Impact of hospital and surgeon volumes in the management of complicated portal hypertension: review of a statewide database in Florida.

Mortality after complex surgical procedures has been shown to be inversely related to hospital volume. The purpose of this study was to determine whether these findings are applicable to radiologic and surgical procedures for complicated portal hypertension. The Agency for Healthcare Administration for the State of Florida database was queried to determine outcomes after transjugular intrahepatic stent shunts (TIPS) or surgical shunts from 2000 to 2003. A total of 1486 patients underwent either TIPS (1321) or surgical shunts (165). Natural breakpoints occurred at two and six procedures per year were correlated with survival for surgical shunts but not TIPS. Overall mortality was not different between TIPS and surgical shunts (11.0 vs. 12.7%, P = 0.51); however, the cost of TIPS was significantly lower (62,000 +/- 58.5 vs. 107,000 +/- 97.8, P < 0.001) as well as the length of hospitalization (9 +/- 9.0 days vs. 15 days +/- 12.6 days, P < 0.001). Surgical procedures for complicated portal hypertension are rapidly being replaced by TIPS. Like with other complex procedures, outcomes are related to hospital volume.

Inflammatory myofibroblastic tumor of the midesophagus.

An inflammatory myofibroblastic tumor (IMFT) is a rare entity that can arise in a multiplicity of organs including the lung, liver, and at any location within the gastrointestinal tract. Typically, an IMFT presents as a localized mass with clinical symptoms dependent upon its site of origin. IMFTs pathologically resemble a neoplastic process but are theorized to arise from an unknown inflammatory event. We present a case of a midesophageal IMFT in a 12-year-old female.

Laparoscopic cholecystectomy: past, present, and future.

Laparoscopic cholecystectomy is one of the most commonly undertaken procedures in General Surgery with more than 500,000 performed annually. Overall, the complication rate is less than 1.5%, and the mortality rate is less than 0.1%. As such, laparoscopic cholecystectomy was considered by most to be at its zenith since its inception in the early 1990 s. Advancements in technology and equipment have opened new doors to physicians and allowed the laparoscopic cholecystectomy to once again evolve. Traditional four-port cholecystectomy has given way to three- and even two-port techniques. Standard 12-mm ports have been replaced by 2-mm ports, and experiments have now been implemented to achieve cholecystectomy with no ports-known as the transgastric technique. The authors reviewed evolution of these techniques that included a synopsis of our experience with the three-port cholecystectomy, as well as the future direction of laparoscopic surgery.

Differential gene expression in patients genetically predisposed to pancreatic cancer.

BACKGROUND: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. PATIENTS AND METHODS: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. RESULTS: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. CONCLUSIONS: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

A complication-free course ensures a survival advantage in patients after regional therapy for metastatic colorectal cancer.

Hepatic artery infusional (HAI) chemotherapy has been shown to favorably impact outcome in patients with metastatic colorectal cancer, but complications often preclude complete treatment. The purpose of this study was to determine whether HAI complications impact survival in these patients. Patients undergoing HAI pump placement at our institution from September 2001 to July 2004 were separated into terciles based on the number of treatments completed: < or = 1 (none), 2 to 4 (partial), and > or = 5 (complete). Complications relating to pump placement or treatment were recorded for each and their impact on survival was determined. Kaplan-Meier survival in 15 patients receiving no treatment was significantly shorter than 7 patients completing therapy (P = 0.02). Thirty-three per cent of patients receiving no therapy were alive at 26 months, whereas 63 per cent of partially and 86 per cent of completely treated patients were alive at 32 and 30 months, respectively. Patients receiving no treatment had more overall complications (80%) and significantly (P < 0.05) more pump-related complications (60%) than those completing therapy (43% and 0%, respectively). Cox regression revealed a significant correlation to gender (hazard ratio, 3.9), tumor size (hazard ratio, 1.17), and carcinoembryonic antigen level (hazard ratio, 1.02) to survival. Patients receiving complete HAI treatment survive longer than those receiving no treatment. Potentially preventable pump-related complications not only impacted the patients' ability to continue therapy, but survival times as well.

EGF receptor antagonism improves survival in a murine model of pancreatic adenocarcinoma.

INTRODUCTION: The purpose of this study was to determine whether inhibition of the epidermal growth factor receptor (EGFR) is a plausible therapeutic strategy in pancreatic cancer. METHODS: A human pancreatic cancer cell line (HPAC) was evaluated for the presence of EGFR with rtPCR and immunohistochemistry. Cells were grown in the presence of either 50 or 100 microM of erlotinib (EGFRI) for 72 hours and evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Eighty-six athymic nude/nude mice underwent orthotopic implantation of 10(7) HPAC cells and were blindly randomized into four groups: (1) Control; (2) Batimastat, a matrix metalloproteinase inhibitor (MMPI) at 400 ng/ml qod; (3) EGFRI at 100 mg/kg qd; and (4) MMPI and EGRRI (both). In vitro and in vivo effects of EGFRI with and without MMPI were compared. RESULTS: HPAC demonstrated high levels of expression of both the EGFR gene and the gene product. In vitro, both doses of EGFRI significantly reduced proliferation of HPAC at 48 (50 microM: 1.15 + 0.05 [st dev] versus 0.63 + 0.09 abs, P < 0.001) and 72 h (50 microM: 1.48 +/- 0.09 versus 0.73 +/- 0.05 abs, P < 0.001, paired Student's t-test). In vivo, each treatment group demonstrated a significant survival advantage (P = 0.0002 group 2, P = 0.0001 group 3, P = 0.012 group 4, log rank test) over controls. Mice treated with EGFRI showed reduced tumor implantation, size, weight, metastatic potential, and jaundice as compared to controls and MMPI-treated mice (all P < 0.05, Fisher's exact test). CONCLUSION: EGF receptor antagonism is not only a plausible therapy for treatment of ductal adenocarcinoma of the pancreas, but is also superior to matrix metalloproteinase inhibition alone or in combination.

Prognostic significance of new onset ascites in patients with pancreatic cancer.

BACKGROUND: The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. METHODS: A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. RESULTS: A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III) underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 +/- 1.32 cm). All but one of the remaining 11 patients (tumor size 4.4 +/- 3.38 cm) presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. CONCLUSION: Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors.

BACKGROUND: Few data exist regarding outcomes after resection versus embolic treatment of symptomatic metastatic carcinoid and neuroendocrine tumors. The purpose of this study was to determine whether cytoreduction provides any benefit over embolic management of diffuse neuroendocrine tumors. METHODS: A prospective database of 734 patients treated at our institution was retrospectively queried for symptomatic metastatic tumors treated with embolization or cytoreduction. Patients were compared with regard to pretreatment performance status, relief of symptoms, and survival. RESULTS: A total of 120 patients were identified: 59 undergoing embolization and 61 undergoing cytoreduction. Twenty-three patients had palliative cytoreduction (gross residual disease). Pretreatment performance status (Eastern Cooperative Oncology Group) was similar for both groups: .7+/-.70 (embolization) versus .8+/-.72 (cytoreduction; P=.27). Complete symptomatic relief was observed in 59% and partial relief in 32% of patients who underwent embolization, with a mean symptom-free interval of 22+/-13.6 months. A total of 69% of patients who underwent cytoreduction had complete symptomatic relief, and 23% had partial relief (P=.08 vs. embolization). The mean duration of relief was 35+/-22.0 months (P<.001 vs. embolization). The mean survival for the patients who underwent embolization was 24+/-15.8 months versus 43+/-26.1 months for those who underwent cytoreduction (P<.001). Survival in patients who underwent palliative cytoreduction was 32+/-18.9 months (P<.001 vs. embolization), whereas it was 50+/-27.6 months in patients who underwent curative resection (P<.001 vs. embolization; P<.001 vs. palliative). CONCLUSIONS: Cytoreduction for metastatic neuroendocrine tumors resulted in improved symptomatic relief and survival when compared with embolic therapy in this nonrandomized study. Cytoreduction should be pursued whenever possible even if complete resection may not be achievable.

Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach.

INTRODUCTION: Staging systems have been developed to predict survival after resection of hilar cholangiocarcinoma. Notably, they have not been validated nor compared for relative predictive ability. METHODS: Forty-two patients underwent resection of hilar cholangiocarcinoma and have been followed through a prospectively collected database. The tumors were staged using the Bismuth-Corlette, Blumgart, and American Joint Committee on Cancer (AJCC) systems, and a significant relationship with survival was sought. RESULTS: Eleven patients were treated by extrahepatic biliary resection alone, while 31 required extrahepatic biliary resections with in-continuity hepatic resections. All patients underwent adjuvant therapy. To date, 30 patients have died with a mean survival time of 30 months +/- 35.0 (SD). Twelve patients are alive with a mean survival of 90 months +/- 61.8. By regression analysis, none of the staging systems had a significant relationship with survival (Bismuth: P = .64; Blumgart: P = .66; AJCC: P = .31). CONCLUSIONS: Most patients with hilar cholangiocarcinoma require in-continuity hepatic resections. Survival after resection promotes an aggressive approach, with cure in as many as 30%. Staging systems should not impact the decision to operate or postoperative management, as all tumors should be aggressively resected and all patients should receive adjuvant treatment.

Twenty-millimeter laparoscopic cholecystectomy: fewer ports results in less pain, shorter hospitalization, and faster recovery.

Improvements in technology offer the ability to refine operations without compromising safety. In this study, we determine whether a modified method of laparoscopic cholecystectomy using three ports and an aggregate incision length of 20 mm offers any advantage or poses increased risk. Using a 5-mm, 30 degree laparoscope, clip applier, and dissector, the gall bladder is removed through an extended umbilical incision. Standard safety principles were followed: achieving the "critical view," lateral retraction of the fundus, double ligation of the proximal structures, and maintaining sterility for specimen removal. Forty-one consecutive standard laparoscopic cholecystectomies were used as a control group to compare complications, length of stay and surgery, pain scores, and return to work. Sixty patients have undergone the modified technique. There were no differences between the modified and standard technique with regard to cost or complications. Length of surgery was significantly shorter, as was length of stay, narcotics use, and return to work for the modified group versus the control. A modified technique for laparoscopic cholecystectomy poses no increased risk to patients but offers potential for shorter surgery and hospital stays, less need for narcotic analgesia, and faster recovery.