Rectus abdominis atrophy after ventral abdominal incisions: midline versus chevron.

PURPOSE: Although many outcomes have been compared between a midline and chevron incision, this is the first study to examine rectus abdominis atrophy after these two types of incisions. METHODS: Patients undergoing open pancreaticobiliary surgery between 2007 and 2011 at our single institution were included in this study. Rectus abdominis muscle thickness was measured on both preoperative and follow-up computed tomography (CT) scans to calculate percent atrophy of the muscle after surgery. RESULTS: At average follow-up of 24.5 and 19.0 months, respectively, rectus abdominis atrophy was 18.9% greater in the chevron (n = 30) than in the midline (n = 180) group (21.8 vs. 2.9%, p < 0.0001). Half the patients with a chevron incision had >20% atrophy at follow-up compared with 10% with a midline incision [odds ratio (OR) 9.0, p < 0.0001]. No significant difference was observed in incisional hernia rates or wound infections between groups. CONCLUSION: In this study, chevron incisions resulted in seven times more atrophy of the rectus abdominis compared with midline incisions. The long-term effects of transecting the rectus abdominis and disrupting its innervation creates challenging abdominal wall pathology. Atrophy of the abdominal wall can not be readily fixed with an operation, and this significant side effect of a transverse incision should be factored into the surgeon's decision-making process when choosing a transverse over a midline incision.

Laparoscopic ischemic conditioning of the stomach prior to esophagectomy.

Several complications after esophagectomy with gastric pull-up are associated with ischemia within the gastric conduit. The aim of this study is to assess the feasibility of laparoscopic ischemic preconditioning of the stomach prior to thoracotomy, esophagectomy, and gastric pull-up with an intrathoracic anastomosis. A retrospective review of 24 consecutive patients between October 2008 and July 2011 with esophageal adenocarcinoma (stage I-III) undergoing laparoscopic gastric ischemic conditioning prior to esophagectomy was conducted. Conditioning included laparoscopic ligation of the left and short gastric arteries, celiac node dissection, and jejunostomy tube placement. Formal resection and reconstruction was then performed 4-10 days later. Of the 24 patients, 88% received neoadjuvant chemotherapy/radiation therapy. Twenty-three of the 24 patients underwent successful laparoscopic ischemic conditioning and subsequent esophagectomy. Total mean number of lymph nodes harvested was 21.8 (±8.0), and a mean of 5.3 (±2.4) celiac lymph nodes identified. There were no conversions to an open procedure. Length of stay was 3.8 (±4.8) days with a median length of stay of 2 (1-24) days. Three patients experienced anastomotic leak, six patients experience delayed gastric emptying, and two patients developed anastomotic stricture. There were no surgical site infections. R0 resection was achieved in all patients who underwent laparoscopic ischemic conditioning followed by esophagectomy. Laparoscopic ischemic conditioning of the gastric conduit has been shown to be feasible and safe.

The effects of bevacizumab on postoperative complications in patients undergoing colorectal and pancreatic cancer resection.

Bevacizumab (Avastin™; rhuMab VEGF), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has seen increased use in the perioperative treatment of colorectal and pancreatic cancer. Little is known, however, regarding its impact on surgical outcomes in patients undergoing resection. The objective of this review was to examine if the addition of bevacizumab to existing neoadjuvant regimens increases morbidity after cancer resection.

Outcomes after pancreatectomy for intraductal papillary mucinous neoplasms of the pancreas: an institutional experience.

PURPOSE: To evaluate the experience with pancreatectomy for intraductal papillary mucinous neoplasm (IPMN) at a single academic institution. METHODS: A prospective pancreatic database was reviewed and identified 43 patients with IPMN who were managed operatively. Clinicopathologic features and predictors of outcome were examined. The World Health Organization pathologic classification of IPMN was utilized. RESULTS: IPMN was diagnosed in 21% of patients who underwent pancreatic resection for solid or cystic mass lesions. Ninety-five percent of patients were symptomatic. Patients were managed with total pancreatectomy, pancreaticoduodenectomy, distal pancreatectomy, central pancreatectomy, or enucleation. Nine patients had adenomas, 14 had borderline neoplasms, 10 had carcinoma in situ, and 9 had invasive carcinoma. Overall, 23 patients (53%) had lesions with main duct involvement. Frozen section transection margins were positive for malignancy in 2 patients. With a mean follow-up of 17 months, the 5-year disease-specific survival for patients with main duct involvement was 67%. The 5-year disease-specific survival for patients with benign lesions was 100%, and 61% for patients with malignant lesions (P = .02). The presence of symptoms, increased CA 19-9, and tumor size were not predictive of malignancy. Increased serum bilirubin concentrations were predictive of malignancy (P = .03). Main duct involvement was also associated with malignancy (P < .02). CONCLUSIONS: Cancer is found in 65% of patients with IMPN involving the main duct. Based on our data, patients with symptomatic, main duct involvement, especially those with an increased serum bilirubin, should be offered resection. Alternatively, patients with side branch IPMN may be managed conservatively.

Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors.

BACKGROUND: We reviewed 36 patients with liver metastases from islet cell tumors of the pancreas (n = 18) and carcinoid tumors (n = 18) who were treated with surgical resection (n = 16) or hepatic chemoembolization (n = 20). METHODS: All resections were complete and included 4 lobectomies, 6 segmental resections, and 6 wedge resections. There were no operative deaths. RESULTS: Median survival has not yet been reached, and the actuarial 5-year survival rate is 70%. Prognostic variables associated with improved disease-free survival included prior resection of the primary tumor and 4 or fewer metastases resected (P <.05). With an average of 3 chemoembolization procedures per patient, 17 of 20 patients (90%) demonstrated either a significant radiographic response (n = 5), stabilization of tumor mass (n = 2), or improvement of clinical symptoms (n = 10). Factors related to a sustained response (more then 1 year) included surgical resection of the primary tumor, 4 or more chemoembolization procedures, and liver metastases of 5 cm or smaller. Median survival after treatment was 32 months (range, 7-63 months), and the actuarial 5-year survival rate was 40%. CONCLUSIONS: Surgical resection of metastatic neuroendocrine tumors provides the best chance for extended survival. Chemoembolization effectively improves clinical symptoms and, in selected patients, may provide sustained tumor control.

Screening for colorectal cancer: developing a preventive healthcare program utilizing nurse endoscopists.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. In 2000, approximately 130,200 new cases of colorectal cancer will be diagnosed, and 56,300 persons will die from the disease (Greenlee, Murray, Boldan, & Wingo, 2000). A survey conducted for the National Colorectal Cancer Roundtable by the Gallup Organization, found that 47% of people over 50 are not being screened. The National Colorectal Cancer Awareness Month, which began in March 2000, will educate Americans age 50 and older and prescribe physicians about the importance of colorectal cancer screening tests. The effect of increased education and directing physicians to include colorectal screening for their patients will create a need for non-physician endoscopists to meet the screening needs of the population. A colorectal cancer screening center was developed at a large Midwestern teaching hospital utilizing nurse endoscopists. The purpose of this article is to provide information for institutions to develop and implement a colorectal cancer screening center utilizing nurse endoscopists.

Organization and expression of the human zo-2 gene (tjp-2) in normal and neoplastic tissues.

One of the tight junction components, zonula occludens protein 2 (ZO-2), is expressed as two isoforms, ZO-2A and ZO-2C, in normal epithelia. In pancreatic adenocarcinoma of the ductal type ZO-2A is absent, but none of the common mechanisms of gene inactivation is responsible for lack of ZO-2A expression. In the current study, we report the complete organization of the human zo-2 gene (tjp-2), its alternative splicing, and its expression in normal and neoplastic tissues of several organ sites. In addition to pancreatic adenocarcinoma, ZO-2 was found to be de-regulated in breast adenocarcinoma, but not in colon or prostate adenocarcinoma. The latter are considered to be of acinar rather than ductal type. Thus, our data indicate the importance of zo-2 (tjp-2) gene regulation in ductal cancer development and should help to understand the defects of intercellular interactions, critical for suppressing the malignant phenotype.

Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: a regimen with unexpected early toxicity.

PURPOSE: We performed a phase I trial of protracted venous infusion (PVI) fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer to determine the maximum-tolerated dose of gemcitabine that could be safely administered. We also sought to identify the toxicities associated with this treatment protocol. PATIENTS AND METHODS: Seven patients with locally advanced pancreas cancer were treated with planned doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m(2)/d) with gemcitabine doses of 50 to 100 mg/m(2)/wk. RESULTS: Two of three patients at the 100-mg/m(2)/wk dose level experienced dose-limiting toxicity (DLT), as did three of four at the 50-mg/m(2)/wk dose level. One patient experienced a mucocutaneous reaction described as a Stevens-Johnson syndrome that was attributed to chemotherapy. Three patients developed gastric or duodenal ulcers with severe bleeding requiring transfusion. One patient developed severe thrombocytopenia lasting longer than 4 weeks. Three of the five episodes of DLT developed at radiation doses < or = 36 Gy. CONCLUSION: Based on this experience, we cannot recommend further investigation of regimens incorporating gemcitabine into regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity remains to be determined.

Primary gastrointestinal sarcomas: analysis of prognostic factors and results of surgical management.

BACKGROUND: This study was done to review the clinical presentation, surgical management, and prognostic factors for primary gastrointestinal sarcomas. METHODS: We reviewed medical records of 55 patients who were treated for primary gastrointestinal sarcomas from 1981 through 1996. Mean follow-up time was 32 months. RESULTS: Clinical findings included gastrointestinal bleeding (51%), palpable mass (36%), and abdominal pain (33%). The stomach was the most common site of disease (53%), followed by the small intestine (33%). Tumors were high grade in 76% of patients and low-grade in 24% of patients. Complete resection of all gross disease was accomplished in 35 patients (64%), incomplete resection in 17 patients (31%), and biopsy only in 3 patients (5%). Adjacent organ resection was required in 19 patients (35%). Overall actuarial survival was 22% (median survival, 32 months). Unfavorable prognostic factors were incomplete resection, high-grade histologic features, and tumor size of 5 cm or more (P<.05). En bloc resection of contiguous organs did not adversely effect survival. In patients with complete resections, tumor grade was the most important prognostic factor (median survival, 55 months vs 19 months for low-grade vs high-grade tumors; P<.05). CONCLUSIONS: Aggressive surgical resection, including en bloc resection of locally advanced tumors, appears warranted. Despite complete resections, patients with high-grade tumors remain at risk for recurrence.

Esophageal leiomyomatosis in a woman with a history of vulvar leiomyoma and Barrett's esophagus: a case report and review of the literature.

BACKGROUND: The diagnosis and treatment of esophageal pathology remains a challenge despite advances in preoperative endoscopy, radiographic staging, and perioperative care. CASE REPORT: In this article, we present an interesting case of esophageal leiomyomatosis in a woman with a history of vulvar leiomyoma and Barrett's esophagus. This paper represents the first reported simultaneous occurrence of these three pathologic entities in the English literature. CONCLUSIONS: The clinical presentation and characteristic pathologic findings in patients with esophageal leiomyomatosis are reviewed. Diagnostic and therapeutic approaches to esophageal masses are discussed including the indications for esophageal resection.

Results of gastric interposition for reconstruction of the pharyngoesophagus.

BACKGROUND: Free jejunal transfer has become the standard technique for reconstruction of the proximal pharynx and hypopharynx. Gastric tube interposition is an effective alternative when resection extends below the thoracic inlet. This study was done to determine current indications, review morbidity and mortality rates, and to define clinical and pathologic determinants of survival associated with this procedure. METHODS: We reviewed the records of 32 patients who underwent gastric tube interposition for reconstruction of the pharyngoesophagus from 1987 to 1997. RESULTS: The overall complication rate was 50%. Complications were more frequent in the reoperative group (22% vs 66%, P < .05). The overall fistula rate was 31%. The overall mortality rate was 12%. Ultimately, 71% of patients resumed oral feedings. The 5-year actuarial survival rate was 22%. Unfavorable prognostic factors associated with significantly reduced survival (P < . 05) included margin positive resection, positive lymph node involvement, and operations done for recurrent tumor CONCLUSIONS: Reconstruction of the pharyngoesophagus with gastric tube interposition is indicated for primary tumors of the hypopharynx and cervical esophagus with inferior extension below the thoracic inlet and recurrent tumors or benign strictures in which free jejunal transfer is not feasible or has failed. It can be done with acceptable morbidity and mortality and provides reasonable expectations for long-term survival and resumption of oral intake.

Learning sentinel node biopsy: results of a prospective randomized trial of two techniques.

BACKGROUND: Evidence indicates that sentinel node (SN) biopsy can accurately predict axillary nodal status. Debate exists as to the optimal method of SN identification. METHODS: Patients with clinical T1 or T2 tumors and negative axillae were randomized to SN localization with blue dye (B) alone (n = 50) or blue dye plus radioactivity (B+R) (n = 42). Patients undergoing needle localization (n = 47) were assigned to blue dye. RESULTS: The SN was identified in 110 patients (79%) and contained metastases in 28. The SN predicted the axillary nodal status in 96% of cases. The SN identification rate did not differ between B (88%) or B+R (86%) but was significantly lower in patients requiring localization (64%). The time to SN identification also did not differ between B and B+R. The number of cases done by an individual surgeon was a significant predictor of SN identification. A stepwise logistic regression analysis of factors influencing the success of SN identification identified tumor location, needle localization, number of operations, and body mass index as significant predictors. CONCLUSIONS: Our study does not identify any advantage for the use of the more expensive and complex method of SN identification using B+R compared with B alone, even for surgeons learning the techniques.

zo-2 gene alternative promoters in normal and neoplastic human pancreatic duct cells.

We have observed that 2 forms of zonula occludens 2 (ZO-2) protein, ZO-2A and ZO-2C, are expressed in normal human pancreatic duct cells, but only ZO-2C in pancreatic duct adenocarcinoma. We report here partial organization of the zo-2 gene. Transcription of 2 forms of ZO-2 mRNA is driven by alternative promoters P(A) and P(C). Lack of expression of ZO-2A in neoplastic cells is caused by inactivation of the downstream promoter P(A). Analysis of the promoter P(A) sequence and function in normal and neoplastic cells demonstrated that neither structural changes (mutations) nor a change in the pool of transcription factors is responsible for its inactivation. Although hypermethylation was found in a large number of cancer clones, treatment with 5-aza-2'-deoxycytidine did not fully cause the promoter function to recover. We conclude that the initial down-regulation of zo-2 promoter P(A) activity in pancreatic duct carcinomas is due to the structural or functional alteration(s) in the regulatory elements, localized outside the analyzed promoter region. Methylation of P(A) is responsible for the inactivation of the suppressed promoter at the late stages of tumor development.

Tight junction protein ZO-2 is differentially expressed in normal pancreatic ducts compared to human pancreatic adenocarcinoma.

Differential display of hamster mRNA identified a fragment present in normal pancreatic duct cells that is not expressed in pancreatic duct carcinoma cells. Sequence analysis showed an 88% and 82% identity, respectively, to the cDNA of the canine and human tight junction zo-2 gene. Semi-quantitative RT-PCR analysis of human ZO-2 revealed a striking difference in the expression of various regions of the ZO-2 transcript in normal and neoplastic cells and the presence of an abnormality at the 5'-end of mRNA. RACE analysis identified 2 human ZO-2 mRNAs that encode proteins of different lengths, designated as ZO-2A and ZO-2C. The difference between the 2 forms of ZO-2 is the absence of 23 amino acid residues at the N terminus of ZO-2C compared with ZO-2A. Although ZO-2C was expressed in normal pancreatic cells and a majority of neoplastic tissues analyzed, ZO-2A was undetectable except in one case in all of the pancreatic adenocarcinomas analyzed. This suggests the presence of a yet to be identified motif important for cell-growth regulation within the 23-amino acid residue N-terminal peptide of ZO-2A, MPVRGDRGFPPRRELSGWLRAPG.

Atypical acinar cell foci in human pancreas. Morphological and morphometric analysis.

CONCLUSION: The morphological and quantitative findings of the present study suggest that atypical acinar cell foci are not neoplastic in nature. BACKGROUND: Atypical acinar cell foci (AACF) are rare and unusual lesions in the human pancreas. The biological nature of AACF is poorly understood, and is not clear whether they represent neoplastic or degenerative changes in the acinar cells. METHODS: To further characterize and understand the significance of AACF in relation to acinar cell tumor development, we have examined these lesions by light and electron microscopy and evaluated the growth pattern by measuring cell proliferation and the size of the foci in the pancreas of a 16-yr-old male. RESULTS: The pancreas was grossly unremarkable. AACF were randomly distributed throughout the pancreas, well delineated, and showed minimal variation in sizes. The constituent cells contained uniform nuclei, pale vacuolated cytoplasm, and exhibited low nuclear-cytoplasmic ratio. Electron microscopic examination showed a few zymogen granules and markedly dilated rough endoplasmic reticulum. Proliferative index in AACF (13%) was less than in adjacent uninvolved acinar tissue (19%). Quantitative stereological analysis showed the pancreas to contain approximately 1800 AACF/cm3 with a mean focal diameter of 360 microns.

Transgenic technology: an overview of approaches useful in surgical research.

Advances in transgenic science have created powerful tools for the investigation of both genetic and protein regulatory systems. Recently, transgenic animals have been utilized in several vascular and transplantation research laboratories. The ability to specifically mutate genes important in oncologic and cardiovascular research is leading to a greater understanding of the role of gene and protein regulatory systems in cancer and cardiovascular disease. The expanding use of transgenic animals will undoubtedly increase our insight into complex problems in surgical research. This review briefly describes the various techniques utilized to create transgenic animals including: transgene design, gene-transfer utilizing transfection, microinjection and retroviral infection, as well as the use of embryonic stem cells, and methods for screening transgenic offspring.