Sherif Abdel-Misih

A Randomized Prospective Multicenter Trial of Pancreaticoduodenectomy With and Without Routine Intraperitoneal Drainage

Objective:To test by randomized prospective multicenter trial the hypothesis that pancreaticoduodenectomy (PD) without the use of intraperitoneal drainage does not increase the frequency or severity of complications. Background:Some surgeons have abandoned the use of drains placed during pancreas resection. Methods:We randomized 137 patients to PD with (n = 68, drain group) and without (n = 69, no-drain group) the use of intraperitoneal drainage and compared the safety of this approach and spectrum of complications between the 2 groups. Results:There were no differences between drain and no-drain cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, baseline quality of life, or operative technique. PD without intraperitoneal drainage was associated with an increase in the number of complications per patient [1 (0-2) vs 2 (1-4), P = 0.029]; an increase in the number of patients who had at least 1 ≥grade 2 complication [35 (52%) vs 47 (68%), P = 0.047]; and a higher average complication severity [2 (0-2) vs 2 (1-3), P = 0.027]. PD without intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess (10% vs 25%, P = 0.027), severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. The Data Safety Monitoring Board stopped the study early because of an increase in mortality from 3% to 12% in the patients undergoing PD without intraperitoneal drainage. Conclusions:This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

A scoring system for the prognosis and treatment of malignant bowel obstruction.

BACKGROUND Malignant bowel obstruction is a common result of end-stage abdominal cancer that is a treatment dilemma for many physicians. Little has been reported predicting outcomes or determining the role of surgical intervention. We sought to review our experience with surgical and nonsurgical management of malignant bowel obstruction to identify predictors of 30-day mortality and of who would most likely benefit from surgical intervention. METHODS A chart review of 523 patients treated between 2000 and 2007 with malignant bowel obstruction were evaluated for factors present at admission to determine return to oral intake, 30-day mortality, and overall survival. Propensity score matching was used to homogenize patients treated with and without surgery to identify those who would benefit most from operative intervention. RESULTS Radiographic evidence of large bowel obstruction was predictive of return to oral intake. Hypoalbuminemia and radiographic evidence of ascites or carcinomatosis were all predictive of increased 30-day mortality and overall survival. A nomogram of 5 identified risk factors correlated with increased 30-day mortality independent of therapy. Patients with large bowel or partial small bowel obstruction benefited most from surgery. A second nomogram was created from 4 identified risk factors that revealed which patients with complete small bowel obstruction might benefit from surgery. CONCLUSION Two nomograms were created that may guide decisions in the care of patients with malignant bowel obstruction. These nomograms are able to predict 30-day mortality and who may benefit from surgery for small bowel obstruction.

Update and review of the multidisciplinary management of stage IV colorectal cancer with liver metastases

BackgroundThe management of stage IV colorectal cancer with liver metastases has historically involved a multidisciplinary approach. In the last several decades, there have been great strides made in the therapeutic options available to treat these patients with advancements in medical, surgical, locoregional and adjunctive therapies available to patients with colorectal liver metastases(CLM). As a result, there have been improvements in patient care and survival. Naturally, the management of CLM has become increasingly complex in coordinating the various aspects of care in order to optimize patient outcomes.ReviewA review of historical and up to date literature was undertaken utilizing Medline/PubMed to examine relevant topics of interest in patients with CLM including criterion for resectability, technical/surgical considerations, chemotherapy, adjunctive and locoregional therapies. This review explores the various disciplines and modalities to provide current perspectives on the various options of care for patients with CLM.ConclusionImprovements in modern day chemotherapy as allowed clinicians to pursue a more aggressive surgical approach in the management of stage IV colorectal cancer with CLM. Additionally, locoregional and adjunctive therapies has expanded the armamentarium of treatment options available. As a result, the management of patients with CLM requires a comprehensive, multidisciplinary approach utilizing various modalities and a more aggressive approach may now be pursued in patients with stage IV colorectal cancer with CLM to achieve optimal outcomes.

Influence of KRAS mutation status in metachronous and synchronous metastatic colorectal adenocarcinoma

Mutations in the v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild‐type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor‐directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy with and Without Routine Intraperitoneal Drainage

Objective: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. Background: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. Methods: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. Results: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. Conclusions: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Perioperative 18F-fluorodeoxyglucose–guided imaging using the becquerel as a quantitative measure for optimizing surgical resection in patients with advanced malignancy

BACKGROUND (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) scanning is a widely accepted preoperative tumor imaging modality. Herein, we evaluate the becquerel (Bq) as a potential novel quantitative PET measure for application of surgical specimen imaging. METHODS Retrospectively, PET-avid lesions that could be followed from preoperative imaging, confidently identified in the operating room, imaged ex vivo, and correlated with histopathology were included in this study. Bq counts from both in vivo (preoperative) and ex vivo (surgical specimen) PET/CT images were measured and correlated with histopathology. RESULTS Fifty-five PET-avid lesions in 37 patients were included. Forty-six of 55 PET-avid lesions identified were found to contain malignancy on histopathology. Mean Bq counts for the PET-avid lesions were significantly higher that the adjacent PET-nonavid areas (background) within both in vivo and ex vivo imaging (P < .001 and P < .001, respectively). When analyzing all 55 lesions, we found significant increases in Bq levels. PET-avid lesions from in vivo to ex vivo images (P < .001) without significant increases in Bq levels in PET-nonavid lesions from in vivo to ex vivo images (P = .06). When comparing Bq levels between the 2 groups (malignant and benign), we found significantly higher Bq counts in the malignant group on in vivo imaging (P = .02) as well as significantly lower Bq counts in FDG-nonavid areas on ex vivo imaging (P = .04) within the malignant group. Significant differences in PET-avid to PET-nonavid Becquerels ratios within both in vivo and ex vivo images (P = .004, P = .002 respectively) were found, with ex vivo ratio being significantly higher (P < .001). CONCLUSIONS (18)F-FDG PET/CT imaging using Bqs is the potential to discern malignant lesions from benign tissues within both in vivo and ex vivo scans.

Appendiceal Mixed Adeno-Neuroendocrine Carcinoma: A Population-Based Study of the Surveillance, Epidemiology, and End Results Registry.

Introduction Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathological diagnosis recently defined by the World Health Organization (WHO) in 2010. Prior to the definition by the WHO, tumors with both adenocarcinoma and neuroendocrine components were given multiple pathological designations making it difficult to characterize the disease. The aim of our study is to better characterize MANEC to better understand its natural history to influence patient care and positively impact outcomes. Materials and methods The surveillance, epidemiology, and end results program database was queried for all patients aged 18 years or older between 1973 and 2012 who had the diagnosis composite carcinoid (n = 249) of the appendix. Composite carcinoid tumors refer to tumors that have both adenocarcinoma and carcinoid tumor components present, consistent with that pathological diagnosis MANEC. For comparison, the database was also queried for carcinoid tumor of the appendix (n = 950), signet ring cell carcinoma of the appendix (n = 579), and goblet cell carcinoid (GCC) tumors of the appendix (n = 944). The data were retrospectively reviewed, and clinicopathological characteristics, treatment regimens, and survival data were obtained. Results The median age of diagnosis of MANEC tumors was 58 years of age. Eighty percent of patients were White, and 49% were female. Fifty-four percent of patients underwent hemicolectomy and 31% had partial/subtotal colectomy as their surgical management. Median overall survival for MANEC was 6.5 years (95% CI 4.5–9.7), which was statistically significantly shorter (p < 0.0001) in comparison to 13.8 years (95% CI 12.1–16.5) for GCC, 2.1 years (95% CI 1.8–2.3) for signet ring cell carcinoma, and 39.4 years (95% CI 37.1–NA) for carcinoid tumors. Discussion MANEC is a more aggressive clinical entity than both GCC of the appendix and carcinoid tumors of the appendix. Based on these findings, patients with MANEC tumors should undergo aggressive multidisciplinary cancer management.

Surgical management of colorectal cancer: a review of the literature.

BackgroundColon cancer management continues to evolve with significant advances in chemotherapy, surgical technique and palliative interventions. As the options of therapy have improved, so have the challenges of management of primary colon cancer.ReviewA review of historical and up to date literature was undertaken utilising Medline/PubMed to examine relevant topics of interest-related to the surgical management. Enhanced knowledge of genetics associated with colon cancer has improved our care of patients with hereditary colon cancer syndromes. Additionally, traditional approaches to surgical intervention for primary colon cancer have been questioned and will be discussed in this review including the role of laparoscopy, use of mechanical bowel preparation, management of the primary tumour in the face of metastatic disease, as well as the role of palliative intervention in select patients.ConclusionColon cancer has seen improvement and expansion of therapeutic approaches to primary colon cancer. Laparoscopy and palliative interventions have become widely accepted with level I evidence to demonstrate good patient outcomes. Traditional dogma with mechanical bowel preparation has been challenged and debunked with regards to the efficacious benefits previously accepted. The management of the primary tumour has now become increasingly complex as it appears to be a reasonable approach to manage the primary tumour non-operatively in select cases of extracolonic disease requiring management.

Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O 6 -methylguanine DNA methyltransferase as a biomarker for response

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression.

The Efficacy of Adjuvant Chemotherapy in Patients With Stage Ii/iii Resected Rectal Cancer Treated With Neoadjuvant Chemoradiation Therapy

Introduction: Patients with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant chemotherapy (CT) per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcomes in patients who did and did not receive adjuvant CT. Materials and Methods: We used a prospectively collected database for patients treated at The Ohio State University, and analyzed overall survival (OS), time to recurrence, patient characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using the &khgr;2 or Fisher exact test. Results: Between August 2005 and July 2011, 110 patients were identified and 71 patients had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor stage, and pathologic complete response between the 2 patient groups. Although patient characteristics showed a difference in age (median age 54.3 vs. 62 y, P=0.01) and advanced pathologic nodal status (43% vs. 19%, P=0.02), there was a significant difference in OS. Median OS was 72.6 months with CT versus 36.4 months without CT (P=0.0003). Median time to recurrence has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for patients across the spectrum of stage II and III rectal cancer.