Sadanori Fuchimoto

Long-term effects of jejunal pouch added to Roux-en-Y reconstruction after total gastrectomy

Background. Jejunal pouch reconstruction after total gastrectomy has been demonstrated to ameliorate postgastrectomy symptoms, with the process of adaptation taking several months. In contrast to the short-term effects of pouch reconstruction, there are few reports about the long-term consequences (more than 2 years after surgery). Methods. In this study, 22 patients with jejunal pouch (PRY group) and 12 patients without jejunal pouch (RY group) who survived for more than 2 years without any recurrence and were available for follow-up were compared. Patients in the two groups were compared 2 years after surgery in terms of postgastrectomy symptoms, and improvements in body weight and nutritional parameters. Results. Eating capacity at a single meal compared with that in the pre-illness state was significantly better in the PRY group than in the RY group. The total score on the gastrointestinal symptom rating scale (GSRS) in the PRY group was less than that in the RY group (3.17 vs 5.25). The GSRS score for reflux syndrome in the PRY group was significantly better than that in the RY group. Assessment according to Cuschieris gradings revealed that the total score in the PRY group was lower than that in the RY group (2.73 vs 5.92). Among the various symptoms examined, the incidence of dietary restriction and that of heartburn were significantly lower in the PRY group. Conclusion. We conclude that, 2 years after total gastrectomy, the pouch reconstruction had alleviated postgastrectomy symptoms to a greater extent than simple Roux-en-Y reconstruction, but the effectiveness could be improved. The long-term effects of pouch reconstruction should be examined more precisely with an adequate and valid scoring system for determining quality of life.

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients

To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg−1i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day−1) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.

The laser treatment of hemorrhoids: results of a study on 1816 patients.

Laser is an effective, simple and harmless clinical procedure used for the treatment of hemorrhoids, as an alternative to medical therapy or surgery. In this report, we describe our experience of applying carbon dioxide laser to hemorrhoids in a total 1816 consecutive patients. The results lead us to conclude that the laser treatment of hemorrhoids is effective in pain alleviation from the first session and that patients so treated have a much more comfortable postoperative course.

A case of esophageal squamous cell carcinoma metastatic to the breast

Metastasis to the breast from extramammary malignancies is rare. There are especially few reports of metastasis from esophageal cancer. We report the pathological and autopsy findings of a 44-year-old man with advanced esophageal cancer and a left breast tumor. Squamous cell carcinoma invading the mammary glands was demonstrated histologically. Immunostains for ER, PgR, and ErbB-2 were negative. At autopsy, metastatic lesions were found in lung, liver, diaphragm, peritoneum, spine, and mediastinal lymph nodes, with no evidence of metastasis to the skin. While metastatic breast tumors are rarely the initial sign of malignancy, it is important to distinguish a metastasis from primary breast cancer to avoid unnecessary conflicting treatments.

Antiproliferative effects of natural human tumor necrosis factor-α, interferon-α, and interferon-γ on human pancreatic carcinoma cell lines

SummaryThe antiproliferative effects of natural human tumor necrosis factor-α (nHuTNF-α), natural human interferon-α (nHuIFN-α), and natural human interferon-γ (nHuIFN-γ) were investigated in human pancreatic carcinoma cell lines. HuP-T3, HuP-T4, and BxPC-3 carcinoma cells exhibited mild growth inhibition after treatment with nHuTNF-α. HuP-T3, HuP-T4, MIA-PaCa-2, and BxPC-3 cells exhibited mild or marked growth inhibition after treatment with nHuIFN-α. Incubation with nHuIFN-γ caused marked growth inhibition of HuP-T4 and BxPC-3 cells, whereas HuP-Tl, HuP-T3, and MIA-PaCa-2 cells showed only mild growth inhibition with the same dose of nHuIFN-7. Combined nHuTNF-a and nHuIFN-a (1:1) demonstrated marked synergism in comparison with their effects as single agents on HuP-Tl, HuP-T3, and MIA-PaCa-2 cells. The combination of nHuTNF-a and nHuIFN-7 (100:1) also demonstrated a marked synergistic effect in comparison with these cytokines alone in four out of five pancreatic carcinoma cell lines (HuP-T1, HuP-T3, HuP-T4, and MIA-PaCa-2 cell lines). The marked increase in efficacy brought about by using combinations of cytokines may enable some improvement in the treatment of pancreatic carcinoma patients in the future.

A case of superior lumbar hernia

A case of a superior lumbar hernia in a 50 year old woman is described herein. She presented with a 7×8 cm soft nontender, smooth-surfaced mass in the left flank, and barium meal with follow through showed herniation of the descending colon. At operation, a 6×5 cm defect was found in the transversalis fascia, which was repaired with mattress sutures to the transversalis fascia together with suturing of the external oblique to the latissimus dorsi. This article presents the above case and reviews the published literature relating to this subject.

Suture line recurrence in jejunal pouch replaced after total gastrectomy for gastric cancer

Abstract:We report a case of suture line recurrence in a jejunal pouch, diagnosed 4 months after total gastrectomy for advanced gastric cancer. The jejunal pouch was made with a linear stapler, without intraluminal irrigation being carried out before anastomosis, and was replaced in an interposition fashion. We propose that the recurrence was caused by the implantation of exfoliated cancer cells in either the intraluminal mucus or on a contaminated stapling device.

Inhibitory effect of nafamostat mesilate on metastasis into the livers of mice and on invasion of the extracellular matrix by cancer cells

Although many agents that interfere with clotting mechanisms have been investigated for their potential to inhibit metastasis, their toxicity has prevented administration of sufficiently high doses to achieve inhibition of metastasis in clinical trials. Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited liver metastasis in a CDF1 mice model with colon 26 adenocarcinoma cells. The apparently dose-dependent inhibitory effect was seen 21 days after all of the doses tested (0.3, 1.0, 3.0 and 10.0 nig/kg for 7 days) but the effect was only statistically significant (P < 0.01) at the highest dose. The blood concentrations 3 min after dosing were less than 10−6 M for all of the doses tested. At a concentration of 10−5 M or less nafamostat mesilate was not cytotoxic towards colon 26 cells in vitro. The results indicate that it may not be difficult to achieve blood nafamostat mesilate concentrations that inhibit metastasis in mouse liver. Possible mechanisms of nafamostat mesilate are inhibition of extravasation and invasion of cancer cells, inactivation of collagenase due to inhibition of plasmin activity and inhibition of the formation of the cancer cell thrombus, and arrest in the capillaries through inhibition of thrombin activity. These preliminary results suggest that peri-operative administration of nafamostat mesilate may prevent metastasis into the liver after surgery for gastrointestinal malignancies.

Antitumor Effect of Recombinant Human Interleukin‐1β Alone and in Combination with Natural Human Tumor Necrosis Factor‐α

In order to investigate the antitumor effect of recombinant human interleukin‐1β (IL‐1β) alone and in combination with natural human tumor necrosis factor‐α (nHuTNF‐α), we used female BDF1 mice bearing Lewis lung carcinoma (3LL). IL‐1β showed an antiproliferative effect against pulmonary metastatic tumors of 3LL in a dose‐dependent manner. We observed 19.6 ± 6.6, 18.6 ± 5.3, 14.1 ± 4.4 and 13.0 ± 6.0 metastatic tumors at doses of 0.5, 1.0, 2.5 and 5.0 μg IL‐1β/mouse/day by daily intravenous administration (the number of metastatic tumors of the control group was 26.3 ± 8.2). Similar results were obtained by intraperitoneal administration, but in this case, mice showed a marked decrease of body weight. When IL‐1β was administered in combination with nHuTNF‐α, pulmonary metastatic tumors decreased much more than when IL‐1β was administered alone. When the control group had 18.6 ± 12.7 metastatic tumors, the nHuTNF‐α group had 12.3 ± 3.9 and the IL‐1β group had 12.8 ± 8.0, the group which was administered both cytokines had a significantly decreased number of 5.6 ± 3.3 metastatic tumors. This antiproliferative effect of IL‐1β in combination with nHuTNF‐α was reduced by the intravenous administration of anti‐asialo GM1 antibody and carrageenan. The number of metastatic tumors was increased from 8.9 ± 8.0 to 18.8 ± 11.4 by anti‐asialo GM1 antibody and from 9.5 ± 6.8 to 28.0 ± 12.3 by carrageenan. It was suggested that asialo GM1‐positive cells and macrophage were two of the most important effectors of the antiproliferative effect of IL‐1β and TNF‐α.

Hyperthermic Enhancement of the Antitumor Effect of Natural Human Tumor Necrosis Factor-α and -β: an in vitro and in vivo Study

A synergistic antitumor effect of natural human tumor necrosis factor‐β (TNF‐β) in combination with hyperthermia was found, in comparison with that of TNF‐α, using an in vitro antiproliferative assay on a human colon cancer cell line (RPMI4788) and an in vivo tumor growth inhibition assay on Meth A sarcoma cells. In vitro combined treatment with TNF‐β (10,000 U/ml) and hyperthermia (at 43° for 60 min) synergistically inhibited the proliferation of the cells. Combined effects of TNF‐α or natural human interferon‐α or ‐γ (IFN‐α, ‐γ) and hyperthermia were also examined, and furthermore, the combinations of TNFs and IFNs were examined in combination with hyperthermia at 42°; their antiproliferative effects were further augmented by hyperthermia. In vivo growth of Meth A sarcoma cells (5 × 105), transplanted subcutaneously into BALB/c mice, was inhibited significantly (P<0.05) with the combination of TNF‐α or ‐β (2 × 105 U/mouse) and hyperthermia (at 43° for 60 min) as compared to either a single intravenous injection of TNF‐α or ‐β alone or the hyperthermia alone. The influence of TNF‐β and hyperthermia on the cell cycle was examined. Flow cytometric analysis showed that RPMI4788 cells treated with TNF‐α or ‐β accumulated in the S phase of the cell cycle, and that hyperthermia (at 42° for 60 min) alone had no influence on the cell cycle and did not augment the S phase accumulation of the cells treated with TNF‐α or ‐β.