Efficacy and Safety of Alogliptin in Patients With Type 2 Diabetes: Analysis of the ATTAK-J Study.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to reduce hemoglobin A1c (HbA1c) in patients with type 2 diabetes, but the reduction varies between patients and adequate glycemic control may not be achieved. We evaluated the efficacy and safety of the DPP-4 inhibitor alogliptin in the real clinical setting, and analyzed factors associated with the improvement of HbA1c by alogliptin treatment. METHODS: A retrospective observational study was performed in patients with type 2 diabetes attending hospitals or clinics belonging to the Kanagawa Physicians Association who received treatment with alogliptin for 1 year or longer. Patients using insulin were excluded from the study. The efficacy endpoints were HbA1c (National Glycohemoglobin Standardization Program value), blood glucose (fasting/postprandial), body weight, blood pressure (systolic/diastolic), liver function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and γ-glutamyl transpeptidase), kidney function (serum creatinine and estimated glomerular filtration rate), serum lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), and serum amylase. Adverse events were compiled to assess safety. RESULTS: Of 330 patients whose case records were collected, 27 patients were excluded for protocol violations, leaving 303 patients to form the full analysis set. Compared with baseline, HbA1c showed a decrease by 0.54±1.22% (mean ± standard deviation) after 12 months of alogliptin treatment. Factor analysis demonstrated that the change of HbA1c after 12 months was significantly influenced by the baseline HbA1c level, duration of diabetes, concomitant use of sulfonylureas, and compliance with diet therapy. In addition, there was a significant reduction of total cholesterol, low-density lipoprotein cholesterol, and the estimated glomerular filtration rate after 12 months of alogliptin treatment, as well as a significant increase in serum creatinine. No significant changes of body weight, blood pressure, or liver function were observed. Symptoms of hypoglycemia occurred in two patients (0.6%). CONCLUSIONS: Alogliptin displayed a significant hypoglycemic effect and excellent safety in routine clinical use. Factors influencing the change of HbA1c with alogliptin therapy may include the HbA1c at the start of treatment, the duration of diabetes, use of sulfonylureas, and compliance with diet therapy.

Unusual bleeding from hepaticojejunostomy controlled by adult variable stiffness colonoscopy: report of a case and literature review.

We herein present a case of a 59-year-old man who had undergone pylorus preserving pancreaticoduodenectomy with regional lymph node dissection prior to episodes of melena. Series of conventional endoscopic investigations failed to identify the bleeding source. Enhanced computed tomography scan revealed complete obstruction of the main portal vein with numerous collateral veins running towards the hepatic hilus. Comprehensively, hemorrhage from the jejunal varices caused by postoperative portal hypertension was highly suspected. As the jejunal loop was out of reach, adult variable-stiffness colonoscope (AVSC) was utilized to solve the Roux-en-Y anatomy. Numerous telangiectasis and small varices at hepaticojejunostomy were observed and in the mean time, bleeding was noticed and endoclips were placed without any delay. Ectopic variceal bleeding in jejunal loop after pancreaticoduodenectomy is difficult to manage. We believe that AVSC is an alternative device when specialized jejunal endoscopy is not available.

Primary papillary hyperplasia of the gallbladder mimicking gallbladder cancer.

Primary papillary hyperplasia of the gallbladder (PPHG) is a rare entity. PPHG is a benign diffuse mucosal projection without any background chronic inflammation-related disease of the gallbladder or bile ducts. Reported cases of PPHG are limited in that its characteristics are not well defined. We herein report a case of PPHG mimicking gallbladder cancer in radiologic investigations and present a review of the literature. Also coincident erythroderma is discussed.

Comparison of effects of angiotensin II receptor blocker on morning home blood pressure and cardiorenal protection between morning administration and evening administration in hypertensive patients: the COMPATIBLE study.

Whether the time of administering the angiotensin receptor antagonist olmesartan influences antihypertensive and renoprotective effectiveness remains unclear. This study compared the effects of olmesartan on morning home blood pressure (MHBP), office BP (OBP) and renoprotective parameters between morning and evening administration. A total of 218 patients with primary hypertension were randomly assigned to receive olmesartan once daily in the morning (morning-dose group) or evening (evening-dose group), and 188 completed the study protocol (morning-dose group, n=95; evening-dose group, n=93). In both groups, morning home systolic BP, morning home diastolic BP, office systolic BP and office diastolic BP decreased significantly. There was no significant difference between the groups in MHBP or OBP after 6 months of treatment. The urinary albumin-to-creatinine ratio (UACR) decreased from 13.9 to 6.9 mg g(-1) (geometric means, P<0.001) in the morning-dose group and from 14.4 to 9.1 mg g(-1) (P<0.001) in the evening-dose group. The changes in UACR after treatment did not differ significantly between the groups. SV1+RV5 decreased significantly from baseline to 6 months in the morning-dose group (P<0.001) and the evening-dose group (P<0.01), and did not differ significantly between the groups. In conclusion, olmesartan effectively decreased MHBP, OBP, SV1+RV5 and UACR regardless of whether the drug was administered in the morning or in the evening. Our results suggest that olmesartan can be prescribed once daily, either in the morning or in the evening.

[A case of locally advanced colorectal cancer with abscess responding to 5-fluorouracil, leucovorin, and oxaliplatin plus bevacizumab].

We encountered a case of colorectal cancer with pelvic abscess treated with radical surgery following colostomy and chemotherapy. The patient was a man in his 60s with advanced rectal cancer. The tumor had expanded locally and formed an abscess. We evaluated the primary lesion as unresectable, and performed chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin( mFOLFOX) plus bevacizumab after colostomy. After 13 courses of chemotherapy, the tumor shrank remarkably. We performed a low anterior resection followed by adjuvant chemotherapy with capecitabine. The patient has had no recurrence for 18 months after surgery.

[A case of vaginal metastasis of rectal cancer post -operation].

Vaginal metastasis is extremely rare, as is metastatic colorectal cancer. A 78-year-old woman was diagnosed with rectal cancer and uterine fibroid. Low anterior resection and simple hysterectomy was performed and the final diagnosis was fStage IIIa. Adjuvant chemotherapy was not performed. One year after the surgery, she was referred to our hospital with the chief complaint of hematuria. A tumor was observed in the posterior wall of the vagina. We performed vaginal mucosal resection and the pathological diagnosis was metastasis of rectal cancer. One year and 5 months after the surgery, we performed left inguinal node dissection and the pathological diagnosis was metastasis of rectal cancer. The patient has remained disease-free for 3 years and 5 months without adjuvant chemotherapy after resection of the vaginal metastasis.

[mFOLFOX6 and FOLFIRI/bevacizumab treatment in a patient on hemodialysis with metastatic colon cancer].

A 58-year-old woman, who was undergoing peritoneal dialysis( PD) for chronic kidney disease (CKD) and had been operated by sigmoidectomy for early colonic cancer, was diagnosed as peritoneal recurrence of the colonic cancer. Her treatment for CKD was switched from PD to hemodialysis. She was administered mFOLFOX6 therapy(reducing the dose to 70%). Hemodialysis was performed 1 hour after administration of oxaliplatin on day 1 and repeated two days later after the completion of drug administration. No serious adverse events were observed. After 10 courses of mFOLFOX6, an ovarian metastasis was appeared. We then changed the regimen to FOLFIRI (70% dose)/bevacizumab (BV). Neutropenia (grade 4) was observed after the second treatment. After some rest, 21 courses of FOLFIRI/BV therapy were performed safely by reducing the dose to 60%. We thought that a reduced dose of FOLFIRI/BV therapy appeared to be safe for a patient with chronic kidney disease who is on hemodialysis.

[A case report of chemoradiotherapy combined with S-1 responding to squamous cell carcinoma of the anal canal].

A 79-year-old woman was reffered to our hospital with the chief complaint of hematochezia. Type-2 tumor was found on anal canal by colonoscopy, and pathologic examination revealed a poorly differentiated squamous cell carcinoma. Computed tomography of the abdomen demonstrated obturatory node metastasis. The patient was diagnosed as having squamous cell carcinoma of the anal cana (l cStage III). After four months from chemoradiation (66 Gy/33 Fr plus S-1), the ulcer side was improved completely to epithelization, and abdominal CT scan showed a remarkable reduction of obturatory node metastasis. She was obtained a complete response. Now the patient is disease-free for ten months after chemoradiation.

[Curative resection of gallbladder cancer with simultaneous liver metastasis].

A 67-year-old man visited our hospital for further check-up of biliary tract disease since his two brothers suffered from biliary tract cancer. Abdominal CT scan revealed a wall thickning at the fundus of gallbladder and its vascularity was rich. Chronic cholecystitis was diagnosed, however, cancer was highly suspected. Cholecystectomy was performed and the frozen section of the gallbladder was compatible for cancer. Therefore, segment-4a and -5 liver resections with regeonal lymph node dissection were added. Although preoperative radiological findings were free of liver metastasis, the resected liver specimen included a nodule of 1 cm in segment-5. Extrahepatic bile duct was not resected because the stump of the cystic duct was free from cancer. The final pathological diagnosis according to the TNM classification was pT3N1M1, Stage IV. We considered the patient to be in the high-risk group of recurrence, adjuvant chemotherapy using both gemcitabine and S-1 was performed. S-1 (80 mg/body/day) was scheduled on day 1-14, and gemcitabine (1,000 mg/body) was scheduled on day 8, day 15. The treatment was continued for two years (a total of 28 courses) without experiencing advese events. The patient is cancer free by means of radiological and hematological studies. Gallbladder cancer with liver metastasis in segment-4a and/or -5 can be considered as "local" metastasis, which a liver resection and adjuvant therapy may lead to a good prognosis.

Patients with gastrointestinal tract disorders receiving parenteral nutrition need a higher dose of vitamin C.

BACKGROUND/AIMS: Appropriateness of the vitamin doses in Japanese commercial multi-vitamin preparations for parenteral nutrition therapy was investigated in patients with gastrointestinal tract disorder by evaluating the vitamin status (blood concentrations and urinary excretions of vitamins B1, B2, B6, and C) of them. METHODOLOGY: Commercial multivitamin preparations were administered continuously with a commercial PN solution over 5 days to 10 patients with gastrointestinal tract disorder. Blood concentrations of vitamins B1, B2, B6, and C were measured on the mornings of day 1, day 4, and day 6. Urinary excretions were measured in 24-h urine collections collected after day 3 and after day 5. RESULTS: Blood concentrations of vitamins B1, B2, and B6 increased but remained within or slightly above the normal throughout the study, and urinary excretion values were normal in all patients. However, blood vitamin C concentration surpassed the lower limit of normal (5.5 microg/mL) only on day 6. Urinary vitamin C excretion was below normal (20.0 mg/day) in all and 7 patients on days 3 and 5, respectively. CONCLUSIONS: In patients with gastrointestinal tract disorder, the doses of vitamins B1, B2, and B6 of Japanese commercial multi-vitamin preparations are adequate but that of vitamin C (100 mg/day) is inadequate and should be increased.

[Two cases of pancreatic cancer with fairly good prognosis].

We report two cases of advanced pancreatic cancer whose prognoses are fairly good with surgery and chemotherapy. Case 1: A 71-year-old male patient was diagnosed as pancreatic head cancer by abdominal ultrasound. The tumor size was about 2 cm in diameter. Whipple's procedure and regional lymphadenectomy were conducted. Pathological diagnosis was pT3N2 with s0 and rp1. Gemcitabine (GEM) was administered in a routine fashion at out-patient clinic. He is free of disease after three years and eight months. Case 2: A 63-year-old male patient was diagnosed as pancreatic head cancer although the mass was not so clearly visible by CT. Pylorus preserving pancreaticoduodenectomy was performed with D2 lymph node dissection. Pathological report was pT3N1 with s0 and rp0. GEM was started six months after the operation but continued for only six months. After the non-treatment interval of six months, GEM was restarted due to the sudden elevation of CA19-9. Soon the number dropped but instead of reaching normal range, it began to increase again. S-1 was added to the regimen which gave a great response. He is well after three and a half years. CA19-9 was almost being normal. Both patients had cancer within the pancreas without an invasion to the surrounding tissue. GEM is a standard regimen for adjuvant chemotherapy. However, S-1 may contribute to the outcome when GEM becomes powerless.

[A case of ruptured hepatocellular carcinoma originated from nonalcoholic steatohepatitis (NASH)].

A 69-year-old woman visited our emergency room because of sudden right lower quadrant abdominal pain. Abdominal CT revealed a ruptured tumor in the anterior segment of the liver. Emergency laparotomy was selected due to interventional radiology was not available. As the patient was in shock status with massive intraabdominal hemorrhage, ligation of the right hepatic artery and suturing of the tumor bleeding point was carried out. Given the patient's history and liver biopsy report, we concluded as hepatocellular carcinoma derived form NASH. Anterior resection of the liver was performed after the patient became stable. About one year later, tumor was detected in the lateral segment and was removed. The patient is free of disease for two and a half years after the initial operation. Carcinogenesis of the hepatocellular carcinoma within NASH is not well described. We herein report a case of ruptured hepatocellular carcinoma originated from NASH.

[Gallbladder carcinoma, progressed along cholecystoduodenal fistula--a case report].

A 75-year-old woman had an operation for gallstone ileus without cholecystectomy in other hospital and she was admitted to our hospital because of duodenal adenoma with severe atypia and small carcinoid in proximal duodenal wall. Distal gastrectomy and cholecystectomy were performed. Histological studies revealed the existence of cholecystoduodenal fistula and suggested the existence of gallbladder carcinoma progressed to the duodenal wall through the fistula. Cystic duct dissection and lymph nodes dissection were performed. It has been theorized that a cholecystoduodenal fistula may represent a significant risk factor in the development of gallbladder carcinoma because of the chronic reflux of duodenal contents which includes pancreatic juice. Our case may support this theory. In this case, we thought that the formation of gallbladder cancer could have been avoided if the cholecystectomy was performed in the first operation for gallstone ileus. It is very important that cholecystectomy should be performed when an existence of cholecystoduodenal fistula is highly suspected.

[A case of hepatocellular carcinoma with advanced gastric cancer treated by radio frequency ablation].

A 69-year-old male patient has been diagnosed hepatitis B a couple of years ago at our hospital. His follow up CT revealed multiple hepatocellular carcinomas (HCCs) in May 2007. Transarterialchemoembolization was selected for treatment. A couple of months later, carcinoma in segment eight was diagnosed viable by CT. Radiofrequency ablation (RFA) therapy was performed for further treatment but was incomplete. On the other hand, gastric cancer was discovered at the same time. Total gastrectomy with regional lymph node dissection and splenectomy were performed. Pathological examination of the dissected lymph nodes revealed not only the metastases of the gastric cancer but also HCC. Recently, RFA treatment is growing in number for HCC. Although lymph node metastases in HCC are seldom seen, our case suggests that RFA may have led to the unexpected metastases to the lymph nodes.

[A case of adenosquamous carcinoma of the liver].

A 60-year-old man underwent abdominal computed tomography due to the chest pressure. Then, a 10 cm sized tumor in the right lobe of the liver was detected. Tumor marker was normal except that CA19-9 was as high as 703 U/mL. We diagnosed as the CCC and performed PTPE, and then, we performed right hepatectomy and adrenal deprivation, and partial resection of the diaphragm and IVC. Pathological diagnosis of the resected specimen was adenosquamous carcinoma of the liver. Metastasis to the costal bone was detected after the operation, and irradiation was performed. Now, S-1/GEM therapy as adjuvant chemotherapy is administered. Adenosquamous carcinoma of the liver is very rare and its prognosis is very poor due to local recurrence and metastasis to the lymph node. Adjuvant therapy is necessary but a unified guideline is not determined.

[A case of locally recurrent rectal cancer responding to radiation and chemotherapy with S-1].

We describe a case of locally recurrent rectal cancer that was successfully treated with radiation and chemotherapy with S-1; this treatment resulted in long-term survival of the patient with a good performance status. A 51-year-old man underwent Hartmann's operation for advanced rectal cancer. At 6 months after the surgery, a pelvic computed tomography (CT) scan showed a local recurrence of the rectal cancer. The patient's serum CA19-9 level had increased to 3,200 U/mL. The tumor was unresectable, so that radiation therapy was administered to the pelvic region at a total dose of 56 Gy, followed by oral chemotherapy with S-1 for 2 years. After these treatments, the serum CA19-9 level returned to normal. No signs of tumor recurrence were observed as of 3 years and 5 months after the confirmation of local recurrence. A combination of radiation therapy and oral administration of S-1 could be a useful treatment for unresectable locally recurrent rectal cancer.

[Adjuvant chemotherapy of S-1 and CDDP for undifferentiated adenocarcinoma of the stomach].

A 67-year-old female visited our department complaining a general fatigue. Gastrointestinal endoscopy revealed a giant ulcer at distal portion of the stomach. NSE was the only tumor marker showing an abnormal value. Pathohistology of the biopsy specimen showed a monotonus massive growth of small irregular tumor cells. Distal gastrectomy with regional lymph node dissection was carried out. Final pathology report was undifferentiated adenocarcinoma of the stomach, exposing itself to serosa with lymph node metastasis. Postoperative chemotherapy was started using S-1. However, despite NSE turning normal, CEA rose that CDDP was added to the regimen. She went into remission for several months but CEA rose again and CDDP was changed to CPT-11. To our great regret, she died six months after the operation. Undifferentiated adenocarcinoma of the stomach is rare disease. Immunohistochemical staining is useful for a differential diagnosis. Prognosis is said to be poor but S-1/CDDP may contribute to prolong prognosis.

Oral rehydration solution for providing water and electrolytes following laparoscopic cholecystectomy and recovery of intestinal function.

BACKGROUND/AIMS: Oral rehydration solution (OS-1: Na+ 50mEq/L, K+ 20mEq/L, Cl- 50mEq/L, and glucose 1.8%) was administered orally to patients from the early phase following laparoscopic cholecystectomy to assess its effects on water and electrolyte supplementation and recovery from postoperative intestinal paralysis. METHODOLOGY: OS-1 group (n = 22) received OS-1 orally and KN3B group (n = 22) received KN3B (an intravenous maintenance solution) intravenously. The OS-1 group was instructed to consume approximately 1000-1500mL of OS-1 postoperatively from as soon as oral intake was possible up to before lunch on postoperative day 1. RESULTS: The average dose in the OS-1 group (1178 +/- 319 mL) was significantly lower than that in the KN3B group (1371 +/- 196 mL), but within the target dose. The two solutions were equally effective and safe for water and electrolyte supplementation. The time for 50% of patients to pass bowel gas after surgery (indicating recovery from intestinal paralysis) was significantly shorter in the OS-1 group (14.00 hours) than in the KN3B group (23.75 hours). CONCLUSIONS: Oral rehydration solution (OS-1), administered from the early postoperative phase, is safe and effective for the provision of water and electrolytes and promotes early recovery from intestinal paralysis as assessed by the passage of bowel gas following laparoscopic cholecystectomy.

Distributing pattern of the bile duct of the caudate lobe on computed tomography with drip infusion cholangiography and its surgical significance.

BACKGROUND/AIMS: It is important to recognize the distribution of the bile ducts in the caudate lobe of the liver for the hepato-biliary surgery. To map the spatial relationship between the bile ducts and the liver parenchyma under physiological conditions, we performed an anatomical analysis of them using computed tomography combined with drip infusion cholangiography (DIC-CT). METHODOLOGY: We identified the bile ducts in the caudate lobe, which was divided into the Spiegel lobe, paracaval portion, and caudate process, with DIC-CT. We then investigated their number and confluence pattern in 132 patients without any abnormality in the hilar bile ducts. RESULTS: The mean number of the bile ducts in the caudate lobe was 2.68 per liver. In the Spiegel lobe, the branches drained into the left hepatic duct system in about 83%. The confluence of the paracaval branch was the left hepatic duct, right hepatic duct, and posterior segmental branch, all with the same frequency of approximately 30%. Almost all of the caudate process branches (92.4%) drained into the posterior segmental branch. CONCLUSIONS: DIC-CT is a useful method for the anatomical analysis of the intrahepatic bile ducts under physiological conditions, and we obtained novel and important findings for surgery.

Nicotiana benthamiana gp91phox homologs NbrbohA and NbrbohB participate in H2O2 accumulation and resistance to Phytophthora infestans.

Active oxygen species (AOS) are responsible for triggering defense responses in plants. Respiratory burst oxidase homologs (rboh genes) have been implicated in AOS generation. We have isolated two rboh cDNAs, NbrbohA and NbrbohB, from Nicotiana benthamiana leaves. NbrbohA was expressed constitutively at a low level and the transcripts were increased after mechanical stress of control leaf infiltration, whereas NbrbohB was induced specifically by the protein elicitor INF1 from the potato pathogen Phytophthora infestans. We examined the function of the Nbrboh genes in AOS generation and in the hypersensitive response (HR) using virus-induced gene silencing (VIGS). VIGS indicated that both genes are required for H2O2 accumulation and for resistance to Phytophthora. VIGS of Nbrboh genes also led to a reduction and delay of HR cell death caused by INF1. We further demonstrate that the induction of HR-like cell death by overexpression of a constitutively active mutant of a mitogen-activated protein kinase kinase, MEK(DD), is compromised by VIGS of NBRBOHB: We found that MEK(DD) induced NbrbohB but not NBRBOHA: This work provides genetic evidence for the involvement of a mitogen-activated protein kinase cascade in the regulation of rboh genes.