An Evaluation of Renal Sinus Fat Accumulation Using the Anteroposterior Diameter of the Renal Sinus on a Computed Tomography Axial Image.

Backgrounds and objectives Renal sinus fat (RSF) is an indicator of obesity-related complications. However, the measurement and imaging process are complicated. For a simple measurement of RSF, we focused on the kidney's shape change caused by RSF accumulation. Thus, this study aimed to investigate whether the anteroposterior diameter of the renal sinus (APDRS) on a computed tomography (CT) axial image is useful for evaluating RSF accumulation. Materials and methods The correlation between APDRS and RSF was investigated in 98 outpatients who underwent abdominal CT. In addition, the correlation between APDRS or RSF and obesity indicators (estimated glomerular filtration rate from serum creatinine levels (eGFRcreat), body mass index (BMI), and visceral adipose tissue (VAT)) was also investigated. We classified patients based on the presence or absence of at least one underlying disease (chronic kidney disease (CKD), cardiovascular diseases (CVD), hypertension, and type 2 diabetes (T2D)) and investigated significant differences between the two groups at APDRS and RSF. The intraclass correlation coefficient (ICC) was also calculated for APDRS. Results There was a strong positive correlation between RSF and APDRS (r = 0.802, P < 0.01). The obesity indicators (eGFRcreat, BMI, and VAT) were correlated with RSF and APDRS (P < 0.01). Out of 98 outpatients, 48 had at least one underlying disease. There were statistically significant differences in APDRS and RSF between the patients with and without at least one of the underlying diseases caused by obesity (P < 0.01). The inter-reader ICC for the measurement of the APDRS was 0.98. Conclusions APDRS on a CT axial image may be useful for the evaluation of RSF accumulation.

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.

A case of an unreported point mutation in promoter 1B of the adenomatous polyposis coli gene, which is responsible for gastric adenocarcinoma and proximal polyposis of the stomach.

A 35-year-old woman of Asian descent with epigastralgia was referred to our hospital. Esophagogastroduodenoscopy revealed gastric cancer in the upper body and carpeting fundic gland polyposis in the fornix and body. Computed tomography revealed no metastases. Total colonoscopy and capsule endoscopy revealed no polyposis, except in the stomach. The patient was diagnosed with advanced gastric cancer and underwent open total gastrectomy. We speculated that her gastric cancer was a hereditary tumor due to its early onset and accompanying fundic gland polyposis. Germline multi-gene panel testing identified a single-nucleotide variant, c.-191 T > G, in exon 1B of the adenomatous polyposis coli gene, which can cause gastric adenocarcinoma and proximal polyposis of the stomach. To our knowledge, this is the first manuscript to report the variant (c.-191 T > G) in promoter 1B of the adenomatous polyposis coli gene, which is related to a predisposition to gastric adenocarcinoma and proximal polyposis of the stomach.

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer.

BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor ß-chain (TCRß), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). RESULTS: Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRß clonality (inverted Pielou's evenness) increased and TCRß diversity (Pielou's evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). CONCLUSION: Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.

Phase I/II clinical trial of nivolumab in combination with oligo-fractionated irradiation for unresectable advanced or recurrent gastric cancer.

BACKGROUND: Although immune checkpoint inhibitors (ICI) targeting for PD-1 axis is a promising approach for advanced gastric cancer (GC) patients, the response rate is still limited. Induction of synergistic effect of irradiation with ICI targeting for the PD-1 axis can be an attractive strategy. The aim of this study was to assess the effect of the combination of irradiation with anti-PD-1 therapy for advanced GC. METHODS: We conducted a single-arm, phase I/II trial in GC patients treated with a combination of nivolumab and oligo-fractionated irradiation (22.5 Gy/5 fractions/5 days) (NCT03453164). Eligible patients (n = 40) had unresectable advanced or recurrent GC which progressed after primary and secondary chemotherapy with more than one lesion. The primary endpoint is the disease control rate (DCR) of non-irradiated target lesions and the secondary endpoints are the median survival time (MST), safety, and DCR of irradiated lesions. RESULTS: We observe that the DCR for the non-irradiated target as the abscopal effect is 22.5% (90% confidence interval (CI), 12.3-36.0), and the DCR for the irradiated lesion is 40.0% (90% CI, 26.9-54.2). The median survival time is 230 days (95% CI, 157-330), and grade 3 and higher adverse events (AEs) are observed in 16 patients (39 %) with no obvious additional AEs when adding irradiation. CONCLUSIONS: The present study suggests that the combination of nivolumab with oligo-fractionated irradiation has the potential to induce a promising anti-tumor effect for advanced GC.

Immunotherapy is a type of treatment that triggers the immune system to kill cancers. Combining immunotherapy with radiotherapy may enhance its effects. We evaluated this in a clinical trial in which we treated patients with advanced or recurrent cancers of the stomach (gastric cancer) with a combination of immunotherapy and radiotherapy. The combination was able to control disease in a subset of patients and was safe, with no obvious additional adverse effects when adding radiotherapy. The median survival time­at which point half of the patients treated are still alive­was 230 days. While these results are promising, larger, more rigorous studies are needed to determine whether this combination therapy is better than alternative approaches to treating advanced or recurrent gastric cancers.

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.

Transitional phase Gd-EOB-DTPA-enhanced MRI: Visual assessment of hepatic function and fibrosis based on uptake rate of Gd-EOB-DTPA.

PURPOSE: The aim of the study is to investigate the feasibility for hepatic function and fibrosis visual assessment using transitional phase imaging based on the uptake process of Gd-EOB-DTPA. MATERIALS AND METHODS: We retrospectively selected 105 consecutive patients who underwent Gd-EOB-DTPA enhanced MRI examination at 1.5 Tesla for intrahepatic lesion evaluation from June 2020 to June 2022. Data were classified into two groups defined by the signal intensity (SI) difference in the hepatic vein against that of the hepatic parenchyma at transitional phase as follows: High and Iso-SI group: hepatic vein SI equal to or greater than the hepatic parenchymal SI; and Low-SI group: hepatic vein SI lower than hepatic parenchymal SI. We evaluated whether significant differences in ALBI score, FIB-4, APRI and LSR of hepatobiliary phase between two groups. We measured cut-off values between two groups in all items according to receiver operating characteristic analysis. Furthermore, the inter-reader reproducibility of the visual assessment on transitional phase images between two readers was evaluated using the ICC. RESULTS: The visual assessment results were as follows: High and Iso- and Low-SI groups included 48, 57, patients, respectively. Significant differences were observed in ALBI score, FIB-4, APRI and LSR between two groups. The cut-off values of ALBI score, FIB-4, APRI and LSR were -2.69, 2.28, 0.49 and 2.15. ICC of transitional phase image visual assessment between two readers was 0.86. CONCLUSIONS: Hepatic function and fibrosis might be assessed by visual assessment of transitional phase images in Gd-EOB-DTPA enhanced MRI.

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.

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.

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.

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.

Successful Conversion Surgery for Stage IV Gastric Cancer after Nivolumab Monotherapy as Third-Line Chemotherapy.

There are few reports of conversion surgery (CS) after nivolumab monotherapy because it is considered as a third-line standard chemotherapy for unresectable or recurrent gastric cancer. Here, we report a rare case of stage IV gastric cancer effectively treated with CS after nivolumab monotherapy as a third-line chemotherapy. A 73-year-old man was referred to our hospital with loss of appetite and abdominal discomfort. Stage IV gastric cancer with liver metastasis was diagnosed via upper gastrointestinal endoscopy and CT. Twelve courses of capecitabine, cisplatin, and trastuzumab were administered as the first-line treatment, 25 courses of paclitaxel plus ramucirumab as the second-line treatment, and 31 courses of nivolumab monotherapy as the third-line treatment. After 31 courses of nivolumab monotherapy, CT showed that the primary tumor shrank with no liver metastasis or ascites. Diagnostic laparoscopy was performed with no peritoneal dissemination (P0), and the peritoneal lavage cytology was negative (CY0). CS was performed with total gastrectomy and D2 lymph node dissection (R0 resection). The pathological diagnosis was U, Ant-Less, Type 2, 70 × 63 mm, poorly differentiated adenocarcinoma (ypT3N0M0 ypStage IIA). R0 resection was performed, and the histological response was grade 1a. The patient did not show recurrence for 9 months after CS.

Diagnostic accuracy of the attenuation value in abdominal contrast enhanced dynamic multi-detector-row computed tomography for esophageal varices in patients with liver cirrhosis.

PURPOSE: To investigate whether the attenuation value obtained by subtracting the CT value obtained from abdominal dynamic contrast enhanced (ADCE)-MDCT imaging of the equilibrium phase from the value obtained from that of the portal phase in hepatic parenchyma is useful in distinguishing normal liver from liver cirrhosis (LC) and to predict the development of esophageal varices (EVs) in patients with LC. MATERIALS AND METHODS: We assigned 72 outpatients to group A (n = 45; normal liver) and group B (n = 27; LC), who underwent ADCE-MDCT. The attenuation value and CT value of the hepatic parenchymal portal and equilibrium phase were compared, and the correlation between attenuation value and biomarkers (ALB, T-bil, PLT, FIB-4, APRI, and AAR) was investigated. Furthermore, we investigated differences in the attenuation value, FIB-4, APRI, and AAR between the two subgroups of group B [without EVs (group a) and with EVs (group b)]. We performed receiver operating characteristic (ROC) analysis of the attenuation value, FIB-4, APRI, and, AAR for subgroup a vs b and evaluated the diagnostic accuracy. RESULTS: Significant differences were observed between groups A and B in all items. The attenuation value correlated with ALB, T-bil, PLT, FIB-4, and APRI. Only attenuation value showed a significant difference between groups a and b. The best cut-off attenuation value, FIB-4, APRI, and AAR for predicting EVs, according to ROC analysis was 13.4 HU, 6.8, 1.9, and 1.5. CONCLUSIONS: Attenuation value can be useful to quantitatively classify normal liver and LC and to predict EVs in patients with LC.

Effect of Prognostic Nutrition Index in Gastric or Gastro-oesophageal Junction Cancer Patients Undergoing Nivolumab Monotherapy.

BACKGROUND/AIM: We hypothesised that the prognostic nutrition index (PNI) is useful for evaluating host immunity and response to immune checkpoint inhibitors. We investigated the effect of PNI on nivolumab monotherapy efficacy in advanced or recurrent gastric cancer (GC) or gastro-oesophageal junction cancer (GOC) patients. PATIENTS AND METHODS: We retrospectively examined 110 patients, divided them into a high-PNI group and a low-PNI group, and compared treatment efficacy, adverse events (AEs), and survival between the groups. RESULTS: Median overall survival (OS) was significantly longer in the high-PNI group than in the low-PNI group (205 vs. 109 days; p<0.001). Multivariate analysis revealed that low PNI was an independent risk factor for OS (hazard ratio=2.398; 95% confidence interval=1.384-4.154; p=0.002). The overall response rate and frequency of AEs were not significantly different between the groups. CONCLUSION: PNI could be a useful prognostic factor in GC or GOC patients undergoing nivolumab monotherapy.

Impact of the Neutrophil-to-Lymphocyte Ratio on the Survival of Patients with Gastric Cancer Treated with Nivolumab Monotherapy.

BACKGROUND: In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. OBJECTIVE: In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy in patients with gastric or gastroesophageal junction cancer. PATIENTS AND METHODS: The long-term outcomes and treatment responses to nivolumab monotherapy were assessed in patients with gastric or gastroesophageal junction cancer. We compared patients with a NLR > 2.5 and those with a NLR ≤ 2.5 at the time of starting nivolumab monotherapy. RESULTS: The proportion of patients who have received three or more regimens was higher in the NLR > 2.5 group than in the NLR ≤ 2.5 group. The disease control rate was significantly worse in the NLR > 2.5 group than in the NLR ≤ 2.5 group (23% and 46%, respectively; p = 0.044). Overall survival was significantly better in the NLR ≤ 2.5 group than in the NLR > 2.5 group. Multivariate analysis showed that the macroscopic type, primary site resection, and the NLR were independent prognostic factors for overall survival (hazard ratio [95% confidence interval], 2.586 [1.286-5.203], 0.473 [0.260-0.861], and 1.736 [1.007-2.992], respectively). CONCLUSIONS: This study demonstrates that the NLR is an independent prognostic factor in patients with gastric or gastroesophageal junction cancer treated with nivolumab monotherapy. Careful attention must be paid when nivolumab monotherapy is used to treat patients with gastric cancer with a NLR > 2.5.