Adjuvant and neoadjuvant therapy in curable pancreatic cancer.

Pancreatic cancer is the tenth most common cancer in the United States and the fourth leading cause of cancer death. Afflicting approximately 37,000 Americans yearly, more than 80% of patients are unresectable and, therefore, incurable at the time of their diagnosis. Although surgical resection offers the only opportunity for cure, it remains largely unsuccessful; most patients who are candidates for surgical resection relapse and die in fewer than 5 years. This mortality leaves a 5-year overall survival of about 4% for patients diagnosed with pancreatic cancer. Perhaps the most daunting realization for physicians involved in the management of this disease is the understanding that these numbers have not changed in more than 30 years. As surgery remains the foundation of curative therapy for pancreatic cancer, this article reviews the data on adjuvant chemotherapy and adjuvant chemotherapy with radiotherapy as efforts to boost cure rates.

Heart period variability of trained and untrained men at rest and during mental challenge.

The effect of aerobic training on parasympathetic reactivity to mental stress is unclear. Thus, the parasympathetic response, as assessed by time series analysis of heart period variability (HPVts), of 10 trained male runners (trained group), 10 inherently low resting heart rate untrained men (low HR group), and 10 normal resting HR men (control group) at rest and to two mental stressors was examined. Participants completed a mental arithmetic and Stroop task. Resting HPVts at high and medium frequencies was significantly greater for the trained and the low HR groups than for the control group. Significantly greater decreases in HPVts at the medium frequency during arithmetic recovery were measured for the trained and low HR groups compared with the response of the control group. Significantly greater decreases in HPVts at both the the high and medium frequencies during the first two epochs of the Stroop occurred only for the trained and low HR groups. These results suggest that the greater HPVts at rest and decline in HPVts during and after mental challenge is influenced by both aerobic training and genetic inheritance.

Heart rate response to psychological stressors of individuals possessing resting bradycardia.

The authors examined the relation between trained and inherent bradycardia and heart rate (HR) and T-wave amplitude response to psychological stressors. They compared cardiac responses to two psychological stressors of 10 trained male runners (MVo2max = 75 mL/kg-1 min-1) possessing low resting heart rate (M = 58 bpm), 10 untrained men (MVo2max = 58 mL/kg-1 min-1) with inherently low resting heart rate (M = 58 bpm), and 10 unconditioned men (MVo2max = 51 mL/kg-1 min-1) with normal resting heart rate (M = 69 bpm). All participants completed a maximal oxygen consumption treadmill test, an easy and a hard mental arithmetic task, and the Stroop Color and Word Test. Their analysis of the data revealed no significant differences in relative heart rate response or T-wave amplitude between groups during or after any stressor. In contrast, absolute heart rates during and after mental arithmetic and during the Stroop test were significantly lower for both the trained and inherently low groups compared with the control group. These findings suggest that the lower absolute HR response during and after stressors was influenced by both aerobic training and genetic inheritance.

Cholangiocarcinoma and Crohn's disease.

Cholangiocarcinoma is an infrequent complication of inflammatory bowel disease. Although increasing numbers of cholangiocarcinomas are being reported in association with ulcerative colitis, the occurrence of this disease in patients with Crohn's disease is rare. To understand this complication better, we have reported the case of a patient with Crohn's disease in whom cholangiocarcinoma subsequently developed and reviewed the literature.

Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis.

BACKGROUND: To control the increased risk of colorectal carcinoma in patients with long-standing ulcerative colitis, surveillance colonoscopy is widely recommended. METHODS: To assess the role of colonoscopic surveillance in affecting colorectal carcinoma-related mortality, an outcome analysis was performed. RESULTS: Among the total of 41 patients who developed carcinoma associated with ulcerative colitis, 19 patients were under colonoscopic surveillance and 22 patients were not. Carcinoma was detected at a significantly earlier Dukes' stage in the surveillance group (P = 0.039). Four patients in the surveillance group died, compared with 11 patients in the no-surveillance group. The 5-year survival rate was 77.2% for the surveillance group and 36.3% for the no-surveillance group (P = 0.026). CONCLUSIONS: These results suggest that colonoscopic surveillance reduces colorectal carcinoma-related mortality by allowing the detection of carcinoma at an earlier Dukes' stage.

Cardiac response of trained and untrained males to a repeated psychological stressor.

The authors examined cardiac response to repeated exposure to a psychological stressor of aerobically conditioned (n = 15) and unconditioned subjects (n = 15). Heart rate and electrocardiographic T-wave amplitude responses of 10 trials of the Stroop Test were monitored during and after performance. Both groups' adaptation patterns were similar, with a plateauing of heart rate response after the third trial. Compared with the unconditioned group, however, the aerobically conditioned subjects recorded lower absolute heart rate responses during and after the stressor for every trial. Relative heart rate responses during the stressor and recovery were similar for both groups. There was also no difference between groups in T-wave response during or after the stressor. These data suggest that absolute heart rate response during and after repeated exposure to a psychological stressor is lower for aerobically trained individuals.

Cancer surveillance in ulcerative colitis.

During a 13-year period, 213 patients with ulcerative colitis who had no clinical or endoscopic evidence of colonic carcinoma were enrolled in a biopsy surveillance program for dysplasia and carcinoma. The aims of the study were to determine whether such a program could decrease the cancer risk in this group of patients, to determine whether patients with a low risk of carcinoma could be identified, thus enabling them to retain their colon, and to accomplish these goals with a reasonable expenditure of resources. Eighteen patients had dysplasia detected in the initial biopsy specimens; 15 of these patients underwent colectomy, and 7 had unsuspected carcinoma (1 Dukes' stage A, 2 stage B, and 4 stage C). Eleven patients had dysplasia detected during follow-up; 7 of these patients had colectomy, and only 1 patient had carcinoma (Dukes' B). Dysplasia developed in 5 of 20 patients with indefinite changes on initial biopsy samples; 3 of these patients underwent colectomy, and 1 patient had carcinoma (Dukes' B). There was no difference in the prevalence of dysplasia between patients with left-sided disease and patients with extensive disease. With the exception of 2 patients with inadequate surveillance, there has been no clinical evidence of carcinoma in any of the 148 patients whose biopsy results remained negative throughout the study; carcinoma has not developed in any of 175 patients without dysplasia on initial biopsy sample. All 4 patients who died of carcinoma had high-grade dysplasia in their initial colonoscopic biopsy samples. It is concluded that a biopsy surveillance program can be an effective aid in helping control the risk of carcinoma in patients with long-standing ulcerative colitis, that the short-term risk of carcinoma for patients with negative biopsy results is low and colectomy for risk of carcinoma can be deferred in this group, and that patients with extensive and left-sided disease share the same risk of the development of dysplasia.

Surgical aspects of sclerosing cholangitis. Results in 178 patients.

Of 178 patients with sclerosing cholangitis treated since 1950, 88 patients had associated inflammatory bowel disease, 72 had no such history, and 18 had iatrogenic injury or stone disease. A total of 233 biliary operations were performed, with a 75% rate of temporary improvement after initial operation. Subsequent operations resulted in a lower success rate and a higher mortality rate. Radiologic findings included predominant extrahepatic, intrahepatic, and diffuse disease in 29%, 28%, and 43% of patients, respectively; no survival differences were noted. Seventy-five of one hundred three deaths (73%) were related to liver failure, bleeding, or sepsis. Of 14 patients undergoing portosystemic shunt, 13 died of surgical complications or related disease. Orthotopic liver transplantation was performed in 16 patients and resulted in eight deaths, mainly in patients who had previously undergone extensive surgical treatment. No survival differences were seen between the patients with inflammatory bowel disease, those without the condition, or those who had colectomy. Surgical treatment in patients with sclerosing cholangitis should be minimized. Orthotopic liver transplantation should be offered as the treatment of choice for patients with portal hypertension, refractory cholangitis, advanced cirrhosis, or progressive liver failure.

Micronodular cirrhosis after thiabendazole.

Hepatotoxicity secondary to the administration of thiabendazole has been rare since this drug was produced in 1964. In 14 of 15 patients reported previously in the literature, severe intrahepatic cholestasis resolved within seven months of the onset of illness. A recent report documented the progression to cirrhosis in a 15th patient. We report the second case of a patient with intrahepatic cholestasis that developed after treatment with thiabendazole and progressed to severe micronodular cirrhosis.

Duodenal Crohn's disease: an analysis of 89 cases.

Duodenal Crohn's disease has an estimated incidence of 1% to 2% among patients with Crohn's disease. We report 89 patients with duodenal Crohn's disease. Common symptoms were upper abdominal pain and symptoms of gastroduodenal obstruction. Contiguous disease of the gastric antrum and duodenum was present in 60% of patients. Endoscopic examination revealed abnormalities in 62 of 67 patients. Granulomas or granulomatous inflammation was found in 37 of 76 patients. Forty-nine patients treated medically were followed up for 2-25 yr (median 9.7 yr). Good to excellent results were obtained in 45 patients. Thirty-three patients required surgical intervention, usually for gastroduodenal obstruction. Reoperation was required in eight patients, seven of whom had had vagotomy with gastroenterostomy or subtotal gastrectomy. In two of these seven patients, marginal ulcers developed. Both patients had had gastroenterostomy and vagotomy. Our experience does not support the routine use of vagotomy when a bypass procedure is performed. Good to excellent results were achieved in 26 of the 30 surgically treated patients followed up for more than 1 yr (1-43 yr; median 11 yr). Measured in terms of need for surgical intervention, gastroduodenal disease generated considerably less morbidity than did distal Crohn's disease (p less than 0.001). Most patients achieved good to excellent results whether treated medically or surgically.

Total parenteral nutrition in pregnancy: conception to delivery.

The delivery of safe and nutritionally successful total parenteral nutrition (TPN), including intravenous lipid emulsion, to a pregnant woman with Crohn's disease and short bowel syndrome from conception to delivery is reported. Maternal nutritional status improved during the pregnancy. Fetal development was normal, and a healthy, full-term infant was delivered. The placenta was normal. Specific intravenous macronutrient and micronutrient requirements during pregnancy are not well defined. Our experience has resulted in the generation of additional recommendations to optimize the intravenous nutritional therapy of this high-risk population.

Screening for colorectal cancer in a high-risk population. Results of a mathematical model.

A mathematical model was used to estimate the cost-effectiveness of colorectal cancer screening strategies for people who are at high risk because of a first-degree relative with colorectal cancer. The model uses indirect evidence about such factors as cancer incidence, sensitivity and specificity of different tests, and treatment effectiveness. The analysis indicates that for screening people over 40 yr old an annual fecal occult blood test may reduce colorectal cancer mortality by about one-third, either colonoscopy or barium enema may reduce mortality by approximately 85%, a 3-5-yr frequency for endoscopies or barium enemas preserves 70%-90% of the effectiveness of an annual frequency, and beginning screening at age 50 reduces effectiveness by 5%-10%. Although both barium enemas and colonoscopies appear to be effective in reducing mortality, the lower cost of the barium enema makes it a more cost-effective strategy. All of these estimates depend on the baseline estimates of each of the factors incorporated in the model; the conclusions are most sensitive to assumptions about the natural history of adenomatous polyps, the bleeding of adenomas and presymptomatic cancers, and the sensitivity of the fecal occult blood test. Recommendations about colorectal cancer screening must also consider factors such as discomfort, inconvenience, and the availability of various technologies.

Segmental pancreatic autotransplantation with pancreatic ductal occlusion after near total or total pancreatic resection for chronic pancreatitis. Results at 5- to 54-month follow-up evaluation.

Reported are eight patients with idiopathic chronic pancreatitis and two patients with alcoholic pancreatitis who had near total distal pancreatectomy for disabling pain and underwent simultaneous segmental pancreatic autotransplantation of the body and tail of the gland to the femoral area in an attempt to prevent or delay the onset of diabetes. The median follow-up period was 31 months, and follow-up study in nine patients ranged from 24 to 54 months. Patency of the grafts was determined by angiography and selected percutaneous venous assays for insulin. Islet cell function was determined by oral glucose tolerance tests, intravenous (I.V.) glucose tolerance tests, and I.V. glucagon stimulation studies. Segmental autotransplantation was technically successful in eight patients, only one of whom required insulin (at 2 years after grafting). The other seven patients with technically successful grafts have remained insulin independent, including two patients who later underwent pyloric preserving pancreatoduodenectomy for completion pancreatectomy. Variable pain relief was observed in patients who underwent near total pancreatectomy, but pain was unrelieved in those patients who underwent limited distal resection. Patients with idiopathic pancreatitis appear to have better pain relief and preservation of endocrine function than alcoholic patients. Segmental pancreatic autotransplantation prevents or delays the onset of diabetes mellitus and should be considered as an alternative for those patients who require extensive pancreatic resection for chronic pancreatitis.

Surgical management of Crohn's disease involving the duodenum.

The experience with 25 patients who required operation for Crohn's disease involving the duodenum is reviewed. Two distinct patterns of duodenal involvement are apparent. Intrinsic duodenal Crohn's disease has a characteristic clinical presentation that is distinct from the symptoms seen in patients with involvement of other portions of the gastrointestinal tract. Among 70 patients with duodenal Crohn's disease seen over a 30 year period, 22 required surgical intervention at the Lahey Clinic. Although hemorrhage and intractable pain were associated problems in several of these patients, unrelenting duodenal obstruction remained the primary indication for operation. Of patients who underwent operative bypass, 78 percent had a good result with a median follow-up period of 12.3 years. The presence of associated gastric Crohn's disease did not influence long-term results. A third of the patients required reoperation for duodenal disease. Marginal ulceration and recurrent gastroduodenal obstruction have been the primary reasons for reoperation. Although the addition of vagotomy to operative bypass has not helped to protect against subsequent marginal ulceration, the absence of appreciable morbidity associated with vagotomy in our series and the high incidence of marginal ulcers reported with gastroenterostomy in other clinical settings lead us to recommend gastroenterostomy with vagotomy as the procedure of choice for duodenal Crohn's disease. Proceeding with vagotomy in persons who have had previous ileocecal or extensive small bowel resection should not be undertaken without careful consideration. Similar caution should also be used in patients who are already troubled with poorly controlled diarrhea. The duodenum may also be involved by duodenoenteric fistulas which represent a complication of Crohn's disease involving other portions of the gastrointestinal tract. Most frequently this occurs in patients with Crohn's colitis who have no evidence of intrinsic duodenal disease. Management of the internal fistula requires resection of the involved colon and closure of the duodenal defect. Three patients with duodenocolic fistula have been so treated.

Segmental pancreatic autotransplantation for chronic pancreatitis.

Three patients who underwent 95 percent removal of the pancreas for chronic pancreatitis with autotransplantation of the body and tail of the gland to the femoral area are described. The follow-up periods are 18, 6, and 2 months. Pain lessened in all patients and none required exogenous insulin. Patency of the graft was documented in all patients by angiography, technetium scan, and Doppler studies. Percutaneous selective venous assays of both external iliac veins showed a high insulin concentration in the transplanted side, both early and late in the postoperative period. In one patient the operative insulin levels obtained at the completion of autotransplantation proved to be highest in the external iliac vein on the transplanted side, lowest in the iliac vein on the nontransplanted side, and intermediate in the portal vein. Subsequent biopsies of the autografts showed fibrosis of the gland and atrophy of the acinar tissue with preservation of islet tissue. This technique appears to offer a means of preserving endocrine function in selected patients who require extensive resection for chronic pancreatitis.

Anal complications in Crohn's disease.

Anal fissures, fistulas, and abscesses occurred as complications in 22 per cent of our population of 1,098 patients with Crohn's disease. Crohn's colitis was much more frequently associated with an anal lesion than Crohn's disease of the small bowel (52 per cent vs. 14 per cent). When an anal lesion is the manifesting sign, Crohn's disease will soon develop elsewhere in the intestine. Since these lesions frequently herald the onset of intestinal Crohn's disease, the physician must always be aware of the possibility of inflammatory bowel disease when dealing with suspicious anal lesions.

Unusual thoracoabdominal duplication associated with pancreaticopleural fistula.

The clinical case is presented of a 16-yr-old patient with thoracoabdominal duplication that communicated with the main pancreatic duct and the right pleural cavity and resulted in pancreaticopleural fistula. Although abdominal duplications communicating with the pancreas have been described before, to our knowledge, such an anomaly with intrathoracic extension has never been reported. Pleural effusions of high amylase content and surgical management of thoracoabdominal duplications are discussed.