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The great majority of pancreatic cancers are unresectable due to local invasion and/or distant metastasis. The treatment options for such patients include bypass operation, celiac plexus block, radiation therapy (RT), chemotherapy and immunotherapy. RT is divided into intraoperative radiation therapy (IORT) and external radiation therapy (ERT). Appropriate palliative treatment remains controversial.Our experience with palliative treatments including bypass operation, celiac plexus block and RT (IORT and ERT) was retrospectively reviewed in 31 Japanese patients with unresectable locally advanced pancreatic cancer. The 31 patients consisted of seven with no RT, six with ERT alone, seven with IORT alone and 11 with both IORT and ERT. Gastrojejunostomy was performed in 25 patients and biliary bypass was done in 29 patients for the therapeutic or prophylactic purpose.No patients developed gastroduodenal obstruction or jaundice until death. Imaging findings after the treatment showed a decrease in tumor size in 11 of the 18 patients examined, an increase in four and no change in the other three. Of 19 patients complaining of back pain before the operation, the pain had disappeared in 12 but persisted in the other seven after the operation. No patients developed back pain after the treatment. Of the 12 patients with pain relief, nine had both RT and celiac plexus block, two RT alone and the other neither RT nor celiac block. Cumulative 0.5-year and 1.0-year survival rates in the group with RT(-), ERT alone, IORT alone IORT and ERT and IORT were 42.9%, 100%, 100%, 100% and 0%, 33.3%, 57.1% and 45.5%, respectively. The survival curve of the RT(-) group was significantly worse than that of the ERT alone group (P = 0.0029), IORT alone group (P = 0.0101) and IORT and ERT group (P = 0.0109). The survival curves of the three RT groups were similar.RT significantly prolonged survival of patients with unresectable locally advanced pancreatic cancer and combined palliative treatments including bypass operation, celiac plexus block and RT (ERT or IORT) are recommended for such patients.

Total pancreatectomy is rarely performed as the treatment of pancreatic carcinoma because of markedly impaired quality of life and poor prognosis. Intraductal papillary-mucinous tumor (IPMT) of the pancreas is characterized by extensive intraductal spread and favorable outcome even in its invasive stage. The role of total pancreatectomy was reappraised in the treatment of IPMT.A total of five Japanese patients with IPMT underwent total pancreatectomy and their clinical follow-up data were reviewed.Total pancreatectomy was performed due to massive involvement of the entire pancreas in two patients, positive surgical margins on frozen section in one, benign IPMT with concomitant pancreatic cancers in one and recurrent IPMT in the remnant pancreas after distal pancreatectomy for IPMT in the other. Three of them underwent total pancreatectomy of the Whipple type, another underwent total gastrectomy and the other underwent the pylorus-preserving method. Surgical margins were negative by histology and no lymph node metastases were evident. Two patients had severe infection including liver abscess in one and pneumonia in the other. The former died on postoperative day 82 and the latter was controlled by medical treatment and discharged on postoperative day 73. The other three patients had an uneventful postoperative course and were discharged from 29 to 62 days after the operation. Long-term follow-up of the four patients revealed that three patients had hypoglycemic attacks, two diabetic retinopathy and two fatty liver. The four patients were doing well from 683 to 4,140 days after the operation without signs of recurrence.Total pancreatectomy would be indicated as a treatment of benign or malignant IPMT with extensive involvement when patients' condition permits and gives a chance of cure, although careful long-term medical care and follow-up are essential.

The clinical course of patients with pancreatic carcinoma remains dismal despite the recent advances of diagnostic and therapeutic procedures. One of the main causes is residual carcinoma cells, especially at the retroperitoneal aspect after pancreatectomy. Radiation therapy (RT) [intraoperative radiation therapy (IORT) and external radiation therapy (ERT)] is a therapeutic strategy to conquer the remaining cancer cells.Effects of RT were retrospectively examined in 81 patients with pancreatectomy for pancreatic cancer together with early and late complications.Preoperative clinical data were not different between the RT(+) and RT(-) groups excluding peripheral lymphocyte counts. Postoperative early complications equally occurred including pancreatic fistula. Regarding late complications (2 months after operation), stomal ulcer, vertebral fracture, pseudoaneurysm, intraabdominal hemorrhage, and liver abscess were present only in patients with RT. Glucose intolerance tended to be more frequent in the RT (+) group, i.e. 12 (63%) of the 19 with RT examined and 14 (42%) of the 33 without RT examined. Follow-up imaging showed recurrence in 27 (71%) of the 38 patients without RT and 13 (52%) of the 25 patients with RT. The sites of the recurrence were not different by the presence or absence of RT. One-year, 3-year and 5-year cumulative survival rates were similar between the RT (-) group (100%, 39%, 21%, respectively) and IORT (+) alone group (100%, 29% and 17%, respectively). The rates in the IORT (+) and ERT (+) group were 100%, 54% and 28%, respectively, which tended to be better than those in the other two groups, but the differences were not statistically significant.These findings suggest that only the combination of IORT and ERT somewhat improves the short-term clinical course of patients with resectable pancreatic cancer, although there are some RT-related late complications. It is recommended that ERT be added to IORT after pancreatectomy for pancreatic cancer to improve the clinical course, once IORT has been performed.

The differentiation between benign and malignant jaundice is sometimes difficult even with modern diagnostic modalities. With recent advances in molecular biology, Ki-ras point mutation in codon 12 and p53 mutation have been reported as novel biomarkers of hepatobiliary and pancreatic carcinoma. The purpose of this study was to compare exfoliative bile cytology and biomarkers of the bile in patients with hepatobiliary and pancreatic diseases.Cytologic examination and novel biomarkers, point mutations of codon 12 of Ki-ras and p53 mutations, were examined in the biliary tract bile aspirated through percutaneous transhepatic biliary drainage (PTBD) tube in 30 Japanese patients with benign and malignant hepatobiliary and pancreatic diseases.Sensitivity of the exfoliative bile cytology for malignant conditions was 31% and specificity 100%, while sensitivity of molecular markers of the bile was 25% and specificity 93%. When the cytologic examination and genetic study were in conjunction, sensitivity increased to 50% and specificity remained 93%.These findings suggest that genetic examinations of the bile, when used in conjunction with cytology, may improve the diagnostic yield for suspected malignant tumors of the hepatobiliary and pancreatic system.

To investigate the therapeutic efficacy of intraoperative radiation for carcinomas of the bile duct and ampulla of Vater.Postoperative morbidity, mortality and survival of patients undergoing surgical resection of ampullary cancer (n = 19) and bile duct cancer (n = 28) were retrospectively compared between two groups with and without intraoperative radiation.Background items (age, gender, preoperative laboratory data, operative time and bleeding volume, tumor stage) did not differ significantly between the two groups. The predominant postoperative complication was leakage of pancreatic juice, which occurred in similar rates in both groups. No significant differences were noted in the 3-year survival rates between the resection plus intraoperative radiation group and resection alone group (60.0% (n = 5) vs. 50.1% (n = 13) for ampullary cancer; 0% (n = 4) vs. 27.1% (n = 24) for bile duct cancer, respectively). The main causes of recurrence were distant metastasis for ampullary cancer and microscopic residue of carcinoma for bile duct cancer.The combination of intraoperative radiation and resection may add no significant benefit to patients with ampullary and bile duct cancer when compared with resection alone.

Activation of reticuloendothelial system functions by the treatment with OK-432 has been reported to enhance liver regeneration. However, its effect on liver regeneration has not been studied after hepatectomy under ischemia/reperfusion which is in clinical use. The aim was to examine the effect of OK-432 on regeneration and energy status of the liver after hepatectomy under ischemia/reperfusion in rats.Rats were randomly divided into two groups; OK-432 pretreatment and saline treatment (control) group. In the OK-432 group, OK-432 (2.5 mg/kg body weight) was administered intraperitoneally 24 hours before hepatectomy. In the control group, the same volume of physiological saline was administered in the same manner. Seventy percent hepatectomy was performed in both groups during the second 15-minute ischemia period after an initial 15-minute ischemia and 15-minute reperfusion periods. The survival after hepatectomy, relative liver weight, deoxyribonucleic acid synthesis rate, and hepatic adenine nucleotide and energy charge levels were examined immediately after hepatectomy and on postoperative days 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and hyaluronic acid were also measured.All rats survived and the relative liver weight and deoxyribonucleic acid synthesis rate were not significantly different in the two groups. Serum total bilirubin and glutamic pyruvic transaminase levels were not significantly different in both groups. The serum concentration of hyaluronic acid immediately after hepatectomy was significantly higher in the OK-432 group than in the control group. The pretreatment with OK-432 had no significant effect on the levels of adenine nucleotides and energy charge in the liver.Under ischemia/reperfusion, pretreatment with OK-432 has no significant effect on regeneration and energy status of the liver after hepatectomy.