[Four Cases of Appendiceal Mucinous Neoplasm Treated with Laparoscopic Surgery].

Appendiceal mucinous neoplasm has a risk for pseudomyxoma peritonei caused by appendiceal perforation.It has been reported that laparoscopic surgery is more risky than open surgery.We investigated 4 patients who underwent laparoscopic surgery for appendiceal mucinous neoplasm.The median age was 69.5(49-85).There were 3 males and 1 female.Three cases of partial laparoscopic resection of the cecum and 1 case of ileocecal resection with lymph node dissection were performed. The pathology was low-grade mucinous neoplasm in all cases.The median hospital stay was 6 days, and there were no postoperative complications(CD Grade 3 or higher)or hospital death.As for long-term results, peritoneal pseudomyxoma developed in 1 case, which had already ruptured at the time of surgery.There were no recurrences in other cases.This result suggests that laparoscopic surgery for appendiceal mucinous neoplasm is safe with optimal selection of the procedure and a protective technique.

[A Case of Overwhelming Post Splenectomy Infection(OPSI)after Operation for Sigmoid Colon Cancer].

A 64-year-old woman was diagnosed with hereditary spherocytosis 30 years ago and underwent splenectomy. She presented to the hospital with lower abdominal pain and was diagnosed with sigmoid colon cancer(cT3N3M1[LYM], H1, Stage Ⅳ)for which sigmoidectomy was performed. On the 7th postoperative day, a fever of 40℃ and an inflammatory reaction were observed. She developed a consciousness disorder the next day, and her condition rapidly deteriorated along with the development of septic shock and disseminated intravascular coagulation(DIC). With the aid of a ventilator, immediate treatment for DIC was started, but reversion of septic shock and DIC was not possible, and the patient died of multiple organ dysfunction on the 17th postoperative day. Computed tomography and urinalysis performed during the course of treatment showed no infected lesion, but Citrobacter spp. was detected thrice in venous blood culture. Hence, the patient was diagnosed as a case of Citrobacter overwhelming post splenectomy infection(OPSI). To our knowledge, this is the first report of Citrobacter spp. infection following an abrupt course of OPSI.

[A Case of Perforated Intestinal Malignant Lymphoma Induced to Remission by Multidisciplinary Therapy].

A 61-year-old man had a sudden severe abdominal pain and visited our hospital. He was diagnosed with intestinal perforation, given the peritoneal irritation symptoms, the thickening of the intestinal wall and free air as shown on enhanced abdominal computed tomography. He then underwent emergent surgery. A tumor with small perforation was found on the intestine about 15 cm distant from the terminal ileum. Partial resection of the ileum was performed. Microscopically, a type 2 tumor of 70×50mm in diameter, was observed in the resected intestine. The tumor was diagnosed as diffuse large B-cell lymphoma via immunochemical staining. He received 6courses of R-CHOP therapy after surgery without recurrence. A primary intestinal malignant lymphoma is easily perforated, which lead to poor prognosis of the patient. We report a case of perforated intestinal malignant lymphoma, which was induced to remission by multidisciplinary therapy.

[A Case Survived Long Period after Repeated Operation against the Small Intestinal GIST with Perforation].

A patient was 60-year-old man. In March 2011, the small bowel tumor with perforation was found and the partial resection of small intestine was urgently performed. KIT of resected specimen was positive. Then, diagnosis as GIST was defined. Oral administration of imatinib was started, but it was finished in 5 months because of development of the systemic edema. In February 2013, the abdominal CT revealed a tumor of 20 cm in size in the pelvis. Upon laparotomy, we detected the GIST recurrence generated at the region of small intestine anastomosis where manipulated previously, then resected all of tumor and partially small intestine. Afterward, we diagnosed as a recurrence of GIST. In March 2014, the abdominal CT found 4 cm sized mesenteric tumor and 2 cm sized abdominal wall tumor. The laparotomy was performed and we found 5 disseminated nodules intraperitoneally. We confirmed that all of these disseminated nodules were successfully removed. We defined them as re-recurrence of GIST. Six years and 5 months have elapsed since the first operation was performed, but there is no sign of three times recurrence.

[Long-Term Survival after Resection for Repeated Abdominal Wall Recurrence of Gallbladder Cancer].

We report the case of a 79-year-old woman with repeated abdominal wall recurrence of gallbladder cancer. The original diagnosis was gallbladder carcinoma. She underwent open liver bed dissection and lymph node dissection. Postoperative pathological examination indicated T2N1M0, Stage III disease. She received 6 courses of postoperative chemotherapy with gemcitabine. Two years and 2 months after the surgery, we detected a 13 mm mass under the abdominal wall scar on CT, and we resected this tumor. Pathological findings indicated adenocarcinoma, which was found to be metastasis of the gallbladder cancer. She was treated with S-1 for 8 courses postoperatively. However, 3 years 4 months after the first surgery, a tumor of 22mm was detected in the abdominal wall on the caudal side away from the previous tumor excision site. We resected the abdominal wall including the tumor. The pathological examination revealed adenocarcinoma, which was again metastasis from gallbladder cancer. The increase of CA19-9 was confirmed around 4 years and 7months after the first operation. An abdominal wall tumor of 45mm was detected in contact with the iliac bone near the last excision site and it proved to be a recurrence of gallbladder carcinoma. We performed abdominal wall tumor resection, again identifying adenocarcinoma, which was the third recurrence of gallbladder cancer. Despite continued abdominal wall recurrence, she is alive and well without metastasis for more than 5 years.

Two-year assessment of the efficacy and safety of sitagliptin in elderly patients with type 2 diabetes: Post hoc analysis of the ASSET-K study.

BACKGROUND: There have only been a few reports about use of dipeptidyl peptidase 4 (DPP-4) inhibitors in elderly patients with type 2 diabetes mellitus (T2DM), suggesting that the safety of these agents has not been sufficiently demonstrated. We performed a comparative review of the efficacy and safety of sitagliptin for Japanese patients with T2DM managed in the real-world clinical setting. METHODS: An age-stratified analysis was performed of 831 patients who were treated with sitagliptin for 2 years. Parameters assessed included the hemoglobin A1c (HbA1c), body weight, serum creatinine, and adverse events. HbA1c and the incidence of hypoglycemia were also evaluated in patients treated with sitagliptin and a sulfonylurea (SU), who were divided into three age groups (<65 years, 65-74 years, and ≥75 years). RESULTS: Comparison of glycemic control parameters, laboratory values, and adverse events revealed significant improvement of HbA1c, casual postprandial plasma glucose, and fasting plasma glucose in each age group with no change in body weight. Serum creatinine increased significantly in all age groups. Hypoglycemia only occurred in patients who received combined treatment with an SU and sitagliptin, and there was no age-related difference in its incidence. CONCLUSIONS: HbA1c was improved by 2 years of sitagliptin therapy in all three age groups, and age did not seem to influence the incidence of hypoglycemic events. These results confirm the efficacy and safety of sitagliptin in patients ≥ 75 years old, suggesting that it is also useful for treating elderly patients with T2DM.

A propensity score-matching analysis comparing the oncological outcomes of laparoscopic and open surgery in patients with Stage I/II colon and upper rectal cancers.

PURPOSE: Previous studies from Western countries have shown similar survival outcomes after both open and laparoscopic resections. In Japan, radical D3 dissections performed by open resection have been routinely performed for ≥T2- or ≥N1-stage cancers, and relatively favorable survival outcomes were obtained. This study compared the survival in patients with Stage I/II colon and upper rectal cancers undergoing laparoscopic and open resection. METHODS: A total of 145 patients were initially enrolled. Propensity score matching was applied to assemble a study cohort. D2 lymph node dissection for T1 cancer and D3 for ≥T2- and ≥N1-stage cancers were applied. The primary outcome measure was the disease-free survival; the cancer-specific and overall survival rates were secondary outcomes. RESULTS: A total of 64 patients were matched for the analysis. The length of hospitalization, postoperative complication rates, number of lymph nodes removed and surgical margins were similar between the groups. The disease-free survival following laparoscopic surgery was better than that following open surgery, but the difference was not statistically significant. Neither the cancer-specific nor overall survival rates following laparoscopic surgery were inferior to those associated with open surgery. CONCLUSIONS: The outcomes of the laparoscopic approach were comparable to those for open surgeries accompanied by radical lymph node dissection.

Chylorrhea following laparoscopy assisted distal gastrectomy with D1+ dissection for early gastric cancer: A case report.

INTRODUCTION: Chylorrhea is a form of lymphorrhea involving digested lipid products absorbed in the small intestine. Here we report a rare case of chylorrhea after laparoscopy-assisted distal gastrectomy (LADG) with D1+ dissection that resolved following administration of a low-fat diet. PRESENTATION OF CASE: A 35-year-old woman with early gastric cancer underwent LADG with D1+ dissection, and on postoperative day 4, the drain output increased and the fluid with a high triglyceride level (740mg/dL) changed from clear to milky. On postoperative day 6, oral intake of a low-fat diet was initiated after a 2-day fast, and the daily drain output decreased from postoperative day 9. The drain tube was withdrawn on postoperative day 15, and the patient was discharged on postoperative day 17. DISCUSSION: D1+ dissection does not typically cause injury to the lymphatic trunks, cisterna chyli, or thoracic duct. The maximum output of chylous ascites was minimal, and thus, we assumed that chylorrhea occurred from slightly injured lymphatics with anatomical variation. CONCLUSION: Chylorrhea after LADG with D1+ dissection is very rare. The fasting of our case followed by a low-fat diet without TPN would be an effective therapy. As a result, our case recovered favorably without further therapy.

Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients.

BACKGROUND: Sitagliptin is a DPP-4 inhibitor that became available for use in Japan three years ago. This study was conducted to identify the pleiotropic effects of sitagliptin other than blood glucose lowering in Japanese type 2 diabetes mellitus patients. METHODS: A retrospective, observational study of 940 type 2 diabetes mellitus patients was conducted. The primary outcome measures were HbA1c, blood pressure, and lipid profiles measured at 0, 4, and 12 weeks of sitagliptin therapy. RESULTS: After 12 weeks of sitagliptin treatment, compared with baseline, HbA1c decreased 0.64% ± 0.86%; systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly; and serum creatinine (Cr) and uric acid (UA) levels were mildly but significantly elevated. A correlation analysis of the changes in systolic blood pressure, diastolic blood pressure, creatinine, and uric acid (ΔSBP, ΔDBP, ΔCr, ΔUA) from baseline to 12 weeks showed significant negative correlations between ΔSBP and ΔCr, ΔSBP and ΔUA, and ΔDBP and ΔCr. Total cholesterol and postprandial triglycerides were significantly decreased at both 4 and 12 weeks. Alkaline phosphatase (ALP) decreased significantly, and there was a significant positive correlation between changes in ALP and HbA1c. CONCLUSIONS: Sitagliptin seems to be effective not only in lowering blood glucose but also in lowering blood pressure, lipid, and ALP levels. Sitagliptin appears to contribute to a Na-diuretic action due to GLP-1.

Cross-sectional survey of diabetic neuropathy in Kanagawa and clinical significance of a touch test using tissue paper.

UNLABELLED: Aims/Introduction: The prevalence of diabetes mellitus is increasing rapidly in Japan, and diabetic neuropathy is a major factor decreasing diabetic patients' quality of life, as well as a risk factor for sudden death. The present study aimed to determine the prevalence of diabetic neuropathy and raise awareness about it among patients and their physicians. MATERIALS AND METHODS: Diabetic outpatients (N = 5077) at 249 medical institutions within Kanagawa Prefecture, Japan, were surveyed by questionnaire and underwent foot examinations. The questionnaire included 10 questions about sensory abnormalities of both feet, muscle cramps and autonomic symptoms. Foot examinations included testing for vibratory perception of the medial malleolus, Achilles tendon reflexes and touch sensation of the bottom of the great toe using tissue paper. RESULTS: Of the 5077 patients surveyed, 70.4% reported symptoms. Overall, 75.4% of the patients underwent vibratory perception testing, of whom 44.9% had abnormal thresholds (≤10 s). On the tissue paper touch test, performed in 94.6% of patients, 11.9% had no touch sensation. Of the 2803 type 2 diabetic patients with known background factors who underwent foot examinations, 49.4% had diabetic neuropathy. There was a high prevalence of diabetic neuropathy (36.1%) in patients with <5-year history. Of the patients with no touch sensation on the tissue paper test, 81.3% had diabetic neuropathy. CONCLUSIONS: The present study identified the prevalence of diabetic neuropathy in Kanagawa Prefecture. The tissue paper test is a simple and excellent method of evaluating decreased superficial sensation that can help evaluate the severity of diabetic neuropathy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00174.x, 2011).

Efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients.

UNLABELLED: (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00221.x, 2012) Aims/Introduction: To determine the efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients after 3 months' therapy. MATERIALS AND METHODS: A retrospective, observational study of 741 type 2 diabetes patients was carried out; 110 received sitagliptin monotherapy, and 631 received combination therapy with sitagliptin when other oral medications were insufficient. The primary outcome measure was glycated hemoglobin (HbA1c) measured at 0, 4 and 12 weeks of sitagliptin therapy. RESULTS: In the monotherapy and combination therapy groups, HbA1c decreased significantly after 12 weeks. Target HbA1c (<7%) was achieved in 39.1% overall. On logistic regression analysis, baseline HbA1c was the strongest contributing factor for achieving target HbA1c; baseline body mass index and duration of diabetes were also significant factors. A total of 82 patients (11%) were unresponsive to sitagliptin. These patients' baseline body mass index was significantly higher and their baseline HbA1c was significantly lower than those of patients who responded to sitagliptin. The most commonly co-administered drugs were sulfonylureas (508 patients). In these patients, the dose of sulfonylurea decreased with time. In 66 patients whose sulfonylurea dosage was reduced when sitagliptin was started, HbA1c and bodyweight decreased significantly after 12 weeks. A total of 24 patients receiving sulfonylureas had mild hypoglycemia, but none discontinued sitagliptin. CONCLUSIONS: Sitagliptin was effective and safe as both monotherapy and combination therapy in Japanese type 2 diabetes patients. When sulfonylureas were ineffective, sitagliptin improved glycemic control. In patients whose sulfonylurea dose was reduced at the start of sitagliptin, blood glucose improved and bodyweight decreased after 12 weeks.

[Weekly paclitaxel therapy leading to complete disappearance of multiple liver metastases and subsequent surgical resection for advanced gastric cancer].

A 59-year-old man visited our hospital. After examination he was diagnosed with advanced gastric cancer with multiple liver metastases. At first, chemotherapy of S-1/CDDP was administered. After two weeks, he had severe diarrhea and anorexia, so the therapy was discontinued. Weekly paclitaxel was selected as the next therapy. Depending on the leukocytopenia, doses and intervals were controlled. After 4 courses, CT and MRI revealed that the liver metastases had disappeared, while the primary lesion remained. Seven months after beginning treatment, distal gastrectomy was performed. After the operation, 6 courses of paclitaxel therapy were given at the same doses and the same intervals as before the operation. Two years have passed since the operation, and no recurrence was seen on CT and MRI. Because of the relatively low frequency of adverse events in the digestive system, continued treatment with paclitaxel is possible. These findings show that paclitaxel is an effective drug for advanced gastric cancer with liver metastasis.

[A case of advanced colon cancer successfully treated with cetuximab diagnosed as EGFR-positive by liver biopsy].

Cetuximab, a monoclonal antibody used to target the epidermal growth factor receptor(EGFR), was approved for refractory and metastatic colon cancer expressing EGFR, and the EGFR expression must be confirmed. But the EGFR expression may become false negative by immunohistochemistry. When we used a past operation specimen for a search in particular, a correct evaluation may be difficult for prolonged formalin fixation. We report a case successfully treated by cetuximab, who was diagnosed as EGFR-negative by the past operation specimen, but as EGFR-positive by the liver biopsy specimen. A 51- year old woman with multiple organ metastases, who had experienced failure with prior oxaliplatin, irinotecan(CPT-11), 5- FU and bevacizumab regimens, was administered cetuximab plus CPT-11 because it was EGFR-positive by liver biopsy, and the tumor was obviously reduced. It is useful to obtain another specimen such as by liver biopsy, when the EGFR expression is negative by a past operation specimen.

[A case of pseudomembranous colitis with febrile neutropenia induced by chemotherapy and effectively treated by vancomycin enemas].

Pseudomembranous colitis, an antibiotic-associated diarrhea, needs early diagnosis and treatment for the high fatality rate in severe cases. We report a case of pseudomembranous colitis following the use of antibiotics in febrile neutropenia (FN). A 74-year-old man with non-curative resected sigmoid colon cancer was treated with cefepime in FN induced by chemotherapy. Complications of diarrhea were seen on day 2. Paralytic ileus and disseminated intravascular coagulation were also complications. He was diagnosed as pseudomembranous colitis for Clostridium difficile toxin-positive. Vancomycin enemas were administered because oral administrations were impossible, and the effect was provided. Vancomycin enemas are an effective therapy for patients with severe pseudomembranous colitis unable to tolerate oral medications because of ileus.

Glomerular hyperfiltration in non-proteinuric and non-hypertensive Japanese type 2 diabetic patients.

Glomerular hyperfiltration (GHF) may be an important factor in the initiation of glomerular damage and in predisposing diabetic patients to the later development of diabetic nephropathy (DN). Previous reports show wide range of prevalence of GHF in type 2 diabetic patients. This cross-sectional study was designed to determine the prevalence of GHF at an early stage of DN in Japanese type 2 diabetic patients and to investigate the relationships between clinical variables and GHF. We measured the glomerular filtration rate (GFR) using the plasma clearance of iohexol in 56 control subjects and 93 type 2 diabetic patients without hypertension or overt proteinuria. We used Altman's method to calculate the age-adjusted 95% reference ranges for GFR from the data of control subjects and classified GHF in type 2 diabetics from the reference ranges. Hyperfiltrators (defined as GFR > mean GFR + 1.96 S.D. of control subjects) was found in 17% patients (16/93). Other 77 patients (83%) were normofiltrators (defined as GFR< or = mean GFR + 1.96 S.D. of control subjects). GFR values, both in hyperfiltrators and normofiltrators, were 140.5 +/- 14.6 and 98.8 +/- 14.0 ml/min/1.73 m2, respectively. Age, sex, BMI, blood pressure, albumin excretion rate, and frequency of microalbuminuria did not differ between the hyperfiltrators and normofiltrators. Fasting plasma glucose and hemoglobin A1c were significantly higher in the hyperfiltrators than the normofiltrators (P<0.001 and 0.004, respectively). GHF exists among Japanese type 2 diabetic patients with no evidence of overt proteinuria or hypertension. Glycemic control might be a significant determinant of GHF in these patients.

[A case of advanced gastric cancer effectively treated by combined chemotherapy of TS-1 and paclitaxel].

A patient was a 66-year-old male who had advanced gastric cancer with left gastric artery lymph node metastasis and invasion of pancreas and spleen. We thought a complete resection was difficult, so he was given neo-adjuvant chemotherapy by combined of TS-1 100 mg/day (2 weeks administration and 1 week rest) and Paclitaxel (PTX) 75 mg/body (day 1, 8). After 2 courses of this neo-adjuvant chemotherapy, tumor and lymph node swelling had decreased in size, and the tumor markers were reduced remarkably (CEA 9 2.5 --> 12.2 ng/ml, CA 19-9 2, 739 --> 19 3 U/ml). He underwent total gastrectomy and Roux-en Y reconstruction. No.4 d and No.7 lymph nodes were swollen and hard, but white with a neurotic-like appearance. On pathological study, no malignancy was seen in the lymph nodes, and a good partial response was achieved. In this chemotherapy, no side effects were seen, and he maintained good quality of life. TS-1/PTX therapy was thought to be an effective neoadjuvant chemotherapy for advanced gastric cancer.