A case of advanced pancreatic neuroendocrine tumor in which octreotide long-acting repeatable was effective after failure of everolimus and sunitinib.

Molecular targeted drugs, such as everolimus and sunitinib, have shown efficacy against advanced pancreatic neuroendocrine tumors. Octreotide, a somatostatin analogue, improves the hormone-related symptoms in patients with neuroendocrine tumors. Furthermore, it has been reported that octreotide has antitumor activity in patients with metastatic midgut neuroendocrine tumors. However, whether octreotide has anti-proliferative effects in patients with advanced pancreatic neuroendocrine tumors is not fully understood. We report a 71-year-old man with multiple liver metastases of pancreatic neuroendocrine tumor. He was treated with everolimus 10 mg daily and sunitinib 25 mg daily on days 1-14 every 3 weeks at the physician's discretion. However, these molecular targeted drugs were discontinued due to disease progression or severe adverse effects. Octreotide long-acting repeatable was administered continuously from the initiation of everolimus treatment. The tumor marker level markedly decreased and the metastatic liver lesions showed shrinkage with octreotide treatment. Immunohistochemistry of tumor specimens obtained before treatment showed that somatostatin receptor 2, a high-affinity receptor for octreotide, was highly expressed. The clinical course of this patient suggested that octreotide long-acting repeatable may be a treatment option for advanced pancreatic neuroendocrine tumors after failure of everolimus and sunitinib. Further clinical trials are warranted to determine whether the expression of somatostatin receptor 2 in tumor tissues is predictive of octreotide efficacy.

[Successful Long-Term Treatment with Intermittent Oxaliplatin Administration for Recurrent Sigmoid Colon Cancer without Developing Neuropathy].

We report a case ofrecurrent sigmoid cancer in which long-term disease control was achieved by intermittent oxaliplatin (L-OHP)administration. A 58-year-old woman underwent first-line chemotherapy with capecitabine and L-OHP(CapeOX) following peritoneal lymph node recurrence of sigmoid cancer. Tumor shrinkage was confirmed by a computed tomography (CT)scan following 4 courses of CapeOX treatment. However, L-OHP administration was discontinued by the 9 course due to peritoneal neuropathy. L-OHP was reintroduced following tumor progression confirmed by CT or elevation of carcinoembryonic antigen levels detected by a blood test. This stop-and-go strategy controlled lymph node recurrence effectively for over 5 years and was not associated with the development ofperitoneal neuropathy. We suggest that the intermittent administration ofL -OHP-containing chemotherapy is an important treatment option for some patients with advanced colorectal cancer, achieving effective long-term disease control with no associated peripheral neuropathy.

Elevated prothrombin time/international normalized ratio associated with concurrent administration of regorafenib and warfarin in a patient with advanced colorectal cancer.

BACKGROUND: Regorafenib and its metabolites may inhibit the activities of several CYP or UDP-glucuronosyltransferase isoforms, including that of CYP2C9. Therefore, pharmacological agents that are CYP2C9 substrates may show elevated circulating levels and enhanced drug efficacy when concurrently used with regorafenib. Previous studies showed that the area under the plasma concentration-time curve of warfarin, which is the substrate for CYP2C9, increased upon co-administration of regorafenib. However, there are no reports indicating that the anticoagulant effects of warfarin increased upon co-administration of regorafenib. CASE PRESENTATION: We report a case of a 76-year-old man with liver metastasis of colon cancer. He was treated with regorafenib at a dosage of 120 mg daily on days 1 to 21 every 4 weeks as a third-line therapy. He had a history of acute myocardial infarction and had taken 2 mg warfarin daily. Three weeks after the treatment began, PT/INR values markedly increased, although there was no hemorrhage. Administration of regorafenib and warfarin was discontinued, and then PT/INR rapidly decreased. Warfarin administration was restarted (0.5 mg daily) and the dose was increased up to 1.5 mg daily. The patient's PT/INR values exhibited a tendency to increase when concurrently used with regorafenib, the dose of which was reduced to 80 mg daily on days 1 to 14 every 3 weeks at a physician's discretion. CONCLUSIONS: The clinical course of this patient suggested that PT/INR might increase during concurrent use of warfarin and regorafenib. Therefore, PT/INR should be periodically monitored during the concurrent use of warfarin and regorafenib.

Impact of New Quick Gold Nanoparticle-Based Cortisol Assay During Adrenal Vein Sampling for Primary Aldosteronism.

CONTEXT: Adrenal vein sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism (PA), but accurate placement of the sampling catheter is technically challenging. Intraprocedural cortisol measurement can confirm the catheter's position, thereby increasing the AVS success rate. OBJECTIVE AND METHODS: We developed a quick cortisol assay (QCA) that uses immunochromatography and gold nanoparticles and can be performed either semiquantitatively or quantitatively. The assay was evaluated in two studies. In a single-center study, PA patients were assigned to undergo AVS incorporating the semiquantitative QCA (n = 30), the quantitative QCA (n = 30), or without the QCA (n = 30), and the rates of successful AVS were determined. In a prospective multicenter randomized, controlled study, the success rates of AVS performed with (n = 148) or without (n = 145) the semiquantitative QCA were determined. RESULTS: Cortisol concentrations were measured during AVS in 6 minutes or less in the radiology suite, without additional technical assistance, and significantly correlated with a conventional reference assay (R(2) = 0.994; P < .001). In the single-center study, the differences in the AVS success rates associated with semiquantitative and quantitative QCAs were not significant (both 93%); however, the success rates were significantly higher than the rate of successful AVS performed without using the QCA (63%; P < .001). The success rate of AVS performed in the multicenter study was 94% for the semiquantitative QCA, which was significantly higher than the rate for the patients without QCA (60%; P < .001). CONCLUSIONS: Our novel QCA was rapidly and easily performed at the point of care and improved the rate of successful AVS.

Long-term administration and efficacy of oxaliplatin with no neurotoxicity in a patient with rectal cancer: Association between neurotoxicity and the GSTP1 polymorphism.

Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients' quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m2 without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.

Perforated gastrointestinal stromal tumor (GIST) in a true jejunal diverticulum in adulthood: report of a case.

A 61-year-old man was referred to us for investigation of acute abdominal pain. Computed tomography showed a 5.9 × 5.3 × 5.0 cm lump of food residue in the jejunum, and a large amount of free air and ascites around the liver and right paracolic gutter. He underwent emergency laparotomy for suspected peritonitis from perforation by a foreign body in the small intestine. We identified purulent exudate in the abdominal cavity and perforation of a jejunal cystic mass, attached ~40 cm from Treitz's ligament at the anti-mesenteric side of the jejunum. Based on a diagnosis of jejunal duplication with perforation, we resected that part of the small intestine and performed intra-abdominal drainage. Pathological findings confirmed the diagnosis of a perforated gastrointestinal stromal tumor (GIST) in a true jejunal diverticulum. Histopathological evidence suggests that intestinal pressure and/or hemorrhage can cause perforation in the background of a true jejunal diverticulum. To our knowledge, this is the first case report of a perforated GIST in a true jejunal diverticulum.

Efficacy of oral administration of Lentinula eododes mycelia extract for breast cancer patients undergoing postoperative hormone therapy.

Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.

Topical nitrate drip infusion using cystic duct tube for retained bile duct stone: A six patients case series.

A retained bile duct stone after operation for cholelithiasis still occurs and causes symptoms such as biliary colic and obstructive jaundice. An endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (EST), followed by stone extraction, are usually an effective treatment for this condition. However, these procedures are associated with severe complications including pancreatitis, bleeding, and duodenal perforation. Nitrates such as glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN) are known to relax the sphincter of Oddi. In 6 cases in which a retained stone was detected following cholecystectomy, topical nitrate drip infusion via cystic duct tube (C-tube) was carried out. Retained stones of 2-3 mm diameter and no dilated common bile duct in 3 patients were removed by drip infusion of 50 mg GTN or 10 mg ISDN, which was the regular dose of intravenous injection. Three other cases failed, and EST in 2 cases and endoscopic biliary balloon dilatation in 1 case were performed. One patient developed an adverse event of nausea. Severe complications were not observed. We consider the topical nitrate drip infusion via C-tube to be old but safe, easy, and inexpensive procedure for retained bile duct stone following cholecystectomy, inasmuch as removal rate was about 50% in our cases.

[Efficacy of low-dose erlotinib against gefitinib-induced hepatotoxicity in a patient with lung adenocarcinoma harboring EGFR mutations].

We report a case of a female in her 80s who was diagnosed with recurrent lung adenocarcinoma after primary surgery. She was treated with a systemic chemotherapy regimen consisting of carboplatin plus paclitaxel until the disease showed progression. On detection of epidermal growth factor receptor(EGFR)mutations, we administered gefitinib, an EGFR tyrosine kinase inhibitor, at a dosage of 250 mg daily. After 6 months of gefitinib therapy, laboratory findings revealed elevated serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels(grade 2), indicative of hepatotoxicity. Gefitinib was discontinued and erlotinib was initiated at a dosage of 50 mg daily. She continued the therapy for 3 years, during which her disease stabilized without any further complications or hepatotoxicity. Thus, low-dose erlotinib may be effective and well tolerated by patients with non-small cell lung cancer harboring EGFR mutations who are intolerant to gefitinib.

[A case of colon cancer with chronic renal dysfunction responding to effective retreatment with FOLFIRI].

A 76-year-old man with renal dysfunction received FOLFIRI due to a relapse in his pelvis after surgery for sigmoid colon cancer. FOLFIRI was continued for approximately 21 months with stabilization of disease observed on CT scans, but his tumor marker levels increased and tumors showed progression. He then began treatment with cetuximab/CPT-11, but disease progression was observed. XELOX in a low-dose was then administered, but this therapy was discontinued because of progression. He could not receive the other antitumor agents, due to mutations of the KRAS gene and renal dysfunction. Therefore, FOLFIRI was restarted, because it can be continued for long periods of time. Consequently, his tumor marker levels decreased with stabilization of disease on CT scans, and he continued the therapy for 7 months while maintaining quality of life. Ultimately, this case suggested that if there was effectiveness from a previous treatment, retreatment would be successful as chemotherapy for colon cancer in the difficult situation of selecting the other effective antitumor agents.

Accuracy of simple predictive equations for visceral fat area after 8 weeks of training.

We previously proposed two predictive equations of visceral fat area applicable in a field setting (Demura & Sato, 2007a, 2007b). One uses the fat mass of the trunk measured by bioelectrical impedance as the main predictor (equation 1) and the other uses internal fat mass estimated from several anthropometric variables (equation 2). In this study, we examined the inter- and intra-individual accuracy of estimated values using these equations after 8 weeks of exercise training. Participants were 42 Japanese adults aged 42.7 +/- 10.3 years (22 males, 20 females). Visceral fat area, body composition, and blood biochemistry were measured at baseline and after 8 weeks. There were no significant differences in reference visceral fat area measured by computed tomography and visceral fat area predicted by the equations either at baseline or after 8 weeks, and the values were highly consistent (equation 1: baseline R(2) = 0.829, after R(2) = 0.860; equation 2: baseline R(2) = 0.832; after R(2) = 0.850). No significant relationship was observed between the reference and change in visceral fat area for equation 1 (males: r = 0.272, P > 0.05; females: r = 0.428, P > 0.05), but there was a significant relationship for females with equation 2 (males: r = 0.279, P > 0.05; females: r = 0.474, P <0.05). Our findings indicate that these equations have high inter-individual consistency but low intra-individual consistency with the reference and are of limited use for the longitudinal evaluation of visceral fat area.

A large cystic tumor with bile duct communication originating around the hepatic hilum.

Biliary cystic tumors are rare neoplasms occurring in the liver and less frequently in the extrahepatic biliary system. Recently, biliary cystic tumors in the liver are thought to be divided into a biliary mucinous cystic neoplasm and intraductal papillary neoplasm of the bile duct. We report a case of a large cystic tumor originating around the hepatic hilum which had luminal communication with the bile duct. A 74 year-old-woman underwent abdominal ultrasonography for a routine checkup. It revealed a large cystic tumor in the liver. CT scan and MRI showed a multilocular cystic tumor about 12 cm in diameter with a mural nodule occupying the medial and anterior segment of the liver. Intraoperative cholangiography showed a communication between the cystic tumor and the bile duct. Central bisegmentectomy of the liver and extrahepatic bile duct resection was performed. A papillary tumor existed in the common hepatic duct and was connected with the cystic tumor in the liver. The tumor was mostly composed of noninvasive papillary adenocarcinoma with adenoma components, and was associated with focal microinvasion of adenocarcinoma. Ovarian-like stroma was not observed. This lesion was diagnosed as a cystic variant of intraductal papillary neoplasm of the bile duct. The patient is alive with no recurrence for 18 months since the surgery.

[Report of a case effectively treated by appropriate therapy for severe anticipatory nausea and vomiting due to FOLFOX or FOLFIRI].

To date, the standard treatments for severe anticipatory nausea and vomiting is not well established. 5-HT3 antagonist is one of the effective drugs to reduce chemotherapy-induced nausea and vomiting, but had no effect on these symptoms for this patient. The patient could be successfully administered standard chemotherapy(FOLFOX or FOLFIRI, q2w)without adverse reactions by appropriate treatments in the form of increased doses of dexamethasone and normal dose administration of prochlorperazine. This report suggests a possibility that FOLFOX or FOLFIRI may be successfully treated by appropriate treatments for severe chemotherapy-induced vomiting colon cancer patients, and that this observation may lead to the improved prognosis of these patients.

[A case of left urothelial carcinoma with multiple bone metastasis, liver metastasis and right adrenal metastasis successfully treated with combination chemotherapy of gemcitabine and carboplatin].

The patient was a 53-year-old male. He had been admitted to another hospital with a complaint of left sciatica. He was referred to our hospital for further examination and therapy. He was diagnosed as left urothelial carcinoma with multiple bone metastasis, liver metastasis and right adrenal metastasis. He was treated with combination chemotherapy of gemcitabine and carboplatin (1,000 mg/m2 day 1 and AUC 2 day 1, respectively) biweekly. After the ninth course, a significant tumor reduction was obtained, and has been maintained. He has been treated on an outpatient basis because of no grade 3 or severer adverse reactions. We report an effective case of biweekly chemotherapy with gemcitabine and carboplatin in the treatment of advanced urothelial carcinoma.

FOLFIRI Is Tolerable after Subtotal Colectomy - A Patient with Familial Adenomatous Polyposis Who Developed Advanced Rectal Cancer.

A 40-year-old female with familial adenomatous polyposis (FAP) had a subtotal colectomy at 16 years of age. At 39 years, she had low anterior resection due to advanced rectal carcinoma. Thereafter, we administrated per os uracil and tegafur for 9 months. Metastatic rectal carcinoma was detected in the liver (S8) by computed tomography (CT). 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) data did not show any other metastasis. This report presents a first case of a patient undergoing subtotal colectomy administered FOLFIRI (CPT-11 180 mg/m(2) as a 90-minute infusion on day 1; leucovorin 400 mg/m(2) as a 2-hour infusion during CPT-11, immediately followed by 5-FU bolus 400 mg/m(2) and 46-hour continuous infusion of 2,400 mg/m(2) every 2 weeks). This regimen was administered without grade 3 or 4 of any adverse reaction for 6 months, although there was a possibility that this patient with subtotal colectomy may have the cause for severe diarrhea. Further investigations are needed to assess the safety in clinical trials of FOLFIRI regimen for patients with subtotal colectomy.