positive (NP). The relationships between tumor characteristics and OMs were analyzed using the Kruskal-Wallis and the Fisher exact test.Results: OMs were identified in 23.4% (25/107) of patients. No significant differences were found in demographics, tumor location, tumor size, and number of nodes examined between groups. Compared with the NN group, patients with OMs had more tumors that were T3/T4 (72% vs 57%; P < .001), had tumors of higher grade (28% vs 12%; P = .022), and had tumors with lymphovascular invasion (16% vs 3%; P < .001).Conclusion: Adverse primary pathologic colon cancer characteristics correlate with OMs. In patients with negative nodes on H&E and stage T3/T4 colon cancer, lymphovascular invasion, or high tumor grade, consideration should be given to performing CK-IHC. The detection of OMs in this subset may influence decisions regarding adjuvant chemotherapy and risk stratification.

Safe alternative transgastric peritoneal access in humans: NOTES - Corrected Proof

2010-02-01

Background: Diagnostic transgastric endoscopic peritoneoscopy has been used to evaluate the abdomen. We present our experience with transgastric endoscopic peritoneoscopy (TEP) to access the peritoneum, direct trocar placement, and perform adhesiolysis without laparoscopic visualization in patients undergoing laparoscopic Roux-en-Y gastric bypass.Methods: Forty patients participated. There are 2 arms to the study. The initial 20 patients underwent pre-insufflation of the abdomen prior to TEP. The second 20 had no pre-insufflation. Ten patients in each arm had no surgical history. The other 10 had previous intra-abdominal procedures. TEP was performed through a gastrotomy created without laparoscopic visualization. Adhesions were visualized and taken down endoscopically prior to trocar placement. Diagnostic findings, operative times, and clinical course were recorded.Results: Average TEP time was 19 min. Three patients had limited visualization due to intra-abdominal adhesions (2) and omental fat (1). Three of the 20 without and 17 of 20 with a history of intra-abdominal surgery had adhesions visualized endoscopically. Endoscopic adhesiolysis was performed in 1 and 4 patients in these groups respectively. Six occult umbilical hernias, 1 inguinal hernia, and 1 hiatal hernia were noted on endoscopic exploration. There were no complications related to intubation of the stomach, accessing the peritoneum, or endoscopic exploration.Conclusion: TEP is a safe and accurate means to access the peritoneum, visualize the abdominal wall, perform adhesiolysis, and direct trocar placement without laparoscopic guidance. Safe and reliable gastric closure remains the sole limitation to its clinical use outside of a protocol necessitating a gastrotomy.

Prognostic relevance of ductal margins in operative resection of bile duct cancer - Corrected Proof

2010-02-01

Background: The clinical relevance of the ductal margins in operative resection of bile duct carcinoma has not been well established. The purpose of this study was to assess the prognostic significance of ductal margins in patients with bile duct carcinoma.Method: A total of 256 patients with bile duct carcinoma were analyzed retrospectively. We compared clinicopathologic features, outcomes, and recurrences among patients who underwent curative resections with free margins (D-FRE: n = 185), noncurative resections only resulting from the involvement of ductal margins with carcinoma in situ (D-CIS: n = 13), noncurative resections only caused by the involvement of ductal margins with invasive foci of carcinoma (D-INV: n = 17), and noncurative resections resulting from any other margin state and/or distant metastases (OTH: n = 41).Results: Histologic grades, node involvements, T classifications, and JSBS staging were significantly associated with the ductal margin state. The 5-year survival rate by Kaplan-Meier analysis was 54.7%, 52.4%, 17.6%, and 16.7% for patients with D-FRE, D-CIS, D-INV, and OTH, respectively. A multivariate analysis by the Cox proportional hazards model has shown that, in addition to lymph node involvement (P = 6.6 × 10–4) and venous invasion (P = 2 × 10–5), D-FRE versus D-INV and D-FRE versus OTH, but not D-FRE versus D-CIS, were independently associated with survival with P values of 8 × 10–4 and 1.4 × 10–5, respectively. Taken together along with the difference in the recurrence rates, patients with D-CIS seem to have outcomes similar to D-FRE but different from D-INV or OTH.Conclusion: Compared with free ductal margins, the ductal margins with invasive foci of carcinoma may involve a significant disadvantage in terms of patients' outcomes in surgical resection for bile duct carcinoma, unlike those with carcinoma in situ.

Postoperative Clostridium difficile-associated diarrhea - Corrected Proof

2010-02-01

Background: Abdominal surgery is thought to be a risk factor for Clostridium difficile-associated diarrhea (CDAD). The aims of this study were to discern pre-operative factors associated with postoperative CDAD, examine outcomes after postoperative CDAD, and compare outcomes of postoperative versus medical CDAD.Methods: Data from 3904 patients who had abdominal operations at Montefiore Medical Center were extracted from Montefiore's clinical information system. Cases of 30-day postoperative CDAD were identified. Pre-operative factors associated with developing postoperative CDAD were identified using logistic regression. Medical patients and surgical patients with postoperative CDAD were compared for demographic and clinical characteristics, CDAD recurrence, and 90-day postinfection mortality.Results: The rate of 30-day postoperative CDAD was 1.2%. After adjustment for age and comorbidities, factors significantly associated with postoperative CDAD were: antibiotic use (OR: 1.94), proton pump inhibitor (PPI) use (OR: 2.32), prior hospitalization (OR: 2.27), and low serum albumin (OR: 2.05). In comparison with medical patients with CDAD, postoperative patients with CDAD were significantly more likely to have received antibiotics (98% vs 85%), less likely to have received a PPI (39% vs 58%), or to have had a prior hospitalization (43% vs 67%). Postoperative patients with CDAD had decreased risk of mortality when compared with medical patients with CDAD (HR 0.36).Conclusion: CDAD is an infrequent complication after abdominal operations. Several avoidable pre-operative exposures (eg, antibiotic and PPI use) were identified that increase the risk of postoperative CDAD. Postoperative CDAD is associated with decreased risk of mortality when compared with CDAD on the medical service.

Late association of hyperparathyroidism in septic patients with multiple organ failure - Corrected Proof

Charles E. Lucas, Anna M. Ledgerwood, Christopher C. Jeffries, Patricia Vernier — 2010-02-01

Background: Hypocalcemia after severe shock or sepsis stimulates release of parathyroid hormone (PTH), which abates with recovery. Sustained sepsis with multiple organ failure (MOF), however, may cause a resurgent release of PTH and life-threatening hypercalcemia.Methods: Thirty critically ill patients with prolonged sepsis developed combined hypercalcemia with elevated serum PTH levels. The primary insult was trauma in 12 patients, peritonitis in 14, and pancreatitis in 4. MOF involved the lungs in 30 patients, kidney in 16, gut in 30, brain in 13, and a coagulopathy in 10. There were 12 deaths; hospital stay averaged 81 days.Results: Hypercalcemia with increased serum levels of PTH occurred usually 3–4 weeks after the septic insult. Bradycardia, thought to be caused by the hypercalcemia, occurred in 19 patients, was attributed to a vasovagal reaction, and was treated with atropine. When asystole resulted, epinephrine and cardiopulmonary resuscitation were administered. Five patients required placement of an intravenous pacemaker. Bradycardia was acutely lethal in 4 patients; in a 5th patient, the decision was made for comfort care alone, and he died 9 days later. Bisphosphonate was given to 7 patients with this hypercalcemic-induced bradycardia and, prophylactically, to prevent bradycardia in 9 others. Hypercalcemia corrected in all patients; bradycardia abated in 7 patients.Conclusion: Hyperparathyroidism may occur with MOF secondary to sepsis. The mechanism is unclear, but the resultant bradycardia can be life threatening. Treatment with bisphosphonate corrects the hypercalcemia and bradycardia. Both the hypercalcemia and the bradycardia normalize when the MOF resolves.

Esophageal replacement by allogenic aorta in a porcine model - Corrected Proof

2010-02-01

Background: Esophageal replacement is a challenging problem requiring complex reconstruction. In response to the recent success of tracheal replacement by fresh allogenic aorta in humans, we assessed in a pig model the feasibility of circumferential segmental esophageal replacement by a fresh aortic allograft.Methods: A 4-cm long aortic allograft was interposed after a circumferential 2-cm long resection of the cervical esophagus in 18 minipigs. Anastomoses were protected temporarily by self-expanding polyester-silicone stents (Polyflex®; Boston Scientific, Montigny-le-Bretonneux, France). No immunosuppression was given. When stenosis occurred after stent removal or migration, a new stent was inserted. After clinical and endoscopic evaluation, pigs were killed sequentially at 1, 3, 6 and 12 months for analysis.Results: Mortality during the first month was 33%. Four animals died from stent migration during the entire follow-up. Maintenance of a lumen through the graft area by a stent was necessary for 6 months, in order to avoid stenosis occurrence. After the sixth postoperative month, esophageal lumen remained patent until the twelfth month, allowing an apparently normal feeding and weight gain. Gradual contraction of the graft area was observed with time. Sequential histologic analysis showed an inflammatory reaction that decreased with time and a progressive epithelialization of the graft area which became similar to native esophageal epithelium. After 12 months, islets of smooth muscle organized as fascicules or in bundles were visible within the fibrotic tissue.Conclusion: Short esophageal replacement by fresh aortic allograft, under the cover of a temporary maintenance of the lumen of the graft area by an esophageal stent, allows the restitution of a patent esophageal lumen and nutritional autonomy.

Real-time, near-infrared, fluorescence-guided identification of the ureters using methylene blue - Corrected Proof

2010-02-01

Background: The aim of this study was to determine whether the invisible near-infrared (NIR) fluorescence properties of methylene blue (MB), a dye already approved by the U.S. Food and Drug Administration for other indications, could be exploited for real-time, intra-operative identification of the ureters.Methods: The optical properties of MB were quantified in vitro. Open surgery and laparoscopic NIR fluorescence imaging systems were employed. Yorkshire pigs were injected intravenously with 0.1-mg/kg MB (n = 8), 10-mg furosemide followed by 0.1-mg/kg MB (n = 6), or 0.5-mg/kg MB (n = 6). The contrast-to-background ratio (CBR) of the kidney and ureters, and the MB concentration in the urine, were quantified.Results: Peak MB absorbance, emission, and intensity in urine occurred at 668 nm, 688 nm, and 20 μmol/L, respectively. After intravenous injection, doses as low as 0.1-mg/kg MB provided prolonged imaging of the ureters, and a dose of 0.5 mg/kg provided statistically significant improvement of CBR. The preinjection of furosemide increased urine volume but did not improve CBR. Laparoscopic identification of the ureter using MB NIR fluorescence was demonstrated.Conclusion: Ureteral imaging using MB NIR fluorescence provides sensitive, real-time, intraoperative identification of the ureters during open and laparoscopic surgeries.

Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents - Corrected Proof

2010-02-01

Background: Iatrogenic bile duct injuries are serious complications with patient morbidity. We hypothesized that the invisible near-infrared (NIR) fluorescence properties of methylene blue (MB) and indocyanine green (ICG) could be exploited for real-time, intraoperative imaging of the extrahepatic bile ducts during open and laparoscopic surgeries.Methods: In all, 2.0 mg/kg of MB and 0.05 mg/kg of ICG were injected intravenously into 35-kg female Yorkshire pigs and the extrahepatic bile ducts were imaged over time using either the Fluorescence-Assisted Resection and Exploration (FLARE) image-guided surgery system (open surgery) or a custom NIR fluorescence laparoscopy system. Surgical anatomy was confirmed using x-ray cholangiography. The contrast-to-background ratio (CBR), contrast-to-liver ratio (CLR), and chemical concentrations in the cystic duct (CD) and common bile duct (CBD) were measured, and the performance of each agent was quantified.Results: Using NIR fluorescence of MB, the CD and CBD could be identified with good sensitivity (CBR and CLR ≥4), during both open and laparoscopic surgeries, from 10 to 120 min postinjection. Functional impairment of the ducts, including constriction and injury were immediately identifiable. Using NIR fluorescence of ICG, extrahepatic bile ducts did not become visible until 90 min postinjection because of strong residual liver retention; however, between 90 and 240 min, ICG provided exquisitely high sensitivity for both CD and CBD, with CBR ≥8 and CLR ≥4.Conclusion: We demonstrate that 2 clinically available NIR fluorophores, MB fluorescing at 700 nm and ICG fluorescing at 800 nm, provide sensitive, prolonged identification of the extrahepatic bile ducts and assessment of their functional status.

Multiple calcifying fibrous tumors: An incidental finding - Corrected Proof

Navya Nair, Fan Chen, David Klimstra, Umut Sarpel — 2010-02-01

A 42-year-old Chinese man with chronic hepatitis B was referred to our clinic for evaluation of an intra-abdominal mass found incidentally on routine imaging screening for hepatocellular carcinoma. The patient had no other past medical history and at the time of admission complained only of mild nausea. Physical examination and laboratory values were unremarkable. Computed tomography (CT) revealed a 2.7 × 3.6 × 3.7-cm mass in the small bowel mesentery. The mass was not associated with any vascular structures and contained peripheral coarse calcifications. The patient was subsequently admitted for a laparoscopic biopsy of the mass.

Role of Akt-dependent up-regulation of hemeoxygenase-1 in resveratrol-mediated attenuation of hepatic injury after trauma hemorrhage - Corrected Proof

Huang-Ping Yu, Shun-Chin Yang, Ying-Tung Lau, Tsong-Long Hwang — 2010-02-01

Background: Protein kinase B (Akt) is known to be involved in pro-inflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of hemeoxygenase (HO)-1, which exerts potent anti-inflammatory effects. The aim of this study is to elucidate whether Akt/HO-1 plays any role in resveratrol-mediated attenuation of hepatic injury after trauma hemorrhage.Methods: Male Sprague-Dawley rats were subjected to trauma hemorrhage. A single dose of resveratrol (30-mg/kg body weight) with or without a PI3 K inhibitor (wortmannin) or an HO antagonist (chromium-mesoporphyrin) was administered intravenously during resuscitation. Various parameters were measured at 24 hours postresuscitation.Results: Results showed that trauma hemorrhage increased hepatic myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels and plasma aspartate and alanine aminotransferases concentrations. These parameters were significantly improved in the resveratrol-treated rats subjected to trauma hemorrhage. Resveratrol treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma hemorrhaged rats. Coadministration of wortmannin or chromium-mesoporphyrin prevented the beneficial effects of resveratrol administration on postresuscitation proinflammatory responses and hepatic injury.Conclusion: These findings collectively suggest that the salutary effects of resveratrol administration on attenuation of hepatic injury after trauma hemorrhage are likely mediated via up-regulation of Akt-dependent HO-1 expression.

Sealing effect of a polysaccharide nanosheet for murine cecal puncture - Corrected Proof

2010-02-01

Background: Recent developments in nanobiotechnology have led us to develop a method of producing a free-standing polymer nanosheet composed of polysaccharides (ie, polysaccharide nanosheet) with a thickness of tens of nanometers. Owing to its enormous aspect ratio, the polysaccharide nanosheet is semi-absorbent and has a physical adhesive strength 7.5-fold greater than that of conventional films of >1 μm thickness. Herein, we have investigated the therapeutic sealing effect of this polysaccharide nanosheet on murine cecal puncture as a wound dressing material.Methods: Murine cecum was punctured and then overlapped with the polysaccharide nanosheet. Thereafter, we evaluated its sealing effect on bacterial peritonitis as well as the protection offered by the polysaccharide nanosheet against bacterial permeability using an in vitro transmembrane assay.Results: The 39-nm-thick polysaccharide nanosheet overlapped tightly the perforated cecum. No adhering agents were required because of the ability of the polysaccharide nanosheet to adhere to the tissue surface by physical adsorption (eg, van der Waals interaction). Sealing the perforated cecum with the polysaccharide nanosheet increased survival rate without postoperative adhesion by comparison with untreated mice (90 vs 30%; P < .01). These data were supported by the improvement in peritonitis related to bacterial counts, white blood cell counts, and the serum tumor necrosis factor level. Moreover, using an in vitro transmembrane assay, we showed that the polysaccharide nanosheet inhibited effectively bacterial penetration.Conclusion: We have demonstrated the potential clinical benefits of the nanosheet-type biomaterial that can be used for repairing a cecal colotomy without chemical bonding agents.

Addressing access to palliative care services in the surgical intensive care unit - Corrected Proof

Ciarán Bradley, Jessica Weaver, Karen Brasel — 2010-01-25

Background: Proactive case-finding using consultation triggers is a currently unexplored technique of increasing access to palliative care for patients in the surgical intensive care unit (SICU).Methods: A retrospective, pre- and postintervention study examined the effect of an initiative involving palliative care consultation in a 21-bed SICU at an urban, tertiary referral center. The initiative identified patients meeting a set of consultation triggers suggested by a group of physicians with expertise in surgical palliative care. The charts of 300 patients were reviewed retrospectively before the initiative (Group I), and 344 charts were reviewed after the initiative (Group II) for the presence of a trigger and/or subsequent palliative care consultation.Results: Triggers were rare in both groups (Group I, 5.7%; Group II, 5.5%). Palliative care consultations were also infrequent, without change before and after the intervention (Group I, 2.3%; Group II, 3.1%). There was no difference in consultations for patients meeting a trigger after the initiative (17.6% to 27.3%; P = .704).Conclusion: Implementation of triggers does not increase palliative care consultations in the SICU. As an isolated intervention, triggers occur in too few patients to improve overall access to palliative care, suggesting that other methods should be further explored.

Hydrostatic intestinal edema induced signaling pathways: Potential role of mechanical forces - Corrected Proof

2010-01-25

Background: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema.Methods: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1–3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine.Results: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength.Conclusion: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.

Functional voice outcomes after thyroidectomy: An assessment of the Dsyphonia Severity Index (DSI) after thyroidectomy - Corrected Proof

2010-01-22

Background: The Dysphonia Severity Index (DSI) is an objective multiparametric acoustic calculation of vocal function; however, its changes after thyroidectomy have not yet been described.Methods: Patient-reported symptoms, as well as auditory perceptual, acoustic, and videolaryngostroboscopic (VLS) data, were collected prospectively before and after thyroidectomy. Voice outcomes (normal versus negative voice outcome [NVO]) at 6 months after thyroidectomy were based on a combination of voice symptoms and objective findings. The DSI was assessed over the perioperative course, and differences were determined with Wilcoxon signed rank tests. The DSI was compared between study groups (normal versus NVO) using t tests, analyses of variance (ANOVAs), or rank sum tests as appropriate. The predictive value of DSI for long-term voice dysfunction was assessed by an area under the receiver operating characteristics curve analysis. Correlations between DSI and Consensus Auditory Perceptual Ratings of Voice (CAPE-V) and the patient reported Voice Handicap Index (VHI) were determined with Pearson's correlation coefficients.Results: In all, 62 patients were evaluated before, 1–4 weeks after, and 6 months after thyroidectomy. Eight (13%) patients were diagnosed with NVO at 6 months. The DSI was different postoperatively between NVO and normal voice (P=.005, repeated measures [RM]-ANOVA), with the NVO group demonstrating a lesser DSI value and greater change from pre-operative assessment at the first postoperative visit when compared with the normal group (P<.006 each). The DSI differed significantly for pre-operative and 6-month assessments according to sex, smoking status, and age. Short-term postoperative DSI (area under the curve [AUC]=0.795) and DSI change from baseline to 1–4 weeks (AUC=0.835) were highly predictive of 6-month NVO. DSI measurements over the post-thyroidectomy course were correlated poorly to moderately (maximum r = –0.62) with CAPE-V and VHI assessments for the same time points.Conclusion: The DSI is decreased in the early post-thyroidectomy period, mostly in persons who were ultimately found to have a long-term NVO. Early postoperative DSI and change of DSI from baseline at 1--4 weeks postoperation predict long-term post-thyroidectomy voice dysfunction. The modest correlations between the DSI and other vocal assessments point to the utility of DSI as an independent predictor of voice dysfunction after thyroidectomy, which can select patients who may benefit from voice therapy.

Does a positive lymphocyte cross-match contraindicate living-donor liver transplantation? - Corrected Proof

2010-01-22

Background: There is still no consensus on the importance of lymphocyte cross-matching (LCM) in the field of living-donor liver transplantation (LDLT).Methods: LCM examinations are routinely performed before LDLT, and the results of complement-dependent cytotoxicity were used in this study. A total of 1157 LDLT cases were evaluated. The recipients were divided into four groups based on the LCM and ABO compatibilities: (1) negative LCM and identical/compatible ABO; (2) negative LCM and incompatible ABO; (3) positive LCM and identical/compatible ABO; and (4) positive LCM and incompatible ABO. The diagnosis of antibody-mediated rejection (AMR) was made based on the clinical course, immunological assays and histopathological findings. C4d immunostaining was added if AMR was suspected.Results: The LCM-positive LDLT recipients showed significantly poorer outcomes than the LCM-negative recipients. Among the LCM-positive recipients, 44.1% of recipients eventually died and 85.2% of recipients revealed positive C4d findings. The survival rate of LCM-positive and ABO-incompatible group was 0.50. The survival days were compared with the LCM-negative and ABO-identical/compatible group, and the LCM-positive and ABO-identical/compatible group clearly showed early death after LDLT, although the ABO-incompatible groups did not show significant. The factors of age, disease, pre-transplant scores, LCM, ABO compatibility and graft-recipient weight ratio showed statistical significance in multivariate analysis for important factors of LDLT outcomes. However, the LCM and ABO compatibilities had no synergetic effects on the LDLT survival.Conclusion: HLA antigens are more widely expressed than ABO antigens, and advanced immunological strategies must be established for LCM-positive LDLT as well as for ABO-incompatible LDLT.

The utility of pre-operative peritoneal lavage examination in serosa-invading gastric cancer patients - Corrected Proof

2010-01-22

Background: Peritoneal dissemination is frequently found during laparotomy in patients with serosa-invading gastric cancer. Detection of exfoliated cancer cells in abdominal lavage cytology is indicative of stage IV because of its strong association with peritoneal dissemination. Herein we have described peritoneal lavage cytology using a bedside procedure under local anesthesia.Methods: A prospective study of 113 patients with serosa-invading gastric cancer but without peritoneal metastases was performed. A drainage tube was inserted into the abdominal cavity for peritoneal lavage. Patients with negative cytology (CY0) were scheduled for curative gastrectomy.Results: The bedside procedure was performed safely without any complications. Lavage cytology identified CY1 in 35 (31.0%) patients and CY0 in 78 (69.0%) patients. Patients with CY0 underwent laparotomy and peritoneal lavage cytology, and 9 were found to have peritoneal disease (3 with operative CY1, 4 with peritoneal dissemination, and 2 with both operative CY1 and peritoneal dissemination). Two other patients had small, distant metastases. Finally, curative gastrectomy was achieved in 67 (59.3%) patients, but not in 46 (40.7%) patients. Thus, our bedside, pre-operative peritoneal lavage detected 76.1% (35/46) of noncurative disease before operative with a false-negative rate for detecting peritoneal disease of 20.5% (9/44). Patients with pre-operative CY1 had a poorer prognosis than pre-operative CY0 (2-year cause-specific survival 26.6% vs 82.6%).Conclusion: Pre-operative bedside peritoneal lavage under local anesthesia followed by cytology is a simple and safe method for the pre-operative diagnosis of peritoneal dissemination and may help to reduce unexpected, noncurative surgery.

Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction - Corrected Proof

2010-01-22

Background: Ghrelin is a peptide hormone with pleiotropic functions including stimulation of growth hormone secretion and appetite, and its levels decrease after esophagectomy. The aim of this study was to evaluate whether exogenous ghrelin administration can meliorate the postoperative decrease of oral food intake and body weight, which are serious complications after esophagectomy.Methods: This prospective randomized, placebo-controlled, clinical trial assigned a total of 20 patients with thoracic esophageal cancer who underwent radical operation into either a ghrelin (n =10) or placebo (n =10) group. Synthetic human ghrelin (3μg/kg) or 0.9% saline placebo was administered intravenously twice daily for 10 days from the day after the start of food intake. The primary end point was calories of food intake. Comparison of appetite and changes in weight and body composition were also made between the 2 groups.Results: Intake of food calories was greater in ghrelin group than placebo group (mean 874 vs 605kcal per day; P =.015). The appetite score tended to be greater in ghrelin group than placebo group (P =.094). Loss of weight was less in ghrelin group (–1% vs –3%; P =.019) and this attenuation was due largely to a decrease of lean body weight loss (0% vs –4%; P =.012). No side effects were observed in either groups.Conclusion: These preliminary results suggest that administration of ghrelin after esophagectomy increased oral food intake and attenuated weight loss together with maintenance of lean body weight.

Identification of the anterior sectoral trunk with particular reference to the hepatic hilar plate and its clinical importance - Corrected Proof

2010-01-18

Background: At the hilum of the liver, there is a structure called the hilar plate, which is of great surgical importance because all variations in the bile ducts and blood vessels occur within this region. The Rex-Cantlie line does not always pass the point of portal bifurcation. Classifying portal vein (PV) variations based on the shape and origin of anterior sectoral trunk (AST) within the hepatic plate system will be of higher anatomical and surgical value than the conventional method based on PV ramification.Methods: We investigated PV variations in the hilar plate in terms of combinations of 4 hepatic sectoral trunks rather than successive ramification of the PV. The combination patterns of each sectoral trunk were analyzed using data from adult cadaver liver dissection (n = 64) and multi-detector computed tomography (n = 216) of human livers.Results: The AST root position on the hilar plate varies, in contrast to the other sectoral trunks, which are relatively consistent in their root position. Three types of PV variations were identified based on the AST root position. In addition, 4 similar but different shapes (I, Y, V, and U) of AST were identified.Conclusion: Not only the root position in the hepatic hilar plate but also the shape of AST can be considered as the major determinants of PV variations.

Obesity and pancreatic cancer: Possible role of the PI3K/Akt pathway - Corrected Proof

Xu-Feng Huang, Jiezhong Chen — 2010-01-18

To the Editors: Epidemiologic evidence is convincing that obesity is associated with the risk of various cancers. We have read with great interest the article by Zyromski et al. This study showed that obesity promotes the growth and dissemination of pancreatic cancer in Lepob and Lepdb mice. Importantly, the authors have shown that increased insulin and decreased adiponectin are associated with cancer growth and dissemination in the mice fed a high-fat diet. Furthermore, this study shows increased blood glucose levels in Lepob and Lepdb mice.

A novel method using the VIO soft-coagulation system for liver resection - Corrected Proof

2010-01-18

Background: The VIO soft-coagulation system (SCS) is a new device for tissue coagulation. The current study evaluated the efficacy of the SCS when used for liver resection.Methods: The 252 patients were divided into 2 groups; in 155 patients (conventional group), liver transection was performed using an ultrasonic dissector and saline-coupled bipolar electrocautery for hemostasis. In 97 patients (SCS group), the SCS was used instead of bipolar electrocautery.Results: The median blood loss and surgical time were less in the SCS group than in the conventional group (350 vs 640 mL, P = .0028; 280 vs 398 min, P < .0001). No significant differences were found in postoperative complications between the SCS group (32.0%) and the conventional group (40.6%). The risk factors for bleeding were nonuse of the SCS (P = .0039), macroscopic vascular invasion of the hepatic tumors (P = .0088), and collagen type IV value in the sera >200 (P = .0250) on multivariate analysis. In a subgroup analysis, in the collagen type IV value >200 subgroup, the tumor diameter >5 cm subgroup, and the inflow nonocclusion subgroup, use of the SCS decreased surgical bleeding (P = .0120, P = .0126, and P = .0032, respectively) and surgical time (P = .0001, P < .0001, and P = .0036, respectively) compared with the conventional group. Furthermore, even in the major hepatectomy group, the SCS use decreased surgical time (P < .0001).Conclusion: The SCS is an effective and safe device for decreasing surgical time and surgical bleeding without increasing the rate of bile leakage and causing other complications.

Endothelin-1-induced contractile responses of human coronary arterioles via endothelin-A receptors and PKC-α signaling pathways - Corrected Proof

2010-01-18

Background: We investigated the contractile function in responses to endothelin-1 (ET-1) in the human coronary microvasculature as well as the roles of endothelin receptors and protein kinase C-α (PKC-α) in these responses.Methods: Human atrial tissue was harvested from patients who underwent cardiac surgery pre- and post-cardioplegia (CP)/cardiopulmanory bypass (CPB). Microvascular constriction was assessed in pre- and post-CP/CPB samples in responses to ET-1, in the presence and absence of an endothelin-A (ET-A) receptor antagonist, an endothelin-B (ET-B) receptor antagonist, or a PKC-α inhibitor, respectively. The expression and localization of the ET-A and ET-B receptors were also examined using immunoblot and immunofluorescence photomicroscopy.Results: The post-CP/CPB contractile response of coronary arterioles to ET-1 was significantly decreased compared with the pre-CP/CPB responses. The response to ET-1 was significantly inhibited in the presence of the ET-A antagonist BQ123 (10−7mol/L), but these values remained unchanged with the ET-B receptor antagonist BQ788 (10−7mol/L). Pretreatment with the PKC-α inhibitor safingol (2.5 × 10−5 mol/L) reversed the ET-1 responses from contraction into relaxation. The total polypeptide levels of ET-A and ET-B receptors were not altered post-CP/CPB. Immunoblot and immunofluorescent staining displayed strong signals for ET-A receptors and relatively weak signals for ET-B receptors localized on coronary microvasculature.Conclusion: CP/CPB decreases the contractile function of human coronary microvessels in responses to ET-1. ET-A receptors are predominantly localized in the human coronary microcirculation, whereas ET-B receptors seem to be less abundant. The contractile response to ET-1 is in part through the activation of ET-A receptors and PKC-α. These results suggest a role of ET-1-induced contraction in the vasomotor dysfunction after cardiac surgery.

Intracolonic capsaicin stimulates colonic motility and defecation in conscious dogs - Corrected Proof

2010-01-18

Background: The aim of this study was to investigate the effects of intracolonic capsaicin on colonic motility and defecation.Methods: The effects of capsaicin (1, 2, 5, and 10 mg) administrated into the proximal colon on ileocolonic motility and defecation were studied in neurally intact dogs with or without various antagonists (atropine, hexamethonium, ondansetron, propranolol, and FK224), dogs with extrinsic denervation of an ileocolonic segment, and dogs with enterically isolated ileocolonic loops equipped with strain gauge force transducers.Results: Capsaicin at 5 and 10 mg evoked giant migrating contractions in a dose-independent manner, and it induced defecations with more than 90% probability in neurally intact dogs. These effects of capsaicin were abolished by atropine and hexamethonium. Ondansetron inhibited the capsaicin-induced increase in colonic motility but did not affect the induction of defecation. The other antagonists had no effect. In dogs with extrinsic denervation, capsaicin did not evoke giant migrating contractions in the colon but still induced defecation in 30–40% of experiments. In dogs with ileocolonic loops, capsaicin did not stimulate colonic motility nor induce defecation.Conclusion: These results indicate that intracolonic capsaicin causes giant migrating contractions and defecation. Intact extrinsic innervation, continuity of the colon, and intraluminal contents were considered necessary for this effect.

Clinical outcome after laparoscopic adrenalectomy for primary hyperaldosteronism: The role of pathology - Corrected Proof

2010-01-18

Background: Primary hyperaldosteronism (PHA) is potentially curable by laparoscopic unilateral adrenalectomy (LUA). Pre-operative assessment rarely differentiates adrenal adenoma from hyperplasia. This study aimed to evaluate the results of LUA for PHA according to pathologic findings when an adrenal mass was identified unequivocally on a CT scan.Methods: A retrospective analysis of LUA for PHA from July 1997 to May 2008 was performed. The minimal follow-up was 6 months. We considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM). Improvement was defined by a decrease of AM.Results: Fifty-seven patients were included. Thirty-six patients (63%) had an adrenal adenoma and 21 (37%) a hyperplasia. The median follow-up was 6.4 years. Hypokalemia was cured in all patients, 33 patients (58%) were cured of their hypertension, and 23 (96% of the 24 noncured patients) were improved with a reduction of the number of AM. Predictive factors for a cure were: gender, age, BMI, duration of hypertension, number of pre-operative AMs, pre-operative arterial systolic blood pressure, creatinin and plasma renin activity. Postoperative predictive factors were pathology, size of the mass, and systolic and diastolic arterial pressures. In the multivariate analysis the only remaining factor was pathology.Conclusion: LUA for PHA cured all patients from their hypokalemia and cured or improved hypertension in 98%. Pre-operative diagnosis of adenoma or hyperplasia is not mandatory but it is important to warn patients that hypertension can persist after adrenalectomy, especially in case of adrenal hyperplasia, although this hypertension is easier to control.

Chilaiditi's syndrome - Corrected Proof

2010-01-18

A 63-year-old man, suffering from arterial hypertension and Parkinson disease, presented to our unit with a 7-day history of respiratory distress, appetite loss, vomiting, aerophagia, and constipation. Physical examination showed a marked abdominal distension, but there were no peritoneal signs. There was no fever or tachycardia. Routine laboratory tests were also unremarkable. In the suspicion of a mechanical sub-occlusion due to a diaphragmatic hernia, an abdominal radiograph was taken. It revealed an elevation of the right hemidiaphragm and the presence of a subphrenic interposition of the colon above the liver (, arrow). An urgent contrast-enhanced computed tomography scan confirmed this clinical sign (, arrow). When asymptomatic, the presence of such interposition on radiograph is referred as “Chilaiditi's sign,” whereas the term syndrome includes abdominal pain, constipation, vomiting, respiratory distress, anorexia, and rarely, volvulus or obstruction.

Pathophysiology and treatment of the systemic inflammatory response syndrome from the perspective of evolutionary medicine - Corrected Proof

Tetsuji Fujita — 2010-01-11

To the Editors: As suggested in the November 2009 issue of Surgery by Lyte, there is increasing evidence in animals indicating that afferent fibers of the vagus nerve transmit intraperitoneal information such as an infectious “threat” to the brain. Little is known, however, about the role of the vagus nerve in the crosstalk between the gut and the brain in humans. We were unable to show the influence of vagotomy on the extent of fever and acute-phase protein response in patients undergoing gastric cancer surgery. The efferent vagus nerve has been implicated as an important antiinflammatory pathway in animal models of sepsis and hemorrhagic shock. Although Lyte mentions that, on the basis of evolutionary principles, the brain must initiate an appropriate response to information from the “leaky” gut, it may be difficult to explain the reason why the efferent vagus nerve sends an antiinflammatory signal from the perspective of evolutionary medicine. I agree with the usefulness of evolutionary concept for a better understanding of the systemic inflammatory response syndrome (SIRS), but I have some concerns about the statement that current therapy, such as the use of inotropic agents and antibiotics, may represent a continuous infectious threat that is responsible for an ever-escalating inflammatory response leading to unfavorable outcomes.

Adrenal ganglioneuromas: A 10-year experience in a Chinese population - Corrected Proof

2010-01-11

Background: Adrenal ganglioneuroma (GN) is extremely rare. The present study is to describe the largest series of this adrenal tumor treated in a single medical center to our knowledge.Methods: Clinical details, radiologic, laboratory, and pathologic findings as well as follow-up data were analyzed retrospectively in 17 patients with incidentally discovered adrenal GN who received operative resection at a tertiary referral hospital in eastern China between June 1999 and June 2009.Results: The mean age of the 17 GN patients was 39.2 years (range, 7–72; male:female ratio, 1:2.4), of whom 13 patients had unilateral GN on the right side, and the remaining 4 on the left side. None of the 17 tumors was hormonally active. Only 6 of the 17 GN cases were diagnosed as benign nerve cell tumors by computed tomography or magnetic resonance imaging before operation. Treatment consisted of open unilateral adrenalectomy in 9 patients and laparoscopy in 8 patients. The mean pathologic size of the adrenal GNs was 6.3 ± 3.1 cm (range, 1.0–13.0). Ultrastructural examination provided additional support for confirming the diagnosis.Conclusion: Although there have been some clues for radiologic diagnosis of adrenal GN, pre-operative mis- and maldiagnosis are not infrequent. We recommend that complete operative resection should be considered once malignancy cannot be excluded by pre-operative evaluation. Laparoscopic adrenalectomy is a reasonable option at least for tumors ≤7 cm.

Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type - Corrected Proof

2010-01-11

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is divided into 4 subtypes: an intestinal type, a gastric type, a pancreatobiliary type, and an oncocytic type. The purposes of this study were to clarify the outcomes and the characteristics of invasive carcinoma derived from IPMN (invasive IPMC) by focusing on these subtypes with a comparison to conventional invasive ductal carcinoma (IDC) of the pancreas.Methods: A total of 30 patients with invasive IPMC were reviewed, and the tumors were divided into 2 pathologic subtypes, intestinal and nonintestinal type. The prognosis and characteristics of the 2 subtypes were evaluated. Furthermore, the prognosis of 119 patients with conventional IDC was compared with that of patients with invasive carcinoma derived from the intestinal or nonintestinal type IPMN.Results: The 5-year survival rate of patients with the nonintestinal type (0.0%) was as poor as that of patients with conventional IDC (19.9%; P = .67). The patients with the intestinal type (66.7%) had a more favorable prognosis than patients with conventional IDC (P < .001). The nonintestinal type was characterized by positive lymphatic invasion and tubular invasive pattern.Conclusion: Invasive carcinoma derived from the nonintestinal type IPMN characterized by lymphatic invasion and tubular invasive pattern is associated with a poor prognosis.

Bone scan demonstration of osteoblastic tumor of the breast - Corrected Proof

Anne Marie Wallace, Robert D. Rosenberg, Melanie E. Royce — 2010-01-04

A 58-year-old woman presented with a 4×5-cm, superficial mass in the right breast that had reportedly doubled in size over 6 weeks. She had no prior history of breast pathology or other malignancies, and no significant family history. There was an obvious contour change owing to the palpable mass, but no concerning lymphadenopathy, inflammatory skin changes, skin dimpling, nipple retraction, or discharge. A routine screening mammogram 6 months before her presentation was negative. Diagnostic mammogram, ultrasonography, and magnetic resonance imaging (MRI) were performed. Mammography demonstrated a hyperdense, calcified mass with soft tissue rimming that corresponded with the physical examination findings. Ultrasonography showed a hypoechoic lesion. MRI identified a mass with worrisome intense peripheral enhancement and significant washout characteristics consistent with a malignancy (). Metastatic workup was negative; however, the bone scan demonstrated very intense uptake in the right breast. An attempt at ultrasound-guided core needle biopsy failed because of the extremely hard nature of the mass.

Administrative considerations when implementing American College of Surgeon Skills Curriculum - Corrected Proof

Deborah Rooney, Carla Pugh, Edward Auyang, Eric Hungness, Debra DaRosa — 2010-01-04

Background: With time and cost constraints, implementing an effective, yet efficient, skills curriculum poses significant challenges. Our purpose is to describe a successful curriculum administrative structure that promoted faculty buy-in and accountability, learner responsibility, and acceptable resource usage.Methods: A total of 14 American College of Surgery (ACS) modules were included in the postgraduate year 1 curriculum. Before arrival, 2 modules were sent to newly matched residents. Remaining modules were administered over a 4-month period, with integrated, independent practice opportunities, as well as 4 mentored and 1 peer practice sessions. A total of 2 verifications of proficiency (VOP) progress exams and 1 final comprehensive VOP were administered. To promote faculty ownership, 1 faculty member was asked to lead each module. Module leaders attended an orientation and development session, and created an instructional management plan. Each module was taught by the leader and 2 additional faculty coinstructors, and evaluated by residents. Equipment, resource costs, and man-hours were tracked.Results: Faculty buy-in was demonstrated by enthusiastic participation, with only 2 absences. Residents gave high ratings to all the modules (range, 4.22–4.89/5). Curriculum costs were approximately $21,500, reduced from potential costs of $187,000 if all simulators would have been purchased new. The estimated budget for year 2 is $17,000.Conclusion: It is critical for new curricula to have resident and faculty buy-in, accountability for quality teaching and learning, and reasonable resource use. We provide suggestions for structuring a curriculum to ensure accomplishment of these important drivers.

Taiwan hospital-based detection of Lynch syndrome distinguishes 2 types of microsatellite instabilities in colorectal cancers - Corrected Proof

2010-01-04

Background: With progress in techniques of molecular biology, the phenotypes and genotypes for Lynch syndrome are more diverse than thought previously. This hospital-based study estimated the incidence and molecular and clinicopathologic features of Lynch syndrome to modify the screening criteria for Taiwanese patients with colorectal cancer (CRC).Methods: A total of 561 CRC patients were enrolled. DNA was extracted from neoplasms, normal mucosa, and/or white blood cells for analyses of microsatellite instability (MSI), BRAF mutation, MLH1 methylation, and sequencing of MMR genes. Immunohistochemistry (IHC) staining for MMR proteins was done for cases that fulfilled revised Bethesda criteria and for high-frequency microsatellite instability (MSI-H) neoplasms.Results: There were 136 (24.2%) and 10 (1.8%) cases that fulfilled the Revised Bethesda and Amsterdam II criteria (ACII), respectively. MSI-H was detected in 41 (7.3%), of which 32 showed abnormalities for ≥1 MMR protein by IHC; low-frequency MSI (MSI-L) or microsatellite stable showed abnormal MSH2 staining in only 1 of 117 neoplasms. Thirteen (2.3%) cases had mutations in MMR genes with MLH1 (n = 10), MSH2 (n = 2), or MSH6 (n = 1). Of 13 Lynch syndrome cases, 3 (23.1%) and 11 (84.6%) fulfilled ACII and revised Bethesda criteria, respectively; 12 cases (93.3%) were MSI-H, and all had expression loss of ≥1 MMR protein. Eight patients were >50 years old, 2 of whom did not fulfill revised Bethesda criteria. For MSI-H neoplasms without definite mutations, 72.4% and 44.8% showed MLH1 methylation and a BRAF (V599E) mutation, respectively. Lynch-associated CRC and sporadic MSI neoplasms shared similar clinicopathologic featuresConclusion: In Taiwan, the incidence of Lynch syndrome was 2.3% among the 561 CRC patients evaluated. For Taiwanese CRC patients who are younger than age 60 whether or not fulfilling the Bethesda criteria should receive MSI or IHC screening for identification of the Lynch syndrome.

Overt diabetes mellitus adversely affects surgical outcomes of noncardiovascular patients - Corrected Proof

2010-01-04

Background: It is known that cardiac surgical patients with diabetes have greater peri-operative mortality and morbidity when compared with nondiabetic patients; the rate of adverse events in other surgery subspecialties has been only investigated minimally. The aim of this study was to test the magnitude of association between overt diabetes mellitus and postoperative complications across a spectrum of noncardiac surgical patients.Methods: Prospective outcome data registries describing 1,343 data sets from a spectrum of surgical subspecialties were examined to establish the prevalence of diagnosed diabetes, the incidence of intra- and postoperative complications, and the difference in proportion of morbidity between diabetic versus nondiabetic patients.Results: There was a significant difference in overall morbidity between diabetic and nondiabetic patients with a 2.0 and 1.6 times increased morbidity risk in known diabetic patients with and without malignancy, respectively. Known diabetes was related to the number of postoperative complications in noncardiovascular patients.Conclusion: This study quantified the association between known diabetes and the occurrence of complications during recovery after a spectrum of noncardiac surgery. Because of a high prevalence of prediabetic and undiagnosed conditions, the strength of associations between glucose dysregulation and operative outcomes may be even greater than we report.

Technologic developments in telemedicine: State-of-the-art academic interactions - Corrected Proof

2010-01-04

What sort of general impression do surgeons have of “telemedicine”? Is it convenient and useful? Or cumbersome and impractical? Or are they simply not interested or do not know about it? Allegedly, many surgeons have a positive impression of telemedicine, but it is likely that many surgeons would be in the latter groups: negative or uninformed, which reflects that telemedicine is not yet popular in the field of surgery. Nonetheless, telemedicine has been gaining popularity in the fields of radiology and pathology, where images are sent electronically from rural area hospitals that lack particular specialists to leading medical institutions to obtain a professional diagnosis. One example of this procedure that has drawn public attention is when clinical images are sent from the United States to India, which enables an overnight diagnosis, thus taking full advantage of the time difference and providing a solution for the shortage of related specialists in the United States. A notable difference between using telemedicine in radiology/pathology and using it in surgery, however, is that the transmitted material is static images and video images, respectively; transmitting detailed images in full motion requires a much larger data transmission volume than the former and makes it challenging technologically to use telemedicine in surgery.

A comparison of laparoscopic and robotic assisted suturing performance by experts and novices - Corrected Proof

2010-01-04

Background: Surgical robotics has been promoted as an enabling technology. This study tests the hypothesis that use of the robotic surgical system can significantly improve technical ability by comparing the performance of both experts and novices on a complex laparoscopic task and a robotically assisted task.Methods: Laparoscopic experts (LE) with substantial laparoscopic and robotic experience (n = 9) and laparoscopic novices (LN) (n = 20) without any robotic experience performed sequentially 10 trials of a suturing task using either robotic or standard laparoscopic instrumentation fitted to the ProMIS™ surgical simulator. Objective performance metrics provided by ProMIS™ (total task time, instrument pathlength, and smoothness) and an assessment of learning curves were analyzed.Results: Compared with LNs, the LEs demonstrated significantly better performance on all assessment measures. Within the LE group, there was no difference in smoothness (328 ± 159 vs 355 ± 174; P = .09) between robot-assisted and standard laparoscopic tasks. An improvement was noted in total task time (113 ± 41 vs 132 ± 55 sec; P < .05) and instrument pathlengths (371 ± 163 vs 645 ± 269 cm; P < .05) when using the robot. This advantage in terms of total task time, however, was lost among the LEs by the last 3 trials (114 ± 40 vs 118 ± 49 s; P = .84), while instrument pathlength remained better consistently throughout all the trials. For the LNs, performance was significantly better in the robotic trials on all 3 measures throughout all the trials.Conclusion: The ProMIS surgical simulator was able to distinguish between skill levels (expert versus novice) on robotic suturing tasks, suggesting that the ProMIS™ is a valid tool for measuring skill in robot-assisted surgery. For all the ProMIS™ metrics, novices demonstrated consistently better performance on a suturing task using robotics as compared to a standard laparoscopic setup. This effect was less evident for experts who demonstrated improvements only in their economy of movement (pathlength), but not in the speed or smoothness of performance. Robotics eliminated the early learning curve for novices, which was present when they used standard laparoscopic tools. Overall, this study suggests that, when performing complex tasks such as knot tying, surgical robotics is most useful for inexperienced laparoscopists who experience an early and persistent enabling effect. For experts, robotics is most useful for improving economy of motion, which may have implications for the highly complex procedures in limited workspaces (eg, prostatectomy).

Effects of isoniazid and niacin on experimental wound-healing - Corrected Proof

2010-01-04

Background: There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.Methods: One 8-mm, full-thickness wound was made in a standardized, ischemic skin flap and 1 in adjacent nonischemic skin on the back of male Sprague-Dawley rats. Starting just after wounding, twice-daily intraperitoneal isoniazid (10 mg/kg b.i.d.), xanthinol nicotinate (30 mg/kg), or saline (control) were given for 14 days. Wound-healing was monitored by planimetry and oxygen tension in periphery of the wound using a microcatheter probe. Cellular proliferation in granulation tissue was assessed by immunohistochemical detection of proliferating cell nuclear antigen. The angiogenic activity of isoniazid and niacin was assessed using in vitro and ex vivo models.Results: Although wound ischemia was evident by decreased oxygen tension (26 ± 10 mm Hg; n = 9) compared with the adjacent nonischemic wounds (51 ± 8 mm Hg; n = 8), neither compound significantly influenced intracutaneous oxygen tension. Isoniazid (P < .0001), but not niacin, promoted ischemic wound-healing even though both compounds increased proliferation measured on day 14 (P < .01). In normal wounds, the cumulative change in relative wound area over 14 days was increased by niacin (P = .002), but not by isoniazid, although both niacin (P = .011) and isoniazid (P = .036) increased cellular proliferation. Neither isoniazid nor niacin showed activity in either an endothelial tube formation assay or organotypic angiogenic assay under normoxic conditions.Conclusion: Isoniazid was capable of stimulating wound-healing in ischemic tissue to the level of nonischemic wounds and might offer a novel treatment option for wounds associated with arterial insufficiency. Although active in normal wounds, niacin did not promote ischemic wound-healing.

Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma - Corrected Proof

2010-01-04

Background: Epidemiologic studies have shown that obesity is associated with an increased risk of thyroid cancer. Leptin, an adipocyte-derived cytokine, can act as a growth factor on certain normal and transformed cells. Aberrant expression of leptin or leptin receptor has been detected in some types of cancer. The aim of this study is to determine immunohistochemical expression of leptin and leptin receptor in papillary thyroid cancer to investigate the relationship between their expression and clinicopathologic features.Methods: The expression of leptin and leptin receptor was assessed in 49 primary neoplasms and 15 lymph node metastases using a semiquantitative immunohistochemical staining method.Results: Leptin and leptin receptor were expressed in 37% and 51% of papillary thyroid cancer, respectively. They were not expressed in normal follicles. In the primary neoplasms and the metastatic nodes, expression of leptin correlated closely with leptin receptor (P < .001 for the primary neoplasms and P = .017 for nodal metastases). Expression of either protein was associated with greater neoplasm size (leptin expression, 32.0 ± 10.7 vs 20.5 ± 8.4 mm; P = .001; leptin receptor expression, 27.9 ± 11.5 vs 21.4 ± 9.0 mm; P = .032). Coexpression of leptin and leptin receptor in primary neoplasms had greater incidence of lymph node metastasis (P = .038).Conclusion: Expression of leptin and/or leptin receptor in papillary thyroid cancer is associated with neoplasm aggressiveness, including tumor size and lymph node metastasis.

Fifty years ago - Corrected Proof

Henry Gans — 2009-12-31

In 1960, whenever we worked late at night, George Schimert, a surgical resident on the cardiac surgery service at the University of Minnesota Hospitals in 1960, and I would meet for the free late-night supper for residents on call. At this meal, we would discuss current events and, of course, our own work. That is how he found out about epsilon aminocaproic acid (EACA). I had told him that I had just received a shipment of this new experimental drug from Merck that was supposed to be effective in the treatment of bleeding caused by fibrinolysis. As far as we knew, this condition occurred only rarely.

Cryoablation induces greater inflammatory and coagulative responses than radiofrequency ablation or laser induced thermotherapy in a rat liver model - Corrected Proof

2009-12-31

Background: Cryoablation (CA), radiofrequency ablation (RFA), and laser induced thermotherapy (LITT) are alternative therapies for patients with unresectable liver tumors. We investigated whether there are different inflammatory and coagulative responses between these techniques.Methods: Livers of 48 rats were subjected to either CA, RFA, LITT, or sham operation (n = 12 in each group). Blood was withdrawn before, and 1, 3, 6, and 24 h after ablation. Liver enzymes as well as inflammatory and coagulation parameters were determined. Whole liver sections from the coagulated liver lobe were stained for quantification of necrosis and morphologic examination.Results: Histologic examination showed similar volume of complete destruction of liver parenchyma after CA, RFA, or LITT. Transaminase levels as well as the inflammatory response upon CA, as reflected by white blood cell count and cytokine levels, were significantly higher than following RFA or LITT. The systemic intravascular procoagulative state in rats that underwent CA, as reflected by platelets, and levels of sensitive markers for activation of coagulation and fibrinolyis, was also significantly higher.Conclusion: CA of liver in rats induces greater inflammatory and coagulative responses than RFA or LITT. The combined activation of inflammation and coagulation may importantly contribute to the higher morbidity after CA.

Incidence of pancreatic anastomotic failure and delayed gastric emptying after pancreatoduodenectomy in 507 consecutive patients: Use of a web-based calculator to improve homogeneity of definition - Corrected Proof

Yasushi Hashimoto, L. William Traverso — 2009-12-17

Background: Many definitions are used in the literature for pancreatic anastomotic failure (PAF) and delayed gastric emptying (DGE) after pancreatoduodenectomy (PD). To promote homogeneity, published reports after 2005 have used the International Study Group on Pancreatic Surgery (ISGPS) consensus definition for PAF and DGE; however, subsequent authors have had to interpret or modify the ISGPS classification to make it useable. The solution might be to create a web-based calculator, test it for ambiguity and reliability with a large number of cases, and then make it available to the public.Methods: Using 507 consecutive patients undergoing PD and 14 questions, we created a web-based calculator based on the ISPGS classification to assess the incidence and grade of clinical impact (none, moderate, or major deviation) for PAF and DGE. As the calculator's formulas were tested, ambiguous terms were identified and resolved.Results: The incidence for cases with clinical impact from PAF was 10% and from DGE it was 12%. Multivariate analysis identified 4 factors predictive for PAF: male sex, body mass index (BMI) >30 kg/m2, soft gland texture, and main pancreatic duct size ≤3 mm. Predictive factors for DGE included 2 factors: not using a surgical microscope, and simultaneous PAF.Conclusion: A web-based calculator was developed to promote homogeneity of method for grading of PAF and DGE after PD. Anyone with access to the web can now compare their results to the current study.

Outcome of repeat hepatectomy in patients with hepatocellular carcinoma aged 75 years and older - Corrected Proof

2009-12-16

Background: We sought to evaluate the influence of age on the outcome of repeat hepatectomies in patients ≥75 years with recurrent hepatocellular carcinoma (HCC).Methods: We studied 121 curative repeat hepatectomies retrospectively. Among the 121 patients, 100, 20, and 1 received second, third, and fourth hepatectomies, respectively. The short-term surgical results of a younger group (<75 years; n = 88) and those of an elderly group (≥75 years; n = 33) were compared. The long-term prognosis of the patients who underwent second hepatectomies was also compared between a younger group (<75 years; n = 77) and an elderly group (≥75 years; n = 23).Results: The patients in the elderly group displayed more comorbid conditions pre-operatively, including hypertension and cardiovascular diseases, than the younger group (P < .05); however, there was no significant difference in the incidence of postoperative complications or the duration of postoperative hospital stay. The long-term prognosis in the elderly group was almost identical to that in the younger group. The 3-year overall survival rates for the younger group and the elderly group were 83 vs 73% (P = .51). Disease-free, 3-year survival rates for the younger group and the elderly group were 35% vs 38% (P = .88).Conclusion: Our findings suggest that advanced age by itself does not have an adverse effect on operative outcomes, including postoperative complications and long-term prognosis. Repeat hepatectomy may, therefore, be justified for recurrent HCC in selected elderly patients.

Effect of heat-shock protein-90 (HSP90) inhibition on human hepatocytes and on liver regeneration in experimental models - Corrected Proof

2009-12-16

Background: Targeting heat shock protein 90 (HSP90) has gained great interest for cancer therapy. However, in view of novel multimodality therapy approaches for treating hepatic metastases, concerns have raised regarding the impact of targeted therapies on liver regeneration and repair. In this study, we investigated the impact of HSP90 inhibition on liver regeneration in murine models.Methods: Effects of HSP90 inhibition on the activation of signaling intermediates, expression of vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were investigated in primary human hepatocytes (PHHs) in vitro. Effects of HSP90 inhibition on liver regeneration and repair were determined in a murine hepatectomy model and in a model with acute carbon tetrachloride (CCl4)-induced liver damage.Results: Inhibition of HSP90 effectively diminished the constitutive phosphorylation of Akt, Erk, and STAT3 in PHHs. Conversely, inhibition of HSP90 significantly increased the expression of both VEGF and HGF mRNA, and induced HSP70 protein in PHH cultures in vitro. In vivo, HSP90 inhibition significantly upregulated constitutive VEGF mRNA and HSP70 in murine livers and did not impair liver re-growth after 70% hepatectomy. Furthermore, BrdUrd-staining and histological quantification of necrotic areas revealed that HSP90 inhibition did not impair liver regeneration following partial hepatectomy, or liver repair that occurs after toxic liver injury with CCl4.Conclusion: Targeting HSP90 does not negatively affect the multifactorial process of liver regeneration and repair in vivo. Hence, the use of inhibitors to HSP90 appears to be a valid option for neoadjuvant therapy of liver metastases when subsequent surgery is intended.

Unknown etiology aortic aneurysm complicated with multiple vertebral erosions and aortoenteric fistula - Corrected Proof

Kilsoo Yie, Sung-Joon Lee, Se-Min Ryu, Hyoung-Rae Kim — 2009-12-16

A 43-year-old man without a specific family medical history was admitted for abrupt onset of massive hematemesis. He was a nonsmoker, and had no history of hypertension, fever, back pain, or trauma. No other abnormal findings were identified on physical examination, chest radiograph, or laboratory values, except anemia. The leukocyte count and C-reactive protein level were normal. Endoscopy showed active pulsatile bleeding from an ulcer in the third portion of the duodenum (, A).

Methodologies for establishing validity in surgical simulation studies - Corrected Proof

2009-12-16

Background: Validating assessment tools in surgical simulation training is critical to objectively measuring skills. Most reviews do not elicit methodologies for conducting rigorous validation studies. Our study reports current methodological approaches and proposes benchmark criteria for establishing validity in surgical simulation studies.Methods: We conducted a systematic review of studies establishing validity. A PubMed search was performed with the following keywords: “validity/validation,” “simulation,” “surgery,” and “technical skills.” Descriptors were tabulated for 29 methodological variables by 2 reviewers.Results: A total of 83 studies were included in the review. Of these studies, 60% targeted construct, 24% targeted concurrent, and 5% looked at predictive validity. Less than half (45%) of all the studies reported reliability data. Most studies (82%) were conducted in a single institution with a mean of 37 subjects recruited. Only half of the studies provided rationale for task selection. Data sources included simulator-generated measures (34%), performance assessment by human evaluators (33%), motion tracking (6%), and combined modes (28%). In studies using human evaluators, videotaping was a common (48%) blinding technique; however, 34% of the studies did not blind evaluators. Commonly reported outcomes included task time (86%), economy of motion (51%), technical errors (48%), and number of movements (25%).Conclusion: The typical validation study comes from a single institution with a small sample size, lacks clear justification for task selection, omits reliability reporting, and poses potential bias in study design. The lack of standardized validation methodologies creates challenges for training centers that survey the literature to determine the appropriate method for their local settings.

The impact of stress on surgical performance: A systematic review of the literature - Corrected Proof

2009-12-14

Background: Safe surgical practice requires a combination of technical and nontechnical abilities. Both sets of skills can be impaired by intra-operative stress, compromising performance and patient safety. This systematic review aims to assess the effects of intra-operative stress on surgical performance.Methods: A systematic search strategy was implemented to obtain relevant articles. MEDLINE, EMBASE, and PsycINFO databases were searched, and 3,547 abstracts were identified. After application of limits, 660 abstracts were retrieved for subsequent evaluation. Studies were included on the basis of predetermined inclusion criteria and independent assessment by 2 reviewers.Results: In all, 22 articles formed the evidence base for this review. Key stressors included laparoscopic surgery (7 studies), bleeding (4 studies), distractions (4 studies), time pressure (3 studies), procedural complexity (3 studies), and equipment problems (2 studies). The methods for assessing stress and performance varied greatly across studies, rendering cross-study comparisons difficult. With only 7 studies assessing stress and surgical performance concurrently, establishing a direct link was challenging. Despite this shortfall, the direction of the evidence suggested that excessive stress impairs performance. Specifically, laparoscopic procedures trigger greater stress levels and poorer technical performance (3 studies), and expert surgeons experience less stress and less impaired performance compared with juniors (2 studies). Finally, 3 studies suggest that stressful crises impair surgeons' nontechnical skills (eg, communication and decision making).Conclusion: Surgeons are subject to many intraoperative stressors that can impair their performance. Current evidence is characterized by marked heterogeneity of research designs and variable study quality. Further research on stress and performance is required so that surgical training and clinical excellence can flourish.

The relevance of transition zones on computed tomography in the management of small bowel obstruction - Corrected Proof

Modesto J. Colon, Dana A. Telem, Debbie Wong, Celia M. Divino — 2009-12-11

Background: Frequently, radiologists emphasize radiographic transition zones (RTZs) on computed tomography (CT), which are areas of abrupt change from dilated to collapsed bowel, as pathognomonic for small-bowel obstruction (SBO) diagnosis and location. The relevance of RTZs to patient management remains unknown. The purpose of this study was to determine the surgical predictive value and intraoperative accuracy of RTZ.Methods: A retrospective review of 200 patients with SBO who underwent abdominal CT at a single institution from 2002 to 2007 was performed. Statistical analysis was conducted using an unpaired t test, a Chi-square test, and multivariate analysis.Results: Of the 200 patients with SBO, 150 (75%) had an RTZ. Seventy-five (38%) patients required operative intervention; 58 (39%) patients had RTZ and 17 (34%) patients did not have RTZ (P=NS). The presence of RTZ was not associated with increased probability of operative versus nonoperative management (odds ratio=1.19; 95% confidence interval [0.61–2.32]). The mean time to operative intervention was 3.6 days. Immediate operative intervention (<24h) was equivalent in patients with versus without RTZ (57% vs 53%; P=NS) as was intervention for failed nonoperative management (43% vs 47%; P=NS). For patients who required operative intervention, RTZ correlated with intraoperative site of obstruction in only 31 (63%) patients.Conclusion: The presence of RTZs does not increase the likelihood of operative intervention or identify patients who will fail nonoperative management. RTZ should, therefore, not be used as a major criterion influencing operative versus nonoperative management decisions in patients with SBO. For patients who required operative intervention, RTZ had a 63% correlation with intra-operative findings, which makes it a useful adjunct to pre-operative planning.

Peritoneal adhesion formation and reformation tracked by sequential laparoscopy: Optimizing the time point for adhesiolysis - Corrected Proof

2009-12-11

Background: In a high proportion of patients, operatively lysed adhesions reform. Using a rabbit adhesiogenesis model, this study assessed the efficacy of adhesiolysis and examined how this relates to the tissue composition of adhesions at the time of lysis.Methods: Polypropylene meshes (5 × 3.5 cm) were implanted on the parietal peritoneum of New Zealand white rabbits. Some animals were killed 3, 7, 14, and 90 days postimplantation to obtain adhesion tissue. Adhesion formation/reformation was monitored by sequential laparoscopy in other animals kept for 90 days and in a separate experimental group subjected to adhesiolysis at 3 days postimplantation. Immune and inflammatory response markers were determined by immunohistochemical, Western blotting, and real-time reverse transcriptase polymerase chain reaction procedures in adhesion tissue; areas occupied by adhesions were quantified in meshes.Results: In animals undergoing adhesiolysis, mesh areas covered by adhesions were significantly decreased at each follow-up time and affected areas became mesothelialized. Increased transforming growth factor (TGF)-β1 expression was detected in adhesions at 3 days. Greatest TGF-β1 and vascular endothelial growth factor (VEGF) protein expressions were observed at 7 days, whereas genetic overexpression was noted at 14 days. Active inflammatory cells peaked at the 7-day time point.Conclusion: Adhesions formed at 3 days; at this critical time, an adhesiolysis was effective in preventing reformation of future adhesions. TGF-β1 gene and protein expression were increased in 3-day adhesions with respect to the omentum. Levels of active TGF-β1 and VEGF were increased at 7 days, along with the inflammatory response at this time point related to tissue remodeling, which led to stabilization of adhesions.

Definition and grading of anastomotic leakage following anterior resection of the rectum: A proposal by the International Study Group of Rectal Cancer∗ - Corrected Proof

2009-12-11

Background: Anastomotic leakage represents a major complication after anterior resection of the rectum. The incidence of anastomotic leakage varies considerably among clinical studies in part owing to the lack of a standardized definition of this complication. The aim of the present article was to propose a definition and severity grading of anastomotic leakage after anterior rectal resection.Methods: After a literature review a consensus definition and severity grading of anastomotic leakage was developed within the International Study Group of Rectal Cancer.Results: Anastomotic leakage should be defined as a defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments. Severity of anastomotic leakage should be graded according to the impact on clinical management. Grade A anastomotic leakage results in no change in patients’ management, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy.Conclusion: The proposed definition and clinical grading is applicable easily in the setting of clinical studies. It should be applied in future reports to facilitate valid comparison of the results of different studies.

Innominate artery aneurysm as presentation of angiosarcoma - Corrected Proof

Chuieng-Yi Lu, Ming-Shian Lu, Yao-Kuang Huang, Feng-Chun Tsai, Pyng Jing Lin — 2009-12-11

Six weeks prior to admission, a 66-year-old man presented at a local clinic with a 4-month history of dysphagia and paresthesia in his right arm. No body weight loss, hoarseness, or hemopytsis was noted. Diagnostic bronchoscopy, panendoscopy, and chest computed tomography (CT) without contrast was performed to determine the existence of a possible mediastinal lesion. No esophageal, endobroncheal, or lung lesion was found. However, chest CT revealed the presence of an anterior mediastinal mass. The mass was oval and measured 5 cm in diameter. CT angiography was performed 2 days later. It revealed the presence of a mediastinal mass bulging from the aortic arch. The mass was eventually identified as an innominate artery aneurysm. The diameter of the aneurysm increased from 50 mm to 65 mm within 2 days ().