[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.

Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals.

BACKGROUND AND AIMS: Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. METHODS: In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). RESULTS: During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. CONCLUSIONS: We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. IMPACT AND IMPLICATIONS: A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

AIM: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS: All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6 mm) and hyperbilirubinemia (≥2.0 mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. CONCLUSIONS: Treatment with SOF/VEL for 12 weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.

Cancer-related FGFR2 overexpression and gene amplification in Japanese patients with gastric cancer.

OBJECTIVE: Fibroblast growth factor receptor 2 (FGFR2) has been proposed as a novel druggable target in unresectable gastric cancer. FGFR2 alteration has been reported as associated with poor prognosis even in patients with gastric cancer who received systemic chemotherapy. This study aimed to evaluate the frequency of FGFR2 overexpression and gene amplification in clinical specimens from Japanese patients with recurrent or unresectable gastric cancer. METHODS: This observational study enrolled patients who were histologically or cytologically confirmed with unresectable HER2-negative or unknown gastric or gastroesophageal junctional adenocarcinoma treated with at least one previous chemotherapy. FGFR2 overexpression and gene amplification in the specimens were evaluated by immunohistochemical staining and fluorescence in situ hybridization methods, respectively. RESULTS: In a total of 173 eligible cases, FGFR2 immunohistochemistry score was evaluated as 0, 1, 2, 3 and 4 for 20, 80, 35, 28 and 10 cases, respectively. In 151 evaluable cases with FGFR2 immunohistochemistry scores of 1-4, FGFR2 copy number expressed as fluorescence in situ hybridization signals were detected as <4, ≥4 < 10 and ≥10 copies for 123, 16 and 12 cases, respectively. FGFR2 copy number showed an increasing tendency along with higher FGFR2 immunohistochemistry scores in the corresponding specimen. The response rate and time to treatment failure for first line chemotherapy did not have any obvious relationship to FGFR2 immunohistochemistry score and FGFR2 copy number. CONCLUSIONS: Although FGFR2 overexpression and gene amplification were shown in Japanese patients with unresectable gastric cancer, these alterations did not impact the effects of cytotoxic agents as first line chemotherapy.

[Evaluation of Risk Factors for Immune-Related Adverse Events Associated with Treatment with Immune Checkpoint Inhibitors].

OBJECTIVE: Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs. METHODS: The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group). RESULTS: The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer. CONCLUSION: At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.

[Impact of Physician Order Support Duties on de novo Hepatitis Prevention].

"Immunosuppression and hepatitis B measures and guidelines for chemotherapy" were announced in 2009. However, a fulminant case that appeared when the guidelines were not observed was reported, and de novo hepatitis prevention is an urgent problem. The rate of compliance with these guidelines as of January 2014 was 20.4%, but this rose to 34.3%after the alert indication for de novo hepatitis prevention was set on an electronic chart system from June 2014. The rate of compliance increased to 63.9% at a hospital where de novo hepatitis alerts were put on clinical cards in April 2015, but it gradually decreased thereafter. HBV-DNA measurement was 100% in compliance with the guidelines from August 2016 when HB antigen, HB antibody, and anti-hepatitis B core antigen measurements were all performed in March 2016 because the pharmacists practiced physician order support duties at that time. This helped to reduce the burden on physicians, and the physician order support duties by the pharmacist were educational. Thus, de novo hepatitis prevention may contribute to safe cancer chemotherapy.

[A Case of Rectal Cancer and Multiple Liver Metastases Treated Using mFOLFOX and Bevacizumab under Maintenance Dialysis].

A 50s man receiving dialysis for chronic kidney disease due to IgA nephropathy underwent laparoscopic reversal via Hartmann 's procedure for rectal cancer and multiple liver metastases, followed by chemotherapy for the liver metastases. Following a single course of mFOLFOX therapy, bevacizumab was administered for 8 courses, resulting in tumor shrinkage and a decrease in tumor marker levels. The initial doses were 60mg/m2 oxaliplatin and 280(bolus injection)and 1,680mg/m2 (continuous infusion)of 5-FU. Subsequently, these doses were adjusted to be administered every 3 weeks. No serious adverse events other than neutropenia(Grade3 ), anorexia(Grade1 ), and hiccups(Grade1)were noted.

Selective balloon-occluded transarterial chemoembolization for patients with one or two hepatocellular carcinoma nodules: Retrospective comparison with conventional super-selective TACE.

AIM: Selective balloon-occluded transarterial chemoembolization (B-TACE) enables strong TACE; infusion of more volume of lipiodol emulsion and forceful injection of embolization materials. The aim of this study is to analyze the efficacy of B-TACE for patients with one or two hepatocellular carcinoma (HCC) nodules compared with conventional super-selective TACE using a microcatheter (C-TACE). METHODS: We retrospectively selected patients without previous history of TACE, with one or two HCC nodules, with performance status 0/1, and with liver function of Child-Pugh score A/B. Between 2008 and 2010, a 3-Fr microballoon catheter was used for targeted TACE (B-TACE group). Between 2005 and 2008, a 2-Fr microcatheter was used (C-TACE group). Control rates of primary nodule, overall survival rates and tumor-free rates in the liver were calculated for each group using the Kaplan-Meier method. Univariate analysis was performed to compare between the groups using the log-rank test. Multivariate analysis was performed for analysis of prognostic factors using Cox's proportional hazard model. The factors were B-TACE versus C-TACE, Child-Pugh score A versus B, single nodule versus double, large nodule versus small , elder versus not, and prior radiofrequency ablation treatment versus not. RESULTS: Control rates of the primary nodule were improved by B-TACE. B-TACE was an independent factor to improve both control rates of the primary nodule and overall survival rates. Child-Pugh score A was an independent factor to increase overall survival rates. There was no statistically significant difference in overall survival or tumor-free survival rates between the groups. CONCLUSION: B-TACE was an independent factor to improve overall survival rates on multivariate analysis, but there was no significant difference in overall survival rates between B-TACE and C-TACE groups on univariate analysis.

[Team Approaches for and Future Challenges to Promoting Perioperative Oral Management].

When the medical fee system was revised in 2012, the category of perioperative oral management was newly organized. However, the calculation of additional fees for such management required referral from medical to dental departments. In addition, requests for such management were limited, possibly owing to an increased burden on doctors engaged in outpatient services. This study examined the usefulness of an approach to promote patients' use of dental services by increasing their awareness of the importance of oral management. In this approach, pharmacists explained doctors' instructions to patients at a chemotherapy center within the study facility. Explanations were provided to 114 patients, 75 (65.8%) of whom subsequently used dental services in the facility. For patients using dental services, oral care was performed most frequently (40; 53.3%), followed by invasive procedures (23; 30.7%). Furthermore, the facility's ethics committee approved a survey to measure the satisfaction of patients undergoing chemotherapy at the center. Of the 110 patients invited to participate in the survey, 77(70.0%) did not respond. Researchers concluded the low response rate was associated with patients' belief that dental services were intended primarily for treating oral cavities and their lack of awareness of the importance of preventive dental care. However, in 2014, the number of calculations of additional fees for perioperative oral management markedly increased each month after the above-mentioned approach, from 62 (January) to 162 (December). Both the hospital-to family and family-to-hospital dentist referral rates significantly increased, from 11.2% and 10.7%, respectively (June 2013), to 21.0% and 41.9%, respectively(June 2014). Future evaluations of the outcomes of perioperative oral management and promoting cooperation between medical and dental communities may be necessary.

Thienopyridine derivatives as risk factors for bleeding following high risk endoscopic treatments: Safe Treatment on Antiplatelets (STRAP) study.

BACKGROUND AND STUDY AIMS: The optimal method of perioperative management of antiplatelet agents during endoscopic procedures that carry a high risk of bleeding is still controversial. The aim of this study was to evaluate the safety of continuing aspirin treatment during these procedures in an Asian population. PATIENTS AND METHODS: A multicenter, prospective, observational cohort study was conducted at six high volume endoscopy centers in Japan. The study included patients at high risk of thromboembolism who were regularly taking antiplatelet agents (e. g. thienopyridine derivatives and aspirin). Enrolled patients continued their aspirin therapy, and underwent endoscopic procedures that had a high risk of bleeding for treatment of lesions in the upper and lower gastrointestinal tracts. The primary end point was the rate of major bleeding complications after endoscopic procedures. RESULTS: The study was terminated in accordance with predetermined safety criteria because 7 of 28 consecutive patients experienced major bleeding complications (25.0 %; 95 % confidence interval 10.7 % - 44.9 %). All major bleeding complications occurred following endoscopic submucosal dissection (ESD; 6 stomach, 1 colon). Univariate analysis showed that postoperative administration of thienopyridine derivatives was the only significant factor associated with postoperative bleeding (P = 0.01). Subanalysis of gastric ESD (23 lesions in 19 patients) confirmed that the administration of thienopyridine derivatives (P = 0.01) and that of multiple agents (P = 0.02) were the significant factors. All bleeding complications (postoperative day 11.2 ±â€Š3.5) occurred after resuming thienopyridine derivative therapy postoperatively (postoperative day 2.3 ±â€Š2.4). CONCLUSION: In Asian patients taking thienopyridine derivatives with aspirin, cautious postoperative care is necessary for those undergoing endoscopic procedures that are associated with a high risk of bleeding, especially gastric ESD. Continuation of aspirin alone during these endoscopic procedures may be acceptable. STUDY REGISTRATION: UMIN000009176.

[Initial Evaluation of the Efficacy and Safety of Tablets Containing Trifluridine and Tipiracil Hydrochloride--Safety Measures Devised by a Multidisciplinary Team Including a Pharmaceutical Outpatient Clinic].

In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf® tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer. The benefits of these tablets in terms of a new therapeutic option have been demonstrated. However, the manufacturer has requested healthcare professionals to help develop safety measures for the appropriate and safe use of the tablets. In this study, we evaluated the efficacy and safety of the tablets in 16 patients who received the tablets at our hospital. Among the 4 evaluable patients, none achieved a complete or partial response. One patient (25.0%) had stable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines outlined in the General Rules of the Study of Colorectal Cancer (The 8th Edition). Lonsurf® is considered to be a third-line (or later) treatment. Among the 16 cases studied, Lonsurf® was used as a third-, fourth-, and fifth-line treatment in 9, 6, and 1 cases, respectively. Therefore, Grade 3 or worse toxicities were a potential concern. Despite a high incidence of Grade 3 or worse neutropenia (7 of the 16 patients [43.8%]), none of the patients were hospitalized due to neutropenia or other treatment-related adverse events. Pharmacists have made 126 proposals to physicians regarding the use of Lonsurf®, 121 (96.0%) of which have been adopted. All of the adverse reactions experienced by our patients were resolved after supportive therapy.

[Appropriate dosing of fosaprepitant for colon cancer patients].

After fosaprepitant (FOS)was added to the National Health Insurance drug reimbursement price list, we switched the route of administration of antiemetics from oral to intravenous in chemotherapy regimens for colon cancer to improve patient medication adherence. However, because the number of patients reporting application-site disorders after administration of FOS increased, we monitored the incidence of these disorders in patients with colon cancer to identify ways to avoid them. In our prospective study, patients receiving conventional FOS dosing regimens (control group)were compared with those receiving diluted FOS solutions (study group). There were no significant differences between the two groups with respect to the incidence of application-site disorders, and contrary to expectations, the incidence was higher in the study group than in the control group. On the basis of the principle of non-maleficence and the availability of alternative therapies using oral aprepitant (APR), we terminated this study early and adopted the basic strategy that all patients with application-site disorders, except for those with central venous access devices, should be treated with oral APR after confirming their preferences.

[Examination of the usefulness of the pharmacists' outpatient clinic for treatment with oral molecule-targeting drugs].

BACKGROUND: In the author's hospital, pharmacists' outpatient clinics were initiated in April 2010, and the department of breast surgery there has provided guidance on oral anti-cancer medication, but with difficulty in adopting proposals for supportive therapy made after the doctor's consultation on the same day. Under such circumstances, this study examined methods for conducting interviews with patients before the doctor's consultation in cases where oral molecular-targeted drugs are necessary. OBJECTIVE: To promote next-generation skill-mix team medicine in order to improve the continuity of treatment and optimize therapeutic effects. METHODS: Patients being treated with oral molecular-targeted drugs in Hitachi General Hospital were studied. INTERVENTION: Outcomes were assessed through medication-monitoring reports, while conducting a questionnaire regarding duties of pharmacists coordinating molecular-targeted drugs. RESULTS: Within the study period, 245/259(94. 6%)of proposals for prescriptions were adopted in 95 patients, among which 212/245(86. 5%) proposed supportive therapy. Improvement in conditions was observed in all patients treated with supportive therapy. The mean duration of sorafenib administration among 19 patients before and after the pharmacist's intervention was 66±20. 3 and 102±30. 8 days, respectively. The main reason for the need of pharmacists coordinating molecular-targeted drugs was: security among all patients; "support for adverse event management"among all doctors; and "proposals for prescription" among all nurses. DISCUSSION: The mean duration of sorafenib administration prolonged by the pharmacist's intervention and consequent reduction in side effects may have directly improved the continuity of treatment. Furthermore, when reflecting on each prescription, the pharmacist's expertise may have facilitated pharmacological intervention. In the future, it may also be necessary to promote pharmacist-led consultations supporting patients' informed choice of drugs.

[An assessment tool for chemotherapy-induced nausea and vomiting and intervention outcomes].

Chemotherapy-induced nausea and vomiting(CINV)is the most unpleasant side effect for patients receiving cancer chemotherapy. Moderately emetic anticancer drugs show a wide range of emetic frequencies, and the use or nonuse of antiemetics is optionally described without specifics. In the present study, we clarified the state of CINV presentation caused by moderately emetic anticancer drugs using the MASCC Antiemesis Tool, a nausea-and-vomiting evaluation tool developed by the Multinational Association of Supportive Care in Cancer(MASCC)for patients with colorectal cancer. Of the 32 subjects, 5 (15.6%)had vomiting and 22(68.8%)experienced nausea. The timing of their occurrence and their nausea scores were accurately and easily clarified. This study's findings suggested that the current regimens need to be reviewed, particularly because all patients exhibited late nausea; therefore, we modified our antiemetic regimens through the Cancer Chemotherapy Regimen Review Board of this hospital. After the modification was introduced, significant improvement was seen in the control of both acute and late nausea/vomiting.

Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan.

OBJECTIVE: A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter pylori eradication. METHODS: 420 patients with gastric low-grade MALT lymphoma who had undergone successful H pylori eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD. RESULTS: 323 patients (77%) responded to H pylori eradication. A logistic regression analysis showed that absence of H pylori, submucosal invasion determined by endoscopic ultrasonography and t(11;18)/API2-MALT1 were independent predictors of resistance to H pylori eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B cell lymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a 'watch and wait' strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival. CONCLUSIONS: The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.

[Nutritional assessment using MUST(Malnutrition Universal Screening Tool) in outpatient chemotherapy].

OBJECTIVE: We set out to see if nutritional assessment(management)using MUST could be useful for patients undergoing outpatient chemotherapy. METHODS: The study sample consisted of 197 patients undergoing outpatient chemotherapy between June 2010 and November 2010. The results of MUST, serum albumin levels, and nutritional intervention were investigated. RESULTS: High- and medium-risk patients requiring nutritional therapy was comprised of 17/78 breast cancer(21. 8%), 16/63 hematologic malignancy(25. 4%), and 26/56 colonic cancer(46. 4%)patients.Moreover, the serum albumin level in high- and medium-risk patients was likely to decrease compared to low-risk patients, suggesting the usefulness of MUST. DISCUSSION AND CONCLUSION: It is important to assess nutritional status focusedon simplicity, objectivity, andspeedin outpatient chemotherapy. Assessment of patients' nutritional status and cancer treatment compliance are expected to be improved using MUST.

Conflicting clinical environment about the management of antithrombotic agents during the periendoscopic period in Japan.

BACKGROUND AND AIMS: Although there are guidelines for the management of antithrombotic agents during the periendoscopic period, gaps between various guidelines create a confusing situation in daily clinical practice. The purpose of this study was to examine the current management of antithrombotic agents during the periendoscopic period in Japan. METHODS: This is a prospective cohort study in 12 high-volume endoscopy centers in Japan. A total of 970 outpatients receiving antithrombotic agents underwent endoscopies (705 esophagogastroduodenoscopies and 265 colonoscopies) with or without invasive procedures. Main outcome measures are adverse events in these patients. RESULTS: Need for cessation of antithrombotics before endoscopy was mostly determined by non-gastroenterologists (51%) who are unfamiliar with the Japan Gastroenterological Endoscopy Society (JGES) guideline, although cessation periods after endoscopy for most patients were determined by endoscopists (78%). Consequently, most patients underwent endoscopy without cessation (25%) or after a cessation period of 6-7 days (33%), indicating low permeation of the JGES guideline in Japan. Among 970 patients, two patients experienced major complications that may be related to thromboembolic events or gastrointestinal bleeding (95% confidence interval [CI]: 0-0.7%). One of these patients died due to sudden onset ventricular tachycardia. Invasive procedures, including 40 biopsies and two mucosal resections, were performed in 42 patients without cessation of antithrombotics, and no patients experienced major complications (95% CI: 0-8.4%). CONCLUSIONS: This study revealed a conflicting clinical environment due to absence of a unified guideline in Japan. Further accumulation of data is mandatory to establish a unified guideline based upon solid evidence.

Prolonged survival in patients with hand-foot skin reaction secondary to cooperative sorafenib treatment.

BACKGROUND: Sorafenib is an oral drug that prolongs overall survival (OS) in patients with hepatocellular carcinoma. Adverse events, including hand-foot skin reaction (HFSR), lead to permanent sorafenib discontinuation. AIM: To clarify the association between interventions for adverse events and patient prognosis. METHODS: We performed a retrospective, multicenter study of patients treated with sorafenib monotherapy between May 2009 and March 2018. We developed a mutual cooperation system that was initiated at the start of sorafenib treatment to effectively manage adverse events. The mutual cooperation system entailed patients receiving consultations during which pharmacists provided accurate information about sorafenib to alleviate the fear and anxiety related to adverse events. We stratified the patients into three groups: Group A, patients without HFSR but with pharmacist intervention; Group B, patients with HFSR and pharmacist interventions unreported to oncologists (nonmutual cooperation system); and Group C, patients with HFSR and pharmacist interventions known to oncologists (mutual cooperation system). OS and time to treatment failure (TTF) were evaluated using the Kaplan-Meier method. RESULTS: We enrolled 134 patients (Group A, n = 41; Group B, n = 30; Group C, n = 63). The median OS was significantly different between Groups A and C (6.2 vs 13.9 mo, p < 0.01) but not between Groups A and B (6.2 vs 7.7 mo, P = 0.62). Group A vs Group C was an independent OS predictor (HR, 0.41; 95%CI: 0.25-0.66; P < 0.01). In Group B alone, TTF was significantly lower and the nonadherence rate was higher (P < 0.01). In addition, the Spearman's rank correlation coefficients between OS and TTF in each group were 0.41 (Group A; P < 0.01), 0.13 (Group B; P = 0.51), and 0.58 (Group C; P < 0.01). There was a highly significant correlation between OS and TTF in Group C. However, there was no correlation between OS and TTF in Group B. CONCLUSION: The mutual cooperation system increased treatment duration and improved prognosis in patients with HFSR. Future prospective studies (e.g., randomized controlled trials) and improved adherence could help prevent OS underestimation.

Factors associated with a reduction in the quality of life of patients with chronic hepatitis C treated by ledipasvir/sofosbuvir therapy.

OBJECTIVE: We investigated factors associated with a reduction in the quality of life and their OR of patients with chronic hepatitis C who underwent ledipasvir/sofosbuvir therapy. METHODS: The subjects were 141 outpatients who had undergone ledipasvir/sofosbuvir therapy under a diagnosis of genotype I chronic hepatitis C or Child-Pugh A compensated cirrhosis at Hitachi General Hospital. The patient background before ledipasvir/sofosbuvir therapy, laboratory data and the Chronic Liver Disease Questionnaire scores during ledipasvir/sofosbuvir therapy were investigated. The Chronic Liver Disease Questionnaire consists of 29 questions, and the mean value is calculated as the overall score through a 7-step assessment by patients. Using two divisions: a Chronic Liver Disease Questionnaire score of <7 (symptoms are present) and that of 7 (no symptoms), as objective variables, patients with a Chronic Liver Disease Questionnaire score of <7 were defined as having a reduced quality of life. Independent factors significantly associated with a reduction in the quality of life were extracted using logistic regression analysis. RESULTS: Based on the multivariate analysis, an alanine aminotransferase level of ≥23 U/L (OR: 4.380, 95% CI: 1.394 to 13.756) was extracted as an independent factor associated with a reduction in the quality of life (p<0.05). CONCLUSION: An increase in the baseline level of alanine aminotransferase was found to play a role in the reduction in the quality of life of patients with chronic hepatitis C who had undergone ledipasvir/sofosbuvir therapy.

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.