Emmanuel E. Zervos

Pushing the Envelope Beyond a Centimeter in Rectal Cancer: Oncologic Implications of Close, But Negative Margins

BACKGROUND The treatment of rectal cancer has improved significantly over the last century. Advances in surgical and adjuvant therapy coupled with a better understanding of the natural history have allowed for acceptance of progressively diminished margins for distal neoplasms. In order to better define oncologically safe distal margins, we performed a meta-analysis of the existing worlds literature. STUDY DESIGN Studies were identified on Medline and ISI Web of Science using key words rectal cancer and margin. Studies were excluded if specific margins and local recurrence rates could not be extracted. All analyses were performed using Comprehensive Meta-Analysis Software (Biostat). RESULTS Twenty-one studies reported outcomes in relationship to distal margins. Seventeen studies, 4,885 patients, reported outcomes with margins of less than 1 cm. Analysis of all studies indicated a nonsignificant trend favoring greater margins. However, in order to understand distal margins in the context of current care standards, additional analyses were performed. Thirteen studies reported application of total mesorectal excision and/or radiation. There was no significant difference in local recurrence rates for margins less than 1 cm. In the 4 studies that reported neither total mesorectal excision nor radiation, a margin greater than 1 cm was favored. Increased recurrence rates and decreased survival were associated with positive final margins. CONCLUSIONS When total mesorectal excision is combined with radiotherapy, excellent local control can be expected with sphincter preservation for distal rectal cancers when margins are less than 1 cm, as long as final pathologic margins are negative.

Amelioration of Insulin Requirement in Patients Undergoing Duodenal Bypass for Reasons Other than Obesity Implicates Foregut Factors in the Pathophysiology of Type II Diabetes

BACKGROUND Foregut diversion and weight loss have been proposed as potential mechanisms for resolution of type II diabetes mellitus (T2DM) observed in patients undergoing gastric bypass for obesity. To support or refute the role of the foregut, we analyzed glycemic control in T2DM patients before and after foregut bypass for reasons other than morbid obesity. STUDY DESIGN Using ICD9/CPT codes, we identified patients undergoing Roux-en-Y gastrojejunostomy (RY) or Billroth II (BII) reconstruction over 10 years. Fasting blood glucose, insulin or oral diabetic agent requirement, and body mass index (BMI) before and after surgery were tabulated and compared using the Students t-test. Linear regression was applied to determine specific factors predictive of resolution or improvement in glycemic control including age, duration of diabetes, antidiabetic regimen, type of operation, and surgical indication. RESULTS Between 1996 and 2006, we identified 24 patients with T2DM out of a cohort of 209 who underwent either RY (12 of 24) or BII reconstruction (12 of 24) for cancer or peptic ulcer disease and survived more than 30 days after operation. Of this group, 75% were overweight (18 of 24 with BMI < 30 kg/m(2)) and 25% were class I morbidly obese (6 of 24 with BMI 30 to 35 kg/m(2)). Seventeen patients (71%) had either complete resolution (7 of 24 or 29%) or significant reduction (10 of 24 or 42%) in medication requirements; 7 patients (29%) did not have any improvement. Logistic regression failed to identify specific factors predicting improved glycemic control. CONCLUSIONS Complete resolution of T2DM in patients undergoing duodenal diverting surgery occurs in about one-third of nonobese patients. Improved glycemic control occurs in more than two-thirds and cannot be explained by surgically related weight loss alone. Surgical cure of T2DM may be possible in carefully selected nonobese patients.

Cutaneous apocrine adenocarcinoma: defining epidemiology, outcomes, and optimal therapy for a rare neoplasm.

Apocrine adenocarcinoma is a rare neoplasm. There is a paucity of data on demographics and survival with no clear consensus on management of at risk lymph nodes, therefore, we analyzed a large cohort of patients identified via a national tumor registry.

Gastrointestinal Malignancies: When Does Race Matter?

BACKGROUND African Americans have a poorer survival from gastrointestinal cancers. We hypothesized that socioeconomic status may explain much of this disparity. STUDY DESIGN Four years of population-based Medicare and Medicaid administrative claims files were merged with the Michigan Tumor Registry. Data were identified for 18,260 patients with colorectal (n = 13,001), pancreatic (n = 2,427), gastric (n = 1,739), and esophageal (n = 1,093) cancer. Three outcomes were studied: the likelihood of late stage diagnosis, the likelihood of surgery after diagnosis, and survival. Bivariate analysis was used to compare stage and operation between African-American and Caucasian patients. Cox proportional hazard models were used to evaluate differences in survival. Statistical significance was defined as p < 0.05. RESULTS In unadjusted analyses, relative to Caucasian patients, African-American patients with colorectal and esophageal cancer were more likely to present with metastatic disease, were less likely to have surgery, and were less likely to survive during the study period (p < 0.05). In a multivariate analysis, African-American patients had a higher likelihood of death from colorectal cancer than Caucasian patients. This difference, however, did not persist when late stage and surgery were taken into account (hazard ratio = 1.15, 95% CI = 1.06 to 1.24). No racial differences in survival were observed among patients with esophagus, gastric, or pancreatic cancer. CONCLUSIONS These data suggest that improvements in screening and rates of operation may reduce differences in colorectal cancer outcomes between African-American and Caucasian patients. But race has little influence on survival of patients with pancreatic, esophageal, or gastric cancer.

Cholangiocarcinoma: An emerging indication for photodynamic therapy

Cholangiocarcinoma (CC) is emerging as an important treatment indication for photodynamic therapy. CCs are generally unresectable locally invasive tumors that occlude the biliary tree leading to fatal cholangitis and liver failure. Biliary decompression via stenting offers symptomatic relief but does not control tumor growth. Founded on an initial case study followed by ever more sophisticated clinical research, including randomized trials, photodynamic therapy has garnered enough momentum to be considered as part of the standard of care for these patients. Further, preliminary clinical data show the potential for benefit of the use of PDT in a neoadjuvant and adjuvant fashion to the minority of patients currently considered resectable or of border line resectability. PDT also impacts interleukin-6 levels and may form the basis for a targeted therapy approach to this disease. We review the clinical rationale, current studies and potential future directions of PDT for patients with CC.

Perforated gastric corpus in a strangulated paraesophageal hernia: a case report

IntroductionPatients with paraesophageal hernias often present secondary to chronic symptomatology. Infrequently, acute intestinal ischemia and perforation can occur as a consequence of paraesophageal hernias with potentially dire consequences.Case presentationAn 86-year-old obtunded male presented to the emergency department with hypotension and severe back and abdominal pain. An emergency abdominal CT scan was ordered with a presumptive diagnosis of ruptured abdominal aortic aneurysm. CT topograms revealed extensive free intra-abdominal air and herniated abdominal viscera into the right hemithorax. Prior to completion of the CT study, the patient sustained a cardiopulmonary arrest. Surgery was consulted, but the patient was unable to be revived. Post-mortem examination revealed gross contamination within the abdomen and a giant, incarcerated, hiatal hernia with organoaxial volvulus and ischemic perforation.ConclusionCurrent recommendations call for prompt repair of giant hiatal hernias before they become symptomatic due to the increased risk of strangulation. Torsion of the stomach in large hiatal hernias frequently leads to a fatal complication such as this warranting elective repair as soon as possible.

Molecular targeted therapy for pancreatic adenocarcinoma: A review of completed and ongoing late phase clinical trials

Molecular targeted therapy is widely utilized and effective in a number of solid tumors. In pancreatic adenocarcinoma, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The purpose of this study is to review therapeutic molecular targets in completed and ongoing later phase (II and III) clinical trials to have a better understanding of the rationale and progress towards targeted molecular therapies for pancreatic cancer. The PubMed database and the NCDI clinical trial website (www.clinicaltrials.gov) were queried to identify phase II and III completed and published (PubMed) and ongoing (clinicaltrials.gov) trials using the keywords: pancreatic cancer and molecular targeted therapy. The search engines were further limited by adding Phase II or III, active enrollment and North American. A total of 14 completed and published phase II/III clinical trials and 17 ongoing trials were identified. Evaluated strategies included inhibition of growth factor receptors (EGFR, PDGFR, VGFR, IGF-1R), tyrosine kinase inhibitors, MEK1/2, mTOR blockade and PI3K and HER2-neu pathway inhibitors. Only one trial conducted by the National Cancer Institute of Canada and the PANTAR trial have demonstrated a survival improvement from EGFR inhibition using erlotinib. These trials ultimately led to FDA approval of erlotinib/Tarceva in advanced stage disease. It remains unclear whether new combinations of cytotoxic chemotherapy or immunotherapy plus molecular targeted therapy will be beneficial in management of pancreatic adenocarcinoma. Despite a number of phase II and III trials, to date, only erlotinib has emerged as an approved targeted therapy in pancreatic adenocarcinoma. There are several ongoing late phase trials evaluating a number of targets, the results of which will become available over the next 1 to 2 years.

Radiotherapy associated with improved survival for high-grade sarcoma of the extremity

The impact of radiotherapy on local control in limb‐preserving surgery for high‐risk sarcoma has been well studied. However, the impact of the use and timing of radiation therapy on survival is unclear.

Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

BackgroundMesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains.MethodsWe analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo.ResultsWe show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice.ConclusionThe mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice.

Assessment of health care cost for complex surgical patients: review of cost, re-imbursement and revenue involved in pancreatic surgery at a high-volume academic medical centre

BACKGROUND Pancreatic surgery is complex with the potential for costly hospitalization. METHODS A retrospective review of patients undergoing a pancreatic resection was performed. RESULTS The median age of the study population was 64 years. Half of the cohort was female (51%), and the majority were white (62%). Most patients underwent a pancreaticoduodenectomy (PD) (69%). The pre-operative age-adjusted Charlson comorbidity index was zero for 36% (n = 50), 1 for 31% (n = 43) and ≥2 for 33% (n = 45). The Clavien-Dindo grading system for post-operative complication was grade I in 17% (n = 24), whereas 45% (n = 62) were higher grades. The medians direct fixed, direct variable, fixed indirect and total costs were