Francis Sutherland

Meta‐analysis of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy

Pancreaticoduodenectomy is the primary treatment for periampullary cancer. Associated morbidity is high and often related to pancreatic anastomotic failure. This paper compares rates of pancreatic fistula, morbidity and mortality after pancreaticoduodenectomy in patients having reconstruction by pancreaticogastrostomy with those in patients having reconstruction by pancreaticojejunostomy.

Evaluating meta-analyses in the general surgical literature: a critical appraisal.

Objective:To assess the methodologic quality of meta-analyses of general surgery topics published in peer-reviewed journals. Summary Background Data:Systematic reviews and meta-analysis are used to seek, summarize, and interpret primary studies on a given topic. Accordingly, systematic reviews and meta-analyses of high-quality primary studies may be the highest level of evidence for issues of prevention and treatment in evidence-based medicine. However, not all published meta-analyses are rigorously performed. Methods:We searched MEDLINE (from January 1, 1997, to September 1, 2002) and reference lists and solicited general surgery specialists to identify relevant meta-analyses. Inclusion criteria were use of meta-analytic methods to pool the results of primary studies in general surgery on issues of diagnosis, causation, prognosis, or treatment. Our search strategies identified 487 potentially relevant articles. After excluding articles based on a priori criteria, 51 meta-analyses fulfilled eligibility criteria. In duplicate and independently, 2 reviewers assessed the quality of these meta-analyses using a 10-item index called the Overview Quality Assessment Questionnaire. Results:Overall concordance between 2 independent reviewers was good (interobserver agreement 81%, and a κ of 0.62 (95% CI 0.55–0.69). Of 51 relevant articles, 38 were published in surgical journals. Most studies had major methodologic flaws (median score of 3.3, scale of 1–7). Factors associated with low overall scientific quality included the absence of any prior meta-analyses publications by authors and meta-analyses produced by surgical department members without external collaboration. Conclusions:This critical appraisal of meta-analyses published in the general surgery literature demonstrates frequent methodologic flaws. The quality of these reports limits the validity of the findings and the inferences that can be made about the primary studies reviewed. To improve the quality of future meta-analyses, we recommend following guidelines for the optimal conduct and reporting of meta-analyses in general surgery.

Feasibility of Identifying Pancreatic Cancer based on Serum Metabolomics

Background: We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery. Methods: Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by 1H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by “targeted profiling” followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. Results: The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308). Conclusions: The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions. Impact: Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry. Cancer Epidemiol Biomarkers Prev; 20(1); 140–7. ©2010 AACR.

Serum metabolomic profile as a means to distinguish stage of colorectal cancer

BackgroundPresently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy.MethodsSera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each platform were compared between the following groups: locoregional CRC (N = 42); liver-only metastases (N = 45); and extrahepatic metastases (N = 25).ResultsThe serum metabolomic profile associated with locoregional CRC was distinct from that associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 × 10-7) and GC-MS (P = 1.79 × 10-7). Similarly, the serum metabolomic profile differed significantly between patients with liver-only metastases and with extrahepatic metastases. The change in metabolomic profile was most markedly demonstrated on GC-MS (P = 4.75 × 10-5).ConclusionsIn CRC, the serum metabolomic profile changes markedly with metastasis, and site of disease also appears to affect the pattern of circulating metabolites. This novel observation may have clinical utility in enhancing staging accuracy and selecting patients for surgical or medical management. Additional studies are required to determine the sensitivity of this approach to detect subtle or occult metastatic disease.

Peri-operative blood transfusion and operative time are quality indicators for pancreatoduodenectomy

BACKGROUND Minimization of blood loss during pancreatoduodenectomy requires careful surgical technique and specific preventative measures. Therefore, red blood cell (RBC) transfusions and operative time are potential surgical quality indicators. The aim of the present study was to compare peri-operative RBC transfusion and operative time with 30-day morbidity/mortality after pancreatoduodenectomy. METHODS All pancreatoduodenectomies (2005 to 2008) were identified using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP). RBC transfusions and operative time were correlated with 30-day morbidity/mortality. RESULTS Pancreatoduodenectomy was completed in 4817 patients. RBC transfusions were given to 1559 (32%) patients (1-35 units). Overall morbidity and mortality rates were 37% and 3.0%, respectively. Overall 30-day morbidity increased in a stepwise manner with the number of RBC transfusions (R = 0.69, P < 0.01). Although RBC transfusions and operative times were not statistically linked (P = 0.87), longer operative times were linearly associated with increased 30-day morbidity (R = 0.79, P < 0.001) and mortality (R = 0.65, P < 0.01). Patients who were not transfused also displayed less morbidity (33%) and mortality (1.9%) (P < 0.05). DISCUSSION Peri-operative RBC transfusion after pancreatoduodenectomy is linearly associated with 30-day morbidity. Longer operative time also correlates with increased morbidity and mortality. Therefore, blood transfusions and prolonged operative time should be considered quality indicators for pancreatoduodenectomy.

Colorectal Liver Metastases Contract Centripetally With a Response to Chemotherapy : A Histomorphologic Study

Recently, there has been considerable interest in neoadjuvant chemotherapy for colorectal liver metastases. However, there is little information that defines how much liver should be removed after a favorable response.

Umbilical hernia repair in the presence of cirrhosis and ascites: results of a survey and review of the literature

PurposeUmbilical hernias are common in cirrhotics, yet, their management poses several challenges. The objective of this paper was to evaluate the indications, selection criteria, and technical aspects of umbilical hernia repair in patients with cirrhosis and ascites.MethodsAn extensive review of the literature since 1980 was performed. A survey was also conducted to obtain expert consensus to supplement any available conclusions from the literature.ResultsNineteen surgeons (45%) responded to the survey. For asymptomatic hernias, all would consider hernia repair in Child’s A cirrhosis, but not in more advanced disease, whereas the vast majority would consider the repair of complicated hernias. This seems to reflect the respondents’ higher estimates of morbidity and mortality with more advanced liver disease. However, because the recent literature demonstrates much lower morbidity and mortality than in the past, many authors now advocate early elective repair. In addition, uncontrolled ascites appear to be strongly predictive of hernia recurrence (relative risk [RR] 8.5; 95% confidence interval [CI] 2.7–26.9).ConclusionsWhile acknowledging the limitations of this study, it appears that the early repair of umbilical hernias in patients with cirrhosis and ascites is safer than it was in the past and can be considered for selected patients. This may avoid increased morbidity and mortality associated with urgent repair later on. The control of ascites is critical to a successful outcome. Urgent repair of umbilical hernia in cirrhotic patients is indicated when complications develop.

Impact of Surgeon Training on Outcomes After Resective Hepatic Surgery

BackgroundHigher hospital and surgeon volumes have been associated with improved outcomes after hepatic resection. Subspecialty training has not previously been associated with improved outcomes after hepatic resection. The objective of this study was to determine what effects, if any, surgeon’s volume and training had on the outcomes after hepatic resection.MethodsAdministrative procedure codes were used to identify all adult patients from the fiscal year 1991–1992 to 2003–2004 who underwent a hepatic resection in two large urban health regions in Canada (Calgary and Capital health regions). The primary outcomes were operative mortality and postoperative complications.ResultsThere were 1107 hepatic resections in the stated time period performed by a total of 72 surgeons. There were 66 deaths, resulting in an in-hospital mortality rate of 6.0%, and an overall complication rate of 46%. Statistically significant predictors of operative mortality were: urgency of admission, diagnosis of primary hepatic malignancy, extent of resection, and increasing burden of comorbid medical illness. Surgeon training along with patient’s sex, the urgency of admission, diagnosis of primary hepatic malignancy, extent of resection, and increasing comorbidity were predictive of postoperative complications.ConclusionsThis study found surgeon training to be highly predictive of postoperative complications after hepatic resection.Higher hospital and surgeon volumes have been associated with improved outcomes after hepatic resection. Subspecialty training has not previously been associated with improved outcomes after hepatic resection. The objective of this study was to determine what effects, if any, surgeon’s volume and training had on the outcomes after hepatic resection. Administrative procedure codes were used to identify all adult patients from the fiscal year 1991–1992 to 2003–2004 who underwent a hepatic resection in two large urban health regions in Canada (Calgary and Capital health regions). The primary outcomes were operative mortality and postoperative complications. There were 1107 hepatic resections in the stated time period performed by a total of 72 surgeons. There were 66 deaths, resulting in an in-hospital mortality rate of 6.0%, and an overall complication rate of 46%. Statistically significant predictors of operative mortality were: urgency of admission, diagnosis of primary hepatic malignancy, extent of resection, and increasing burden of comorbid medical illness. Surgeon training along with patient’s sex, the urgency of admission, diagnosis of primary hepatic malignancy, extent of resection, and increasing comorbidity were predictive of postoperative complications. This study found surgeon training to be highly predictive of postoperative complications after hepatic resection.

Morbidity and Mortality Following Multivisceral Resections in Complex Hepatic and Pancreatic Surgery

Complex multivisceral resections in major hepatic and pancreatic surgery are relatively infrequent, and information regarding the morbidity and mortality associated with such resections is scant. The purpose of this paper is to describe the outcomes following such aggressive surgical treatment. A retrospective review of the outcomes following multiorgan resection in the setting of major liver or pancreatic resection was conducted from 2002 until July 2006. Patients who had a major hepatic or pancreatic resection plus resection of at least one other organ were included. The primary outcome measures analyzed were the postoperative morbidity and mortality. Secondary outcomes included recurrence rates and survival. Twenty-seven patients met the inclusion criteria. There were two postoperative deaths (7%). Complications occurred in 59% of patients. Complications were minor in 26% and severe in 33%. Complications were more frequent in older patients and in patients with pancreatic resections. Mortality was significantly increased in the setting of a pancreaticoduodenectomy. These more aggressive procedures should be considered to carry a higher risk of complications, particularly in patients undergoing pancreaticoduodenectomies. Patients should be selected carefully when undertaking complex multivisceral resections in major hepatic and pancreatic surgery.

A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases

BackgroundChemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides in vivo chemosensitivity data.MethodsA phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety.Results35 patients were accrued. During preoperative chemotherapy, 16 patients (46%) had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55%) had grade 3/4 toxicities. Deep venous thrombosis (DVT) occurred in 11 patients (34%) at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort.ConclusionA short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line.Trial RegistrationClinicalTrials.gov NCT00168155.