A minimal dose of N-methyl-N-nitrosourea carcinogenic to heterotopically transplanted rat urinary bladder

The present investigation was conducted to determine a singledose of the carcinogen N-methyl-N-nitrosourea (MNU) which remainssubcarcinogenic in a heterotopically transplanted rat urinarybladder with a communicating reservoir (HTB) either in a urine-freeor urine-existing environment. A single dose of MNU, either0.1 mg or 0.025 mg, was instilled directly into the HTB, andwas followed by weekly instillation of normal rat urine or 2.1%NaCl solution (equiosmolar to the urine) for up to 52 weeks.Bladder tumors observed were divided into 2 categories dependingupon their location. Those arising at the hyperplastic fociwhich were induced by mechanical irritation by the connectortip were referred to as inflammatory polyp (IP)-related tumorsand those arising in the region free from the IP changes werereferred to as IP-unrelated tumors. The results indicated thatboth carcinogen levels fail to induce IP-related or IP-unrelatedtumors in the urine-free environment. In the presence of urine,however, the high MNU dose (0.1 mg) was tumorigenic at bothIP-related and IP-unrelated sites, whereas, the low MNU doseexhibited tumorigenicity only at the TP-related site. Physicalirritation by the connector enhanced MNU-initiated tumorigenesisat the connector tip only in the presence of urine in bladderlumen. Physical irritation per se induced tumors at the connectortip even without prior carcinogen treatment provided urine waspresent in the HTBs.     

Antipyrine test predicts pharmacodynamics in docetaxel and cisplatin combination chemotherapy

To clarify the role of cytochrome P450 in docetaxel and cisplatin combination chemotherapy, cytochrome P450 activity was measured by simple antipyrine test, and its correlation with the drugs' pharmacodynamics was assessed. Twenty-five patients with advanced non-small cell lung cancer received an antipyrine test and were treated with docetaxel and cisplatin. Plasma antipyrine concentration (C) was measured 4 and 24h after oral administration of 500 mg antipyrine. Antipyrine disappearance rate (ADR) was calculated by: [(C(4h)-C(24h))/C(4h)]x100. ADR correlated significantly with neutropenia nadir. ADR and alpha(1)-acid glycoprotein were selected for independent predictors of neutropenia by multiple regression analysis. In addition, 25 patients were separated into "low ADR" (<40%) and "high ADR" groups (>40%). Grade 3--4 neutropenia was observed in 7/9 "low ADR" patients (77%), whereas grade 3--4 neutropenia was observed in 5/16 "high ADR" patients (31%). We concluded that antipyrine test and cytochrome P450 play an important role in predicting toxicities of docetaxel and cisplatin combination chemotherapy.     

Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24553 patients with Hashimoto's disease

There are few large‐scale reports of primary thyroid lymphoma (PTL). This study clinically and pathologically reviewed 171 patients with PTL and 24 553 patients with Hashimoto’s disease at Ito Hospital between January 1990 and December 2004, to investigate the clinical features and the treatment outcomes of PTL. The median age of the patients with PTL was 67 years (range, 27–90 years). The pathological diagnosis of PTL patients included diffuse large B‐cell lymphoma (DLBCL) (n = 74), DLBCL with mucosa‐associated lymphoid tissue (MALT) lymphoma (n = 13), MALT lymphoma (n = 80) and others (n = 4). Of the 167 patients with B‐cell lymphoma, treatment included combined modality therapy (CMT) (n = 95), radiation therapy (RT) alone (n = 60) and chemotherapy alone (n = 6). Information on treatment was not available in six patients. Information on treatment response was available in 154 patients; 149 patients (97%) responded to treatment. According to the institutional treatment strategy of Ito Hospital, 45 of 54 patients with stage IE disease received RT alone, and 87 of 113 stage IIE patients received CMT. The 5‐year overall survival rate was 85% (95% confidence interval, 79–91%). This study demonstrated that PTL showed good response to radiotherapy and chemotherapy and had a favourable prognosis.     

Risk factors for the incidence and progression of radiographic osteoarthritis of the knee among Japanese

This longitudinal study aimed to identify risk factors for the incidence and progression of radiographic knee osteoarthritis (OA). We examined the inhabitants of Miyagawa village aged ≥65 years every two years between 1997 and 2007. Anteroposterior radiographs of both knees were graded for OA using the Kellgren-Lawrence (K/L) grading system. Knee OA was defined as grade ≥2. We recorded the incidence of knee OA among participants in whom both knees changed from K/L grades 0 or 1 to ≥2 over a four-year follow-up period. We also recorded the progression of knee OA using this threshold among patients in whom one or both knees changed from K/L grades 2 or 3 to any higher grade over the follow-up period. Baseline data obtained from standard questionnaires, physical findings and X-rays included age, gender, body mass index (BMI), osteoporosis, Heberden’s nodes, knee range of motion (ROM), knee pain and cigarette smoking. The rates of incidence and progression of knee OA among 360 participants (241 women, 119 men) who fulfilled the study criteria were 4.0 and 6.0% per year, respectively. Female gender (odds ratio [OR] 2.849, 95% confidence interval [CI] 1.170–6.944) and high BMI (OR 1.243, 95% CI 1.095–1.411) were significantly associated with the incidence of knee OA, and restricted knee ROM (OR 0.941, 95% CI 0.892–0.992) was significantly associated with knee OA progression. Patients with a low knee ROM relative to grade of radiographic knee OA require more careful follow-up than those with a higher ROM.     

Improvement of Long-Term Outcomes in Hepatitis C Virus Antibody–Positive Patients with Hepatocellular Carcinoma after Hepatectomy in the Modern Era

Background  

The present study was conducted to clarify the causes of recent improvement of outcomes after hepatectomy in patients with hepatitis C (HC)–related hepatocellular carcinoma (HCC).     

Secondary resistance of extra-gastrointestinal stromal tumors to imatinib mesylate: report of a case

Extra-gastrointestinal stromal tumors (EGISTs) that do not originate in the digestive tract are rare. We report a case of multiple EGISTs, which was monitored closely by KIT gene mutation analysis and other investigations. The patient was a 52-year-old man in whom multiple tumors in the abdominal cavity were diagnosed as EGISTs. Immunohistochemical analysis revealed positive staining for c-kit; however, no mutations were found in the KIT gene. The tumors decreased in size remarkably following treatment with imatinib mesylate, but after 2 years of this treatment, multiple liver metastases and some regrowth of the abdominal masses were found simultaneously. The liver metastasis and the abdominal masses were excised, and further analysis of the KIT gene revealed the same mutation in exon 11 in the KIT gene in the metastatic tumors. We speculate that the treatment might have triggered development of the imatinib mesylate-resistant clone, which may have existed in the primary lesion as a KIT gene mutant. This report provides valuable insight into the mechanisms of recurrent GISTs after treatment with imatinib mesylate.     

Gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis

Surgical palliation of malignant obstructive pancreatitis poses a considerable burden to patients, especially those with extensive disease. We herein present a novel technique for performing gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis. The main pancreatic duct was punctured via the wall of the pyloric antrum. After the insertion of a guidewire, a double pigtail-type tube stent with side holes was inserted into the main pancreatic duct through the wall of the pyloric antrum. This technique was useful as a means of accomplishing less invasive palliative treatment, and has the potential to improve the quality of life for patients with malignant obstructive pancreatitis.     

Living donor liver transplantation for end-stage liver disease with severe hepatopulmonary syndrome: report of a case

Hepatopulmonary syndrome (HPS) is a serious complication of terminal liver disease, which manifests as severe hypoxia without any pulmonary anatomic or functional causes. The precise indications for liver transplantation in patients with severe HPS also remain unclear. A 49-year old woman was referred to our department for investigation and management of liver cirrhosis with severe hypoxia (PaO₂, 38 mmHg). A pulmonary perfusion scintigram showed an intrapulmonary shunt ratio of 40%, confirming a diagnosis of severe HPS. She underwent living donor liver transplantation using a right lobe graft donated by her 27-yearold daughter. Her post-transplant graft function was excellent, and her oxygenation recovered slowly but steadily. She was discharged from hospital on posttransplant day 39 with an SpO₂ of 94% under 3 l/min of O₂, delivered nasally. Despite the severity of the HPS, her postoperative recovery was smooth after the liver transplant.