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Purpose: Cancer cachexia leads to poor outcomes, especially for patients with advanced stage disease. The cachexia index (CXI), a novel biomarker for cancer cachexia, has been identified as a prognostic indicator for several malignancies. The present study aimed to clarify the prognostic significance of the CXI for patients with recurrent pancreatic cancer., Methods: This retrospective study enrolled 113 patients diagnosed with recurrence following pancreatectomy for pancreatic cancer, to analyze the association between the CXI and prognostic survival., Results: The 2-year overall survival rate and median survival of all patients were 28.5% and 12.6 months, respectively. The 2-year overall survival curve in the high CXI group was significantly better than that in the low CXI group (p < 0.001). The rate of chemotherapy after recurrence was significantly lower in the low CXI group than in the high CXI group (p = 0.002). Multivariate analysis identified the CXI as an independent prognostic factor for patients with recurrent pancreatic cancer (p = 0.011)., Conclusions: The CXI proved useful for predicting the post-recurrence prognosis of patients with recurrent pancreatic cancer. Patients with a low CXI at the time of recurrence have poorer prognostic outcomes than those with a high CXI., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC)., Methods: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed., Results: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS., Conclusions: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background and Purpose: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer., Methods: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT., Results: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87)., Conclusion: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC)., Methods: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021., Results: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXI high group than in the CXI low group. The prognosis based on MST was significantly better in the CXI high group than in the CXI low group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors., Conclusions: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: In this research, we analyzed the expression of serpinB9 in hepatoblastoma and investigated the factors which enhance its expression., Method: SerpinB9 expression in hepatoblastoma cell lines and macrophages co-cultured with each other or stimulated by anticancer agents was examined using RT-qPCR and western blotting. Immunohistochemistry for SerpinB9 in hepatoblastoma specimens was performed. Single-cell RNA-sequence data for hepatoblastoma from an online database were analyzed to investigate which types of cells express SerpinB9., Result: HepG2, a hepatoblastoma cell line, exhibited increased expression of SerpinB9 when indirectly co-cultured with macrophages. Immunohistochemistry for the specimens demonstrated that serpinB9 is positive not in hepatoblastoma cells but in macrophages. Single-cell RNA sequence analysis in tissues from hepatoblastoma patients showed that macrophages expressed SerpinB9 more than tumor cells did. Co-culture of macrophages with hepatoblastoma cell lines led to the enhanced expression of SerpinB9 in both macrophages and cell lines. Anticancer agents induced an elevation of SerpinB9 in hepatoblastomas cell lines., Conclusion: In hepatoblastoma, SerpinB9 is thought to be more highly expressed in macrophages and enhanced by interaction with hepatoblastoma cell., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: SP142 and 22C3 assays are approved companion diagnostic assays for anti-PD-1/PD-L1 therapy selection in metastatic triple-negative breast cancer (TNBC). The discordance in PD-L1 status between primary and metastatic tumors in the same patient has been poorly characterized. Here, we examined the concordance of PD-L1 status between the two assays and between primary tumors and metastases for each assay., Methods: We retrospectively evaluated tumor samples from 160 patients with TNBC, including 45 patients with paired primary and metastatic tumors. PD-L1 status was assessed using SP142 and 22C3 assays, to determine the immune cell (IC) score, tumor cell (TC) score (SP142 and 22C3), and combined proportion score (CPS: 22C3)., Results: The concordance of PD-L1 positivity at diagnostic cutoffs for SP142 (IC ≥ 1) and 22C3 (CPS ≥ 10) was substantial (κ = 0.80) in primary tumors and moderate (κ = 0.60) in metastatic tumors. In comparison, between primary and metastatic tumors, the concordance with 22C3 was moderate (κ = 0.50), whereas that with SP142 was poor (κ = -0.03). Among patients who were PD-L1 negative for both assays in primary tumors, 7/30 (23.3%) were PD-L1 positive for both or either 22C3 or SP142 in the metastatic tumors., Conclusions: The inter-assay concordance of PD-L1 positivity at diagnostic cutoffs was substantial in primary tumors and moderate in metastatic tumors. Discordance between PD-L1 status in primary and metastatic tumors was frequently observed, especially with SP142. Some patients with a PD-L1-negative status in primary tumors may still be candidates for immunotherapy, depending on the PD-L1 status in their metastatic tumors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The impact of frailty and sarcopenia in patients with gastric cancer is unclear. This study aimed to comprehensively examine the impact of frailty and sarcopenia on the short- and long-term outcomes in elderly patients undergoing radical gastrectomy for gastric cancer., Methods: We retrospectively assessed 246 patients aged ≥ 65 years who underwent radical gastrectomy. Frailty and sarcopenia were assessed using the modified frailty index (mFI) and psoas muscle mass index (PMI), respectively., Results: There were 30 (12.2%) and 60 (24.4%) patients with High-mFI and Low-PMI, respectively. As the age increased, both sexes showed significant correlations with PMI and mFI (r = - 0.238, 0.322, P = 0.003 and 0.002, respectively). High-mFI and Low-PMI did not affect the short-term outcomes. However, High-mFI was an independent risk factor for non-home discharge (P = 0.004) and was a significant predictor of 3- and 5-year overall survival (OS) (HR = 2.76 and 2.26; P = 0.002 and 0.005, respectively) and 1-, 3- and 5-year non-cancer-specific survival (non-CSS) (HR = 4.88, 8.05, and 4.01; P = 0.017, < 0.001, < 0.001, respectively). Low-PMI was a significant predictor of only 5-year OS (HR = 2.03, P = 0.003) and non-CSS (HR = 2.10, P = 0.020)., Conclusions: Frailty is significant predictor of non-home discharge and 1-, 3-, 5-year OS and 3- and 5-year non-CSS. Sarcopenia is a significant predictor of 5-year OS and non-CSS. Preoperative assessment of both frailty and sarcopenia can help surgeons to select adequate treatment strategies for the elderly population., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Purpose: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC)., Methods: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method., Results: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC., Conclusions: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: This study investigated the expression of interleukin 32 (IL-32) in hepatoblastoma, the most common primary pediatric liver tumor, and its possible roles in tumorigenesis., Methods: IL-32 expression was investigated in two hepatoblastoma cell lines (Hep G2 and HuH 6) in the steady state and after co-culture with macrophages by RNA-seq analysis and RT-qPCR, and after stimulation with chemotherapy. Cultured macrophages were stimulated by IL-32 isoforms followed by RT-qPCR and western blot analysis. IL-32 immunohistochemical staining (IHC) was performed using specimens from 21 hepatoblastoma patients. Clustering analysis was also performed using scRNA-seq data downloaded from Gene Expression Omnibus., Results: The IL-32 gene is expressed by hepatoblastoma cell lines; expression is upregulated by paracrine cell-cell communication with macrophages, also by carboplatin and etoposide. IL-32 causes protumor activation of macrophages with upregulation of PD-L1, IDO-1, IL-6, and IL-10. In the patient pool, IHC was positive only in 48% of cases. However, in the downloaded dataset, IL-32 gene expression was negative., Conclusion: IL-32 was detected in hepatoblastoma cell lines, but not in all hepatoblastoma patients. We hypothesized that stimulation such as chemotherapy might induce expression of IL-32, which might be a critical mediator of chemoresistance in hepatoblastoma through inducing protumor activation in macrophages., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The goal of this study was to determine which markers are the most useful as first- and second-line pre-treatment markers in patients with unresectable or recurrent gastric cancer (URGC)., Methods: This study included 101 URGC patients who were treated with first- and second-line chemotherapy. Several prognostic scores based on nutrition and inflammation were analyzed using a receiver operating characteristic (ROC) analysis to determine the most useful prognostic marker., Results: The lymphocyte-to-C-reactive protein ratio (LCR) had the highest area under the curve for both first- and second-line chemotherapy, according to an ROC analysis. An ROC analysis was used to determine the optimal LCR cut-off for the median survival time before first- and second-line chemotherapy, and patients were divided into high- and low-LCR groups. Patients with a high LCR had a significantly longer survival than those with a low LCR before first- and second-line chemotherapy (p = 0.004, p < 0.001, respectively). A low LCR before both first- and second-line chemotherapy was an independent poor prognostic factor in a multivariate analysis., Conclusions: URGC patients with a low LCR before both first- and second-line chemotherapy had a significantly worse prognosis than those with a high LCR in this study. Nutritional intervention during chemotherapy induction may lead to a better prognosis., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: We determined the usefulness of the estimation of physiologic ability and surgical stress (E-PASS), initially reported as a predictive factor for postoperative morbidity and mortality, as a prognostic indicator in stage II colorectal cancer (CRC)., Methods: Overall, 739 patients who underwent proctocolectomy for CRC at Tottori University Hospital and affiliated hospitals and histologically diagnosed with stage II CRC were included in the current study., Results: A receiver operating characteristic (ROC) analysis of the five-year recurrence-free survival indicated that the comprehensive risk score (CRS) of E-PASS predicted postoperative recurrence. A multivariate analysis revealed that the presence of preoperative perforation, T4, v ≥ 2, and CRS High (≥ 0.2267) were independent predictors of postoperative recurrence. Patients were assigned a score using these factors, as follows: the presence of perforation = 1, the absence of preoperative perforation = 0, T4 = 1, T3 = 0, v2/3 = 1, v0/1 = 0, CRS High  = 1, and CRS Low  = 0 (total score: 0-4). Accordingly, the respective 5-year relapse-free survival rates were 91.0%, 83.6%, 70.3%, and 52.0% among those with scores of 0, 1, 2, and both 3 and 4 (P < 0.001)., Conclusions: The CRS predicts postoperative recurrence in patients with stage II CRC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: This study was performed to investigate the predictive value of the perioperative D-dimer concentration for the development of postoperative deep vein thrombosis (DVT) after hepatobiliary-pancreatic (HBP) surgery., Methods: The subjects of this retrospective study were 178 patients who underwent HBP surgery in our hospital between January, 2017 and December, 2021. The D-dimer concentration was measured preoperatively and on postoperative days (POD) 1, 3, and 5. Postoperative DVT was diagnosed based on compression ultrasonography in both lower limbs on POD 6 or 7., Results: Postoperative DVT developed in 21 (11.8%) of the 178 patients. The D-dimer concentration was significantly higher in the patients with than in those without postoperative DVT before surgery and on PODs 1, 3, and 5. The highest area under the curve of the D-dimer concentration for predicting DVT was 0.762 on POD 3. Multivariate analysis revealed that the D-dimer concentration on POD 3 was an independent predictive risk factor for postoperative DVT, along with the preoperative estimated glomerular filtration rate. Preoperative albumin and D-dimer concentrations were also identified as independent predictive factors of an increase in D-dimer concentration on POD 3., Conclusions: The D-dimer concentration on POD 3 is a useful predictor of DVT after HBP surgery., (© 2023. The Author(s).)

Purpose: The present study examined the changes in and risk factors for body composition (BC) during the first postoperative month when dynamic biological reactions occur., Methods: We retrospectively assessed 202 patients who underwent gastrectomy. The BC was assessed using a bioelectrical impedance analysis and evaluated within 1 month preoperatively, 1 week postoperatively, and 1 month postoperatively. Multiple regression analyses were performed to identify predictive factors for BC change., Results: The mean reduction rate in BC at 1 month postoperatively was - 6.0, - 10.5, - 5.6, - 1.1, - 10.1, and + 1.2% for body weight, body fat, skeletal muscle, bone mineral, extracellular water/total body water, and the whole-body phase angle, respectively. A multiple regression analysis revealed that independent risk factors for weight loss were complications, operative time, and type of gastrectomy (P = 0.004, 0.011, 0.015, respectively), and those for skeletal muscle loss were complications and gastrectomy type (P = 0.002, 0.010, respectively). A segmental lean mass analysis revealed that the lower limbs were markedly reduced at 1 week postoperatively (- 8.0%), and these independent risk factors were the female sex and Stage II/III disease (P = 0.008, 0.036, respectively)., Conclusion: Detailed analyses of BC might help elucidate the mechanisms underlying postoperative physical changes, which might be useful for perioperative management., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: In Japan, the number of distal gastrectomy for patients ≥ 80 years old is increasing, whereas that of total gastrectomy is decreasing. Surgeons seem to avoid total gastrectomy for elderly patients. Total gastrectomy is reported to have a poorer prognosis than distal gastrectomy, and postoperative pneumonia may be involved in the cause., Methods: The medical records of 39 and 108 patients ≥ 80 years old who underwent total and distal gastrectomy, respectively, at 2 affiliated institutions between 2010 and 2019 were retrospectively reviewed. Prognoses were compared between the two groups, focusing on death from pneumonia., Results: The median overall survival time after total and distal gastrectomy was 21.3 and 74.1 months, respectively, with a significantly poorer prognosis after total gastrectomy than after distal gastrectomy (p < 0.01, hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.37-3.53). The gastric cancer-specific survival time was significantly worse after total gastrectomy than after distal gastrectomy (p < 0.01, HR 2.73, 95% CI 1.29-5.79). The pneumonia-specific survival time was also significantly worse after total gastrectomy than after distal gastrectomy (p = 0.01, HR 3.44, 95% CI 1.25-9.48)., Conclusions: Patients who underwent total gastrectomy had a poorer prognosis than those who underwent distal gastrectomy, because many patients died of pneumonia early after total gastrectomy., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan., Methods: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery., Results: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes., Conclusion: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD., (© 2022. The Author(s).)

Purpose: Deciding whether or not surgery should be performed for elderly patients is sometimes difficult. This study examined the prognosis of patients ≥ 80 years old with gastric cancer who underwent surgery or not., Methods: The medical records of 111 patients who underwent surgery (surgery group) and 35 who received best supportive care (BSC group) were retrospectively reviewed, excluding those with clinical stage IVB disease, those with a performance status of 4, and those who underwent endoscopic submucosal dissection. The overall survival was compared between the two groups., Results: The patients in the BSC group were significantly older and had worse performance status scores, worse physiological scores, and lower prognostic nutritional indexes than those in the surgery group. The patients in the surgery group showed a significantly better survival than those in the BSC group (median survival time, 38.9 vs. 11.4 months; p = 0.01) even after propensity score matching. In the subgroups of patients ≥ 90 years old and those with a performance status of 3, no marked difference in the survival between the 2 groups was observed., Conclusions: Surgery imbued a survival benefit to elderly gastric cancer patients, except for those ≥ 90 years old and those with a performance status of ≥ 3. The surgical indication of patients ≥ 90 years old and those with a performance status of ≥ 3 requires careful deliberation., (© 2021. Springer Nature Singapore Pte Ltd.)

Purpose: Large prospective studies of chemotherapy for metastatic or recurrent adenoid cystic carcinoma (ACC) of the head and neck are lacking due to the rarity of ACC. The aim of this study is to evaluate the efficacy of carboplatin plus paclitaxel toward ACC and perform an exploratory investigation of the prognostic factors to investigate the optimal strategy for metastatic or recurrent ACC., Methods: We retrospectively analyzed recurrent or metastatic ACC patients treated with carboplatin plus paclitaxel between April 2007 and September 2019 in our hospital. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated, and an exploratory analysis of the prognostic factors was conducted., Results: A total of 26 ACC patients were enrolled. ORR and DCR were 11.5 and 76.9%; the median PFS and OS were 8.1 and 22.3 months, respectively. From the results of the multivariate analysis, higher (≥ 6%/month) tumor growth rate (TGR) was associated with worse PFS (hazard ratio [HR] 7.00, 95% CI 1.34-36.53, p = 0.02) and OS (HR 29.33, 95% CI 3.38-254.80, p < 0.01). The median PFS (10.6 vs. 6.6 months, log-rank p < 0.05) and OS (48.5 vs. 16.9 months, log-rank p < 0.01) were significantly shorter in patients with higher TGR., Conclusions: Carboplatin plus paclitaxel showed modest efficacy for recurrent or metastatic ACC patients. Watchful waiting may be optimal for ACC patients with lower TGR. Systemic chemotherapy should be considered when TGR increases during active surveillance.

Background: Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE)., Methods: We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens., Results: We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p < 0.001) differed significantly between the 3 clusters. Those in cluster 3 had a significantly higher prevalence of dysphagia (35.5% vs. 73.3%, p = 0.030), and higher EREFS with respect to rings (0.3 vs. 0.9, p = 0.003) and strictures (0.0 vs. 0.13, p = 0.011) compared to those in cluster 1., Conclusions: IgE-mediated allergic sensitization patterns are associated with clinical features of patients with EE. Use of a diagnostic panel that detects multiple allergen-specific IgEs can help to explain the heterogeneous phenotype of this patient cohort.

Purpose: This FAEISS study was designed to confirm the superior efficacy of reactive topical corticosteroid strategies employing serially ranking-DOWN from very strong steroid levels for the treatment of facial acneiform rash induced by epidermal growth factor receptor (EGFR) inhibitors (EGFRIs), in comparison with strategies employing serially ranking-UP from weak steroid levels. This article reports the primary results of the non-small cell lung cancer (NSCLC) part of the trial., Methods: Patients with EGFR-mutated advanced NSCLC treated with erlotinib or afatinib were enrolled in the first registration. All patients received preemptive therapy with oral minocycline and heparinoid moisturizer from the initiation of an EGFR inhibitor. Enrolled patients who developed facial acneiform rash within 2 weeks were randomized at second registration to either a ranking-UP (WEAK) group or a ranking-DOWN group. The primary endpoint was incidence of grade ≥ 2 facial acneiform rash over 8 weeks., Results: Fifty-one patients were enrolled at the first registration and received EGFRIs (n = 30 for afatinib, n = 21 for erlotinib). However, 35 patients did not develop facial acneiform rash within 2 weeks; one patient discontinued preemptive treatment. Fifteen patients (29.4%) were enrolled in the second registration; nine were assigned to the WEAK group and six to the DOWN group. There was no significant difference in the incidence of grade ≥ 2 facial acneiform rash between the WEAK group (one patient, twice) and the DOWN group (one patient, twice; p = 0.8417). No patients developed severe facial acneiform rash within 10 weeks., Conclusion: In NSCLC patients who received EGFRIs, preemptive therapy of oral minocycline and heparinoid moisturizer reduced facial acneiform rash incidence., Trial Registration: UMIN000024113.

Background: Development of laparoscopic gastrectomy and the Enhanced Recovery After Surgery (ERAS) protocol enable early discharge to home of patients with gastric cancer (GC). However, a significant proportion of patients are still discharged to inpatient facilities after surgery. We aimed to identify predictive factors of non-home discharge in patients with GC who undergo gastrectomy., Methods: We enrolled 517 patients with histopathologically confirmed diagnosis of GC who underwent gastrectomy., Results: The number of patients with non-home discharge was 23 (4.4%), and non-home discharge was only observed in patients with GC aged ≥65 years. Patients were divided into the mFI High (≥0.272) and mFI Low (<0.272) groups according to the cut-off value determined by ROC analysis. The mFI High classification was significantly more frequent in patients aged ≥75 years, who underwent either total or proximal partial gastrectomy, who underwent limited lymph node dissection, and with non-home discharge than in patients aged <75 years (p = 0.0002), those who underwent distal partial gastrectomy (p = 0.032), those who underwent standard lymph node dissection (p = 0.036), and those without non-home discharge (p = 0.0071). Multivariate analysis revealed mFI as an independent predictive indicator of non-home discharge, along with postoperative complications and surgical approach, in patients with GC aged ≥65 years. The frequency of patients with non-home discharge was significantly associated with the number of these three predictive factors in GC patients aged ≥65 years (p < 0.0001)., Conclusions: The combination of mFI, postoperative complications, and surgical approach is useful for predicting non-home discharge in patients aged ≥65 years who underwent gastrectomy for GC.

Background: Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK., Methods: We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries., Results: Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P < 0.001). Japanese patients had significantly lower prevalence of excessive SGB (18.5%) than the UK (36.1%) irrespective of reflux phenotype (P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09-7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0-4.9)] compared to the UK [35% (0-54.1)] (P = 0.071)., Conclusions: The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

Remarkable progress has been made in treating pancreatic cancer over the past century, including refinement of our surgical techniques and improvements in adjuvant and neoadjuvant therapies. Despite these advances, the incidence of pancreatic cancer is rising globally, and it remains a deadly disease. In this review, we highlight the historical perspectives of pancreatic cancer treatment and outline the areas of future advancement that will assist progression towards better outcomes. Areas of future advancement include improving prevention strategies and early detection, refining our molecular understanding of pancreatic cancer, identifying more effective systemic therapies, and improving quality of life and surgical outcomes. Furthermore, systems need to be put in place to ensure all patients with pancreatic cancer receive high quality care and are given the appropriate options and sequence of therapy. This is best achieved through multidisciplinary care.

The prevalence of eosinophilic esophagitis (EoE) has been increasing in Japan. Although the diagnosis of EoE is based on simple criteria that include the presence of esophageal symptoms and esophageal eosinophilia on biopsies, there are several important issues associated with the diagnostic approach. Following an extensive literature search, the symptoms of 886 EoE cases in Japanese adults were analyzed and divided into three categories as follows: (1) typical symptoms, such as dysphagia (53%); (2) other upper GI symptoms (40%); and (3) no symptoms found during screening or medical examination, i.e., "asymptomatic esophageal eosinophilia" (19%). The diagnostic approach was reviewed according to these categories as well as according to the presence or absence of esophageal eosinophilia. The present manuscript describes the current therapeutic strategy of EoE and ultimately proposes a symptom-based diagnostic approach for EoE.

Recent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.

Purpose: The platelet distribution width (PDW) is reportedly useful as a prognostic indicator for some cancers. However, its prognostic significance in esophageal squamous cell carcinoma (ESCC) is unclear., Methods: We enrolled 104 patients with thoracic ESCC, who underwent curative esophagectomy., Results: Receiver operating curve analyses indicated that the optimal cut-off values of pre- and postoperative PDW were 16.9 and 17.0, respectively. The 5-year overall survival (OS) rate was significantly lower in patients with a high-preoperative PDW (≥ 16.9; 52.6%) than in those with a low-preoperative PDW (< 16.9; 61.0% P = 0.045). The 5-year disease-specific survival (DSS) rates were 64.3% in patients with a high-preoperative PDW and 69.3% in those with a low-preoperative PDW (P = 0.13). Regarding the postoperative PDW, the 5-year OS rate was significantly lower in patients with a high-postoperative PDW (≥ 17.0; 35.7%) than in those with a low-postoperative PDW (< 17.0; 66.8% P = 0.0017). The 5-year DSS rates were 52.2% in patients with a high-postoperative PDW and 73.2% in those with a low-postoperative PDW (P = 0.037). Finally, a multivariate analysis revealed that the postoperative PDW but not the preoperative PDW was an independent prognostic factor., Conclusions: The postoperative PDW was useful for predicting the prognosis of patients with ESCC.

Purpose: The prognostic significance of the peripheral platelet count × serum C-reactive protein level multiplier (P-CRP) has not been widely studied in patients with esophageal squamous cell carcinoma (ESCC)., Methods: We retrospectively analyzed data from 116 thoracic ESCC patients who underwent curative esophagectomy., Results: The patients were divided into the P-CRP High ( > 1.674) and P-CRP Low ( ≤ 1.674) groups, according to a cut-off value determined by a receiver operator curve. The 5-year overall survival (OS) rates significantly differed between the groups (P-CRP High : 46.4% and P-CRP Low : 77.3%; P = 0.0056). In the multivariate analysis, the P-CRP was an independent prognostic factor. We also evaluated the survival in the subgroup of patients who received neoadjuvant chemotherapy (NAC; n = 49). Among 28 patients who were P-CRP High before NAC, 20 remained. P-CRP High after NAC, while eight became post-P-CRP Low . Among 21 patients who were P-CRP Low before NAC, 16 remained post-P-CRP Low after NAC, while five became post-P-CRP High . The 5-year OS rate for patients who were P-CRP Low both before and after NAC was 92.9%, compared with 30.2% in other patients (P = 0.0034). In the multivariate analysis, the combination of P-CRP + post-P-CRP was an independent prognostic factor in ESCC patients who underwent NAC., Conclusions: The P-CRP is useful for predicting the prognosis in ESCC patients.

Purpose: Postoperative complications worsen the prognosis of gastric cancer patients. The Clavien-Dindo classification is used to evaluate postoperative complications. The prognostic significance of the comprehensive complication index (CCI), a new tool for evaluating postoperative complications, remains unclear., Methods: This study included 452 gastric adenocarcinoma patients who underwent curative surgery., Results: The CCI values were significantly higher in older patients ( ≥ 70 years; P < 0.0001), male patients (P < 0.0001), those with lymphatic invasion (P = 0.039), and those with vascular invasion (P = 0.037). The five-year overall survival (OS) and disease-specific survival (DSS) rates were significantly higher in patients without postoperative complications and those with Clavien-Dindo grade 1 complications in comparison to those with Clavien-Dindo grade 2-4 complications (80.4% vs. 66.2%, P = 0.0011; 89.7% vs. 82.3%; P = 0.045, respectively). Among patients with Clavien-Dindo grade 2-4 complications, the 5-year OS and DSS rates in the CCI High group ( ≥ 32.15) were significantly lower than those in the CCI Low group ( < 32.15; 47.5% vs. 74.9%, P = 0.0086; 63.1% vs. 90.0%, P = 0.0003). A multivariate analysis identified the CCI as an independent prognostic indicator in patients with Clavien-Dindo grade 2-4 complications., Conclusions: The CCI was closely associated with the prognosis of patients with Clavien-Dindo grade 2-4 complications and may be a prognostic indicator.

Purpose: The association between the preoperative absolute neutrophil count (NC), lymphocyte count (LC), and monocyte count (MC) in the peripheral blood and the prognosis of gastric cancer (GC) patients has not been investigated widely., Methods: We enrolled 445 patients who underwent surgery for GC between January, 2005 and April, 2013 to analyze the correlations among NC, LC, and MC and their prognoses., Results: Based on cut-off values calculated by ROC analysis, patients were sub grouped as having: NC ≥ 4477 (NC High ), NC < 4477 (NC Low ); and as LC ≥ 1447 (LC High ), LC < 1447 (LC Low ); and as MC ≥ 658.5 (MC High ), MC < 658.5 (MC Low ). Each group was assigned as follows; NC High group = 1, NC Low group = 0, LC High group = 0, LC Low group = 1, MC High group = 1, MC Low group = 0, and the sum of each score was defined as the lymphocyte-monocyte-neutrophil score (LMN score). The overall 5-year survival rates were 89%, 74%, 57.8%, and 53.3% for LMN scores of 0, 1, 2, and 3, respectively (P = 0.0004). Multivariate analysis indicated that the LMN score was an independent prognostic indicator., Conclusions: The combination of preoperative NC, LC, and MC appears to be a useful indicator of GC prognosis.

Purpose: We conducted this study to evaluate the impact of the postoperative mean arterial pressure (MAP) on surgical complications after hepatic resection., Methods: The subjects of this study were 199 patients who underwent hepatic resection for primary liver malignancy between 2004 and 2013. A clinically relevant postoperative complication was defined as a Clavien-Dindo grade ≥ III complication., Results: Based on an MAP cut-off value of 81.1 mmHg, the patients were grouped as follows: low MAP on both postoperative days (PODs) 1 and 2 (continuously low MAP), normal MAP on both PODs 1 and 2 (normal MAP), and others (transiently low MAP). The continuously low MAP group had the highest incidence of complications and the normal MAP group had the lowest incidence of complications compared with the expected incidence for this cohort (p < 0.01 and p = 0.01, respectively). Multivariate analysis revealed that both a continuously and transiently low MAP were independent predictors of postoperative complications (p = 0.03 and p < 0.01, respectively). Among the subtypes of complications, a low MAP had a significant relationship with ascites/pleural effusion and respiratory complications (p < 0.01 and p = 0.03, respectively)., Conclusions: A low MAP on POD 1 and/or 2 is an independent predictor of postoperative complications.

Purpose: Inflammation, together with immune and nutritional status, are associated with the progression of various cancer types. We evaluated the prognostic significance of the postoperative ratio (post-CLR) of the maximum C-reactive protein value (post-CRP Max ) to the minimum peripheral lymphocyte count (post-LC Min ) in patients with gastric cancer (GC)., Methods: The subjects of this retrospective study were 227 patients who underwent curative surgery for histopathologically diagnosed gastric adenocarcinoma., Results: The 5-year overall survival (OS) rates differed significantly between the post-CLR High (≥ 152.6) group and the post-CLR Low (< 152.6) group for all patients (45.0% vs. 68.4%, respectively; P < 0.001). The 5-year disease-specific survival (DSS) rates were also significantly related to post-CLR for all patients, (80.6% vs. 64.3% for the post-CLR Low and the post-CLR High groups, respectively; P = 0.002). Among patients without infectious complications, the CLR affected both the 5-year OS rate (48.4% vs. 69.2% for the post-CLR High and the post-CLR Low groups, respectively; P = 0.006) and the 5-year DSS rate (80.2% vs. 67.0% for the post-CLR Low and the post-CLR High groups, respectively; P = 0.027). Multivariate analysis revealed that post-CLR was an independent prognostic indicator for both the OS and DSS of all patients., Conclusions: Our finding show that the post-CLR can help predict the prognosis of GC patients.

Purpose: Associations between the preoperative absolute neutrophil count (NC), lymphocyte count (LC), and monocyte count (MC) in the peripheral blood and the prognosis of colorectal cancer (CRC) patients have not been widely studied., Methods: We enrolled 361 patients who underwent surgery for CRC between January 2007 and December 2013 to analyze correlations among the LC, MC, and NC and prognosis., Results: Based on cut-off values determined by a receiver operating characteristic analysis, patients were subgrouped as Lymph High or Lymph Low (cut-off: LC = 1460 cells/µL); as Mono High or Mono Low (cut-off: MC = 421 cells/µL); and as Neut High or Neut Low (cut-off: NC = 3247 cells/µL). Patients were then given lymphocyte-monocyte-neutrophil (LMN) scores by adding the points of their different subgroups (1 point each for Lymph Low , Mono High and Neut High ; 0 points for Lymph High , Mono Low and Neut Low ). The 5-year overall survival rates significantly differed by the LMN score (0: 89.7%, 1: 80.6%, 2: 68.8%, and 3: 57.4%; P < 0.0001). In the multivariate analysis, the LMN score was found to be an independent prognostic indicator., Conclusions: The combination of the preoperative absolute number of lymphocytes, monocytes, and neutrophils is a useful prognostic indicator in CRC patients.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased. Non-alcoholic steatohepatitis (NASH) shows progression of liver fibrosis in NAFLD. It remains unclear which patients with NAFLD will show progression of liver fibrosis. Therefore, we aimed to investigate the risk factor associated with the progression of liver fibrosis among patients with NAFLD., Methods: This observational study enrolled 157 patients with biopsy-proven NAFLD. Thirty-two patients were excluded because of lack of data. The accuracy of the formulae for estimating liver fibrosis, i.e., the FIB-4 index, APRI, and Forns index, was compared. Using serial changes of the best formula for liver fibrosis, we identified factors associated with the progression of liver fibrosis. Histological liver fibrosis was quantified using the Brunt stage., Results: Sixty-three patients were diagnosed as having NASH. The FIB-4 index provided the best diagnostic accuracy for liver fibrosis [Brunt stage 0 versus 1-4, areas under the curve (AUC) 0.74; 0-1 versus 2-4, AUC 0.77; 0-2 versus 3-4, AUC 0.78; and 1-3 versus 4, AUC 0.87]. The association between body mass index, sex, observation period, and histological findings (liver fat content, bridging fibrosis, and hepatocyte ballooning) with the change in the FIB-4 index was evaluated among patients with NASH, using multivariate analysis. Among these factors, hepatocyte ballooning was associated with an increase in the FIB-4 index., Conclusion: The FIB-4 index was the best formula for estimating liver fibrosis in patients with biopsy-proven NAFLD, and the presence of ballooned hepatocytes was a risk factor for the progression of liver fibrosis.

Purpose: Inflammation is closely related to cancer development and progression. This retrospective study investigated the prognostic value of the combination of pre- and postoperative C-reactive protein (CRP) levels in patients with colorectal cancer (CRC)., Methods: The subjects of this study were 406 patients who underwent surgery for CRC., Results: Based on receiver-operating characteristic analysis, patients were divided into the following groups: those with a preoperative CRP of ≥ 0.5 mg/dL (pre-CRP High ), those with a preoperative CRP of < 0.5 mg/dL (pre-CRP Low ), those with a postoperative CRP of ≥ 17.0 mg/dL (post-CRP High ), and those with a postoperative CRP of < 17.0 mg/dL (post-CRP Low ). They were then allocated to one of the following three groups: Group A, comprised of those in the pre-CRP High and post-CRP High groups; Group B, comprised of those in either the pre-CRP High and post-CRP Low or pre-CRP Low and post-CRP High groups; and Group C, comprised of those in the pre-CRP Low and post-CRP Low groups. The disease-specific 5-year survival rates were 53.8%, 72.8%, and 87.2% in Groups A, B, and C, respectively, and these differences were significant. Finally, multivariate analysis revealed that the combination of pre- and postoperative CRP levels was an independent prognostic indicator., Conclusions: The combination of pre- and postoperative CRP was predictive of the prognosis of CRC patients.

Background: Thrombocytosis develops in association with malignant tumors and may reflect the inflammation status in cancer patients. This study retrospectively investigated the prognostic significance of two platelet-based inflammatory indicators, the platelet × C-reactive protein multiplier value (P-CRP), and platelet-lymphocyte ratio (PLR), in gastric cancer patients., Methods: The 453 enrolled patients had a histopathological diagnosis of gastric adenocarcinoma and underwent curative surgery., Results: P-CRP correlated significantly with age, tumor size, depth of invasion, lymph node metastasis, and disease stage. A high PLR correlated significantly with tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, venous involvement, and disease stage. In the ROC analysis, the optimal cutoff value of P-CRP and PLR was 3.689 and 173.3, respectively. Five-year survival rates were 62.9 and 82.1% in patients with P-CRP High (≥3.689) and P-CRP Low (<3.698), respectively (P < 0.0001). Five-year survival rates were 66.3 and 81.3% in patients with PLR High (≥173.3) and PLR Low (<173.3), respectively (P = 0.0022). The prognosis of the P-CRP High /PLR High group was significantly worse than that of the P-CRP High or PLR High and P-CRP Low /PLR Low groups in terms of overall survival (P < 0.0001) and disease-specific survival (P = 0.029). In a multivariate analysis, the combination of P-CRP and PLR was an independent prognostic indicator., Conclusions: The combination of P-CRP and PLR may be useful in predicting prognosis in gastric cancer patients.

Purpose: Hand-foot syndrome (HFS) is a major side effect of pegylated liposomal doxorubicin (PLD). Regional cooling during PLD infusion was shown to improve severe HFS. We investigated the utility of frozen gloves and socks (FGS) as a simpler cooling method., Methods: To evaluate the utility and safety of regional cooling with FGS for PLD-induced HFS, we retrospectively analyzed patients with advanced ovarian cancer who used FGS during PLD-containing regimens., Results: Ninety-six patients were analyzed. The incidence of HFS was 51% (≥ grade 2, 32%) in the PLD group and 38% (≥ grade 2, 6%) in the PLD + CBDCA group. The respective percentages of patients who underwent PLD dose modification/discontinuation were 41%/75% in the PLD group and 9%/30% in the PLD + CBDCA group. The reasons for discontinuation of PLD and PLD + CBDCA therapy were progressive disease, HFS, allergy, oral mucositis, and others. HFS was the only reason for PLD dose modification in both the PLD and PLD + CBDCA groups. The completion rate of FGS was 96%, with discontinuation in three cases due to pain from cooling., Conclusions: Our study indicates that FGS is a safe, simple method with good tolerability. A prospective study is needed for further assessment.

Background: The ratio of C-reactive protein to albumin (CRP/Alb) is a biochemical marker of systemic inflammatory response and has been associated with poor survival in cancer. This study retrospectively investigated the relationship between the CRP/Alb ratio and prognosis in gastric cancer patients., Methods: This study enrolled 453 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery., Results: A statistically significant weak correlation was observed between CRP/Alb ratio and neutrophil/lymphocyte ratio (NLR) (r = 0.19; P < 0.0001). There were statistically significant correlations between high CRP/Alb ratio and age (P = 0.0004), tumor size (P = 0.02), depth of invasion (P = 0.012), and lymph node metastasis (P = 0.022). A high NLR was significantly correlated with age (P = 0.0027), tumor size (P = 0.0006), depth of invasion (P < 0.0001), lymphatic involvement (P = 0.0031), venous involvement (P = 0.0022), and stage of disease (P = 0.0024). Based on results by receiver operating characteristic analysis, patients were divided as follows: CRP/Alb ratio ≥ 0.0232 (CAR High ), CRP/Alb ratio < 0.0232 (CAR Low ), NLR ≥ 2.43 (NLR High ), and NLR < 2.43 (NLR Low ). Five-year survival rates of patients with both CAR High and NLR High , either CAR High or NLR High , and both CAR Low and NLR Low were 59.6, 75.8, and 87.5%, respectively, with statistically significant differences (P < 0.0001). Multivariate analysis revealed that the combination of CRP/Alb ratio and NLR was an independent prognostic indicator., Conclusions: The combination of CRP/Alb ratio and NLR may be useful in predicting prognosis in gastric cancer patients.

Purpose: Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management., Methods: Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HU min , HU max , and HU mean , respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HU SD ) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria., Results: The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HU SD (odds ratio 3.092; 95% CI 1.018-9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001-1.00022) as significant risk factors for PF., Conclusions: The HU SD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

Background and Purpose: Venous thromboembolism (VTE) is a potentially fatal perioperative complication. Understanding the risk factors for deep vein thrombosis (DVT) and initiating appropriate prophylaxis is pivotal for reducing the risk of VTE. The purpose of this study was to clarify the perioperative risk factors for DVT in patients undergoing surgery for gastric cancer., Methods: We reviewed the findings of lower limb ultrasonography performed in 160 patients who underwent gastrectomy for gastric cancer., Results: The preoperative and postoperative incidence of DVT was 4.4% (7/160) and 7.2% (11/153), respectively. All postoperative DVTs were of the distal type, whereas preoperative DVTs were of the proximal (n = 3) and distal type (n = 4). None of the patients suffered symptomatic VTE. Multivariate analysis indicated that depth of invasion and D-dimer concentration were independent risk factors for preoperative DVT and that gender and performance status were risk factors for postoperative DVT. Receiver operating characteristic analysis revealed that the optimal cut-off D-dimer concentration was 1.4 μg/mL., Conclusions: The incidence of perioperative DVT was low for patients undergoing gastric cancer surgery. Therefore, the risk-stratified application of perioperative pharmacologic thromboprophylaxis is thought to be more appropriate than routine pharmacologic thromboprophylaxis for Japanese patients undergoing surgery for gastric cancer.

Background: Total gastrectomy (TG) and proximal gastrectomy (PG) are used to treat upper-third early gastric cancer. To date, no consensus has been reached regarding which procedure should be selected. The aim of this study was to validate the usefulness of preserving the stomach in early upper-third gastric cancer., Methods: Between 2004 and 2013, 201 patients underwent PG or TG at our institution for treatment of upper-third early gastric cancer. According to the defined inclusion and exclusion criteria, 192 cases were enrolled in this study. One-to-one propensity score matching was performed to compare the outcomes between the two groups., Results: The operation time was shorter in the PG group. Although no significant difference was observed, the PG group had less bleeding and fewer postoperative complications. R0 resection rate was 100%, and no surgery-related deaths were observed. The frequencies of reflux symptoms and anastomotic stenosis were significantly higher in the PG group, but could be controlled by balloon dilation and drug therapy. The maintenance rates of body mass index and lean body mass were significantly higher in patients who underwent PG than TG. The total protein and serum albumin values were higher in the PG group than in the TG group and remained statistically superior., Conclusion: PG group exhibited better perioperative performance. Furthermore, better nutritional results were obtained in the PG group. Although the late stenosis and reflux symptoms must be addressed, the PG is a preferable surgical procedure for the treatment of early proximal gastric cancer.

Purpose: The prognostic nutritional index (PNI) is considered useful for predicting the prognosis of patients with gastric cancer (GC). This retrospective study investigated the relationship between both the pre- and postoperative PNI and the prognosis of GC patients., Methods: The subjects of this study were 254 patients who underwent curative surgery for histopathologically diagnosed GC., Results: Patients were divided according to their pre- and postoperative PNI as follows: preoperative PNI of ≥ 52 (pre-PNI High ), preoperative PNI of < 52 (pre-PNI Low ), postoperative PNI of ≥ 49 (post-PNI High ), and postoperative PNI of < 49 (pre-PNI Low ). Both pre- and postoperative PNI were significantly associated with GC prognosis. Patients were then divided as follows: group A, patients with pre-PNI High and post-PNI High ; group B, patients with either pre-PNI High and post-PNI Low or pre-PNI Low and post-PNI High ; and group C, patients with pre-PNI Low and post-PNI Low . The 5-year survival rates were 100.0, 83.0, and 67.1% for groups A, B, and C, respectively. Multivariate analysis indicated that the combination of pre- and postoperative PNI was an independent prognostic indicator., Conclusions: Combined analysis of the pre- and postoperative PNI offers accurate information about the prognosis of patients with GC.

Background: This report focuses on the surgical manipulation and spread of cancer cells. Our previous study suggested an association between a poor prognosis and positive pleural lavage cytology after resection of esophageal cancer without preoperative treatment. However, little is known regarding the clinical significance of the lavage procedure in esophageal cancer patients who undergo preoperative treatment., Methods: A cohort of 94 patients with squamous cell carcinoma of the esophagus who underwent esophagectomy with radical lymph node dissection was prospectively analyzed for free cancer cells in the pleural cavity after mediastinal lymphadenectomy. Reverse transcription-polymerase chain reaction was performed to detect free cancer cells in the pleural lavage fluid by measuring squamous cell carcinoma-related antigen (SCC) and carcinoembryonic antigen (CEA)., Results: Forty-two patients (44.7%) were positive for SCC after thoracic lymphadenectomy, and 15 patients (15.9%) were positive for CEA. SCC positivity was significantly associated with venous invasion (p = 0.037) and with the clinical response to preoperative treatment (p = 0.001). Furthermore, SCC positivity was associated with poor prognosis compared with negative SCC (p = 0.026). Multivariate analysis revealed that SCC positivity was an independent prognostic factor. Regarding recurrence patterns, SCC positivity tended to be associated with hematogenous recurrence (p = 0.063). Conversely, positive CEA was not associated with any clinicopathological finding, treatment response, prognosis, or recurrence pattern., Conclusions: Tumor spillage during the evaluated surgical manipulation was assessed in esophageal cancer patients who underwent preoperative treatment. Tumor spillage as evaluated by SCC mRNA was associated with a poor prognosis.

Background: Interruption of sedation due to a poor response to modified neuroleptanalgesia (m-NLA) with midazolam often occurs during endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) because most patients have a history of heavy alcohol intake. Recently, propofol has been used feasibly and safely during endoscopic procedures. The aim of this study was to clarify the efficacy and safety of propofol compared with that of midazolam during ESD for ESCC., Methods: This was a single-blind, randomized controlled trial in a single center. Patients with ESCC scheduled for ESD were included in the study. Patients were randomly assigned to one of two groups: the propofol group and the midazolam group. The main outcome was the incidence of discontinuation of the procedure due to a poor response to sedation. Secondary outcomes included risk factors for a poor response to sedation., Results: Between April 2014 and October 2015, 132 patients (n = 66 per group) who underwent ESD for ESCC were enrolled in this study. The incidence of discontinuation due to a poor response to sedation in the propofol and midazolam groups was 0% (0/66) and 37.9% (25/66), respectively (p < 0.01). Multivariate analyses revealed that use of midazolam [Odds ratio (OR), 7.61; 95% confidence interval (CI), 2.64-21.92; p < 0.01] and age (OR, 0.93; 95% CI, 0.86-0.98; p < 0.01) were risk factors for a poor response to sedation., Conclusions: Our study indicates that, compared with midazolam, propofol is a more efficient sedative for m-NLA during ESD for ESCC.

Purpose: The neutrophil-lymphocyte ratio (NLR) is a biochemical marker of the systemic inflammatory response and has been associated with prognosis for various types of cancer. This retrospective study investigates the relationship between the pre- and postoperative NLR and the prognosis of gastric cancer patients., Methods: The subjects were 280 patients who underwent curative surgery for histopathologically diagnosed gastric adenocarcinoma., Results: The preoperative NLR was significantly correlated with tumor size, tumor depth, lymphatic invasion, venous invasion, and disease stage. In contrast, there was no correlation between the postoperative NLR and the various clinicopathological variables. Prognosis was significantly worse for patients with a high preoperative NLR than for those with a low preoperative NLR. Prognosis was also significantly worse for patients with a high postoperative NLR than for those with a low postoperative NLR. Furthermore, the prognosis was worse for gastric cancer patients whose pre- and postoperative NLRs were both high. Multivariate analysis indicated that a high pre- and postoperative NLR was an independent prognostic indicator., Conclusions: The combination of pre- and postoperative NLRs appears to be useful for predicting the prognosis of gastric cancer patients.

Purpose: Neoadjuvant chemotherapy (NAC) with cisplatin and fluorouracil is the recommended standard treatment for resectable locally advanced esophageal cancer (EC) in Japan. We investigated the effects of NAC on the safety and feasibility of thoracoscopic esophagectomy with total mediastinal lymphadenectomy for EC., Methods: This retrospective study analyzed data from 225 consecutive patients who underwent thoracoscopic esophagectomy with lymph node dissection between April 2007 and December 2015. Patients with clinical stage IB, IIA, IIB, IIIA, or IIIB EC, and no active concomitant malignancy were included. We compared intraoperative outcomes, and postoperative morbidity and mortality between patients who received NAC (n = 139; NAC group) and patients who did not (n = 86; non-NAC group)., Results: Preoperative laboratory data revealed that anemia, thrombopenia, and renal dysfunction were more common in the NAC group than in the non-NAC group. There were no differences between the groups in operating times, blood loss, number of dissected lymph nodes, overall complication rates, or length of postoperative hospital stay., Conclusion: Based on our findings, thoracoscopic esophagectomy is safe and effective for locally advanced EC, even after NAC.

Purposes: Pancreatic fistula (PF) is a challenging complication of pancreaticoduodenectomy (PD). 'Soft pancreas' is reported as a risk factor for PF; however, palpation by the surgeon is not an objective method of evaluating pancreatic texture. We conducted this study to investigate whether a texture analyzer called a "Tensipresser" can be used to quantify pancreatic tissue hardness and predict the development of postoperative PF., Methods: We assessed pancreatic texture in 85 patients who underwent PD. After surgeons assessed the texture of the pancreas subjectively, the physical properties were measured on the pancreatic margin intraoperatively, by the two-bite method using the "Tensipresser". The incidence and severity of PF were based on the definitions of the International Study Group on Pancreatic Fistula., Results: Symptomatic PF (grade B and C) developed in 16% of the patients. Patients were divided into two groups based on the Tensipresser measurement: those with a soft and fragile pancreas with hardness < 2070 gw/cm 2 and cohesiveness < 0.65 (SF group); and all other patients (non-SF group). In the univariate and multivariate analysis, a small pancreatic duct diameter (<4 mm), no conduction of preoperative chemoradiation therapy, and inclusion in the SF group were significant predictors of PF., Conclusion: The Tensipresser can evaluate pancreatic texture objectively, helping to define intraoperatively, those at risk of the development of PF.

Background: Total pharyngolaryngoesophagectomy (PLE) is used as a curative treatment for synchronous laryngopharyngeal and thoracic esophageal cancer or for multiple cancers in the cervical and thoracic esophagus. Gastric pull-up is commonly used after PLE, but postoperative complications are common. The present study evaluated these procedures in patients with esophageal cancer., Methods: Fourteen patients (7 with synchronous pharyngeal and thoracic esophageal cancer, 4 with synchronous cervical and thoracic esophageal cancer, and 3 with cervicothoracic esophageal cancer) underwent reconstructive surgery after PLE involving gastric pull-up combined with free jejunal graft between 2004 and 2015., Results: Esophagectomy via right thoracotomy was performed in 9 patients, and transhiatal esophagectomy was used in 5. The posterior mediastinal route was used in 13 patients, excluding one patient with early gastric cancer. Interposition of a free jejunal graft included microvascular anastomosis using two arteries and two veins in all patients. Anastomotic leakage and graft necrosis did not occur in any of the 14 patients who underwent the above surgical procedures. Tracheal ischemia close to the tracheostomy orifice occurred in 4 patients (28.6%), but none of these patients developed pneumonia. No hospital deaths were recorded., Conclusions: The results indicate that gastric pull-up combined with free jejunal graft is a feasible reconstructive surgery after PLE. This procedure is a promising treatment strategy for synchronous pharyngeal and thoracic esophageal cancer or multiple cancers in the cervical and thoracic esophagus. Larger series are needed to show the distinct advantages of this procedure in comparison with conventional methods of reconstruction after PLE.

Purpose: Successful cases have shown that conversion surgery after chemotherapy improves the prognosis of advanced gastric cancer. However, it is necessary to carefully select patients who have no unresectable factors prior to surgery. We recently reported that diagnostic laparoscopy with photodynamic diagnosis using oral 5-aminolevulinic acid (ALA-PDD) is a promising tool for diagnosing early peritoneal metastasis in gastric cancer. We herein evaluated the usefulness of this technique for detecting peritoneal metastases of advanced gastric cancer after chemotherapy., Methods: Diagnostic laparoscopy using sequential white light (WL) and ALA-PDD observations was performed in 38 patients with advanced gastric cancer after chemotherapy. The sensitivity of ALA-PDD for detecting peritoneal disease was compared with that of WL. The relationship between the state of peritoneal metastasis assessed by ALA-PDD and a cytological examination of the peritoneal fluid was evaluated., Results: Twelve of the 38 patients (32 %) were diagnosed with peritoneal metastases by conventional laparoscopy. However, laparoscopy with ALA-PDD detected peritoneal metastases in 4 (11 %) of the 26 remaining patients. Three of these 4 patients had negative cytological results from the evaluation of the peritoneal fluid., Conclusions: Diagnostic laparoscopy using ALA-PDD is a useful technique for detecting metastases and determining treatment strategies to select patients with advanced gastric cancer who have received chemotherapy.