[Clinicopathological Study of Small Intestinal Carcinoma].

We analyzed the clinicopathological characteristics, preoperative diagnosis, surgical operations, chemotherapy regimens, and prognoses of 6 patients with primary small intestinal carcinomas that were resected at our hospital between January 2004 and December 2014. The patients(3 men and 3 women)were 65 to 77 years old(mean: 70 years old). We were able to diagnose 3 patients pathologically before surgery via double balloon endoscopy and endoscopy of the large intestine. We performed partial resection of the jejunum in 3 patients, partial resection of the ileum in 1 patient, laparoscopic ileocecal resection in 1 patient, and right hemicolectomy in 1 patient. The histological type was well-differentiated adenocarcinoma in 2 patients, moderately differentiated adenocarcinoma in 2 patients, papillary adenocarcinoma in 1 patient, and poorly differentiated adenocarcinoma in 1 patient. The tumor depth was T2 in 1 patient, T3 in 2 patients, and T4 in 3 patients. The pathological stage was I in 1 patient, II A in 1 patients, II B in 2 patient, III A in 1 patient, and III B in 1 patient. The postoperative median duration of follow-up was 44 months(range: 10-127). Regarding prognosis, 5 patients are alive without recurrence, and 1 patient died of peritoneal dissemination. The overall 5-year survival rate was 75%. We suggest that it is very important to perform radical resection with lymph node dissection for patients without distant metastases.

Perioperative supplementation with bifidobacteria improves postoperative nutritional recovery, inflammatory response, and fecal microbiota in patients undergoing colorectal surgery: a prospective, randomized clinical trial.

The use of probiotics has been widely documented to benefit human health, but their clinical value in surgical patients remains unclear. The present study investigated the effect of perioperative oral administration of probiotic bifidobacteria to patients undergoing colorectal surgery. Sixty patients undergoing colorectal resection were randomized to two groups prior to resection. One group (n=31) received a probiotic supplement, Bifidobacterium longum BB536, preoperatively for 7-14 days and postoperatively for 14 days, while the other group (n=29) received no intervention as a control. The occurrences of postoperative infectious complications were recorded. Blood and fecal samples were collected before and after surgery. No significant difference was found in the incidence of postoperative infectious complications and duration of hospital stay between the two groups. In comparison to the control group, the probiotic group tended to have higher postoperative levels of erythrocytes, hemoglobin, lymphocytes, total protein, and albumin and lower levels of high sensitive C-reactive proteins. Postoperatively, the proportions of fecal bacteria changed significantly; Actinobacteria increased in the probiotic group, Bacteroidetes and Proteobacteria increased in the control group, and Firmicutes decreased in both groups. Significant correlations were found between the proportions of fecal bacteria and blood parameters; Actinobacteria correlated negatively with blood inflammatory parameters, while Bacteroidetes and Proteobacteria correlated positively with blood inflammatory parameters. In the subgroup of patients who received preoperative chemoradiotherapy treatment, the duration of hospital stay was significantly shortened upon probiotic intervention. These results suggest that perioperative oral administration of bifidobacteria may contribute to a balanced intestinal microbiota and attenuated postoperative inflammatory responses, which may subsequently promote a healthy recovery after colorectal resection.

[Clinicopathological Outcome of Perforated Colorectal Cancer].

We investigated the clinicopathological findings of 90 patients with colorectal perforation who underwent emergency surgery between January 2008 and July 2015.T he patients were divided into 2 groups, namely those with perforation due to colorectal cancer(colorectal cancer group, n=20)and those with perforation due to benign colorectal disease(non-colorectal cancer group, n=70).We investigated the clinicopathological findings of the 2 groups.The SOFA score was significantly lower in the colorectal cancer group than in the non-colorectal cancer group.Of the 20 cases of primary cancer, 11 were located in the sigmoid colon; 5, in the rectum; 2, in the transverse colon; 1, in the ascending colon; and 1, in the cecum.The perforation occurred at the tumor site in 8 patients and at the oral site of cancer in 12.Eleven patients had stage II cancer, 1 had stage IIIa, and 8 had stage IV.Ten patients underwent curability A resection; 1, curability B resection; and 8, curability C resection.Recurrence was observed in 6 of the 10 patients who had undergone curability A resection and in 1 patient who had undergone curability B resection.The initial recurrence site was the liver in 3 cases, the peritoneum in 2 cases, and a local site in 2 cases.Even if the patents underwent curative operation, the recurrence rate was high.Therefore, we conclude that adjuvant chemotherapy is required along with careful follow-up.

Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study).

BACKGROUND: We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. PATIENTS AND METHODS: The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. CONCLUSION: UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.

Phase II study of first-line chemotherapy with uracil-tegafur plus oral leucovorin in elderly (≥75 years) Japanese patients with metastatic colorectal cancer: SGOSG-CR0501 study.

BACKGROUND: Oral uracil-tegafur and leucovorin (UFT/LV) therapy for elderly patients with metastatic colorectal cancer (mCRC) requires careful handling in Western countries because of a high incidence (≥20 %) of grade 3 diarrhea. However, its efficacy and safety for elderly Asian patients have not been investigated. METHODS: In this multicenter cooperative phase II study, the eligibility criteria were: age of 75 years or older, no prior chemotherapy, and histologically confirmed colorectal cancer with one or more measurable lesions. UFT 300 mg/m(2)/day and LV 75 mg/day were administered orally for 28 days followed by a 7-day rest period. RESULTS: Twenty-one patients were enrolled in this study (prior to study termination after approval of bevacizumab), and all patients were eligible for efficacy and safety analysis. The median age was 79 years (range, 75-83 years). The majority of patients (95 %) had ECOG Performance Status 0 or 1. The overall response rate was 33 % (95 % confidence interval [CI], 18-53 %). The median progression-free and overall survivals were 5.3 months (95 % CI 4.0-7.9 months) and 18 months (95 % CI 13-21 months), respectively. Grade 3 or greater adverse events included anorexia (10 %), diarrhea (10 %), and leukopenia (5 %). These results were compatible with those seen in Japanese patients in a previous bridging study between Japan and the US, in which patients under 75 years old were evaluated. CONCLUSIONS: UFT/LV therapy was safe and feasible in elderly Japanese patients with mCRC, and further study of UFT/LV therapy in combination with bevacizumab is warranted.

[A case of locally advanced gastric cancer responding to pathological CR treated with S-1/CDDP neoadjuvant chemotherapy].

A 75-year-old woman was referred to our hospital because of locally advanced gastric cancer. Gastrointestinal fiberscopy revealed type 3 advanced gastric cancer in the posterior wall of the gastric cardia extending to the middle body. Abdominal CT scan revealed direct invasion of pancreas and regional lymph node metastases, indicating clinical stage IV (cT4N2H0P0M0). After two courses of S-1/CDDP, neoadjuvant chemotherapy was administered, and total gastrectomy with D2 lymphadectomy was performed. Histological examination revealed no residual cancer cells in the surgically obtained stomach and lymph nodes, suggesting a complete pathological response (Grade 3). She was treated with S-1 for one year after operation and presently, 16 months after operation, she is in good health without recurrence.

[Feasibility and anti-tumor activity of postoperative adjuvant chemotherapy with gemcitabine for resected pancreatic cancer].

The feasibility and anti-tumor activity of gemcitabine (GEM) as postoperative adjuvant chemotherapy were evaluated retrospectively. Between September 1998 and June 2007, patients with resected invasive pancreatic cancer (stage III, IVa, IVb) were given adjuvant chemotherapy with GEM (GEM group, n=10) or did not receive chemotherapy (n=11). Started the administration of GEM 38.5 days after surgery, and the mean duration was 15.4 months. Grade 3 or 4 adverse event was not observed in the GEM group. There was a significant difference in overall survival between the GEM group and the no-chemotherapy group (p=0.037), but there was no significant difference in disease-free survival between the two groups. Adjuvant chemotherapy with GEM was feasible and showed a benefit in patients with invasive pancreatic cancer.

[Two cases of advanced low rectal cancer, preoperative chemo-radiation therapy leading to complete histological response].

We report two cases of advanced low rectal cancer, with preoperative chemo-radiation therapy leading to a complete histological response. Case 1 was a 74-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+oral 5'-DFUR 800 mg/day for 3 weeks) was performed. Then, 30 days after chemo-radiation, we conducted a low anterior resection with lymph node dissection. Histological examination revealed no residual cancer cells in the resected specimen. Case 2 was a 35-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+5-FU 500 mg/day+CDDP 10 mg/day for 3 weeks) was performed. 28 days after chemo-radiation, we conducted an abdominoperineal resection with lymph node dissection and a partial resection of the liver. Histological examination revealed well-differentiated adenocarcinoma in the resected liver tissue, but a rectal tumor was replaced by scar tissue with no viable cells.

[Effectiveness of preoperative chemoradiotherapy for advanced rectal cancer].

To determine the pathologic effectiveness of preoperative chemoradiotherapy (CRT) in patients with advanced rectal carcinoma, we reviewed clinical records of 76 patients who received preoperative pelvic radiation +/- chemotherapy. Since 2 patients refused operation and 2 died before surgery, 72 patients underwent operation with a mean delay of 19.9 days after completion of irradiation. Pathologic tumor regression grade (Grade 0-3) was determined by the amount of viable tumor versus necrosis and fibrosis. Grade 0, 1 a, 1 b, 2, and 3 (pCR) were observed in 0%, 25.0%, 38.9%, 27.8% and 2.8% of patients, respectively. The pathologic response (PR) rate was 75.0% when PR was defined as greater than grade 1 b (tumor regression more than 1/3). Downstaging was observed in 35.8% of patients, in which 5-year overall survival was significantly better than in patients without downstaging (90.0% vs. 50.1%, p<0.05). No correlation could be observed between PR and downstaging. CRT is a useful tool with a high PR rate in patients with advanced rectal cancer. More accurate and careful clinical staging is important to select adequate candidates for CRT. Multi-institutional clinical trials as well as standardizing the surgical procedure including LN dissection are required to validate the advantages of CRT for Japanese patients.

Familial epidermoid cysts of the spleen: report of two cases.

The familial occurrence of epidermoid cysts of the spleen is rare, with only six cases having ever been reported, to our knowledge. We recently diagnosed epidermoid cysts of the spleen in a mother and son. First, a 15-year-old boy was admitted to our hospital for management of blunt abdominal trauma. Computed tomography (CT) showed a ruptured large splenic cyst with an intraabdominal hematoma. We performed a splenectomy, and histopathological examination confirmed the existence of an epidermoid cyst of the spleen. About 2 years and 6 months later, the family physician found that the patient's 41-year-old mother had a large splenic cyst, and she was referred to our hospital for further investigation. CT showed a 10 x 8 cm cyst occupying most of the spleen. The patient underwent splenectomy, and a pathological diagnosis of an epidermoid cyst of the spleen was confirmed. Although the etiology of epidermoid cysts of the spleen is unclear, this familial occurrence may support the hypothesis of congenital malformation as a result of genetic change.

[Improved quality of life in a patient with carcinomatous meningitis from invasive lobular carcinoma treated with intrathecal MTX and Ara-C in combination with systemic docetaxel].

Carcinomatous meningitis from breast cancer is rare and has a poor prognosis with a life expectancy of approximately 80 days. We performed intrathecal MTX and Ara-C in combination with systemic docetaxel treatments in the patient, a 44-year-old woman with carcinomatous meningitis from invasive lobular carcinoma previously treated with anthracycline and paclitaxel. Although the patient died 128 days after the onset, intrathecal chemotherapy in combination with systemic docetaxel reduced the number of malignant cells and induced degeneration of the cells in CSF, resulting in improved quality of life.