Effect of Oral Branched-Chain Amino Acids and Glutamine Supplementation on Skeletal Muscle Atrophy After Total Gastrectomy in Rat Model.

BACKGROUND: Sarcopenia is closely related to short-term outcomes of surgery and long-term prognosis. After gastrectomy, a decrease in muscle strength occurs because of insufficient nutrient intake and disturbed digestive function. Branched-chain amino acids (BCAAs) and glutamine (Gln) play vital roles in the signaling pathways regulating protein synthesis and protein degradation. In this study, we investigated the effects of BCAA and Gln supplementation alone or in combination on skeletal muscle atrophy after total gastrectomy in a rat model. METHODS: Male Wistar rats were divided into five groups: (1) sham operation (n = 8); (2) total gastrectomized rats (TG [control group], n = 16); (3) TG with BCAA (TG-B, n = 16); (4) TG with Gln (TG-G, n = 16); and (5) TG with BCAA and Gln (TG-BG, n = 16). In all groups, body weight, muscle weight, and marker for muscle metabolism were examined. RESULTS: Weight gain was significantly greater in the TG-BG group (130.5%) than in the TG group (108.1%) at 15 wk (P < 0.05). The gastrocnemius muscle weight was significantly higher for TG-BG (2.84 g) than for TG (2.44 g) at 15 wk (P < 0.05). Western blotting indicated that atrogin-1 and MuRF1 levels were lower in the TG-BG group than in the TG group but were not suppressed in the TG-B or TG-G group. CONCLUSIONS: In a rodent sarcopenia model induced by TG, the administration of BCAA in combination with Gln more effectively inhibited muscle atrophy than the administration of BCAA or Gln alone.

Prognostic Factors of Malignant Peritoneal Mesothelioma Experienced in Japanese Peritoneal Metastasis Center.

BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment. METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively. CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Effects of Cytoreductive Surgery Combined with Perioperative Chemotherapy on Long-Term Survivals of Colorectal Cancer Patients with Peritoneal Metastasis, with Special Reference to the Involved Peritoneal Sectors and Organs.

Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment, named comprehensive treatment for peritoneal metastasis(PM)from colorectal cancer(CRC). The present study demonstrated the efficacies of the treatment regarding the peritoneal sectors and organs involved with PM from CRC. MATERIALS AND METHODS: Among 365 patients received laparotomy, 278 CRC patients with PM underwent complete cytoreductive surgery(CC-0). RESULTS: After CC-0 resection Grade 3, Grade 4, and Grade 5 postoperative complication were found in 20(7.2%), 26(9.3%), and 6(2.2%). Five- and 10-year survival rate(YSR)of CC-0 resection were 24.5%, and 11.6% with median survival time(MST)of 42.0 months. Regarding the peritoneal cancer index(PCI)of small bowel(SB-PCI), all patients of PCI B3 died of the disease. In contrast, 10-YSR of patients with SB-PCI of 0, 1, and 2 were 26.1%, 19.5%, and 6.2%, respectively. Ten-YSR of patients with the number of involved peritoneal sectors C9 ranged from 6.9% to 29.8%. MST of patients with PM in each peritoneal sector(sector 0 to sector 8)ranged from 26.4 months to 49.2 months, and 10-YSR ranged from 4.2%to 17.2%. Ten-YSR of patients with involvement of rectum, stomach, liver capsule, seminal vesicle, ureter, uterus, or ovary ranged from 0% to 16.9%. CONCLUSIONS: From the present data, PM should be removed aggressively to achieve complete cytoreduction, when the patients with PCIC26, involved peritoneal sectorsC9 and SB-PCIC2 are supposed to receive complete cytoreduction of PM.

Preventive effect of oral hangeshashinto (TJ-14) on the development of reflux-induced esophageal cancer.

BACKGROUND: Prostaglandin E2 is one of the potential products that promotes development of tumors and also is a strong inducer of M2 phenotype macrophages, which contribute to tumor development in the immunosuppressed microenvironment. Hangeshashinto (TJ-14), a Japanese traditional medicine (Kampo medicine), has been reported to be effective in preventing chemotherapy-induced oral mucositis through the reduction of prostaglandin E2. We previously developed a surgical rat reflux model of esophageal cancer and used this well-established animal model to investigate the action of TJ-14 in preventing esophageal cancer. We also assessed the effect of TJ-14 on the downregulation of prostaglandin E2 production, utilizing esophageal squamous cell carcinoma cell line exposed to bile acid. METHODS: An end-to-side esophagojejunostomy was performed for the reflux model. A daily oral diet was subsequently administered, consisting of either diet-incorporated TJ-14 or standard diet as a control group. The rats were killed at 40 weeks after surgery. The incidence of esophageal cancer, Barrett's metaplasia, and proliferative hyperplasia were assessed histologically. CD163, a M2 phenotype macrophage marker, was assessed with immunohistochemistry. Prostaglandin E2 enzyme immunoassay and lactate dehydrogenase assay were performed on chenodeoxycholic acid or gastroesophageal reflux contents exposed to esophageal squamous cell carcinoma cell line. RESULTS: Sixty-seven percent of the controls (n = 12) developed esophageal cancer, but animals that received TJ-14 (n = 10) had a cancer incidence of 10% (P=.007). Barrett's metaplasia was found in 83% of the rats in the control group and 50% of the rats in the TJ-14 indicating a protective tendency of TJ-14 (P=.095). All of the rats developed proliferative hyperplasia. The number of M2 phenotype macrophage were significantly decreased in the TJ-14 group compared to the control group in both Barrett's metaplasia and esophageal cancer lesions. TJ-14 inhibited chenodeoxycholic acid or gastroesophageal reflux content-induced prostaglandin E2 production in esophageal squamous cell carcinoma cell. CONCLUSION: TJ-14 reduced the incidence of reflux-induced esophageal cancer and the infiltration of M2 macrophages in a surgical rat model or suppressed prostaglandin E2 production in esophageal squamous cell carcinoma cell. Further investigation is required regarding the potential clinical use of TJ-14 as an esophageal cancer chemopreventive agent.

[A Case of Spontaneous Esophageal Rupture That Required Operation during Adjuvant Chemotherapy for Transverse Colon Cancer].

A 75-year-old male underwent adjuvant chemotherapy with tegafur uracil(UFT)plus Leucovorin(LV)after surgery for transverse colon cancer(pT3pN0M0, ly1, v2, pStageⅡ). Although he had diarrhea(Grade 3)and vomiting(Grade 2)from day 15, he continued to take the medicine at his own discretion. He visited a hospital because of acute renal failure from severe dehydration. He went into shock after evacuation, and the computed tomography(CT)finding suggested a diagnosis of spontaneous esophageal rupture at the lower esophagus. We made a diagnosis of intrathoracic perforation of the esophagus by using thoracic drainage. Then, we performed an operation for mediastinal drainage via a transabdominal approach and the lesser omentum. He started ingestion from POD36 and transferred to another hospital on POD85. He had no disease recurrence in our outpatient care. We think that the spontaneous esophageal rupture occurred because of the frequent vomiting caused by the continued chemotherapy despite the severe side effects. Treatments must be selected by considering patients' life background and medical compliance, and common guidance in taking medications must be provided to elderly patients at the start of chemotherapy.

Colonic stenosis caused by infection of an intraperitoneal access port system: a rare complication of intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis.

BACKGROUND: Intraperitoneal (i.p.) chemotherapy is garnering attention as an effective treatment for gastric cancer with peritoneal metastasis. We report the case of a patient who developed colonic stenosis caused by infection of an i.p. access port system during i.p. chemotherapy. It was difficult to differentiate whether the extrinsic colonic stenosis arose from a catheter infection or peritoneal metastasis of the gastric cancer. CASE PRESENTATION: A 66-year-old Japanese man underwent total gastrectomy for gastric cancer. Because the intraoperative findings revealed peritoneal metastasis, a port system was implanted for subsequent i.p. chemotherapy. Two months after initiation of chemotherapy, he complained of vomiting and abdominal pain. A computed tomography scan revealed marked thickening of the sigmoid colon wall adjacent to the catheter of the i.p. access port system. A barium enema demonstrated extrinsic irregular stenosis of the sigmoid colon. Although it was difficult to distinguish whether infection or peritoneal metastasis had caused the colonic stenosis, we removed the port system to obtain a therapeutic diagnosis. Coagulase-negative staphylococci were detected by catheter culture. The wall thickening and stenosis of the sigmoid colon completely resolved after removal of the port system. CONCLUSIONS: We report the case of a rare complication in association with an i.p. access port system. Infection of the port system should be considered as a differential diagnosis when colonic stenosis adjacent to the catheter is observed during i.p. chemotherapy.

5-Fluorouracil, methotrexate, leucovorin, CDDP and epirubicin (FEPMTX): a wide-spectrum regimen of salvage chemotherapy for high-grade advanced gastric cancer.

BACKGROUND/AIMS: Twenty-one patients with primary stage IV gastric cancer were treated with a wide-spectrum regimen, designated as FEPMTX therapy to establish an effective salvage chemotherapy. METHODOLOGY: FEPMTX therapy consisted of 5-fluorouracil and the triple biochemical modulators in addition to epirubicin. The schedule comprised 3 days continuous administration of 5-fluorouracil (350 mg/m2/day) and; methotrexate (MTX; 35 mg/m2) on day 1, calcium leucovorin (LV; 30 mg/m2) on day 2 and 3, cisplatin (CDDP; 30 mg/m2) and epirubicin (20 mg/m2) on day 3 every 2 weeks in principle. RESULTS: Eleven partial responses, five no changes and five progressive diseases were obtained, and the response rate was 52%. Ten patients (partial response 7, no change 2, progressive disease 1) received gastrectomy (resectability rate 48%). The survival of responders was significantly longer than that of non-responders (median survival time, 356 days vs. 152 days) while there was no significant prolongation by resection of the primary lesion. Adverse effects such as myelosuppression, anorexia and fatigue sometimes occurred, but were mild and the regimen was well tolerated by all the patients. CONCLUSIONS: FEPMTX is thought to be an effective regimen for neoadjuvant chemotherapy with longer survival and little toxicity for patients with high-grade advanced gastric cancer.

Long-term survival of a patient with primary papillary serous carcinoma of the peritoneum treated by subtotal peritonectomy plus intraoperative chemohyperthermia.

We report the long-term survival of a patient with primary papillary serous carcinoma of the peritoneum, treated by subtotal peritonectomy combined with continuous hyperthermic peritoneal perfusion. After subtotal peritonectomy and continuous hyperthermic peritoneal perfusion, early postoperative intraperitoneal chemotherapy with cisplatin and three cycles of cisplatin-based intravenous chemotherapy were administered. The patient currently remains alive 23 months after surgery. This long-term survival suggests that treatment of primary papillary serous carcinoma of the peritoneum requires aggressive cytoreduction surgery followed by chemotherapy using adequate methods to enhance chemosensitivity.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary colorectal cancer show a relationship to clinical effects of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy.

Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine), an intermediate metabolite of capecitabine, to 5-fluorouracil (5-FU). While dihydropyrimidine dehydrogenase (DPD) catalyzes 5-FU to inactive molecules. We investigated TP and DPD levels in tumor tissue to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR adjuvant chemotherapy. A total of 88 colorectal cancer patients were classified into Dukes' B and C groups and treated for 2 years with oral 5'-DFUR (800 mg/body/day). During the follow-up period, 20 of the 88 patients developed a recurrence. All the patients were examined retrospectively for primary tumor TP and DPD levels and clinical response to 5'-DFUR. Results showed that: a) median levels of TP and DPD in the primary tumor, measured by enzyme-linked immunosorbent assay (ELISA), were, respectively, 43.6 and 32.3 U/mg protein. Primary tumor TP levels of the 20 patients who had a recurrence were lower than those of the 68 patients with no recurrence (p=0.07); b) although there were no significant differences in clinicopathologic features between high and low median TP level groups, disease-free survival was better in the high TP than in the low TP group (89% vs. 64%, at year 4); and c) of patients classified into 4 groups such as high TP/DPD, high TP but low DPD, low TP but high DPD, and low TP/DPD, patients with high TP but low DPD had the best disease-free survival, whereas the low TP but high DPD group had the worst survival. These results suggest that TP and DPD levels in primary colorectal tumors may be a useful indicator for selecting patients likely to respond to 5'-DFUR adjuvant chemotherapy and probably capecitabine, a prodrug of 5'-DFUR.