Purpose: To determine the maximal tolerated dose of radiation delivered to the primary tumor bed, in combination with full-dose gemcitabine (1000 mg/m(2) weekly x 3), after resection of pancreatic cancer.Methods and Materials: Patients with resected pancreatic carcinoma and poor prognostic features, a positive resection margin, or involved lymph nodes were eligible. Radiotherapy (RT) was directed at the preoperative tumor volume with a conformal technique. Regional lymph node basins were not included. The initial starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in 0.2-Gy increments, keeping the duration of RT to 3 weeks. Gemcitabine was given i.v. for 30-40 min at a dose of 1000 mg/m(2) before RT on Days 1, 8, and 15 of a 28-day cycle. After completion of RT and chemotherapy, an additional cycle of gemcitabine was delivered.Results: Between November 1997 and October 2001, 32 patients were entered: 30 after Whipple resection (positive margins in 2, positive nodes in 22, and both in 6), 1 after distal pancreatectomy, and 1 after incomplete resection of a tumor involving the body (both patients with positive margins and nodes). Treatment was well tolerated. Of the 32 patients, 27 completed all protocol therapy and 29 maintained their pretreatment weight within 5%. Five patients experienced dose-limiting toxicity, four with Grade 3 vomiting requiring hospitalization and one fatal toxicity secondary to pneumonia/sepsis. At the final radiation dose level (42 Gy), 2 patients experienced GI dose-limiting toxicity. At the 39-Gy-dose level, 5 of 6 patients were without dose-limiting toxicity. Isolated local or regional progression was documented in 1 patient. Distant progression was documented in 26 of 32 patients (6 with concurrent local or regional progression). The median survival was 16.5 months (95% confidence interval 12.3-19.9)Conclusion: The results of our study indicate that the maximal tolerated radiation dose, administered using conformal techniques targeted to the tumor bed, is 39 Gy. In this high-risk population, data on locoregional control suggest that the reduction in radiation dose and field size minimizes toxicity and does not result in excess failures at these sites. (C) 2004 Elsevier Inc.

Currently there is uncertainty in diagnosis between the serous (benign) and mucinous (premalignant) forms of cystic neoplasms of the pancreas without operation. Our objective is to evaluate resectional therapy as a treatment for these lesions. A retrospective review of cases from 1985 to 1999 were performed. There were 14 cases of serous cystadenoma (SCA), 11 cases of mucinous cystadenoma (MCA), and five cases of mucinous cystadenocarcinoma (MCAC). A female predominance was seen in all lesions (100% in SCA, 64% in MCA, and 80% in MCAC) with a mean age at presentation of 59 years. Most patients presented with pain (SCA = 64%, MCA = 55%, and MCAC = 80%). Weight loss was seen in 35 per cent of all patients and was present in all cases of MCAC. Importantly 36 per cent of MCA patients were asymptomatic. Lesions were identified as multicystic on CT reports of 62 per cent of SCA patients, 50 per cent of MCA patients and 75 per cent of MCAC patients. Size was similar between groups. All patients were treated with surgical resection; operative morbidity was 27 per cent and mortality was zero. Actuarial 5-year survival for SCA, MCA, and MCAC was 100, 100, and 33 per cent, respectively. Differentiating serous from mucinous is not possible based on presenting symptoms and radiologic findings. Surgical resection is justified on the basis of low morbidity and negligible mortality rates.

Hereditary pancreatitis is an uncommon cause of chronic pancreatitis in Western society. It should be suspected when chronic pancreatitis presents in young adults. The diagnosis is made when chronic pancreatitis is present in several members of the same family who are determined not to have other risk factors for chronic pancreatitis. Molecular research focusing on mutations in the trypsinogen gene has uncovered the genetic defects associated with hereditary pancreatitis, and this knowledge has suggested the possible pathophysiologic mechanism of this disease. Because patients with hereditary pancreatitis develop their disease early in life they are very likely to require treatment for complications. As in patients with chronic pancreatitis of other etiologies those with hereditary pancreatitis should be treated medically for acute exacerbations. When complications occur or when the disease causes intractable pain surgery is recommended. Surgical therapy is tailored to the patient's pancreatic anatomy based on endoscopic retrograde cholangiopancreatography or CT scan. The two patients described in this report underwent successful longitudinal pancreaticojejunostomy (Puestow procedure) with good results. Finally it has been shown that patients with hereditary pancreatitis are at increased risk for developing pancreatic adenocarcinoma. Although not widely used pancreatic cancer screening programs have been suggested for surveillance of these patients.

PURPOSE: The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Thirty seven patients with unresectable (n = 34) or incompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine was administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Radiation therapy was initiated on day 1 and directed at the primary tumor alone, without prophylactic nodal coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in increments of 0.2 Gy, keeping the duration of radiation constant at 3 weeks. A second cycle of gemcitabine alone was intended after a 1-week rest. RESULTS: Two of six assessable patients experienced dose-limiting toxicity at the final planned dose level of the trial (42 Gy in 2.8-Gy fractions), one with grade 4 vomiting and one with gastric/duodenal ulceration. Two additional patients at this dose level experienced late gastrointestinal toxicity that required surgical management. CONCLUSION: The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiotherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data.

BACKGROUND:Education is a major function of academic medical centers. At these teaching institutions residents provide a substantial amount of care on medical and surgical services. The attitudes of patients about the training of surgical residents and the impact of residents on patients' perceptions of care in a surgical setting are unknown. STUDY DESIGN:Patients admitted to the gastrointestinal surgery service completed a 30-item survey designed for this study. Patients included in the study underwent operations and had a postoperative inpatient hospital stay. We analyzed patients' answers to determine frequency and correlations among answers. RESULTS:Two hundred patients participated in the study during a 7-month period between July 1999 and January 2000. A majority of patients were comfortable having residents involved in their care (86%) and felt it was important to help educate future surgeons (91%). Most did not feel inconvenienced by being at a teaching hospital (71%) and felt they received extra attention there (74%). Patients were more willing to participate in resident education if they expected to have several physicians involved in their care, felt that they received extra attention, or if the teaching atmosphere did not inconvenience them. Despite the stated willingness of patients to help with surgical resident education, 32% answered that they would not want residents doing any of their operation. CONCLUSIONS:Surgical resident education is well received and considered important by patients. Patient orientation to the resident education process is vital to patients' perceptions of care and may render patients more willing to participate in educational activities.

Prevention of postoperative hepatic failure is important after hepatic resection. In patients with cirrhosis, impaired liver function and regenerative capacity after major hepatic resection are associated with increased morbidity and mortality. In this study, a combination of epidermal growth factor (EGF) and insulin were used as hepatotrophic factors in an attempt to stimulate DNA synthesis after 70% hepatectomy (HTX). Regenerative capacity was evaluated in normal and cirrhotic rat liver by measuring DNA synthesis in vivo. Micronodular liver cirrhosis was established by the simultaneous oral administration of CCl4 and phenobarbital. Epidermal growth factor plus insulin was injected subcutaneously immediately after and 12 h after HTX or sham operation was performed. Rats were killed 24 h after the operation and liver regeneration was estimated by [3H]-thymidine incorporation into DNA as well as an autoradiographic nuclear labelling index. Hepatectomy increased [3H]-thymidine incorporation significantly in both normal and cirrhotic rats. In cirrhotic rats, [3H]-thymidine incorporation after HTX was significantly lower than in normal rats and administration of a combination of EGF and insulin after HTX enhanced [3H]-thymidine incorporation. In conclusion, DNA synthesis 24 h after HTX is decreased in cirrhotic rats compared with normal rats and EGF supplementation with insulin accelerates DNA synthesis in hepatectomized cirrhotic rats. The data suggest that administration of combinations of exogenous hepatotrophic factors may play a useful role in the treatment of cirrhotic patients undergoing major hepatic resection.

Postsurgical gastroparesis syndrome (PGS) is characterized by postcibal nausea and vomiting and is associated with functional gastric dysmotility. Patients frequently present with marked weight loss and malnutrition requiring hospitalization and prolonged parenteral nutrition. Typically, these patients fail to respond to prokinetic agents. Gastric reoperations are frequent and usually unsuccessful. Near-completion gastrectomy (NCG) has proved useful in small series of patients, but long-term follow-up has been lacking. The purpose of this study is to assess the safety and durability of NCG in a large group of patients with PGS. Eighty-one patients with documented PGS who failed to respond to prokinetic drug therapy were treated with NCG over an 11-year period. NCG was standardized with a 55-cm Roux-en-Y reconstruction. Patients were evaluated by a retrospective chart review and a prospective phone interview that compared pre- and postoperative health status based on a standardized severity of symptoms score. There were no operative deaths or complications related to the anastomosis. Average patient follow-up was 56.1 months (range, 2-142 months). Fifteen patients died of unrelated causes, and 14 patients were lost to follow-up. The remaining 52 patients showed a significant overall decrease in severity of symptoms score largely due to reduction in gastrointestinal symptoms and to a smaller but significant reduction in systemic symptoms. Nearly 80 per cent of patients reported long-term relief of symptoms. NCG is the procedure of choice for carefully selected patients with documented. Low morbidity and durable results can be anticipated in the majority of patients.

Few patients with pancreatic cancer have resectable disease at the time of diagnosis, and a variety of nonsurgical techniques are available to provide effective palliation of jaundice and pain. Accurate preoperative staging is essential to identify patients with unresectable disease, thereby minimizing unnecessary surgery. Currently used diagnostic tests include contrast-enhanced computerized tomography (CT), visceral angiography, endoscopic ultrasound, and laparoscopy, but their utility remains controversial. To evaluate the accuracy of these various diagnostic tests, 30 consecutive patients with histologically proven pancreatic or ampullary adenocarcinoma treated between 1992 and 1996 were evaluated. All 30 patients had contrast-enhanced CT and laparoscopy, 22 patients (73%) had visceral angiography, and 16 patients (53%) had endoscopic ultrasound. Individual and combined predictive values of resectability and unresectability as well as the sensitivities and specificities were determined for all diagnostic tests and compared with intraoperative findings. When CT, visceral angiography, and laparoscopy were combined, the predictive values of resectability and unresectability were 75 and 90 per cent, respectively, with a sensitivity of 75 per cent and a specificity of 90 per cent. Therefore, the combined use of selected diagnostic tests proved more effective than any single diagnostic test for accurately staging patients with pancreatic head and ampullary cancers and should be considered to minimize unnecessary surgery.

Primary sclerosing cholangitis is a chronic cholestatic disease that may ultimately progress to hepatic parenchymal dysfunction and death from premature liver failure. Symptomatic patients should undergo radiological evaluation to exclude secondary causes of cholangitis and to evaluate the extent and location of biliary ductal disease. A percutaneous liver biopsy is advisable in any patient with clinical or biochemical evidence of cirrhosis. Patients with diffuse ductal involvement should initially receive medical treatment, preferably in a center conducting prospective clinical trials. Liver transplantation should be considered the initial procedure in primary sclerosing cholangitis patients with diffuse ductal involvement, complications of cirrhosis or deteriorating liver function. Nontransplant procedures should be restricted to symptomatic patients with a dominant extrahepatic stricture. In properly selected patients, effective and durable palliation of symptoms can be anticipated with biliary enteric drainage. Many currently available techniques obviate the need for long-term transanastomotic stenting, thus minimizing the risk of recurrent cholangitis and the need for repeated tube changes. These patients may also be candidates for percutaneous or endoscopic balloon cholangioplasty. Liver transplantation should also be considered in patients with a dominant stricture and histologic evidence of biliary cirrhosis or hepatic deterioration following a nontransplant procedure.

Endogenous vasoactive mediators such as bradykinin and nitric oxide may affect the severity and outcome of acute pancreatitis by altering the capillary integrity of the pancreatic microcirculation. Protease inhibitors such as gabexate have a small beneficial effect on pancreatitis-related morbidity but are not cost effective. Secondary pancreatic infection after necrotizing pancreatitis can be mitigated by selective gut decontamination but requires both oral and intravenous antibiotic administration. Combined modality treatment of pancreatic duct stones is safe and effective but may not have better or even equivalent long-term efficacy as compared with traditional surgery. Duodenum-preserving resections (Beger and Frey procedures) are especially useful in patients with chronic pancreatitis who have predominant involvement of the pancreatic head, and such procedures have fewer metabolic and nutritional consequences as compared with standard pancreatoduodenectomy. Islet autotransplantation combined with pancreatic resection for patients with small-duct disease not amenable to surgical duct decompression is safe and provides effective long-term pain relief. Cyst fluid analysis in patients with problematic pancreatic cysts may help to differentiate neoplastic cysts from pseudocysts, especially when other diagnostic studies yield inconsistent results. Mucin-hypersecreting tumors of the pancreas comprise a recently identified group of tumors with varied histopathology and malignant potential. Resection is generally recommended. Combined modality staging in patients with pancreatic cancer is strongly recommended to identify patients most likely to benefit from attempted surgical resection. Pylorus-sparing resection results in less impairment of digestive function than conventional pancreatoduodenectomy with no difference in survival. More effective adjuvant or neoadjuvant therapies are needed to extend the long-term survival benefits of surgery in patients with potentially resectable disease.

The role of somatostatin (SS‐14) in the regulation of rat liver regeneration was examined by using thymidine incorporation into hepatocyte DNA labeled with tritiated thymidine, a nuclear‐labeling index, and the binding of 125 I‐tyr 11 ‐SS‐14 to hepatocytes isolated at various times after partial hepatectomy. The data demonstrated no suppressive effect of SS‐14 on insulin and glucagon‐stimulated thymidine incorporation into hepatocyte DNA as early as 2 h after partial hepatectomy. These data were substantiated by a nuclear labeling index studies. At 2 h, 125 I‐tyr 11 ‐SS‐14 binding to its specific sites on isolated hepatocytes was undetectable. There was a time‐dependent increase in binding of 125 I‐tyr 11 ‐SS‐14 to hepatocytes obtained at various times after partial hepatectomy. There was a significant decrease in the number of binding sites after partial hepatectomy as determined by Scatchard analysis. The data were supported by autoradiography analysis of affinity labeled 125 I‐tyr 11 ‐SS‐14‐binding protein complex followed by SDS‐PAGE. SS‐14 also inhibited intracellular cAMP in hepatocytes obtained at 18 h after hepatectomy. The data are consistent with the hypothesis that SS‐14 participates via its own receptor in the regulation of the liver regeneration. © 1995 Wiley‐Liss, Inc.

Cirrhotic livers are considered to regenerate less actively than normal livers after hepatic resection. Little is known about the mechanisms responsible for impaired capacity of regeneration in cirrhotic liver. In the present study, we investigated the effect of phorbol ester on hepatocyte proliferation in healthy and cirrhotic hepatocytes, using one of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which has a direct effect on activation of protein kinase C (PKC). Cirrhosis was established by the administration of carbon tetrachloride and phenobarbital to rats. Healthy and cirrhotic hepatocytes were isolated from Wistar male rats by a two-step collagenase perfusion technique. DNA synthesis was estimated by [3H]thymidine incorporation into DNA and by autoradiographic nuclear labeling index. [3H]Thymidine incorporation was measured 24 hr after hepatocytes were stimulated by appropriate reagents. TPA (50 nM) stimulated [3H]thymidine incorporation in healthy hepatocytes (control vs TPA, 991 +/- 247 vs 2569 +/- 766 mean +/- SEM cpm/microgram DNA; P < 0.05), whereas TPA (50 nM) failed to stimulate in cirrhotic hepatocytes (control vs TPA, 1144 +/- 184 vs 1304 +/- 187 cpm/microgram DNA; NS). Staurosporine, a specific PKC inhibitor, suppressed [3H]thymidine incorporation in TPA-stimulated healthy hepatocytes (806 +/- 263 cpm/microgram DNA; P < 0.05); however, it had no effect on cirrhotic hepatocytes (1295 +/- 180 cpm/microgram DNA; NS). An autoradiographic nuclear labeling index exhibited the same results with [3H]thymidine incorporation. We conclude that TPA stimulates hepatocyte proliferation in healthy rat hepatocytes but has no effect on cirrhotic hepatocytes.

The scope of blood loss and replacement with liver surgery is important in the final results of such surgery. Although intraoperative death from bleeding was once a significant consideration with liver resections, it is now an uncommon cause of death for elective liver operations. Nevertheless, control of blood loss remains an important issue. There is a strong correlation between blood loss in excess of 4–5 liters and postoperative complications and hospital mortality in patients undergoing liver resection [1,2]. Significant intraoperative bleeding obscures the operative field such that accidental injury to biliary structures is more likely to occur and location and control of bleeding vessels are more difficult. Large transfusion requirements frequently result in coagulopathies with additional bleeding. Hypotension and hypoperfusion associated with blood loss have negative physiologic consequences for many organ systems. There is a risk of serious viral infection correlating with the amount of blood products administered. Finally, for patients in whom liver resection is for treatment of malignancy, evidence is mounting that there is an increased rate of recurrence of malignancy when substantial blood transfusions are given in the perioperative period [3,4].

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin (AVP) deficiency. This suggested that AVP might have a direct effect on cultured rat hepatocytes. Hepatocytes from male Sprague-Dawley rats were isolated using a two-step collaganase perfusion technique and plated at a density of 105/16-mm Primaria plate. After a suitable attachment period, hepatocytes were incubated with minimal essential media, AVP, AVP plus a specific AVP antagonist, or oxytocin. Hepatocyte proliferation was measured by [3H]thymidine incorporation ([3H]Thy) into hepatocyte DNA. AVP (10 nM) increased [3H]Thy significantly (and this effect was blocked by an AVP-specific antagonist (50 nM). Oxytocin had no effect on hepatocyte DNA synthesis. To further investigate the influence of AVP on hepatocyte proliferation, the effect of AVP on transforming growth factor-α (TGF-α)-stimulated hepatocyte proliferation was also studied. This combination was chosen based on the ability of AVP to inhibit the biologic effects of EGF (a TGF-α analog). There was significant attenuation of TGF-α (50 nM)-stimulated [3H]Thy in the presence of AVP (10 nM). In summary: (l) AVP stimulates proliferation of cultured rat hepatocytes. (2) The effect of AVP can be significantly abolished by a specific AVP antagonist. (3) The proliferative response of AVP is specific. (4) AVP significantly attenuates TGF-α-stimulated hepatocyte hepatic DNA synthesis. Further studies should elucidate the mechanisms for the effects of AVP on hepatic proliferation alone or in combination with other factors.

A multicenter, open-label randomized trial was conducted to evaluate the efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) compared with combination therapy with clindamycin and an aminoglycoside (C+A) for treatment of 117 patients with serious intra-abdominal infections. Fifty-three patients (45%) received I-C and 64 patients (55%) received C+A. The overall clinical success rate was 96.2% for the I-C patients and 92.2% for the C+A patients. Clinical failure rates were 3.8% and 7.8%, respectively (P = NS). Eradication or suppression of pathogens was observed in 81.8% and 82.2% of patients, respectively. Uniform bacteriologic response was observed among all infection subgroups. Fourteen of 145 patients experienced adverse symptoms, including six of 66 (9.1%) monotherapy patients and eight of 79 (10.1%) combination-therapy patients (P = NS). The results of this study demonstrate that I-C monotherapy was as effective as C+A combination therapy for the treatment of serious intra-abdominal infections, regardless of the site or severity of infection or the clinical status of the patient. Both regimens also were found to be comparable in tolerability.

Injection sclerotherapy (IS) has become an effective modality for the treatment of bleeding esophageal varices. Despite improvements in equipment, sclerosant solutions and operator technique, injection sclerotherapy-induced esophageal strictures (ISES) remain a significant cause of patient morbidity. To analyze the risk factors and prognosis of ISES, the records of 117 patients who underwent IS over a 6-year period at a single teaching institute were reviewed. The predictive value of multiple risk factors including the patient's age, Child's risk classification, previous bleeding episodes, etiology of varices, cumulative amount of sclerosant used, and the number of IS treatments were determined using ANOVA. A P value of less than 0.05 was considered significant. In all cases, a free-hand injection technique, flexible endoscopes and sodium morrhuate were used. During a mean follow-up period of 228 days (1-1,469 days), 41 patients (35%) died and 24 patients (20.5%) developed symptomatic strictures. The cumulative amount of sclerosant used (81.4 +/- 9.5 ml) and the number of IS treatments (6.5 +/- 0.7) required in the stricture group was significantly greater than in the nonstricture group (49.1 +/- 2.7 and 4.0 +/- 0.3, respectively). The risk of stricture formation did not correlate with the volume of sclerosant injected per treatment, cause of varices, number of previous bleeds, or Child's hepatic risk class. A mean of 3.6 +/- 4.5 dilations was required for treatment of established strictures and 18 patients (75%) required r 4 dilations. One esophageal perforation occurred following dilation. Mortality correlated with hepatic risk class as 30/41 (73%) of deaths occurred in Child's C patients.(ABSTRACT TRUNCATED AT 250 WORDS)