Upper gastrointestinal endoscopic submucosal dissection using an ultrathin endoscope: a retrospective, single-center evaluation.

BACKGROUND: Recent studies have reported the therapeutic use of endoscopic submucosal dissection (ESD) using an ultrathin endoscope for targeting pharyngeal and distal side lesions in the stenosis or as a less invasive treatment via the nasal route. However, the effectiveness and safety of these treatments remain undetermined. Therefore, this study aimed to review treatment outcomes and discuss the advantages and precautions of the treatments based on our experience. METHODS: This study included 13 patients with 14 lesions who underwent 14 sessions of upper gastrointestinal ESD using an ultrathin endoscope between December 2021 and August 2023. The outcome measures included lesion background, en bloc resection rate, en bloc complete resection rates, and incidence of adverse events (including post-operative bleeding, intraoperative perforation, and delayed perforation). RESULTS: The lesions in the esophagus, stomach, and duodenum were eight, three, and three, respectively, and the median length (range) of each located lesion was 16.5 (6-26), 17 (9-36), and 10 (4-16) mm, respectively. En bloc resection and en bloc complete resection rates were 100 and 92.9%, respectively. The only adverse event was an intraoperative perforation observed during duodenal ESD, resulting from the assistant's inadvertent expansion of the SOUTEN at the final dissection stage. CONCLUSION: Our results demonstrate that ESD with an ultrathin endoscope effectively reaches lesions in difficult locations and enables treatment within a small working space. Therefore, ESD using an ultrathin endoscope is a treatment option for lesions located distally to gastrointestinal stenosis, highly fibrotic lesions, and duodenal tumors.

Real-World Treatment Sequencing in Vulnerable Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: Data regarding treatment sequence for vulnerable patients with metastatic colorectal cancer (mCRC) in a real-world setting are lacking. OBJECTIVE: We aimed to assess treatment outcomes in second-line or later chemotherapy for vulnerable patients with mCRC in a real-world setting. PATIENTS AND METHODS: Vulnerable patients with mCRC who received less intensive treatment ('vulnerable') regimens, i.e. fluoropyrimidines with or without biologics (FP), reduced-dose doublet regimens with or without biologics (Doublet), and anti-epidermal growth factor receptor monotherapy (Anti-EGFR), as first-line therapy between June 2015 and December 2018 were retrospectively reviewed. RESULTS: A total of 210 patients from 15 hospitals were analyzed. The median age was 78 years (range 28-90), and 44 patients (21%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 2. In the entire population, the median time to treatment failure (TTF) and overall survival (OS) were 7.6 and 21.4 months, respectively. Following the failure of first-line therapy in 195 patients, 74 (38%), 24 (12%), and 13 (7%) patients received vulnerable regimens, full-dose doublet regimens with or without biologics, and other regimens, respectively, whereas 84 (43%) received best supportive care (BSC). In patients receiving vulnerable regimens as second-line therapy, the median TTF and OS were 4.4 and 13.7 months, respectively, while response rate and disease control rate were 18% and 62%, respectively. In 84 patients who received BSC, the median OS was 3.5 months. CONCLUSIONS: Second-line chemotherapy for vulnerable patients with mCRC showed clinically meaningful outcomes; however, few patients received second-line therapy, and survival among patients who received BSC was dismal.

Clinical Effect of the C-Reactive Protein to Serum Albumin Ratio in Patients with Metastatic Gastric or Gastroesophageal Junction Cancer Treated with Trifluridine/Tipiracil.

Trifluridine/tipiracil (FTD/TPI) is an oral anticancer agent used as a third- or later-line treatment for patients with metastatic gastric cancer/gastroesophageal junction cancer (mGC/GEJC). The C-reactive protein-to-serum albumin ratio (CAR) is an inflammation-based prognostic marker in gastric cancer. This retrospective study evaluated CAR's clinical significance as a prognostic factor in 64 patients with mGC/GEJC administered FTD/TPI as a third- or later-line therapy. Patients were categorized into high- and low-CAR groups based on pre-treatment blood data. This study evaluated associations between CAR and overall survival (OS), progression-free survival (PFS), clinicopathological features, treatment efficacy, and adverse events. The high-CAR group had significantly worse Eastern Cooperative Oncology Group performance status, a higher prevalence of patients administered with a single course of FTD/TPI, and a higher rate of patients not administered chemotherapy after FTD/TPI therapy than the low-CAR group. Median OS and PFS were significantly poorer in the high-CAR group than in the low-CAR group (113 vs. 399 days; p < 0.001 and 39 vs. 112 days; p < 0.001, respectively). In multivariate analysis, high CAR was an independent prognostic factor for OS and PFS. The overall response rate was not significantly different between the high- and low-CAR groups. Regarding adverse events, the high-CAR group had a significantly lower incidence of neutropenia and a higher incidence of fatigue than the low-CAR group. Therefore, CAR may be a potentially useful prognostic factor for patients with mGC/GEJC treated with FTD/TPI as third- or later-line chemotherapy.

Evaluation of Irinotecan and Trifluridine/Tipiracil as Fourth-line Treatments After Third-line Nivolumab for Advanced Gastric Cancer.

BACKGROUND/AIM: Irinotecan and trifluridine/tipiracil (FTD/TPI) are fourth-line treatment options after third-line nivolumab for advanced gastric cancer (AGC). However, the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab remains unclear. This study aimed to evaluate the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab. PATIENTS AND METHODS: We identified 137 AGC patients treated with nivolumab as third-line treatment in our institute between October 2017 and July 2021. Of these, we recruited 19 AGC patients who initiated irinotecan and 23 AGC patients who initiated FTD/TPI in the fourth-line setting until September 2021. RESULTS: The median overall survival was 5.83 months for irinotecan and 6.31 months for FTD/TPI. Median time-to-treatment failure was 2.07 months for irinotecan and 1.64 months for FTD/TPI. While the frequency of all-grade diarrhea was higher in irinotecan (36% vs. 17%), grade ≥3 neutropenia tended to be higher in FTD/TPI (21% vs. 35%). CONCLUSION: Irinotecan and FTD/TPI may be clinically useful as fourth-line treatments after nivolumab.

Clinical Significance of Neutrophil-to-Lymphocyte Ratio/Serum Albumin Ratio in Patients With Metastatic Gastric or Gastroesophageal Junction Cancer Administered Trifluridine/Tipiracil.

BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is an anticancer-agent that is administered as third-line or later chemotherapy for metastatic gastric/gastroesophageal junction cancer (mGC/GEJC). Although inflammatory and nutritional statuses have attracted attention as prognostic factors for patients with mGC/GEJC in this therapy, their usefulness has not been fully clarified. Thus, this study investigated the clinical significance of prognostic nutritional index (PNI), neutrophil/lymphocyte ratio (NLR), and NLR/serum albumin (Alb) ratio in patients administered FTD/TPI. PATIENTS AND METHODS: This retrospective study included 64 patients who underwent FTD/TPI treatment for mGC/GEJC at Kanagawa Cancer Center, Kanagawa, Japan, between October 2019 and June 2022. Patients were divided into high and low PNI, NLR, and NLR/Alb groups according to their pretreatment blood data. This study evaluated the associations between the inflammatory and nutritional indexes and survivals. RESULTS: Overall survival (OS) and progression-free survival (PFS) of patients with low PNI were significantly poorer than those with high PNI. However, low PNI was not an independent prognostic factor for OS and PFS. There was no significant association between NLR and OS or PFS. In contrast, the OS of patients with high NLR/Alb was significantly poorer than those with high PNI and low NLR/Alb. Furthermore, multivariate analysis showed that high NLR/Alb was an independent prognostic factor for OS. CONCLUSION: The NLR/Alb may be a useful prognostic factor in patients with mGC/GEJC being administered FTD/TPI as third-line or later chemotherapy.

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.

BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.

Endoscopic mucosal resection using a ligation device for duodenal neuroendocrine tumors: a simple method.

Introduction: Duodenal neuroendocrine tumors (DNETs) smaller than 1 cm in diameter, without invasion to the muscularis propria, have a low risk of metastasis. Therefore, DNETs are frequently resected endoscopically. However, among the various procedures, the best fit for DNET in terms of feasibility, effectiveness, and simplicity is unclear. Methods: Patients with DNET who underwent endoscopic submucosal resection using a ligation device (ESMR-L) at Kanagawa Cancer Center between May 2003 and December 2020 were studied retrospectively to evaluate clinical characteristics and short-term and long-term outcomes. Results: Eleven consecutive patients with 12 lesions were treated with 12 sessions of ESMR-L. Lesions were discovered in patients at a median age of 68 (range, 50-83) years. One patient had two lesions at the time of the initial ESMR-L session. Eleven of the 12 lesions (91.7%) existed in the duodenal bulb, of which 10 (83.3%) were in the anterior wall, and the remaining one (8.3%) existed in the descending part of the duodenum. The en bloc and R0 resection rates were 100% and 75%, respectively. The rates of bleeding and perforation were both 0%. Among the four patients who had non-curative resections, two patients underwent additional surgery after ESMR-L. One patient had a local remnant tumor, and the other had lymph node metastasis. In cases of local remnant tumors, the vertical margin was positive in the ESMR-L specimen. In that case, ligation by the O-ring was insufficient, retrospectively. All patients had no recurrence during the median follow-up period of 5.7 years. Discussion: ESMR-L was the best fit for DNET within the indications for endoscopic resection. It is a simple procedure that enables easy and complete resection of DNETs without complications.

Successful resection of gastric cancer arising from a heterotopic gastric gland in the submucosa by endoscopic submucosal dissection.

Heterotopic gastric gland (HGG)-originating early gastric cancer was endoscopically resected. We resected the HGG, widely marked the perimeter outside the submucosal tumor-like area, injected from outside the markings into the submucosa, dissected the muscular layer, and used fine-tip hood. HGG removal and ensuring negative horizontal and vertical margins are critical.

Feasibility, efficacy, and cautionary note of endoscopic resection for gastric tube cancer after esophagectomy.

BACKGROUND: Gastric tube cancer (GTC), whose usual histology is adenocarcinoma, occurs frequently as a result of improved survival after esophagectomy. Whether endoscopic resection (ER) for GTC is safe and suitable and guidelines for treatment and follow-up remains unclear. METHODS: Patients with GTC who underwent ER at Kanagawa Cancer Center Hospital between 1997 and 2020 were studied retrospectively to evaluate clinical characteristics and short- and long-term outcomes. RESULTS: Twenty-two consecutive patients with 43 lesions were treated in 42 sessions of ER. Lesions were discovered at a median of 9.0 (0-21.8) years after esophageal surgery. Nine (40.9%) patients had multiple lesions at the time of the initial ER session. However, six (54.5%) of the 11 co-existing lesions were overlooked. The location of the middle third was an estimated risk factor for overlooking (p = 0.028). In endoscopic submucosal dissection (ESD) cases, the en bloc dissection rate was as high as 97.1%, and the rates of bleeding, perforation, and aspiration pneumonitis were 17.6%, 0%, and 2.9%, respectively. The bleeding rate was relatively higher than that in usual gastric ESD. Twelve patients (54.5%) experienced synchronous and/or metachronous multiple GTCs during their life span. Thirteen (61.9%) patients died during the median follow-up period of 5.9 (0.7-15.5) years. One patient (7.7%) died of GTC recurrence, 15.4 years after the initial non-curative ER date; 3 (23.1%) patients died of esophageal cancer recurrence, and 3 (23.1%) died of other organ malignancies. The 5-year overall survival rate was 85.0%, and the 5-year disease-specific survival rate was 100%. CONCLUSIONS: ER is feasible for GTCs. However, the rate of bleeding was high in ESD cases. Life-long endoscopic screening of metachronous lesions is desirable. Care should be taken not to overlook lesions in the middle third of the gastric tube. Early detection of esophageal cancer recurrence and other organ malignancies may improve prognosis.

Prognostic Impact of Immune-related Adverse Events in Gastric Cancer Patients Treated With Nivolumab.

BACKGROUND/AIM: To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC). PATIENTS AND METHODS: Patients with unresectable advanced GC and recurrence after curative resection who received nivolumab monotherapy were included in the study. Survival was compared between patients who did and did not develop irAEs, and between those who continued and discontinued treatment due to irAEs. RESULTS: Of 110 GC patients, 22 developed irAEs. Grade ≥3 IrAEs included rash and diarrhoea associated with enteritis. Progression-free and overall survival (OS) were significantly better in patients with irAEs than in those without. The overall survival of patients who continued treatment despite irAEs was better than that of those who discontinued treatment. CONCLUSION: irAE development was associated with better survival in patients with GC who received nivolumab monotherapy. Continuing nivolumab with appropriate treatment in GC patients with irAEs may improve survival.

Feasibility of gastric endoscopic submucosal dissection in elderly patients aged ≥ 80 years.

BACKGROUND: Endoscopic resection, especially endoscopic submucosal dissection (ESD), is increasingly performed in elderly patients with early gastric cancer, and lesions beyond the expanded indications are also resected endoscopically in some patients. It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications. AIM: To assess the efficacy and feasibility of gastric ESD for elderly patients, and define high-risk lesions and prognostic indicators. METHODS: Among a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014, 179 sessions (15.3%) were performed in patients aged ≥ 80 years, and 172 of these sessions were done in patients with a final diagnosis of gastric cancer. These patients were studied retrospectively to evaluate short-term outcomes and survival. The short-term outcomes included the rates of en bloc resection and curative resection, complications, and procedure-related mortality. Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010. Fisher's exact test was used to statistically analyze risk factors. Clinical characteristics of each group were compared using Fisher's exact test and Mann-Whitney U test. Survival rates at each time point were based on Kaplan-Meier estimation. Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test. To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model including factors curative/ noncurative, age, gender, body mass index, prognostic nutritional index, Charlson comorbidity index (CCI), Glasgow prognostic score, neutrophil-to-lymphocyte ratio, and antithrombotic agent use. We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation. P < 0.05 was considered statistically significant. RESULTS: The en bloc dissection rate was 97.1%, indicating that a high quality of treatment was achieved even in elderly patients. As for complications, the rates of bleeding, perforation and aspiration pneumonitis were 3.4%, 1.1% and 0.6%, respectively. These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients. A dissection incision > 40 mm, lesions associated with depressions, and lesions with ulcers were risk factors for post-ESD bleeding, and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients (P < 0.05). Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding. The overall survival (OS) did not differ significantly between curative and noncurative ESD (P = 0.69). In patients without additional surgery, OS rate was significantly lower in patients with a high CCI (≥ 2) than in those with a low CCI (≤ 1) (P < 0.001). CONCLUSION: Gastric ESD is feasible even in patients aged ≥ 80 years. Observation without additional surgery after noncurative ESD is reasonable, especially in elderly patients with CCI ≥ 2.

A case of esophageal granular cell tumor diagnosed by mucosal incision-assisted biopsy.

For an esophageal submucosal mass suspicious of granular cell tumor (GCT) based on gross appearance and endoscopic ultrasound findings, a sufficient number of biopsy specimens is required for a definite diagnosis using immunohistochemical examination. When the specimen obtained by forceps biopsy is insufficient, endoscopic ultrasound-fine needle aspiration (EUS-FNA) is believed to be an useful alternative. However, it may be difficult to obtain an adequate amount of tumor material using EUS-FNA. Mucosal incision-assisted biopsy (MIAB) is a simple method that can collect larger amounts of specimens. This procedure is helpful for physicians who encounter the problem of obtaining an adequate amount of biopsy material from esophageal tumors suspicious for GCT. We present a case of esophageal GCT that was successfully diagnosed through MIAB.

Feasibility and efficacy of chemoradiotherapy with concurrent split-dose cisplatin after induction chemotherapy with docetaxel/cisplatin/5-fluorouracil for locally advanced head and neck cancer.

Chemoradiotherapy (CRT) with concurrent high-dose cisplatin (CDDP) is a standard treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Docetaxel plus CDDP and 5-fluorouracil (TPF) induction chemotherapy (ICT) prior to CRT is considered for patients at high risk of distant metastases. The purpose of the current study was to evaluate the feasibility and efficacy of CRT with split-dose CDDP after TPF-ICT for LA-SCCHN. A total of 21 LA-SCCHN patients treated with TPF-ICT followed by concurrent CRT with split-dose CDDP between January 2011 and December 2017 were retrospectively analysed. The patients' characteristics were i) median age 66 years (48-75 years); ii) male/female, 21/0; iii) performance status 0-1/2, 20/1; iv) larynx/hypopharynx/oropharynx/oral cavity, 4/8/8/1 and v) clinical stage III/IV, 3/18. The numbers of TPF-ICT cycles 1/2/3 were 2/3/16. Median cumulative doses of CDDP in TPF-ICT and CRT were 180.0 and 206.7 mg/m2, respectively. All patients completed 70 Gy RT. The complete response rate was 76.2%. At a median follow-up of 51.5 months, median PFS and OS were not reached and 65.5 months, respectively. The most common grade 3 or worse toxicities during CRT-ICT were stomatitis (48%), dysphagia (21%), anorexia (17%) and leukopenia (14%). However, no grade 2 or worse nephrotoxicity, neurotoxicity or ototoxicity was observed. The results demonstrated that concurrent CRT with split-dose CDDP after TPF-ICT is feasible and effective for LA-SCCHN.

Hepatic Arterial Infusion Chemotherapy for Metastatic Breast Cancer Patients With Resistance to Standard Systemic Chemotherapies.

BACKGROUND/AIM: Hepatic arterial infusion chemotherapy (HAIC) is a treatment option for metastatic breast cancer (MBC) patients with extensive liver metastasis (LM); however, the appropriate regimen and the treatment effects have not been discussed. The aim of this study is to evaluate the efficacy and safety of HAIC with the 5-FU, epirubicin, and mitomycin-C (FEM) regimen. PATIENTS AND METHODS: We reviewed MBC patients with critical LM who were resistant to standard systemic chemotherapies and had received HAIC with an FEM regimen. RESULTS: We identified 57 patients who received HAIC between 2003 and 2017. The patient characteristics were as follows: i) median age=56 (30-80), and ii) Eastern Cooperative Oncology Group Performance Status, 0/1/2=43/11/3. The median number of LMs was 8 (range 1 to ≥20), the median diameter of LM was 5.2 cm (range=1.6 to 20.1). The median overall survival from the initiation of HAIC was 11.3 months (95% confidence interval=8.5-15.6). The objective response rate of LM was 63%. CONCLUSION: HAIC with an FEM regimen is an effective salvage treatment for MBC patients with advanced LM.

Comparison of enteral nutrition with total parenteral nutrition for patients with locally advanced unresectable esophageal cancer harboring dysphagia in definitive chemoradiotherapy.

BACKGROUND: The nutritional status of patients with esophageal squamous cell carcinoma (ESCC) harboring dysphagia is often poor. The efficacy and safety of enteral nutrition (EN) versus total parenteral nutrition (TPN) have not been addressed in patients with ESCC requiring nutritional support during definitive chemoradiotherapy (dCRT). METHODS: We performed a retrospective analysis of 51 locally advanced unresectable ESCC patients with dysphagia receiving EN (n = 28) or TPN (n = 23) during dCRT between 2009 and 2016. RESULTS: Patient characteristics in EN vs. TPN were as follows: median age (range), 67 (34 to 82) vs. 66 (57 to 83); ECOG performance status 0/1/2, 11/15/2 vs. 7/14/2; dysphagia score 2/3/4, 11/15/2 vs. 14/8/1; and primary tumor location Ce/Ut/Mt/Lt/Ae, 4/6/14/3/1 vs. 2/2/16/1/2. Median changes in serum albumin level one month after dCRT were +8.8% (-36 to 40) in EN and -12% (-64 to 29) in TPN (P = 0.00377). Weight, body mass index, and skeletal muscle area were not significantly different between the groups. Median durations of hospitalization were 50 days (18 to 72) in EN and 63 days (36 to 164) in TPN (P = 0.00302). Adverse events during dCRT in EN vs. TPN were as follows: catheter-related infection, 0 vs. 6 (27%); aspiration pneumonia, 3 (11%) vs. 2 (9%); mediastinitis, 3 (11%) vs. 1 (5%); grade ≥3 neutropenia, 6 (21%) vs. 14 (64%) (P = 0.00287); and febrile neutropenia, 0 vs. 6 (27%) (P = 0.00561). CONCLUSIONS: EN may be advantageous for improving serum albumin level, and reducing hematological toxicity and duration of hospitalization compared with TPN during dCRT in ESCC patients.

Clinical and pathological features of sarcopenia-related indices in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sarcopenia is diagnosed with the skeletal muscle index (SMI) or the sarcopenia index (SI). We previously reported that the ratio of skeletal muscle mass to body fat mass (SF ratio) was a novel index of sarcopenia in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to evaluate sarcopenia with these indices in patients with NAFLD. METHODS: One hundred and fifty-six consecutive patients with biopsy-proven NAFLD and alanine aminotransferase (ALT) >40 IU/L were enrolled. Liver function and body composition were evaluated in 121 patients after 12 months. We evaluated the relationship between histological findings, changes in liver function, and the SMI, SI, and SF ratio. RESULTS: Of the 156 patients enrolled, 13.5% and 26.3% were diagnosed with sarcopenia with the SMI and SI. In patients with hepatic fibrosis stage <2, the SI and the SF ratio were significantly greater than in patients with fibrosis stage ≥2. There was no difference in SMI between groups. In the cohort assessed at baseline and 12 months later, transaminase activity and SMI decreased significantly, and the SF ratio increased over time. A multivariate analysis revealed the presence of the PNPLA3 G allele and an increase in SF ratio (odds ratio, 7.406) as predictive factors of ALT reduction >30% from baseline. CONCLUSIONS: Due to the high prevalence of obesity, we should consider both skeletal muscle mass and body fat mass in the diagnosis and treatment of NAFLD. The SF ratio could be a useful index in sarcopenic NAFLD.

Increase in the skeletal muscle mass to body fat mass ratio predicts the decline in transaminase in patients with nonalcoholic fatty liver disease.

BACKGROUND: The aim of this retrospective study was to determine the effect of skeletal muscle and body fat on liver function in patients with nonalcoholic fatty liver disease (NAFLD) diagnosed by liver biopsy. METHODS: Among the 219 patients with NAFLD enrolled in this study was a cohort of 139 patients who had their body composition measured with Inbody720 at baseline and at ≥ 1 year postbaseline, to elucidate the relationship between liver function and changes in skeletal muscle and body fat mass. Multivariate analysis was used to identify factors influencing low skeletal muscle mass index (SMI, defined as 7 kg/m2 in men, and 5.7 kg/m2 in women) and the skeletal muscle mass to body fat mass ratio (SF ratio). RESULTS: Of the 219 patients enrolled, 27 (12.3%) had a low SMI. Patient age (> 70 years) and female gender were identified as risk factors for low SMI. Hepatic fibrosis was not associated with SMI. In the cohort followed up at baseline and 12 months later, transaminase activity, body fat mass, and SMI significantly decreased over time. Changes in the SF ratio were significantly associated with changes in liver function. An increase in the SF ratio [hazard ratio (HR) 10.99 in men, 6.849 in women] was a predictor of reduced ALT, independent of age and other backgrounds. CONCLUSIONS: In the patients with NAFLD, SMI was decreased, even in the early stages of NAFLD. Therapeutic strategies for NAFLD require a reduction in body fat mass and the maintenance of skeletal muscle is also needed.

Presence of varices in patients after hepatitis C virus eradication predicts deterioration in the FIB-4 index.

AIMS: The liver function of patients with hepatitis C virus (HCV) infection who obtained sustained virologic response (SVR) has been known to improve after HCV eradication. However, a predictor of liver function after SVR has not been definitively identified. The aim of this retrospective study was to identify a predictor of deteriorated liver function and Fibrosis-4 (FIB-4) index after SVR was achieved by direct-acting antiviral (DAA) treatment. METHODS: This study retrospectively enrolled 248 patients who obtained SVR by DAA treatment. None of the patients developed hepatocellular carcinoma during this study. Liver function was assessed at the end of treatment (EOT) and at 24, 48, 72, and 96 weeks after EOT. RESULTS: At 96 weeks after EOT, the serum aspartate aminotransferase and alanine aminotransferase levels were significantly decreased from those at EOT. The platelet count was significantly increased from 14.9 × 104 /µL at EOT to 17.1 × 104 /µL at 96 weeks after EOT. Ten patients showed an increased FIB-4 (>1.00) index. Multivariate analysis with 171 patients who underwent endoscopic assessment revealed that the presence of varices was an independent predictor of deterioration in the FIB-4 index (odds ratio, 5.56; P = 0.041). CONCLUSION: Most of the study patients who obtained SVR showed improved liver function after EOT. Patients without increasing platelet counts after SVR due to DAA therapy should be evaluated for complications induced by portal hypertension.

Impact of Insufficient Response with an Increase in Tumor Number in Predicting Transcatheter Arterial Chemoembolization Refractoriness for Hepatocellular Carcinoma.

AIM: In Japan, transcatheter arterial chemoembolization (TACE) refractoriness for hepatocellular carcinoma has been defined as an insufficient therapeutic effect after ≥2 procedures. Insufficient TACE for intrahepatic lesions is defined as the presence of > 50% viable lesions (ineffective) or an increase in their number (progressive). This study aimed to examine the possibility of earlier evaluation of TACE refractoriness. METHODS: Patients who underwent TACE for hepatocellular carcinomas > 3 cm in size or with > 3 nodules at our hospital between 2010 and 2014 were analyzed. The cases assessed as TACE insufficient for the first time were divided into 2 groups: the "either" group, evaluated as either "ineffective" or "progressive," and the "both" group, that is, both "ineffective" and "progressive." RESULTS: The study participants included 40 of 212 consecutive patients who underwent TACE, divided into the either (n = 23) and both (n = 17) groups. Seventeen of 23 (73.9%) patients in the either group and all 17 (100%) in the both group had TACE refractoriness (p = 0.0295). CONCLUSIONS: Patients with both "ineffective" and "progressive" lesions are extremely likely to be TACE -refractory at a significantly higher frequency than are those with either condition. Thus, when both of these factors are observed, switching to other therapies should be considered.

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy.

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.