[Effectiveness of Intraoperative Histologic Assessment of Surgical Margins for Breast-Conserving Surgery].

BACKGROUND: The effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery is unclear. In this study, we investigated the effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery. METHODS: Sixty-six patients who underwent breast-conserving surgery for breast cancer at our hospital between January 2007 and December 2013 were retrospectively examined for an association between the surgical margin status and locoregional recurrence. The surgical margins were then evaluated by intraoperative histologic assessment. RESULTS: The median observation period was 52 months. Positive margins were found in 14 patients (21%). A total mastectomy was performed in 9 patients, and additional resection in 5 patients. In the permanent tissue sample, the intraoperative assessment was found to be false negative in 2 patients (3.8%), who received boost irradiation postoperatively. No locoregional recurrence was observed in all patients who underwent additional resection or total mastectomy due to positive margins. The rate of margin positivity was significantly higher in invasive lobular carcinomas and in cancers with intraductal extension. CONCLUSIONS: Intraoperative histologic assessment of the surgical margin was useful for reducing the rate of local recurrence.

[A Case of Locally Advanced Breast Cancer Treated with Modified Radical Mastectomy with Immediate Reconstruction Using a Tissue Expander after Endocrine Therapy].

We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted.

Retrospective analysis of capecitabine and oxaliplatin (XELOX) plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer.

XELOX plus bevacizumab is an effective treatment strategy and has a manageable tolerability profile when administered to Japanese patients with metastatic colorectal cancer (mCRC). In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efficacy and safety in clinical practice. In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a first-line treatment between September, 2009 and April, 2012. Eligible patients had histologically confirmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks of a 3-week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. The median progression-free survival (PFS) was 290 days [95% confidence interval (CI): 222-409 days] and the median OS was 816 days (95% CI: 490 days-not calculated). The response rate (RR; complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. The most common adverse events observed following administration of XELOX plus bevacizumab were neurosensory toxicity (82.5%), anorexia (50%), hypertension (45%) and a decrease in the platelet count (40%). The most common grade 3/4 adverse events were neurosensory toxicity (15%) and fatigue (15%). In conclusion, XELOX plus bevacizumab may be considered a routine first-line treatment option for patients with mCRC. Notably, the combination of capecitabine and bevacizumab was safe with an acceptable toxicity profile and induced a significant rate of disease control.

[A case of emergency resection of a giant gastrointestinal stromal tumor of the stomach associated with hemorrhagic shock].

We report a case of emergency resection of a giant gastrointestinal stromal tumor of the stomach associated with hemorrhagic shock. A 79-year-old woman was admitted to our hospital because of massive hematemesis. Laboratory analysis revealed a hemoglobin level of 6.5 g/dL. Abdominal computed tomography (CT) and upper gastrointestinal endoscopy revealed a submucosal tumor, 12 cm in diameter, in the fornix of the stomach. As a Dieulafoy-like lesion was present, we attempted coagulation hemostasis in the exposed blood vessels. Endoscopic hemostasis was not successful. The patient went into hemorrhagic shock. Emergency surgery was performed: total gastrectomy with distal pancreatosplenectomy. The resected specimen measured 10×12×7 cm and was hard. Immunohistologically, the tumor was positive for c-kit and CD34 and negative for alpha smooth muscle actin (αSMA), desmin, and S-100. Histological examination revealed that the patient had a high-risk gastrointestinal stromal tumor of the stomach with no nodal metastasis. The postoperative course was uneventful and the patient has remained alive without recurrence for 4 years.

[Clinical experience of chemotherapy with S-1/CDDP for highly-advanced gastric cancer].

BACKGROUND: We evaluated the efficacy and safety of chemotherapy with S-1/CDDP for advanced and recurrent gastric cancer at Fuchu Hospital. METHODS: The participants were 24 patients treated at our hospital. S-1 was given orally at 80 mg/m/2 for days 1-21, and 60 mg/m2 of CDDP was administered on day 8, followed by a 2-week rest period, within a 5-week course. RESULTS: Results were rated as a partial response in 12 cases and a stable response in 4 cases. The response rate was 50% (12/24), and median survival time was 273 days. The total incidence of grade 3 or greater adverse reactions including leucopenia, neutropenia, anemia, general fatigue, and eruption, was 25% (6/24). CONCLUSION: The combination of S-1/CDDP therapy appears to be highly efficacious and safe and showed promise as a useful treatment strategy, even in an outpatient clinic.

A synergistic antitumor effect of interleukin-2 addition with CD80 immunogene therapy for peritoneal metastasis of gastric carcinoma.

The co-stimulatory molecule CD80 is a ligand of CD28, which plays a key role in the induction of cell-mediated immune responses. Many tumors, including gastric cancer, decrease the expression of CD80, which results in the failure of immune recognition. We evaluated the effect of interleukin-2 addition combined with CD80 infection on the peritoneal metastasis in gastric cancer. CD80 infection combined with interleukin-2 addition significantly increased the activated cytotoxicity of mononuclear cells compared to CD80 gene infection and compared to the lacZ control group. In vivo, the survival of animals with intraperitoneal tumor was longest in those given CD80 infection with interleukin-2 addition (median survival, 46 days), followed by those given interleukin-2 (39 days), those given CD80 infection (37 days), and those given lacZ (29 days). These results suggest that interleukin-2 addition might contribute to improving the observed outcome of CD80 immunogene therapy in peritoneal metastasis of gastric carcinoma.

Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma.

The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial-mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [(3)H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10(-5) and 10(-6) M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial-mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts.

Laparoscopic adrenalectomy on a patient with primary aldosteronism during pregnancy.

A pregnant 26-year-old woman was referred for evaluation and management of progressive hypertension and hypokalemia at 14 weeks of gestation. Her plasma aldosterone level was markedly elevated and magnetic resonance imaging showed a right adrenal tumor. Primary aldosteronism due to an aldosterone producing-adenoma was diagnosed. Because of progressive severe hypertension, a laparoscopic adrenalectomy was performed at 17 weeks of gestation. The procedure was completed without complication, and plasma aldosterone and potassium levels rapidly improved post-operatively. However, her hypertension persisted and the growth retardation of the fetus was found. Regrettably, intrauterine fetal death was confirmed at 26 weeks of gestation. Histological examination of the placenta revealed that the placental artery had very thick walls which had apparently caused a critical failure in fetal blood flow. The optimal timing of laparoscopic surgery during pregnancy and perioperative management were subsequently discussed.

[Changes in tumor marker levels as a predictor of gemcitabine effect on patients with unresectable or recurrent pancreatic cancer].

We studied on possible association between the tumor marker (CEA, CA 19-9, and SPan-1) change and the clinical outcome after treatment with gemcitabine (GEM) in 23 patients with unresectable or recurrent pancreatic cancer. GEM was administered intravenously at a standard dose of 1000 mg/m2 weekly. One course consisted of weekly administration for 3 weeks followed by 1 week's rest. When the adverse effect did not allow the weekly administration, GEM was given bi-weekly without dose modification. Objective responses were evaluated by computed tomography and tumor marker change. Two or more courses were given for only 6 (26.1%) patients. The number of patients, administered GEM 6 or more times including by the weekly and bi-weekly method, was 12 (52.2%). Antitumor effects were evaluable in 16 patients. The clinical efficacies were 1 partial response (PR), 6 stable disease (SD), and 9 progressive disease (PD). Decreases in tumor marker levels were recognized in 9 of the 16 patients. The median survival time (MST) of the PR+NC group was significantly longer than that of the PD group (9 vs 3.5 months; p=0.0151). MST of those in the decreasing tumor marker group was significantly longer than the group with no decreases in the tumor markers (7.0 vs 5.5 months; p = 0.0478). The adverse effects at grade 3 or more were 4 (17.3%) leukopenia, 2 (8.7%) thrombocytopenia, and 1 (4.3%) skin toxicity. In conclusion, the tumor marker change after GEM treatment may be a predictor of preferable prognosis in patients with pancreatic cancer.

Prognostic predictive value of endoscopic ultrasound findings for invasive ductal carcinomas of pancreatic head.

OBJECTIVES: Accurate preoperative prediction of the prognosis of patients with invasive ductal carcinoma of pancreatic head (pancreatic head cancer) is important for selecting treatment methods. We retrospectively examined the prognostic predictive values of endoscopic ultrasound (EUS) findings for patients with this disease. METHODS: The subjects were 66 patients with pancreatic head cancer who had undergone EUS. We examined each EUS finding as a possible prognostic predictor, including heterogeneity of internal echo, irregularity of peripheral echo, clarity of boundary echo, dilatation of the main pancreatic duct (MPD), dilatation of the common bile duct, lymph node swelling, vessel invasion, and the presence of ascites, by univariate and multivariate analysis for survival. RESULTS: Irregular peripheral echo, portal vein invasion, superior mesenteric artery/celiac artery invasion, and the presence of ascites were significant predictors of a poorer prognosis by univariate analysis for survival. In resectable cases, EUS findings of MPD dilatation and portal invasion were significant prognostic predictors by univariate analysis, and MPD dilatation was an independent prognostic predictor by multivariate analysis. CONCLUSION: EUS may be useful for predicting the prognosis of patients with pancreatic head cancer, based on the accuracy it provides in evaluating locoregional spreading.

Usefulness of inhibiting the lymph node metastasis in human gastric carcinoma by B7-1 gene transfection.

INTRODUCTION: Lymph node metastasis is one of the crucial prognostic factors in gastric cancer. We have reported that ICAM-1 gene transfection was effective against lymph node metastases of gastric cancer. B7-1, one of the co-stimulatory factors, was reported to induce cytotoxic T lymphocytes when using melanoma and bladder cancer cell lines, as well as ICAM-1. In this study, we investigated the inhibitory effect of B7-1 on lymph node metastasis by B7-1 gene transfection into gastric cancer cells. MATERIALS AND METHODS: We transfected B7-1 genes into a gastric cancer cell line (OCUM-2MLN) and analyzed the effect of B7-1 transduction on lymph node metastasis, the in vitro adhesiveness and cytotoxicity assay of mononuclear lymphocytes to cancer cells and lymph node metastatic ability after orthotopic implantation of gastric cancer cells in vivo. RESULTS: We revealed that mononuclear lymphocytes showed significantly stronger adherence and cytotoxicity to B7-1 transfected cells (2MLN/B7) than its parent OCUM-2MLN cells. The tumor growth rate of 2MLN/B7 xenograft was significantly slower than OCUM-2MLN xenograft in nude mice. In orthotopic implantation experiments for nude mice, 2MLN/B7 cells in stomach developed significantly less lymph node metastasis than OCUM-2MLN cells. Histologic findings showed that leukocytes were intensively infiltrated in both the 2MLN/B7 tumors and its metastatic lesions, however, were scarcely observed in the lesions associated with 2MLN cells. CONCLUSION: B7-1 may play an important role in inhibiting lymph node metastasis by the mechanism of enhanced immunogenicity, and that B7-1 gene transduction might be effective against lymph node metastases of gastric cancer.

CD80 gene therapy for lymph node involvement by gastric carcinoma.

The co-stimulatory molecule, CD80 (B7-1), is a ligand of CD28 and plays a key role in the induction of cell-mediated immune responses. Many tumors, including gastric cancer, have decreased expression of CD80 which leads to a failure of immune recognition. Lymph node spread is a factor of poor prognosis in gastric cancer. In this study, we transfected the CD80 gene by an adenovirus vector into a human gastric cancer cell line, OCUM-2MLN, and analyzed the effect on lymph node disease in vitro and in vivo. After transfection of CD80 in vitro, the adhesive ability of cancer cells for peripheral blood mononuclear cells and their cytotoxicity showed significant regression (p<0.01). Intratumoral injection of AdCD80 caused significantly growth of subcutaneous tumors. In vivo lymph node spread was suppressed by injection of AdCD80 into gastric tumors. Histopathologic findings revealed CD80-positive cells around the tumor. These results suggest that CD80 gene transfer into cancer cells using an adenovirus vector might be a promising approach for in vivo cancer therapy.

ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.

PURPOSE: Human scirrhous gastric carcinoma develops peritoneal dissemination with high frequency, and the prognosis of patients with peritoneal metastasis is poor. There have been few reports of an immunogene therapy for peritoneal dissemination. Intercellular adhesion molecule (ICAM)-2 is a second ligand of leukocyte function-associated antigen-1, which functions as a costimulatory molecule for effector cells. In the present study, we examined whether ICAM-2 transfection using adenovirus vector is effective gene therapy for peritoneal metastasis of gastric cancer. EXPERIMENTAL DESIGN: We constructed an adenovirus vector, AdICAM-2, that encodes the full-length human ICAM-2 gene under control of the cytomegalovirus promoter. This vector expresses high levels of ICAM-2 on the human gastric cancer cell line OCUM-2MD3, which has high peritoneal metastatic ability in nude mice. We investigated the antitumor effects of gene transfer of ICAM-2 using the adenovirus vector AdICAM-2 in vitro and in vivo. RESULTS: ICAM-2 expressed on OCUM-2MD3 cells by AdICAM-2 demonstrated significantly high adhesiveness to and cytotoxicity against peripheral blood mononuclear cells in vitro compared with the control adenovirus vector AdlacZ. Intratumoral injection of AdICAM-2 significantly inhibited the growth of s.c. tumor. Mice with peritoneal metastasis survived for a significantly longer time after AdICAM-2 injection, compared with injection of AdlacZ. Histopathological findings revealed that many natural killer cells infiltrated the peritoneal metastatic lesions after AdICAM-2 injection. CONCLUSIONS: These findings suggest that transduction of ICAM-2 into cancer cells enhances the adhesion and activation of natural killer cells, resulting in a reduction of peritoneal metastasis. ICAM-2 transfection using adenovirus vector might be an effective form of gene therapy for peritoneal metastasis of gastric cancer.

Suppression of peritoneal metastasis in human gastric carcinoma by enhanced immunogenicity of B7-1 transfection.

B7-1, a co-stimulatory factor, has been reported to induce cytotoxic T lymphocytes (CTL). In the present study, we transfected B7-1 genes into a gastric cancer cell line (2MD3) and analyzed the effects of B7-1 transduction on peritoneal metastasis in vitro and in vivo. We revealed that mononuclear lymphocytes show significantly stronger adherence and cytotoxicity to B7-1 transfected cells (2MD3/B7) than to their parent 2MD3 cells. We also demonstrated that mice inoculated with 2MD3/B7 cells in the peritoneal cavity have a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.01). Histologic findings showed that leukocytes intensively infiltrate the 2MD3/B7 metastatic nodules, but can scarcely be observed in the nodules associated with 2MD3 cells. These findings indicate that the B7-1 may play an important role in suppressing peritoneal metastasis by the mechanism of enhanced immunogenicity, and that B7-1 gene transduction might be effective against peritoneal metastases of gastric cancer.

Prepancreatic postduodenal portal vein: report of a case.

We report an unusual case of a prepancreatic postduodenal portal vein (PPPV), incidentally discovered during total gastrectomy. If it had not been noticed, this portal vein might have been ligated and divided with disastrous consequences. This anomaly was not diagnosed preoperatively, but it could have been. Although embryological anomalies of the portal venous system, such as PPPV and preduodenal portal vein, are rarely encountered in abdominal surgery, surgeons must be aware of their possibility and be able to recognize them to avoid major intraoperative injury.

[Validity of two-hour continuous hepatic arterial infusion chemotherapy with low-dose 5-FU for unresectable liver metastasis from colorectal cancer].

The significance of hepatic arterial infusion chemotherapy for unresectable liver metastases from colorectal cancer was evaluated in 50 patients, who received either of the following regimens: 1 shot 5-FU + epirubicin + MMC (FAM group); hepatic arterial infusion of 5-FU for 2 hours + MMC (MF group); hepatic arterial infusion of 5-FU for 2 hours (5-FU group). There were no differences in the clinicopathological backgrounds of the patients among the groups. The mean survival time was 10.3 months, 16.0 months and 16.2 months in the FAM, MF and 5-FU groups. The effective percentages were 0%, 40% and 31% in the FAM, MF and 5-FU groups and the survival time of the effective cases was 18.1 months and 21.8 months in the MF and 5-FU groups. The MF group and 5-FU group showed significant improvement in prognosis. Concerning side effects, myelo-suppression and gastrointestinal toxicity appeared frequently in the MF group. In conclusion, 2-hour continuous hepatic arterial infusion with low-dose 5-FU for unresectable liver metastases from colorectal cancer may be helpful for improvement of prognosis.