Cryoglobulinemic Vasculitis Associated with Monoclonal Gammopathy of Undetermined Significance Developed after Sustained Virologic Response of Hepatitis C.

A 72-year-old woman had a history of chronic hepatitis C virus (HCV) infection previously treated with interferon to achieve a sustained virologic response. Thereafter, she developed polyarthritis and purpura of the lower extremities as well as progressive renal dysfunction with hypertension and proteinuria that had occurred in the last three months. Laboratory investigations revealed seropositivity for cryoglobulin but negative findings for HCV RNA. She was ultimately diagnosed with cryoglobulinemic glomerulonephritis complicated by monoclonal gammopathy of undetermined significance (MGUS) based on the pathological findings of the kidney and bone marrow, indicating that MGUS-induced cryoglobulinemic vasculitis may occur even after HCV elimination.

Eligibility of Feline Calicivirus for a Surrogate of Human Norovirus in Comparison with Murine Norovirus, Poliovirus and Coxsackievirus.

Feline calicivirus (FCV) is frequently used as a surrogate of human norovirus. We investigated eligibility of FCV for anti-viral assay by investigating the stability of infectivity and pH sensitivity in comparison with other viruses. We found that infectivities of FCV and murine norovirus (MNV) are relatively unstable in infected cells compared with those of coxsackievirus (CoV) and poliovirus (PoV) , suggesting that FCV and MNV have vulnerability. Western blotting indicated that inactivation of FCV was not due to viral protein degradation. We also demonstrated sensitivity of FCV to low pH, the 50% inhibitory pH value being ca. 3.9. Since human norovirus is thought to persist longer, in infectivity and to be a resistant virus, CoV, which is robust and not restrained in use as PoV, may be more appropriate as a test virus for disinfectants, rather than FCV and MNV.

Effects of linagliptin versus voglibose on treatment-related quality of life in patients with type 2 diabetes: sub-analysis of the L-STEP study.

Treatment-related quality of life (QOL) is an important aspect of diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet and exercise therapy. Among 366 subjects in the original study, 182 in the linagliptin group and 173 in the voglibose group were included in this analysis. The outcome of this study was change in QOL as assessed by the Diabetes Therapy-Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12. Compared with baseline data, total DTR-QOL17 scores were significantly higher after 12 weeks of linagliptin and voglibose treatment. The change in the total DTR-QOL17 score and the score of one domain, burden on social activities and daily activities, was significantly greater in the linagliptin group than in the voglibose group. In addition, only linagliptin treatment was identified as a factor associated with an increased total DTR-QOL17 score. Linagliptin is superior to voglibose in terms of improving treatment-related QOL in Japanese patients with T2DM.

The role of endoscopic biliary sphincterotomy for the treatment of type 1 biliary dysfunction (papillary stenosis) with or without biliary stones.

BACKGROUND: This study assesses the safety and effectiveness of endoscopic biliary sphincterotomy (ES) in the treatment of papillary stenosis (PS) with and without biliary stones. METHODS: The records of all patients who had endoscopic retrograde cholangiopancreatography (2,689 patients) from January 1, 1991, to August 1, 2010, were reviewed. There were 117 patients with PS who had ES. RESULTS: All patients had biliary pain, a dilated common bile duct (CBD) with a maximum diameter of 10 to 25 mm, and elevated liver function tests. There were 46 patients who had prior cholecystectomy of whom 20 patients had CBD stones. The remaining 71 patients had no prior biliary surgery; there were no biliary stones in 14 patients. All patients were symptom free after ES with or without CBD stone retrieval. CONCLUSIONS: ES is the optimal treatment for PS in patients with or without biliary stones. ES eliminates pain, corrects CBD dilation, and restores LFTs to normal.

Utility of preoperative chemoradiotherapy for advanced esophageal carcinoma.

BACKGROUND AND AIMS: The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three-field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three-field lymphadenectomy. METHODS: A total of 127 cases of advanced esophageal carcinoma were objected, among which 32 had NACRT, being the cases suspected to cT3-T4 or, < cT3 with multiple lymph node metastasis. ≥ T2 of 95 cases were treated by surgery alone (NACRT [-] case). The effect of NACRT was evaluated by histological examination and corrected with the clinicopathologic factors, including postoperative prognosis. After reports JCOG9907, we treated eight cases with neoadjuvant chemotherapy at stages II and III. We examined Musashi-1 staining for these eight cases. RESULTS: Histological good response to NACRT group showed good prognosis. Lymph node metastasis is a predictive factor for prognosis. In this additional study, Musashi-1 was positive after neoadjuvant chemotherapy in three cases. The histological response was grade 1 in all of them and recurrence was observed within a short period of time. Two cases of grade 3 were negative staining to Musashi-1 and showed no recurrence. CONCLUSIONS: This study shows that NACRT plus surgery with three-field lymphadenectomy is a feasible therapeutic approach for the cases with multiple lymph node metastases. Prognosis was significantly better in cases with marked histological improvement. It is important to find the predictive factors of histological improvement. Musashi-1 might be a candidate maker for histological response and prognosis, and further studies are needed to prove it.

Pancreaticobiliary maljunction and carcinogenesis to biliary and pancreatic malignancy.

BACKGROUND: It is widely accepted that congenital choledochal cyst is associated with pancreaticobiliary maljunction (PBM). But, PBM is an independent disease entity from choledochal cyst. PBM is synonymous with "abnormal junction of the pancreaticobiliary ductal system", "anomalous arrangement of pancreaticobiliary ducts", "anomalous union of bilio-pancreatic ducts", etc. Cases with PBM not associated with biliary duct dilatation are often found, and these cases are frequently complicated gallbladder cancer. The Japanese Study Group of Pancreaticobiliary Maljunction was started in 1983, and defined diagnostic criteria and nationwide registration system of PBM cases was started. PBM is defined as a union of the pancreatic and biliary ducts which is located outside the duodenal wall. Bile and pancreatic juice reflux and regurgitate mutually. BILIARY CARCINOGENESIS: The most bothersome problem is biliary carcinogenesis. Gallbladder cancers arise in 14.8% and bile duct cancers arise in 4.9%. The incidence of the gallbladder carcinoma of PBM without bile duct dilatation is 36.1%. Many investigators have tried to clarify the carcinogenic process, from various aspects. The biliary epithelia are injured by harmful substances, and in the course of repair, multiple alterations of oncogenes and tumor suppressor genes are followed, and they lead to carcinoma through multistage interaction. In the biliary epithelia of PBM, incidence and degree of hyperplasia are characteristic. K-ras gene mutations are observed in the cancerous as well as noncancerous lesions of biliary tract of PBM patients. Mutations of p53 gene and overexpression of p53 protein are also found in the cancerous and noncancerous lesions. These changes are called "hyperplasia-carcinoma sequence". TREATMENT: Total excision of the extrahepatic bile duct with gallbladder followed by hepaticojejunostomy, Roux-en-Y, or end-to-side hepaticoduodenostomy are treatment of choice, even for cases with not dilated bile duct, because the incidence of cancer in the nondilated bile duct is not negligible, and genetic changes are seen in a nondilated bile duct.

Treatment of thoracic esophageal carcinoma invading adjacent structures.

T4 esophageal cancer is defined as the tumor invading adjacent structures, using tumor-node-metastasis (TNM) staging. For clinically T4 thoracic esophageal carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, has generally been performed. However, the prognosis of patients with these tumors remains poor. Another strategy is needed to achieve curative treatment. In the present article, the treatment strategies employed to date are reviewed. Furthermore, the strategies for these malignancies are reassessed, based on our experiences. R1/2 and R0 resections are regarded as those with residual and no tumor after surgery. The present data show that patients who underwent R1/2 resection after neoadjuvant CRT experienced little survival benefit, while complete response (CR) cases after definitive CRT had comparatively better results. Therefore, curative surgery should not be attempted without down-staging, and definitive CRT should be the initial treatment. Then surgery is indicated for the eradication of residual cancer cells. Close surveillance is essential for early detection of relapse even after CR, because the operation will gradually become increasingly difficult due to post-CRT fibrosis. In conclusion, multimodality therapy consists of definitive CRT followed by R0 resection, which can be the treatment of choice for T4 esophageal carcinoma. These challenging treatments have the potential to constitute the most effective therapeutic strategy.

Abdominal wall abscess associated with perforated jejunal diverticulitis: report of a case.

We report a case of abdominal wall abscess caused by diverticulitis of the jejunum penetrating through the abdominal wall. A 53-year-old Japanese woman visited a local hospital complaining of abdominal pain and a mass in the left lower abdomen. An abdominal computed tomography scan showed a tumor with isodensity in the left lower abdominal wall. Magnetic resonance imaging showed a mass in the abdominal wall with isointensity in the T1-intensified image and high intensity in the T2-intensified images. The mass was heterogeneous inside and protruded partially toward the intraperitoneal cavity. Ultrasound examination showed a heteroechoic mass extending into the intraperitoneal cavity. Laparotomy revealed a tumor in the abdominal wall with a fistulous tract extending to the jejunum. We resected the abdominal wall tumor with partial resection of the small intestine. The resected specimen contained a tumor with a fistulous tract passing through the abdominal wall. Histological examination revealed remarkable infiltration of neutrophils and a bacterial mass in the abdominal wall tumor, with a fistulous tract connected to the area adjacent to the mesenteric border of the jejunum. These findings suggested that diverticulitis of the jejunum had penetrated through the abdominal wall, leading to the formation of an abscess. We report this case to highlight the need for complete gastrointestinal evaluation with gastrointestinal barium studies and imaging analysis to examine extension of intra-abdominal lesions in patients with an unexplained abdominal wall abscess.

Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary?

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63-year-old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.

Intraductal papillary-mucinous tumor of the pancreas head with complete absence of the ventral pancreatic duct of Wirsung.

A case of intraductal papillary mucinous tumor of the pancreas with complete absence of the ventral pancreatic duct of Wirsung is presented. A 74-year-old Japanese man was admitted to our hospital because of elevated serum amylase concentration. Abdominal computed tomography (CT) scanning revealed diffuse dilatation of the main pancreatic duct and a diffuse and uncircumscribed area with heterogeneous density in the pancreas head. Endoscopic retrograde cholangiopancreatography revealed that the main pancreatic duct was connected with an accessory papilla and was diffusely dilated, without any irregularity of the duct wall being observed in the entire length of the duct. The common bile duct was detected only by cannulation through Vater's papilla, and no pancreatic duct or its communicating branch was found. Some branches, directed to the dorsal portion of the pancreas head, were found arising from the accessory pancreatic duct. Intraductal ultrasound examination performed through the accessory papilla and the common bile duct revealed a small tumor with a heterogeneous echo level in the pancreas head. From these findings, intraductal papillary-mucinous tumor (IPMT) occurring in the pancreas head was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen revealed IPMT in the pancreas head. A roentgenographic study of the resected specimen revealed a defect caused by the tumor located in the pancreatic duct connected with the accessory papilla and showed that there was complete absence of the pancreatic duct connected with Vater's papilla. Surgical resection enabled us to completely analyze the duct system of pancreas divisum. Although it is not known whether there is a relationship between the pathogenesis of IPMT and embryological anomaly of the pancreatic duct system, this case may provide an insight into the pathogenesis of IPMT.

Changes in thymidylate synthase and its inhibition rate and changes in dihydropyrimidine dehydrogenase after the administration of 5-fluorouracil with cisplatin to nude mice with gastric cancer xenograft SC-1-NU.

BACKGROUND: Although 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum (cisplatin) in combination have synergistic cytotoxicity against both murine and human neoplasms, the precise mechanism of the synergism, and the effects on thymidylate synthase and its percent inhibition, and the effects on dihydropyrimidine dehydrogenase (DPD) remained to be elucidated. METHODS: Experimental chemotherapy was performed using SC-1-NU, a human gastric carcinoma xenograft. SC-1-NU was maintained by serial transplantation in male BALB/c nude mice. The nude mice received various chemotherapeutic regimens consisting of 5-FU and/or cisplatin, with different dosages and periods of administration. After the treatment, we examined the in vivo effects of 5-FU and cisplatin in each regimen on thymidylate synthase and its percent inhibition, and the effects on DPD, in addition to the observation of tumor growth inhibition. RESULTS: The combined use of 5-FU (20 mg/kg per day) and cisplatin (either 1.5 or 7.5 mg/kg per day) showed a synergistic antitumor effect, regardless of the different doses of cisplatin. The long-term administration of 5-FU significantly increased both total thymidylate synthase and the percent thymidylate synthase inhibition rate. The short-term administration of 5-FU significantly decreased DPD. Nevertheless, these changes showed no relation to the combined use of cisplatin. CONCLUSION: Combined administration of cisplatin with 5-FU did not further increase thymidylate synthase inhibition over that occurring with 5-FU alone, which does not support the hypothesis that cisplatin combined with 5-FU modulates thymidylate synthase inhibition in enhancing the anticancer effect of 5-FU. Changes in DPD after the administration of 5-FU may provide an insight into tumor sensitivity and resistance to 5-FU.

Perforated duodenal diverticulum successfully diagnosed preoperatively with abdominal CT scan associated with upper gastrointestinal series.

Although duodenal diverticulum is not uncommon, precise preoperative diagnosis is occasionally difficult. We report a patient with perforated duodenal diverticulum successfully diagnosed preoperatively by an upper gastrointestinal series followed by abdominal computed tomography (CT) scanning. An 81-year-old Japanese woman visited a local hospital because of right-sided abdominal pain. Physical examination revealed diffuse muscle guarding localized in the entire right-side of the abdomen indicative of peritonitis. While plain abdominal X-ray film revealed no free air, abdominal ultrasound and abdominal CT scanning revealed fluid collection and gas in the anterior perirenal space. An emergency upper gastrointestinal series, using water-soluble contrast media, demonstrated multiple diverticula in the descending portion and the horizontal portion of the duodenum. Leakage of the contrast material was found by the upper gastrointestinal series followed by the abdominal CT scanning, suggesting that the peritonitis was caused by the perforated duodenal diverticulum, and an emergency laparotomy was performed. The diverticulum in the descending portion of the duodenum was mobilized from the retroperitoneum and complete resection and peritoneal drainage were performed. The resected specimen showed that the diverticulum was 42 x 23 mm in size, and two separate sites of perforation were identified. The present case suggests that upper gastrointestinal series followed by CT scan is useful for the preoperative diagnosis of perforated duodenal diverticulum.

[A case of Barrett's esophageal carcinoma successfully treated with TS-1 in an elderly patient].

A 92-year-old man was admitted to the hospital for rehabilitation. Upper gastrointestinal endoscopy was performed 2 weeks after admission because of vomiting which was found to be due to a Barrett's esophageal carcinoma at the lower esophagus. We chose chemotherapy with TS-1 at the dose of 50 mg/day in consideration of his age and performance status. His difficulty in swallowing disappeared rapidly. After 7 days of treatment, grade 3 anorexia appeared, so the dosage of TS-1 was reduced to 25 mg/day. After the reduction of TS-1, anorexia soon disappeared. The regimen consisted of TS-1 every 6 weeks as 1 cycle. After 7 cycles of treatment, upper gastrointestinal endoscopy and upper gastrointestinal series revealed that the tumor had a completely disappeared. The effects of chemotherapy were judged as CR. This case suggests that administration of TS-1 is an effective choice of chemotherapy not only for gastric carcinoma but also Barrett's esophageal carcinoma.

Risk of second primary malignancy after esophagectomy for squamous cell carcinoma of the thoracic esophagus.

PURPOSE: To assess the risk of subsequent malignancies after esophagectomy for squamous cell carcinoma of the thoracic esophagus for the establishment of an adequate follow-up program. PATIENTS AND METHODS: We statistically analyzed clinical factors in 114 cases of second malignancy after esophagectomy that developed in 94 of 679 patients who underwent curative resection. The cancer incidence rates in the general population estimated by the Research Group for Population-Based Cancer Registration in Japan were used as standards for comparison. RESULTS: The 10-year cumulative risk of second malignancy was 34.5%, and the overall relative risk (RR) was 2.98 (95% CI, 2.41 to 3.65). The risk of head and neck cancer was markedly elevated (RR, 34.9; 95% CI, 24.3 to 48.6), followed by the risks of lung cancer (RR, 3.24; 95% CI, 1.89 to 5.19) and stomach cancer (RR, 2.00; 95% CI, 1.17 to 3.21). Multifactor analysis demonstrated that independent factors affecting the risk of subsequent malignancies were presence of other malignancies detected before esophagectomy and any of the following factors: masculine sex, alcohol consumption, and smoking. The 5-year survival rate after detection of subsequent malignancy was 45%. The outcome in patients with subsequent head and neck cancer was significantly less favorable as a result of difficulty in early detection. CONCLUSION: Patients had a remarkably high risk of subsequent cancer of the upper aerodigestive tract after esophagectomy, in particular, head and neck cancer. Minute postoperative surveillance is strongly recommended, especially in patients with a history of malignancies before esophagectomy. Early detection of second malignancies allowed less invasive treatment with favorable outcome.

[Sustained NC status for a long period after combined chemotherapy of TS-1 and CDDP for residual lesions following gastrectomy for gastric cancer].

A 71-year-old man with nausea and epigastralgia was referred to our hospital and was diagnosed with type 3 gastric cancer. Palliative resection was performed since radical surgery was impossible due to massive tumorous invasion to the retroperitoneum. Chemotherapy with TS-1 100 mg p.o. was started for the residual cancer lesions, with CDDP i.v. 50 mg added from the 3rd course. We did not find any remarkable side effects except for grade 1 loss of appetite. This chemotherapy was ended after the eighth course. The residual tumor did not disappear but did not grow, and a no change status was maintained for twelve months after the gastrectomy.

[A surgically resected case of advanced gastric carcinoma with peritoneal dissemination after treatment with combined chemotherapy of TS-1 and CDDP].

A 60-year-old female had undergone laparoscopic oophorectomy for right ovarian tumor. At the time of surgery, peritoneal dissemination and ascites was observed. Histological examination revealed that the resected ovary, peritoneal nodes and floating cells in the ascites were metastatic adenocarcinomas. Later, the primary malignant lesion was found to be a type 4 gastric carcinoma. The carcinoma was judged to be unresectable and treated by combination chemotherapy with TS-1 and CDDP every 6 weeks. After 3 courses of treatments, upper gastrointestinal series and endoscopic examinations were conducted and revealed a marked reduction of the tumor size. No carcinoma cells were detected by endoscopic biopsy. CT-scan showed complete disappearance of metastatic lesions. Staging laparoscopy was performed for evaluation of the effects of chemotherapy, and no adenocarcinoma cells at peritoneal nodes or ascites were found histologically. We performed total-gasterectomy with D1 + alpha lymph node dissection. Histopathologically, resected specimens showed severe fibrosis in most parts of the stomach. Following chemotherapy, the carcinoma was judged to be Grade 2 by histopathological examination.

Weekly administration of paclitaxel attenuated rectal stenosis caused by multiple peritoneal recurrence 8 years after the resection of gastric carcinoma.

We report a patient with rectal stenosis caused by peritoneal recurrence 8 years after a curative resection of advanced stage gastric carcinoma; the recurrence was effectively treated with the weekly administration of paclitaxel. The patient was a 66-year-old Japanese woman who was admitted to our hospital complaining of abdominal pain and frequent bowel movements. She had undergone total gastrectomy, due to advanced-stage gastric carcinoma with extensive lymph node metastasis, 8 years before, and had taken an oral anticancer agent, fluoropyrimidine, for 4 years after the operation. Colonofiberscopy performed on admission revealed circumferential rectal stenosis located 10 cm from the anal verge. Barium enema study demonstrated extensive poor expansion of the upper and lower rectum and irregularity of the descending colon. Abdominal computed tomography (CT) scanning revealed wall thickening in the rectum and descending colon. These findings were compatible with rectal stenosis caused by the peritoneal recurrence of gastric carcinoma. Weekly administration of paclitaxel was started. The abdominal symptoms soon disappeared when the second cycle of paclitaxel was completed, and they have not appeared since then. The rectal stenosis was attenuated, as confirmed by imaging analyses. Weekly paclitaxel has been effective for more than 13 months, suggesting that the patient is in a state of tumor dormancy of recurrent gastric carcinoma.