Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

OBJECTIVE: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. METHODS: The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (-) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. CONCLUSION: The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.

Purification of docosahexaenoic acid ethyl ester using a silver-ion-immobilized porous hollow-fiber membrane module.

Docosahexaenoic acid ethyl ester (DHA-Et) was purified by adsorption on Ag-ion-immobilized membranes via selective interaction between silver ion and carbon-carbon double bonds of DHA-Et. Silver ions were immobilized onto sulfonic-acid-group-containing porous hollow-fiber membranes at an Ag ion density of 1.4 mol/kg of membrane, and 30 membranes were housed in one module (inner diameter = 18 mm and effective length = 80 mm). The adsorption isotherms of DHA-Et in various organic solvents revealed that DHA-Et was adsorbed on the immobilized Ag ions with a DHA-Et/Ag ion molar binding ratio of 1/5 in methanol, and that acetonitrile was the solvent of choice for the elution of the adsorbed DHA-Et. Permeation of bonito oil ethyl ester solution in methanol through the Ag-ion-immobilized hollow-fiber membrane module demonstrated that the displacement adsorption of other lower unsaturated fatty-acid ethyl esters by DHA-Et proceeded along the membrane thickness. The purity of DHA-Et was improved to 99 wt % by permeating first bonito oil ethyl ester containing 95 wt % DHA-Et and then acetonitrile through the module.

5-fluorouracil sensitivity and dihydropyrimidine dehydrogenase activity in advanced gastric cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Several studies have demonstrated the clinical importance of DPD in cancer patients, suggesting that the efficacy of 5-FU may be related to DPD activity in tumor tissue. In the present study, DPD activity and chemosensitivity to 5-FU were evaluated in advanced gastric cancer. MATERIALS AND METHODS: Thirty-four gastric cancers from 32 patients were studied and chemosensitivity to 5-FU was evaluated by histoculture drug response assay. RESULTS AND CONCLUSION: DPD activity and tumor inhibition of 5-FU among all cases showed no significant correlation, but among 14 histologically differentiated cases significant correlation was observed. DPD activity may be useful in determining the 5-FU sensitivity of differentiated gastric cancer.

High-speed recovery of germanium in a convection-aided mode using functional porous hollow-fiber membranes.

A porous hollow-fiber membrane capable of recovery of germanium from a liquid stream was prepared by radiation-induced graft polymerization of an epoxy-group-containing vinyl monomer, glycidyl methacrylate, and subsequent functionalization with 2,2'-iminodiethanol, di-2-propanolamine, N-methylglucamine, and 3-amino-1,2-propanediol. The functional group density was as high as 1.4 mol per kg of the resultant hollow fiber. The polymer chains containing functional groups surrounding the pores enabled a high-speed recovery of germanium during permeation of a germanium oxide (GeO2) solution through the pores of the hollow fiber. Because of a negligible diffusional mass-transfer resistance, germanium concentration changes with the effluent volume, i.e., breakthrough curves, overlapped irrespective of the residence time of the solution, which ranged from 0.37 to 3.7 s across the hollow fiber. After repeated use of adsorption and elution, the adsorption capacity did not deteriorate.

[Difficulty in using RP, PL, and EW factors in the Japanese classification of pancreatic carcinoma].

The classification of pancreatic carcinoma by the Japan Pancreas Society reflects the prognosis of each stage better than does the TMN classification. On the other hand, there are too many factors to examine in the Japanese system, some of which are difficult to use and have low accuracy in pre- and/or intraoperative diagnosis (RP and PL), and their analysis requires various specimen handling procedures (EW). We propose that: 1) a simple, easy decision flow chart be established for ew and 2) EW/ew be designated as (-) or (+) and for EW/ew (+) cases other factors (ly, v, pl, and direct tumor invasion) be added (for example, ew (+)-pl).

Evaluation of pylorus-preserving pancreatoduodenectomy with the Imanaga reconstruction by hepatobiliary and gastrointestinal dual scintigraphy.

BACKGROUND: Following pylorus-preserving pancreatoduodenectomy (PPPD), most surgeons use gastrointestinal reconstruction with an end-to-side duodenojejunostomy placed distally to the pancreatojejunostomy and choledochojejunostomy. In contrast, the authors have consistently used PPPD with the Imanaga reconstruction (PPPD-Imanaga) which consists of end-to-end duodeno- jejunostomy, end-to-side pancreatojejunostomy and choledochojejunostomy, performed in that order. In this study, the movement of bile and food after PPPD-Imanaga was evaluated to document the functional advantages of this method. METHODS: Twenty-four patients who had undergone PPPD-Imanaga were subjected to hepatobiliary and gastrointestinal dual scintigraphy. The interval between operation and scintigraphy ranged from 28 days to 67 months. Six of the 24 patients underwent repeated dual scintigraphy for the observation of temporal changes in gastrointestinal function. RESULTS: The incidence of biliogastric reflux and bile stasis in the jejunal loop was markedly decreased at times later than 2 months after operation. Delay of gastric emptying and bile evacuation, sometimes accompanied by stasis in the jejunal loop, affected the mixing status of bile and food at 1 h after the beginning of imaging. A majority of the patients, however, had a satisfactory mixing status at 2 h. CONCLUSION: The Imanaga reconstruction appears to be a recommendable procedure following PPPD, in light of the bile and food movement achieved in the gastrointestinal tract.

Results of surgery and adjuvant radiotherapy for pancreatic cancer.

We retrospectively reviewed the cases of 34 patients with pancreatic cancer who underwent resection between January 1988 and December 1996. Adjuvant radiotherapy was performed in 24 patients, with 13 receiving both intra- and postoperative radiotherapy, 2 receiving postoperative radiotherapy (PORT) alone, and 9 receiving intraoperative radiotherapy (IORT) alone. The 1- and 3-year survival rates for all 34 patients were 59% and 19%, respectively, with a median survival of 13 months. At the time of the analysis, three patients were still alive. Recurrence patterns were assessed in 25 patients who had had no distant metastases at the time of surgery, had survived more than 3 months after surgery, and had undergone close surveillance for recurrence. Based on computed tomography (CT) and autopsy findings, a total of 15 (60%) of these 25 patients had local recurrence, 13 (52%) had liver metastases, and 8 (32%) had both. Eight (62%) of the 13 patients who received IORT and/or PORT developed local recurrence, and we failed to detect any survival advantage of IORT and/or PORT over surgery alone. However, autopsies revealed a suppressive effect of radiation on cancer growth, and local recurrence was not considered to be the direct cause of death in any of the patients, nor did any of the patients develop gastrointestinal obstruction due to local recurrence. The incidence of liver metastasis in the patients with and without tumor invasion of the portal system was 80% (8/10) and 33% (5/15), respectively. The patients who did not develop liver metastasis had significantly longer survivals than who did. Further improvements of survival await effective prophylactic treatment for liver metastases.

Preoperative radiotherapy for cancer of the extrahepatic bile duct.

From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At restaging, 1 patient was found to have liver metastases and the remaining 11 patients were taken to surgery. Nine patients underwent resection, and 8 of the 9 received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of whom died postoperatively. The 2 patients who died of intraabdominal complications received both preoperative radiation doses of more than 55 Gy and intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of irradiation effects was present in all specimens. Irradiation effects on perineural invasion were observed in varying degrees. Two of the four patients who had marked irradiation effects on perineural invasion developed local recurrence, which was found at autopsy to have infiltrated the hepatic hilum without obstructing the hepatic ducts. One patient who had minimal irradiation effects on perineural invasion developed local recurrence with obstructing the hepatic ducts. Of the 2 patients who had positive margins, the patient with marked irradiation effects on perineural invasion survived 18 months, but the patient with slight irradiation effects on perineural invasion survived only 5 months. The high complication rate requires modification of this strategy. The propriety of combining preoperative radiotherapy with intraoperative radiotherapy as well as the radiation dose should be reinvestigated.

Complications after pylorus-preserving pancreatoduodenectomy with gastrointestinal reconstruction by the Imanaga method.

BACKGROUND: Pylorus-preserving pancreatoduodenectomies (PPPDs) have been performed for disorders of the pancreatic head and periampullary region. The most commonly used reconstructive technique anastomoses the duodenum end-to-side to the jejunum, with pancreatic and biliary anastomoses placed proximally to the end-to-side duodenojejunostomy. In contrast, we have favored PPPD with gastrointestinal reconstruction by the Imanaga method (PPPD-Imanaga), which consists of end-to-end duodenojejunostomy, end-to-side pancreatojejunostomy, and choledochojejunostomy, performed in that order, because the PPPD-Imanaga provides a physiologic mixture of food, pancreatic juice, and bile in the upper portion of the jejunum. STUDY DESIGN: To identify their postoperative complications, we retrospectively reviewed the cases of 55 patients who underwent a PPPD-Imanaga between December 1986 and December 1996. In all cases, the right gastric artery was divided and the pancreatic duct was sewn directly to a small opening in the jejunal mucosa. Twenty patients with malignancy received adjuvant radiotherapy. RESULTS: Five patients died without being discharged, including one who died of cancer progression, for a postoperative mortality rate of 9%. These deaths were limited to patients who had received adjuvant radiotherapy, with only two deaths being procedure related. Delayed gastric emptying, pancreatic leak, and marginal ulcer were observed in 25 (45%), 3 (5%), and 3 (5%) patients, respectively. The delay in gastric emptying was transient and resolved spontaneously, with no patients undergoing reoperation. Only one patient required a reoperation, for the control of intraabdominal bleeding. CONCLUSIONS: A PPPD-Imanaga can be performed with acceptable morbidity and mortality risks. We conclude that the Imanaga method is a favorable complement to PPPD.

[Indication and results of pancreatectomy with combined resection of vessels for adenocarcinoma of the pancreas].

Of 192 patients who received pancreatectomy for invasive adenocarcinoma of the pancreas, 107 (55. 7%) underwent combined resection of vessels at Keio University Hospital and Tochigi Cancer Center, from July 1974 until March 1996. Vascular resections included the portal and/or mesenteric vein in 103, the common hepatic artery in 14, the superior artery in 2 and the celiac axis in 5 cases. The morbidity and mortality rate are 20.2%, 1.2% in the standard resected group and 23.1%, 5.6% in the vessel resected group, respectively. Comparison of the survival rate of curability A and B patients between two groups shows no significant difference. Six patients who underwent resection of the portal and/or mesenteric vein survived more than 5 years. The longest survivor is living 13 years 6 months after surgery. Among the patients who underwent resection of the artery, two patients survived 44 and 22 months after distal pancreatectomy with resection of the celiac axis and the common hepatic artery preserving whole stomach.

Significance of para-aortic lymph node dissection in patients with advanced and recurrent gastric cancer.

Among 243 patients who underwent radical gastrectomy for advanced gastric cancer, 19 patients underwent radical gastrectomy with extended lymphadenectomy including cancer-positive para-aortic lymph nodes. Their prognosis was unexpectedly good, with a mean postoperative survival time of 24.1 months and a 2-year-survival rate of 42.4 percent. Another 4 patients developed para-aortic lymph node recurrence detected by computed tomographic scan during a follow-up examination. These 4 patients were treated with macroscopic curative dissection of the para-aortic lymph nodes. Although 2 of the 4 patients died within 6 months after re-operation, the prognosis of the other two patients was rather good when treated with active combination chemotherapy consisting of 5-fluorouracil, adriamycin and cisplatin. Dissection of para-aortic lymph nodes is considered of valuable in the treatment of advanced gastric cancer, and dissection of the para-aortic lymph node recurrence may also be valid when combined with potent chemotherapy.

[Treatment of advanced colorectal cancer with long-term continuous infusion of 5-fluorouracil].

The purpose of the study was to evaluate the efficacy of long-term continuous administration of 5-fluorouracil (5-FU) in ambulatory patients with colorectal cancer. Nineteen patients with advanced colorectal cancer were treated with continuous intravenous infusion of 5-FU (500 mg/day). The minimum duration of therapy was projected to be four weeks. In some patients 4 weeks interval therapy was selected and in other patients the duration of therapy was open-ended. A portable pump was used to deliver 5-FU continuously into the venous system at home. The pump had a subcutaneously placed port connected to a central venous catheter. In 19 patients, the duration of 5-FU infusion was 56 to 427 days (median: 139 days), and cumulative doses of 5-FU ranged from 28 to 173.5 g (median 69.5 g). Five patients achieved partial response (response rate: 26.3%), and the response lasted 80 to 339 days (median: 204 days). The fifty-percent survival time was 17 months. In 16 patients whose serum CEA level was elevated, there was a decrease to less than 50% among 11 patients (69%). Dose limiting toxicity was stomatitis in 4 patients and hand-foot syndrome in one, but they recovered after interruption of the infusion. Hematological toxicity was generally mild. No infusion-system related complication was encountered. Patients were able to be discharged and live at home during 82% of their survival period, while receiving this therapy. We concluded that this treatment is effective with tolerable toxicity and can be conducted at home.

A pharmacodynamic and pharmacokinetic study of fluoropyrimidines in a nude mouse system and in postoperative patients with gastric cancer.

To evaluate the effect of the oral fluoropyrimidines, tegafur and uracil (UFT) and 5-fluorouracil (5-FU), a pharmacodynamic analysis was conducted using a nude mouse system and patients. In the nude mouse system, UFT and 5-FU showed similar marginal effects against the human tumor xenograft Co-4, and the concentration of 5-FU in serum 1 h after the last administration being 0.04 micrograms/ml, which was assumed to be the minimum effective concentration. (MEC). Postoperative patients were subdivided into three groups, being: those who underwent subtotal gastrectomy and received UFT; those who underwent subtotal gastrectomy and received 5-FU; and those who underwent total gastrectomy and received UFT. In the UFT groups, the concentration of 5-FU in the portal and peripheral blood showed similar elimination in terms of the peak concentration (Cmax) and the area under the curve (AUC). In the 5-FU groups, the AUC and Cmax were significantly higher in portal blood than peripheral blood. The concentrations in the portal blood of the 5-FU group and in the portal and peripheral blood of the UFT group were significantly higher than the MEC (0.04 micrograms/ml). From these pharmacodynamic data, it was concluded that postoperative chemotherapy with oral fluoropyrimidines can achieve the MEC in portal and peripheral blood.

Breast cancer developing after chemotherapy for osteosarcoma: a case report.

A 24-year-old patient who developed breast cancer 16 years after chemotherapy for osteosarcoma is presented. She had no family history of cancer. She had also not had radiotherapy. She had been given chemotherapy consisting of VAOMT (vincristine 10.2 mg, cyclophosphamide 900 mg, mitomycin C 15.2 mg, chromomycin A3 25.8 mg) pre- and post-operatively in the treatment of her osteosarcoma. Careful long-term follow-up is required after treatment of malignant neoplasms because there is a possibility of developing a second malignancy.

[An esophageal cancer with a renal metastasis that was detected and resected as the only focus of recurrence].

Reported is the case of an esophageal cancer presenting a renal metastasis, which was detected and resected as the only recurrent focus. The patient was a 62-year-old male. Five months after an esophagectomy, a left renal mass was detected by abdominal computerized tomography, and a rise in the SCC antigen. The urinary cytology suggested a renal metastasis of the esophageal cancer. Thus, chemotherapy and irradiation was performed, followed by a resection. The histology of the resected mass showed a squamous cell carcinoma, similar to the findings at the primary site. A renal metastasis of an esophageal carcinoma usually is latent, but not rarely found on postmortem examination. A nephrectomy for a renal metastasis of an esophageal cancer is rare, and only 8 cases are reported in the literature.