[A case of immune-related gastroesophagitis with laryngopharyngitis caused by immune checkpoint inhibitors in nonsmall cell lung cancer].

With the advent of immune checkpoint inhibitors (ICI), cancer treatment options have widened in recent years. However, ICI-specific adverse events (irAEs) have been reported. Lower gastrointestinal lesions, such as colitis and enteritis, account for most gastrointestinal irAEs, and reports of upper gastrointestinal lesions are rare. We report a rare case of gastroesophagitis associated with ICI. The patient was a 64-year-old male. He was diagnosed with lung adenocarcinoma stage IIIB (cT2aN3M0), and pembrolizumab (PEM) was started as a first-line treatment. Severe gastroesophagitis with laryngopharyngitis was confirmed 5 months after PEM administration. These improved after withdrawal of PEM and steroid administration. Reports of ICI-associated gastritis remain limited, especially with laryngopharyngitis;therefore, we consider this case as valuable, in which we confirmed the clinical features of ICI-associated gastroesophagitis and its therapeutic effects.

Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7.

The identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with tumor-forming activity are enriched in cancer stem cell-like CD13+CD166- cells and this cell population gradually decreases during culture in conventional culture medium (RPMI1640 containing 10% fetal bovine serum). When Li-7 cells are cultured in mTeSR1, a medium developed for human pluripotent stem cells, CD13+CD166- cells, and their tumorigenicity is maintained. Here, we sought to identify the mechanisms of tumorigenicity in this sub-population. We compared gene expression profiles of CD13+CD166- cells with other cell sub-populations and identified nine overexpressed genes (ENPP2, SCGN, FGFR4, MCOLN3, KCNJ16, SMIM22, SMIM24, SERPINH1, and TMPRSS2) in CD13+CD166- cells. After transfer from mTeSR1 to RPMI1640 containing 10% fetal bovine serum, the expression of these nine genes decreased in Li-7 cells and they lost tumorigenicity. In contrast, when these genes of Li-7 cells were forcibly expressed in cultures using RPMI1640 containing 10% fetal bovine serum, Li-7 cells maintained tumorigenicity. A metabolome analysis using capillary electrophoresis-mass spectrometry showed that two metabolic pathways, "Alanine, aspartate and glutamate metabolism" and "Arginine biosynthesis" were activated in cancer stem-cell-like cells. Our analyses here showed potential therapeutic target genes and metabolites for treatment of cancer stem cells in hepatocellular carcinoma.

High total Joule heat increases the risk of post-endoscopic submucosal dissection electrocoagulation syndrome after colorectal endoscopic submucosal dissection.

BACKGROUND: We hypothesized that thermal damage accumulation during endoscopic submucosal dissection (ESD) causes the pathogenesis of post-ESD electrocoagulation syndrome (PECS). AIM: To determine the association between Joule heat and the onset of PECS. METHODS: We performed a retrospective cohort study in patients who underwent colorectal ESD from May 2013 to March 2021 in Japan. We developed a novel device that measures swift coagulation time with a sensor adjacent to the electrosurgical coagulation unit foot switch, which enabled us to calculate total Joule heat. PECS was defined as localized abdominal pain (visual analogue scale ≥ 30 mm during hospitalization or increased by ≥ 20 mm from the baseline) and fever (temperature ≥ 37.5 degrees or white blood cell count ≥ 10000 µ/L). Patients exposed to more or less than the median Joule heat value were assigned to the high and low Joule heat groups, respectively. Statistical analyses included Mann-Whitney U and chi-square tests and logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: We evaluated 151 patients. The PECS incidence was 10.6% (16/151 cases), and all patients were followed conservatively and discharged without severe complications. In multivariate analysis, high Joule heat was an independent PECS risk factor. The area under the ROC curve showing the correlation between PECS and total Joule heat was high [0.788 (95% confidence interval: 0.666-0.909)]. CONCLUSION: Joule heat accumulation in the gastrointestinal wall is involved in the onset of PECS. ESD-related thermal damage to the peeled mucosal surface is probably a major component of the mechanism underlying PECS.

Early colonoscopy and urgent contrast enhanced computed tomography for colonic diverticular bleeding reduces risk of rebleeding.

BACKGROUND: Colonoscopy within 24 h of hospital admission for colonic diverticular bleeding (CDB) is recommended. However, little is known about rates of rebleeding within 30 d. We posited that a group of patients who underwent contrast-enhanced computed tomography (CT) within 4 h of the last hematochezia and colonoscopy within 24 h would experience fewer incidences of rebleeding. AIM: To evaluate the outcomes of early colonoscopy for CDB among different groups of patients. METHODS: Data from 182 patients with CDB who underwent contrast-enhanced CT and colonoscopy between January 2011 and December 2018 at the study site were retrospectively reviewed. Patients were divided into groups based on the timing of the CT imaging, within or at 4 h were defined as urgent CTs (n = 100) and those performed after 4 h were defined as elective CTs (n = 82). Main outcomes included rebleeding within 30 d and the identification of stigmata of recent hemorrhage (SRH) (i.e., active bleeding, non-bleeding visible vessels, or adherent clots). RESULTS: In total, 182 patients (126 men and 56 women) with median ages of 68.6 (range, 37-92) and 73.7 (range, 48-93) years, respectively, underwent CT imaging and colonoscopy within 24 h of the last hematochezia. Patients for whom CT was performed within 4 h of the last hematochezia were included in the urgent CT group (n = 100) and patients for whom CT was performed after 4 h were included in the elective CT group (n = 82). SRH were identified in 35.0% (35/100) of the urgent CT cases and 7.3% (6/82) of the elective CT cases (P < 0.01). Among all patients with extravasation-positive images on CT, SRH was identified in 31 out of 47 patients (66.0%) in the urgent CT group and 4 out of 20 patients (20.0%) in the elective CT group (P < 0.01). Furthermore, rates of rebleeding within 30 d were significantly improved in the urgent CT and extravasation-positive cases (P < 0.05). Results from the evaluation of early colonoscopy did not show a difference in the ability to detect SRH identification or rebleeding rates. Only cases by urgent CT reduced risk of rebleeding due to the evidence of active bleeding on the image. CONCLUSION: To improve rates of rebleeding, colonoscopy is recommended within 24 h in patients with extravasation-positive CT images within 4 h of the last hema-tochezia. Otherwise, elective colonoscopy can be performed.

A Neuroendocrine Tumor of Unknown Primary Origin that Responded to Treatment Based on Tumor Grade Progression.

The standard chemotherapies for neuroendocrine tumors (NETs) are somatostatin analog (SSA) and targeted-agents for NET G1/G2 and platinum-based chemotherapy for neuroendocrine carcinoma (NEC), classified according to the WHO criteria of 2010. We report a case of NET, in which tumors were successfully treated with platinum-containing chemotherapy after remarkable progression with SSA. A 46-year-old man with multiple lymph nodes and liver metastases of unknown primary origin was diagnosed with NET G2 based on the examination of a biopsy specimen. His tumors were stable with SSA for a year, but rapidly became enlarged. A second biopsy revealed NEC. He received cisplatin plus etoposide, and his tumors showed a marked reduction in size.

Efficacy of adjuvant chemotherapy after resection of pulmonary metastasis from colorectal cancer: a propensity score-matched analysis.

BACKGROUND: Pulmonary metastases from colorectal cancer are resected due to the favourable 5-year overall survival rates of 30-60% reported in many studies. However, the efficacy of subsequent adjuvant chemotherapy remains unclear. PATIENT AND METHODS: We retrospectively collected clinical data of 1237 patients who underwent surgical resection of pulmonary metastasis from colorectal cancer at 46 Japanese institutions between 2004 and 2008. Patients with non-curative resection, pre-operative chemotherapy, extra-thoracic metastasis, complications after surgery, and inadequate data were excluded. Then, a 1:1 propensity score nearest-neighbour matching between patients with and without adjuvant chemotherapy was performed, considering relevant co-variables, and survival of patients between groups was compared. RESULTS: Data of 524 patients (surgery alone, 269 patients; surgery with adjuvant chemotherapy, 255 patients) were used for matching. From each group, 192 patients with similar background characteristics between groups were selected. Adjuvant chemotherapies included fluoropyrimidine alone (71%), an oxaliplatin-containing regimen (23%), or an irinotecan-containing regimen (6%). In the surgery alone and adjuvant chemotherapy groups, 5-year overall survival rates were 68% and 69%, and 5-year disease-free survival rates were 40% and 34%, respectively. There were no significant differences between the two groups in terms of overall survival (hazard ratio [HR]: 1.00, 95% confidence interval [CI]: 0.69-1.45, P = 1.00) and disease-free survival (HR: 1.07, 95% CI: 0.82-1.39, P = 0.62). CONCLUSIONS: Adjuvant chemotherapy after curative resection of lung-limited metastasis from colorectal cancer did not show a survival benefit in the propensity score-matched analysis and should not be recommended without further clinical trials.

Oncolytic Virotherapy and Gene Therapy Strategies for Hepatobiliary Cancers.

Advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. Effective therapeutic agents for these cancers have not been established. Oncolytic viruses (OVs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. Moreover, clinical trials are demonstrating promising results. Numerous OVs are being tested in preclinical models of hepatocellular carcinoma (HCC). The lead agent Pexa-Vec (pexastimogene devacirepvec, JX-594), a recombinant Wyeth strain vaccinia virus, has demonstrated preliminary evidence of safety and efficacy for HCC in clinical trials. Few other OVs have entered clinical testing. Relatively few preclinical studies and clinical trials exist for biliary cancers. In this review, we introduce various approaches using OVs to treat the intractable hepatobiliary cancers.

Successful Treatment with Modified FOLFOX6 and Panitumumab in a Cecal Cancer Patient Undergoing Hemodialysis.

Combination chemotherapy of mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) plus panitumumab, a fully human monoclonal antibody against epidermal growth factor receptor (EGFR), is one of the standard treatments for metastatic colorectal cancer (mCRC) without KRAS mutation. A few reports suggested no need of dose adjustment of cetuximab, a similar chimeric anti-EGFR antibody, in patients with renal impairment. However, panitumumab combined with cytotoxic drugs for hemodialysis patients has not been reported. We herein report a case of a hemodialysis mCRC patient successfully treated with mFOLFOX6 and panitumumab combination therapy.

Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer.

BACKGROUND: To develop a triplet regimen containing gemcitabine, cisplatin, and S-1 (GPS), we assessed the recommended dose for patients with untreated advanced biliary tract cancer in this phase I study. METHODS: Dose-limiting toxicities (DLTs) were evaluated for the following two dose levels: gemcitabine (1000 mg/m(2) for level 1 and 1200 mg/m(2) for level 2 on day 1), cisplatin (30 mg/m(2) fixed dose on day 1), and S-1 (40-60 mg/day fixed dose twice a day for 7 days), every 2 weeks until progression. DLTs for each level were evaluated in six or more patients during the first two cycles. RESULTS: A total of 18 patients were enrolled and 16 patients were evaluated. DLTs at level 1 were observed in two of 10 patients. At level 2, a DLT was observed in one of six patients. The main grade 3 or 4 treatment-related adverse events were neutropenia and leukopenia, and a few non-hematological toxicities were observed. Among 14 patients with measurable lesions, the best response rate was 50%. CONCLUSIONS: GPS with a relative dose intensity corresponding to 90% of the standard gemcitabine plus cisplatin regimen could be administered safely, and showed preliminary antitumor activity. Survival benefits will be studied subsequently.

[A retrospective analysis of cetuximab or panitumumab monotherapy for KRAS wild-type metastatic colorectal cancer in clinical practice].

We performed a retrospective study on the use of cetuximab or panitumumab alone in patients with KRAS wild-type metastatic colorectal cancer between November 2008 and February 2012. Twenty-two patients were analyzed and classified as PS 0/1 (good PS group)and PS 2/3/4 (poor PS group)with 11 patients in each group. The response rate, disease control rate, median progression-free survival, and median overall survival were 9%, 73%, 5.1 months (95%confidence interval[CI]: 1.5-8.7), and 16 months (95% CI: 8.8-24), respectively, in the good PS group, and the corresponding values in the poor PS group were 0%, 18%, 0.7 months (95% CI: 0.3-1.0), and 1.5 months (95% CI: 0.7-2.4). Grade 3 or 4 adverse events were skin toxicities (2 patients with grade 3 toxicities), panitumumab-related interstitial lung disease (1 patient with grade 4 toxicity), and cetuximab infusion-related reaction (1 patient with grade 4 toxicity). No treatment-related deaths were observed. In conclusion, the efficacy and safety of cetuximab or panitumumab monotherapy in patients with a good PS in our study were similar to those reported in previous clinical trials, whereas patients with a poor PS showed poorer outcomes.

[A case of malignant peritoneal mesothelioma with the epithelioid histological type, successfully treated with pemetrexed plus cisplatin].

A 45-year-old man presented with severe abdominal distention with massive ascites due to a diffusely disseminated peritoneal tumor. A core needle biopsy specimen was obtained from the peritoneal lesion. Histological diagnosis was epithelioid type mesothelioma. He did not choose to receive chemotherapy. For 2.5 years, he went without medical intervention, and his disease gradually progressed, leading to a worsening of his symptoms. The patient then chose to be treated with combination chemotherapy of cisplatin and pemetrexed, followed by pemetrexed alone. There was remarkable tumor shrinkage and his symptoms improved. These effects have been sustained for two years after the initial chemotherapy. Chemotherapy appears to have contributed to survival prolongation for this patient. This case exemplifies the fact that malignant peritoneal mesothelioma may progress slowly when fits with some good prognostic factors, and it is important to consider the prognostic factors.