Promoting notification and linkage of HBs antigen and anti-HCV antibody-positive patients through hospital alert system.

BACKGROUND: In Japan, approximately 0.9% and 1% of the whole population are infected with HBV and HCV, respectively. Doctors from departments other than gastroenterology often order viral hepatitis tests before an invasive examination or an operation. However, the notification of positive results to the patients and linkage to care is not appropriately performed. The in-hospital alert system was constructed to promote the notification and referral to gastroenterologists for patients with positive viral hepatitis tests, and its efficacy was evaluated. METHODS: The patients who tested HBsAg and anti-HCV antibody by chemiluminescent enzyme immunoassays and chemiluminescent immunoassays were investigated for whether they were notified of the positive results and if they were referred to gastroenterologists at our hospital. The notification and referral rate was compared before (from January to December 2014) and after the introduction of the alert system (from February to September 2016). RESULTS: HBsAg-positive rate was 1.1% (69/6543) before the introduction of the alert system and 0.8% (41/5403) after it. The notification rate has significantly improved from 46% to 73% (p = 0.0061) and the referral rate has improved from 16% to 27%, while not significant. Positive rate of anti-HCV antibody was 2.1% (139/6481) before the introduction of the alert system and 2.4% (128/5322) after it. The rate of notification and referral has significantly improved from 35% to 62% (p < 0.0001) and from 6% to 23% (p < 0.0001), respectively. CONCLUSIONS: The in-hospital alert system increased the rates of notification and referral of the patients with positive viral hepatitis tests. Enlightenment of doctors other than gastroenterologists on viral hepatitis and cooperation of medical staffs would be helpful to improve the notification and referral rates.

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.

The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with every second week cetuximab and irinotecan in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with wild-type KRAS metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated in 5 patients. From May 2009 to February 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 patients who were treated with biweekly cetuximab plus irinotecan, partial response was observed in 9 patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%). The median progression-free survival was 5.3 months and median overall survival was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one treatment related death due to pneumonia was observed. Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS.

Phase II study of combination chemotherapy with irinotecan and cetuximab for pretreated metastatic colorectal cancer harboring wild-type KRAS.

The aim of this study was to prospectively evaluate the efficacy of combination irinotecan and cetuximab chemotherapy in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. KRAS status was evaluated using the Cycleave PCR method; only patients without KRAS mutations were included. Cetuximab was administered initially at 400 mg/m² followed by weekly 250 mg/m² infusions. Irinotecan was administered biweekly. From October 2008 to April 2009, a total of 30 patients were enrolled. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 80.0% (95% CI, 61.4-92.3%). Among the 15 patients with stable disease, 11 patients experienced >10% tumor shrinkage. Median progression-free survival was 5.8 months (95% CI, 4.1-7.6). Median overall survival was not reached at a median follow-up of 10.1 months. Grade 2 skin toxicity was observed in 23 patients, while no grade 3 skin toxicity was observed. Combined irinotecan and cetuximab is effective for pretreated metastatic wild-type KRAS colorectal cancer.

[A case of intractable hepatic encephalopathy successfully treated by oral administration of vancomycin hydrochloride, with subsequent improvement of hepatic function reserve enabling transcatheter arterial chemoembolization against hepatocellular carcinoma].

We report a case of an 80-year-old male who suffered from intractable hepatic encephalopathy and hepatocellular carcinoma( HCC), associated with hepatitis type C-related liver cirrhosis. He was unable to receive HCC treatment due to the deterioration of his liver. His hepatic encephalopathy was resistant to oral administration of laxatives, lactulose, and kanamycin sulfate, etc. His blood ammonia concentration averaged about 130 mg/dL, and often exceeded 200 mg/dL(normal range: <80 mg/dL). Later, an oral administration of vancomycin hydrochloride, 0. 5 g once every 3 days, was initiated. Soon after ward, his blood ammonia concentration declined to the normal range(about 50 mg/dL), and the clinical symptoms of hepatic encephalopathy showed a remarkable improvement. By the continuation of vancomycin administration, the normalization of his state of consciousness was achieved, improving his quality of life, and his activities of daily living. Three months after beginning treatment, he was able to receive transcatheter arterial chemoembolization for the treatment of HCC, because his liver function reserve improved(Child-Pugh score decreased from 10 to 7).

High incidence of colonic perforation during colonoscopy in hemodialysis patients with end-stage renal disease.

BACKGROUND & AIMS: Colonic perforation is a rare but life-threatening complication of colonoscopy. We evaluated the incidence of colonic perforation that resulted from colonoscopy in patients who underwent hemodialysis compared with those who did not have this procedure (controls). METHODS: Data from a total of 15,098 consecutive patients who underwent colonoscopy from January 2001 to December 2008 in Nagoya Kyoritsu Hospital were analyzed retrospectively. Patients were divided into 2 groups: 1106 hemodialysis patients and 13,992 controls. The incidence of colonic perforation, patient characteristics, and locations of perforation during colonoscopy were compared between the 2 groups. Furthermore, perforated mucosa samples from colons were examined by pathology analysis. RESULTS: Colonic perforations occurred in 5 hemodialysis patients and 3 controls. The incidence of colonic perforation was markedly higher in the hemodialysis group than in the control group (0.45% vs 0.02%; odds ratio, 21.17; 95% confidence interval, 5.05-88.73; P < .0001). Even after multivariate analysis of age, sex, and patients who received polypectomies, hemodialysis still was associated independently with the risk of colonic perforation during colonoscopy (odds ratio, 19.91; 95% confidence interval, 4.61-85.93; P < .0001). Pathologic examination of perforated mucosa was performed in 3 hemodialysis patients and 3 control patients. beta2-microglobulin deposition was observed in all 3 hemodialysis patients. In contrast, beta2-microglobulin deposition was not detected in control patients. CONCLUSIONS: There is a higher risk of colonic perforation during colonoscopy among patients who received hemodialysis compared with those who did not. beta2-microglobulin deposition might have a role in perforation in patients who receive hemodialysis.

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for pre-treated metastatic colorectal cancer harboring wild-type KRAS.

Standard weekly cetuximab and irinotecan is an effective regimen in heavily pre-treated patients with metastatic colorectal cancer. The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pre-treated metastatic colorectal cancer harboring wild-type KRAS. A total of 30 patients will be enrolled at four medical institutions. The primary endpoint is response rate. The secondary endpoints include adverse events, progression-free survival and overall survival. The pharmacokinetics of cetuximab will also be evaluated in five patients.

[A case of metastatic pancreatic cancer with a remarkable response to combination therapy of gemcitabine and adoptive immune cell therapy].

A 52-year-old woman with a chief complaint of epigastric distress was diagnosed as having pancreatic cancer with multiple liver metastases. After insertion of a metallic stent for biliary stenosis, combination therapy of gemcitabine (GEM) and adoptive immune cell therapy (AICT) was initiated. GEM 1,000 mg/m2 was administered on day 1, 8 and 15 every 4 weeks, while AICT using MUC1 peptide-pulsed dendritic cells (DC) and anti-CD3-activated T lymphocytes (CAT) was given biweekly. After 6 courses of GEM and 9 courses of DC-CAT, the patient was considered to have a complete response (CR) on CT and MRI examination. CR has still been maintained by the continuous administration of GEM and CAT. The combination therapy of GEM and AICT was suggested to be effective against advanced pancreatic cancer.

Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan.

BACKGROUND: Primary tumor location is a critical prognostic factor that also impacts the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in wild-type RAS (KRAS/NRAS) metastatic colorectal cancer (CRC). However, the association between the incidence of BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and primary tumor location remains unclear. METHODS: We prospectively collected tumor samples and clinical data of patients from 15 hospitals between August 2014 and April 2016 to investigate RAS, BRAF, and PIK3CA mutations using a polymerase chain reaction-based assay. According to the primary tumor location, patients were classified to right-sided (from cecum to splenic flexure) and left-sided (from descending colon to rectum) tumor groups. RESULTS: In total, 577 patients with CRC were investigated, 331 patients (57%) had CRC with wild-type RAS; of these 331 patients, 10.5%, 4.8%, and 5.9% patients harbored BRAFV600E, BRAFnon-V600E, and PIK3CA mutations, respectively. BRAF/PIK3CA mutations were more frequent in females, patients with right-sided tumors, and patients with peritoneal metastasis cases and less frequent in patients with liver metastases. The prevalence rates of BRAFV600E and PIK3CA mutations were higher in patients with right-sided tumors than in those with left-sided tumors (32.3% vs. 4.8% and 17.2% vs. 3.6%, respectively). CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC.

[A case of hepatitis B-related multiple hepatocellular carcinomas, most of which lead to necrosis possibly due to the implantation of an arterial infusion catheter].

The patient was a 59-year-old male with chronic hepatitis type B. He was diagnosed as having multiple hepatocellular carcinomas (HCCs), most of which showed hypervascular features on contrast-enhanced CT scan. He underwent the implantation of a 5-french catheter by" GDA coil method" for hepatic arterial infusion of chemotherapy. After the implantation, he suffered from high fever with a sharp elevation in transaminase levels. Since his liver function gradually deteriorated, he was not able to receive hepatic arterial infusion of chemotherapy. However, three weeks after catheter implantation, most of the tumors were no longer enhanced on dynamic CT scan, suggesting a loss of tumor vascularity, ie, induction of tumor necrosis. It was speculated that necrosis of the tumors was caused by the reduction of hepatic arterial blood flow due to the catheter placement.

Synchronous rectal and esophageal cancer treated with chemotherapy followed by two-stage resection.

We report a case of 61-year-old male who had synchronous advanced rectal cancer involving the urinary bladder massively associated with multiple liver metastases, and esophageal cancer successfully treated by neoadjuvant chemotherapy followed by two-stage resection. Although complete resection of each of the lesions was considered possible by performing anterior pelvic exenteration, liver resection, and esophagectomy, it might be impossible for the patient to endure the stress of all of these operative procedures at once. Therefore, we planned to perform staged treatment with prioritizing consideration. First, we instituted chemotherapy with the FOLFOX (oxaliplatin + fluorouracil + leucovorin) plus cetuximab regimen, which could adequately control both rectal and esophageal cancer. After 6 cycles of chemotherapy, high anterior resection combined with cystoprostatectomy and lateral segmentectomy plus partial hepatectomy was performed followed by staged esophagectomy with three-field lymph node dissection. It was possible to use oxaliplatin and cetuximab safely as neoadjuvant therapy not only for advanced rectal cancer but for esophageal cancer, and it was effective.

Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer.

The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n=60) and a group given off-protocol treatment (n=27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n=23), stable disease (n=38), or progressive disease (n=26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ=0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.

Hypofractionated stereotactic body radiotherapy for primary and metastatic liver tumors using the novalis image-guided system: preliminary results regarding efficacy and toxicity.

www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.