Influence of incomplete bile duct obstruction on the occurrence of cholangiocarcinoma induced by diisopropanolnitrosamine in hamsters

This study was performed to clarify the influence of incomplete bile duct obstruction (IBDO) on the occurrence of cholangiocarcinoma, using Syrian golden hamsters. These hamsters underwent simple laparotomy (SL) or IBDO at the choledochus and received diisopropanolnitrosamine (DIPN) once weekly for 20 weeks (SL-DIPN or IBDO-DIPN groups). Histological examination in the liver showed increased bile ductules, goblet cell metaplasia of the bile duct epithelium and cholangiocarcinoma in the two groups. The occurrence rates of cholangiocarcinoma at 20 weeks were 35% in the SL-DIPN group and 89% in the IBDO-DIPN group (p less than 0.01). The mean numbers of tumors per hamster in the IBDO-DIPN group were significantly higher than those in the SL-DIPN group (p less than 0.01). Regarding the composition of bile acid in the intraductal bile, both groups revealed an increase in primary bile acid, consisting of more than 80% of cholic acid. Bacteria were detected in the group with IBDO throughout the whole course. These results suggest that IBDO has an influence as promoter on the occurrence of DIPN-induced cholangiocarcinoma.     

Sentinel node navigation surgery in early-stage gastric carcinoma: a limited gastric resection with lymphatic basin dissection in sentinel node-negative patients

The high accuracy of sentinel node biopsy in clinical T1 gastric cancer leads to the idea of excluding conventional D2 from node-negative patients. The question now arises of what to do when sentinel nodes are missed during surgery and micrometastases are over looked in frozen tissue sections. To avoid and correct a mistaken diagnosis, surgeons should remove the lymphatic basin even in the case of negative sentinel nodes, because the basin is exclusively associated with the involved nodes. We call this procedure "lymphatic basin dissection." Gastric lymphatic basins were divided into five compartments corresponding to the feeding artery, and clinical T1 gastric cancer involved a single basin in 42% of patients, two in 47% and three in 12%. Patients with one or two basins can be treated with limited gastric resection, because the devascularization does not cause insufficient blood supply to the remnant stomach. Since 1995, 123 patients have undergone lymphatic basin dissection and limited gastric resection (segmental resection, local resection, proximal gastrectomy, and limited distal gastrectomy) in our institution. There was no recurrence in the limited surgery patients with a median follow-up period of 3.8 years. The overall survival curve after surgery in the limited group is almost the same as that in the conventional group. Quality of life was significantly higher in the limited group than in the conventional group.     

Prevention of the pancreatic complications after surgical procedures of the pancreas

In order to find a way to prevent postoperative complications believed to be caused by pancreatic enzymes, we studied the effects on the pancreas of 5-fluorouracil (5-FU), daunomycin (DAU), actinomycin D (ACD), vincristine (VCR), and methotrexate (MTX), all of which have an inhibitory effect on protein synthesis. The effects of these drugs were tested on the exocrine cells of Donryu rats and in 12 patients who had had surgical procedures for pancreatic diseases. In control experiments, the uptake of labeled amino acid and autoradiographic studies showed that enzyme synthesis by pancreatic exocrine cells was diminished transiently after surgery but recovered in a short time. All of the drugs produced a decrease of⁷⁵Se-selenomethionine uptake in the pancreas.³H-leucine uptake in the pancreatic protein fraction and autoradiographic studies showed a significant reduction of radioactivity and a decrease of grain counts on zymogen granules in rats treated with 5-FU and VCR. On the basis of these experimental results, 5-FU was selected as the most favorable drug. Of 12 patients treated with 5-FU, one developed a small pancreatic fistula for a short period of time and another had leakage from a pancreaticojejunostomy after pancreaticoduodenectomy. The others had no postoperative complications even when operations were performed in the presence of pancreatitis. 5-FU produced a decrease in the amount of protein and the activity of amylase in pancreatic juice obtained postoperatively from a catheter in the pancreatic duct of several patients.

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Résumé A la recherche d'une méthode de prévention des complications postopératoires qui sont peut-être dues aux enzymes pancréatiques, nous avons étudié les effets sur le pancréas d'inhibiteurs des synthèses protéiniques: 5-fluorouracil (5-FU), daunomycine (DAU), actinomycine D (ACD), vincristine (VCR), et méthotrexate (MTX). Ces effets ont été testés sur le pancréas exocrine de rats Donryu et chez 12 malades opérés pour affection pancréatique. Dans les expériences de contrôle, des études de fixation d'acides aminés marqués et des autoradiographies ont montré que les synthèses enzymatiques dans le pancréas exocrine sont temporairement réduites après l'opération, mais reviennent rapidement à la normale. Toutes les drogues testées diminuent la fixation de 75 Se-sélénométhionine dans le pancréas. Chez les rats traités au 5-FU ou à la VCR, la fixation de 3 H-leucine sur la fraction protéinique, la radioactivité et le nombre de grains de zymogène sont réduits. Sur la base de ces résultats expérimentaux, nous avons choisi le 5-FU comme drogue la plus efficace. Douze malades ont été traités. L'un a présenté une petite fistule pancréatique de courte durée; au autre a fait, après duodénopancréatectomie, un lâchage de la pancréaticojéjunostomie. Les autres malades n'ont pas eu de complication, même dans les opérations faites en cas de pancréatite. Chez plusieurs patients, le 5-FU a réduit la quantité de protéines et l'activité amylasique du suc pancréatique recueilli en postopératoire par un cathéter drainant le canal pancréatique.

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Presented at the XXVIIth Congress of the Société Internationale de Chirurgie, Kyoto, Japan, September 3–8, 1977.     

Impact of the biliary diversion procedure on carcinogenesis in Barrett's esophagus surgically induced by duodenoesophageal reflux in rats

OBJECTIVE: To determine whether the elimination of bile reflux in the established esophagojejunostomy model of Barrett's esophagus (BE) will reduce or eliminate the risk of developing esophageal adenocarcinoma. SUMMARY BACKGROUND DATA: Reflux of duodenal juice as well as gastric acid plays an important role in the pathogenesis of BE and adenocarcinoma. Duodenoesophageal reflux (DER) per se induces these diseases without carcinogen. However, it is unclear whether antireflux surgery induces regression of BE and prevents adenocarcinoma. METHODS: Two hundred F344 male rats underwent one of following 3 operations: (1) total gastrectomy and esophagojejunostomy to induce DER, followed by killing after 20 (n = 13), 30 (n = 12), and 50 weeks (n = 30); (2) biliary diversion procedure, converted to Roux-en-Y method, to avoid bile regurgitation into the esophagus at 20 (n = 29) and 30 weeks (n = 32) after the operation to induce DER, followed by killing 50 weeks after initial operation; or (3) total gastrectomy and Roux-en-Y esophagojejunostomy followed by killing after 50 weeks served as controls (n = 28). RESULTS: BE developed in more than half of the animals exposed to DER for 20 weeks, in more than 90% of rats with DER for 30 weeks, and in 100% of animals exposed to DER for 50 weeks. In the incidence and the length of BE, there is no difference between the animals that underwent biliary diversion at 20 (62%) and 30 weeks (94%) and those that had DER for 20 (54%) and 30 weeks (92%), respectively. Incidence of adenocarcinoma was significantly lower in the rats that underwent the biliary diversion procedure after 30 (19%) and 20 weeks (3%) than in the rats that had DER for 50 weeks (60%) (P < 0.005). None of the control animals that underwent Roux-en-Y esophagojejunostomy developed BE and carcinoma. CONCLUSIONS: It is likely that the converting procedure from the esophagojejunostomy to induce DER to biliary diversion does not lead to regression of BE but prevents the development of esophageal adenocarcinoma in the rats.     

A case of carcinoma arising from an anal fistula

Carcinoma arising from a chronic anal fistula is an uncommon condition. A 53-year-old woman visited our clinic, complaining of refractory anal fistulas that had persisted for over a period of 15 years, which had started to discharge pus and mucus through external fistulous openings several months ago. A cytologic study of the perianal discharges and a biopsy of the external openings were useful in preoperatively detecting a cancer complicating an anal fistula. An abdominoperineal rectal amputation with an extended dissection of the relevant lymph nodes was performed. Histopathological findings revealed a mucus-producing adenocarcinoma with ly1, v0 in vessel invasion, and the stage of cancer was determined as being stage II, H0P0a2n0 (0/129). It is emphasized that cancer should be suspected whenever examining an old fistula, especially one with mucous discharges.     

Influence of pancreatic neurotomy on regeneration of residual pancreas after major pancreatectomy in rats

This study was performed to examine the influence of pancreatic neurotomy (N) on pancreatic regeneration after 90% pancreatectomy (P), excluding the parabiliary segment. One hundred and fifty male Wistar rats were divided into three groups, consisting of the PN, P, and laparotomy (L) groups. The ratios of wet wt of residual pancreas to body wt in groups with P increased after the procedures. The ratios in the P group reached their maximum at 10 d, and then decreased slightly, whereas those in the PN group rose gradually for a 60 d period. Regarding changes in the labeling indices in autoradiograms using 3H-thymidine and mitotic indices in exocrine cells, those indices in groups with P reached a peak at 3 d after the procedures, and then rapidly declined. Both indices in the PN group were lower during the first 10 d and thereafter higher than those in the P group. These results suggest that following pancreatic neurotomy, the potential for pancreatic regeneration continues over a longer period after major pancreatectomy.     

Clinical effect of postoperative adjuvant chemotherapy for advanced colorectal cancer--comparisons of between tegafur (FT) and UFT

A randomized controlled study was conducted on a FT 600 mg/day daily oral administration group and a UFT 400 mg/day daily oral administration group as an adjuvant chemotherapy after curative operation for colorectal cancer patients with injection of Mitomycin 30 mg (20 mg during operation and 10 mg on the day following), and the results were examined. FT and UFT were administered orally for one year from the 3rd week after operation. The 5-year survival rate was slightly higher in the UFT administration group. Five-year survival was 82.7% for colon cancer and 82.1% for rectal cancer in the UFT administration group, against 72.6% and 72.0 % in the FT administration group. The same trend was observed when the survival rate was studied by various factors such as the size of tumor, depth of cancer invasion of the wall, histological type, lymph node metastasis, vascular invasion and the degree of progression. There was no difference between both groups in the patterns and times of recognition of the recurrences and in the appearance rate of side effects. The results suggest that UFT 400 mg/day is equal to or better than FT 600 mg/day in therapeutic effect for colorectal cancer patients, although the UFT dose is only 2/3rd the FT dose.