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Background Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression. Methods TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high-throughput quantitative fluorescence in situ hybridization using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis was analyzed. Results There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC, and RCC. Conclusions Longer telomeres are associated with worse prognosis in ADC, SCC, and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.

Postoperative pancreatic fistula (POPF) is one of the major critical complications after pancreatic resection. Recently, postoperative acute pancreatitis (POAP), a new concept for a pancreatic-specific complication following pancreatic resection, has been advocated, and its association with POPF has been reported. The present study examined the clinical features of POAP and identified the associations of POAP with POPF and other postoperative morbidities in pancreatic ductal adenocarcinoma (PDAC) patients undergoing pancreatic resection.A total of 312 consecutive patients who underwent pancreatic resection for PDAC at our institution from 2013 to 2019 were enrolled in this study. POAP was defined as an elevated serum amylase level above the upper limit normal on postoperative day (POD) 0 or 1, based on Connor's definition. The severity of POPF was assessed by the International Study Group on Pancreatic Surgery definition.A total of 184 patients (58.9%) had POAP. POAP occurred in 58.5% of subtotal stomach-preserving pancreatoduodenectomy patients and 60% of distal pancreatectomy combined with splenectomy patients. The presence of POAP was significantly associated with the development of clinically relevant POPF, higher rates of severe morbidity, and a prolonged hospital stay after pancreatic resection. A multivariate analysis showed that the presence of POAP and elevated C-reactive protein levels on POD 3 were independent predictors of clinically relevant POPF after subtotal stomach-preserving pancreatoduodenectomy.POAP is associated with the development of POPF, higher rates of severe morbidity, and a prolonged hospital stay after pancreatic resection and is an independent risk factor for clinically relevant POPF after pancreatoduodenectomy. POAP represents an important indicator for planning treatment strategies to prevent serious complications, including POPF.

Background/aim The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). Patients and methods We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. Results High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. Conclusion Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.

Background/aim This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). Patients and methods PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. Results No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). Conclusion PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

Sarcopenia often affects patients with various types of cancer, and has been reported to affect patient prognosis and therapeutic effects. However, to the best of our knowledge, there are no reports on the relationship between gemcitabine plus nab-paclitaxel combination therapy (GnP) and sarcopenia in patients with unresectable pancreatic cancer. The present study analyzed the relationship between overall survival (OS), progression-free survival (PFS), response rate, disease control rate, adverse events (AEs) and sarcopenia in patients with pancreatic cancer treated with GnP. A total of 121 consecutive patients with advanced pancreatic cancer who received GnP as first-line chemotherapy between January 2015 and December 2017 were retrospectively analyzed. GnP consisted of 1,000 mg/m

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse‐free survival (odds ratio = 2.37; P = .033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT., This study sought to investigate any potential alterations in the distribution and clinical impact of immune cells in patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemoradiation therapy (NACRT). The present analysis revealed that NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT.

Background/aim Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC). Patients and methods Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction. Results Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival. Conclusion High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.

We present the case of a 35-year-old man with intractable nausea, vomiting, and severe anemia. A computed tomography (CT) scan of the chest, abdomen, and pelvis showed a circumferential lesion thickening of up to 3.5 cm at the level of the third portion of the duodenum. No aortocaval, retroperitoneal lymphadenopathy, nor secondary lesion was observed. Esophagogastroduodenoscopy (EGD) revealed a circumferential mass within the third portion of the duodenum. Histopathology of biopsy materials from the duodenal mass showed it most likely to be a poorly differentiated adenocarcinoma. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. Histologically, tumor cells with basophilic cytoplasm and pleomorphic nuclei showed a solid pattern, and expressed CD30 and SALL4 immunohistochemically, leading to a diagnosis of embryonal carcinoma-like tumor. No other primary tumor could be identified, and the location of the tumor, mainly on the mucosal surface, suggested a duodenal origin. The UICC TNM staging was T3N2M0, stage IIB. This is a rare case of primary duodenal carcinoma with features of embryonal carcinoma.

BACKGROUND/AIM To identify prognostic factors for patients with stage IV gastric cancer (GC) and a single stage IV factor before chemotherapy who underwent conversion surgery (R0 resection). PATIENTS AND METHODS This study retrospectively analysed 32 GC patients with a single stage IV factor before chemotherapy and who underwent conversion surgery (R0 resection) between January 2001 and September 2015. The univariate and multivariate analyses were performed to identify independent prognostic factors. RESULTS The five-year survival rate was 39.6%, and the median survival time was 47.0 months. In the univariate analysis, diffuse-type according to Lauren classification was significantly associated with worse overall survival (p

To assess the utility of the Glasgow Prognostic Score (GPS) obtained before curative resection for predicting outcomes in patients with advanced gastric cancer (GC). This study retrospectively analyzed the outcomes of 337 consecutive patients with GC who underwent curative surgery for locally advanced gastric cancer between January 2003 and June 2014. GPS was assessed within 4 days prior to surgery. The number of patients with GPS scores of 0, 1, and 2 was 302, 26, and 9, respectively. There was significantly more blood loss during surgery and more postoperative complications in the GPS 1/2 group than in the GPS 0 group. Patients in the GPS 1/2 group had significantly poorer overall survival than those in the GPS 0 group (p = 0.001). On multivariate analysis, GPS 1/2 was identified as an independent factor for poor survival (p = 0.019). GPS before curative resection might be a useful predictive factor for perioperative complications and survival in locally advanced GC.

Supplemental digital content is available in the text., Objective The combination of gemcitabine plus nab-paclitaxel (GnP) has not been studied in Japanese patients with resectable pancreatic cancer (PC). This study aimed to assess the tolerability of adjuvant GnP in Japanese patients with resected PC. Methods This was a Phase I, open-label, multicenter, single-arm study of patients with resected PC in Japan. Patients received 125 mg/m2 of nab-paclitaxel and 1000 mg/m2 of gemcitabine on days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles. The primary end point was tolerability, defined as the absence of specific grade 3 or higher treatment-related adverse events by the end of cycle 2. Secondary end points included safety, disease-free survival, and overall survival. Results Forty-one patients were enrolled between June 2016 and February 2017 (median age, 68 years; 51% male; stage II, 95%). Gemcitabine plus nab-paclitaxel met the tolerability criteria in 39 of the 40 patients included in the tolerability analysis set (97.5%). The most common treatment-related adverse events were leukopenia, neutropenia, alopecia, and peripheral sensory neuropathy. After a follow-up of 30.1 months, median disease-free survival was 17.0 months and median overall survival was not reached. Conclusions These results show that adjuvant GnP is tolerable in Japanese patients with resected PC. Clinical Trial Registration No.: JapicCTI-163179

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.

INTRODUCTION Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe. PATIENTS AND METHODS We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019. RESULTS The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P

Background/aim Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). Patients and methods GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. Results Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. Conclusion GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

Background Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD). Methods Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients. Results A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors. Conclusions The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. 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. 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. 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). 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.

Mucinous cystadenocarcinoma (MCAC) with malignant ascites is rare. We report a case of a 28-year-old woman who presented with epigastric pain. The ascites in the Douglas fossa was identified at a nearby gynecology clinic. Computed tomography showed a multiloculated cystic lesion (9.5 × 6.4 cm) in the tail of the pancreas, which was diagnosed as mucinous cystic neoplasm on imaging. Staging laparoscopy was performed, and rapid cytology of ascites revealed adenocarcinoma, leading to a diagnosis of unresectable MCAC. Subsequently, combination chemotherapy with gemcitabine plus S-1 was initiated. Although there were no remarkable changes in the imaging findings, the peritoneal dissemination node was not consistently recognized in any of the imaging findings, and distal pancreatectomy was performed. A peritoneal dissemination node was not observed in the laparotomy findings, but the peritoneal lavage cytology was positive. The postoperative pathological result was non-invasive MCAC, and the ascites was suspected to be caused by cyst rupture. The patient has been recurrence-free, including the reappearance of ascites, for > 8 years after adjuvant therapy with S-1. Although careful follow-up will be required in the future, the very good prognosis in this case suggests that MCAC with malignant ascites without obvious peritoneal dissemination should be considered for surgical resection.

Interlineage communication within a cancer microenvironment can augment cancer cell behaviour and impact response to therapy. Patient-derived cancer organoids provide an opportunity to explore cancer cell biology, however it is a major challenge to generate a complex cancer microenvironment in vitro. Here, we established a stromal tumoroid culture system modeling pancreatic ductal adenocarcinoma (PDAC) that reconstitutes multilineage interactions between cancer, endothelial, and fibroblast cells and recapitulates several aspects of primary tumors. Whole-mount immunohistochemistry on cleared tumoroids reveals organized vessel, desmoplastic fibroblast, and glandular cancer cell phenotypes that emerge over time. Time-course scRNA-seq measurements show that tumoroid formation activates fibroblasts, altering the extracellular matrix (ECM) composition and inducing cancer cell signal-response signatures and metabolic state change. Comparison between tumoroids with normal or cancer associated fibroblasts (CAFs) reveals different ECM compositions, as well as differential effects on cancer cell behaviors and metabolism. We identify Syndecan 1 (SDC1) and Peroxisome proliferator-activated receptor gamma (PPARG) as receptor and metabolic nodes involved in cancer cell response to CAF signals, and blocking SDC1 disrupts cancer cell growth within the tumoroid. Tumoroids from multiple PDAC patients revealed co-existence of subpopulations associated with classical and basal phenotypes, and CAF-induced migration behaviors emerged in certain patient tumoroids. Comparisons between patient tumoroids revealed a multigene migration signature that develops over time reflecting a stress response mechanism that correlates with worse clinical outcome. Altogether, stromal tumoroids can be used to explore dynamic and reciprocal interactions between cancer, CAF and endothelial cell states, and our data provides new inroads into the discovery of personalized pancreatic cancer therapies.

Recent evidence indicates that RNA-dependent RNA polymerase (RdRP) activity of human telomerase reverse transcriptase (hTERT) regulates expression of target genes and is directly involved in tumor formation in a telomere-independent manner. Non-canonical function of hTERT has been considered as a therapeutic target for cancer therapy. We have previously shown that hTERT phosphorylation at threonine 249 (p-hTERT), which promotes RdRP activity, is an indicator of an aggressive phenotype and poor prognosis in liver and pancreatic cancers, using two cohorts with small sample sizes with polyclonal p-hTERT antibody. To clarify the clinical relevance of p-hTERT, we developed a specific monoclonal antibody and determined the diagnostic and prognostic value of p-hTERT in cancer specimens using a large cohort. A monoclonal antibody for phosphorylated hTERT (p-hTERT) at threonine 249 was developed and validated. The antibody was used for the immunohistochemical staining of formalin-fixed, paraffin-embedded specimens from 1523 cases of lung, colon, stomach, pancreatic, liver, breast, and kidney cancers. We detected elevated p-hTERT expression levels in cases with a high mitotic activity, high pathological grade, and high nuclear pleomorphism. Elevated p-hTERT expression was an independent prognostic factor for lung, pancreatic, and liver cancers. Furthermore, p-hTERT expression was associated with immature and aggressive features, such as adenosquamous carcinoma (lung and pancreas), invasive type of cancer (lung), high serum alpha-fetoprotein level (liver), and triple-negative status (breast). In conclusion, RdRP activity indicated by p-hTERT expression predicts aggressive cancer phenotypes in various types of cancer. Thus, p-hTERT is a novel biomarker for the diagnosis of aggressive cancers with a poor prognosis. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

677 Background: Results from the phase III Prep-02/JSAP-05 trial demonstrated the efficacy and safety of gemcitabine plus S-1 as neoadjuvant chemotherapy for resectable pancreatic cancer. However, consensus on neoadjuvant chemotherapy for pancreatic cancer has not yet been established, and the effects of neoadjuvant therapy on clinical features of the tumor and improvement in prognosis have not been fully investigated. We aimed to investigate the effect of neoadjuvant chemotherapy on resectable pancreatic cancer. Methods: Between 2013 and 2021, 291 patients who underwent curative resection for resectable pancreatic cancer at our hospital were enrolled. The patients were categorized into groups of those who received neoadjuvant chemotherapy (NAC group: n = 91) and those who received up-front surgery (US group: n = 200). Prognostic predictors were examined in (i) all patients, (ii) US group, and (iii) NAC group. Statistical significance was considered at p < 0.05. Results: The median follow-up periods were 20.7 and 33.2 months in the NAC and US groups, respectively. In the NAC group, 84 of the 91 patients (94.5%) received gemcitabine-based chemotherapy, and three (3.3%) received chemoradiotherapy. There was no difference in overall survival (OS) and recurrence free survival (RFS) between the two groups. In the background, the NAC group had lower preoperative CA19-9 levels, lower lymph node ratio (LNR), and smaller tumor size than in the US group. During multivariable analysis of OS, preoperative CA19-9 levels, LNR, modified Glasgow prognostic score (mGPS), resection margin, and tumor size were identified as possible prognostic predictors in all patients and in the US group, whereas LNR and mGPS were identified in the NAC group. Conclusions: The prognostic significance of preoperative CA19-9 level, tumor size, and LNR were counteracted in the NAC group. These findings may indicate the effect of neoadjuvant chemotherapy for resectable pancreatic cancer.

We aimed to evaluate pancreatic cancer (PC) with positive peritoneal lavage cytology (CY1) outcomes following a change in adjuvant therapy.The clinicopathological data of patients with pancreatic adenocarcinoma with CY1 at 14 institutions, between 2007 and 2015, were collected and analyzed.Of the 124 eligible patients, 114 underwent macroscopically curative resection. Of the 114 patients, 80 (70%) did not have early recurrence and received postoperative chemotherapy that was S-1 in 43 (54%), gemcitabine in 31 (39%), and others in six (7%). The median overall survival was 21.0 months in S-1 and 19.2 in gemcitabine therapy (p=0.23), whereas the median relapse-free survival was 10.2 and 7.1 months (p=0.03), respectively.Following the change in adjuvant therapy, most PC patients with CY1 who underwent macroscopically curative resection received S-1; however, it was insufficient. Further development of postoperative chemotherapy is required.

Background/aim Cancer stem cells (CSCs) are reported to associated with cancer metastasis, relapse, and chemoresistance. This study examined the clinical significance of the expression of two CSC markers, the transporter associated with antigen processing 1 (TAP1) and the Delta-like 4 (DLL4) protein, in patients with locally advanced GC. Patients and methods This study was performed using samples obtained from 413 pathological stage II/III GC patients after curative gastrectomy. We examined TAP1 and DLL4 expression using immunohistochemical analysis with tissue microarray and examined the association between TAP1 or DLL4 expression, clinicopathological factors and survival. Results High TAP1 expression was associated with better overall survival compared to low TAP1 expression (p=0.004). Furthermore, in multivariate analysis, high TAP1 expression was defined as a predictive factor for good survival. There was no significant difference between DLL4 expression and clinicopathological features and overall survival. Conclusion TAP1 expression may be a useful prognostic marker in patients with locally advanced GC.

Purpose Despite improvements in surgical techniques and devices and perioperative care of gastric cancer (GC), the rate of postoperative complications still has not decreased. If patients at high risk for postoperative complications could be identified early using biomarkers, these complications might be reduced. In this study, we investigated usefulness of the preoperative Glasgow Prognostic Score (GPS) as a predictive factor for complications after surgery in patients with stage II/III GC. Methods This study retrospectively analyzed the outcomes of 424 patients who underwent curative surgery for pathological stage II/III GC from February 2007 to July 2019 at a single center. The GPS was assessed within 4 days before surgery. To identify independent risk factors for postoperative complications, univariate and multivariate analyses were performed using a Cox proportional hazards model. Results The numbers of patients with a GPS of 0, 1, and 2 were 357, 55, and 12, respectively. The rate of complications after surgery was significantly higher among patients with a GPS of 1 or 2 than among patients with a GPS of 0 (p = 0.008). Multivariate analysis identified a GPS of 1 or 2 as an independent predictive factor for postoperative complications (p = 0.037). Conclusion The preoperative GPS may be a useful predictive factor for postoperative complications in patients with stage II/III GC. Being aware of the risk of complications after surgery as indicated by the GPS before surgery may promote safe and minimally invasive surgery that we expect will improve outcomes in patients with a GPS of 1 or 2.

BACKGROUND Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. AIM We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. METHODS The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. RESULTS The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p

Background/aim Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. Patients and methods The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. Results A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). Conclusion ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

Purpose The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.

BACKGROUND/AIM The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.

Laparoscopic gastrectomy is becoming more commonly performed, but acquisition of its technique remains challenging. We investigated whether laparoscopy-assisted distal gastrectomy (LDG) performed by trainees (TR) supervised by a technically qualified experienced surgeon (QS) is feasible and safe. The short-term outcomes of LDG were assessed in patients with gastric cancer between 2008 and 2018. We compared patients who underwent LDG performed by qualified experienced surgeons (QS group) with patients who underwent LDG performed by the trainees (TR group). The operation time was longer in the TR group than in the QS group (median time: 270 min vs. 239 min, p

Background: The predictive roles of secreted protein acidic and rich in cysteine (SPARC) in pancreatic ductal adenocarcinoma (PDAC) patients after curative resection have not been clarified. We investigated the correlations between the SPARC expression and the postoperative prognosis. Methods: We retrospectively analyzed the clinical data from consecutive patients who underwent curative resection for pancreatic cancer in our institution from 2005 to 2014. Stromal SPARC expression was analyzed by immunohistochemistry on tumor tissue microarrays (TMAs) from the patients. Results: A total of 179 patients were enrolled to this study. The median follow-up period of the present study was 62.1 months. Seventy patients had positive SPARC expression (39.1%). There were no significant differences between the positive SPARC-positive group and the SPARC-negative group. In the survival analysis, there was a significant difference between the SPARC-positive and SPARC-negative groups in the 5-year overall survival (OS) rates after surgery, which were 8.1% and 19.8%, respectively (p=0.0316). A univariate analysis showed that the SPARC expression, size of tumor, lymph node metastasis, and residual tumor were possible prognostic factors. A multivariate analysis showed that the SPARC expression (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.017-2.051), lymph node metastasis (HR: 2.019, 95% CI: 1.318-3.091), and residual tumor (HR: 1.648, 95% CI: 1.132-2.401) were independent prognostic factors. Conclusions: The stromal SPARC expression in resectable pancreatic cancer patients might be useful as a prognostic marker.

Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120.We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis.The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively.The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody.The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut-off point and suggests that S-1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S-1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.

This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC).PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated.No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049).PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

Background/aim The changes of dietary intake (DI) after gastrectomy have not been objectively reported. It has not been clear how much DI loss is experienced after total gastrectomy (TG) in comparison to after distal gastrectomy (DG). This study quantified the changes of DI after gastrectomy, and clarified how much DI loss is experienced after TG. Patients and methods This was a prospective observational study. Patients who underwent gastrectomy for gastric cancer were enrolled. The DI loss was evaluated at 1 and 3 months postoperatively. Results Thirty-three patients underwent TG, and 117 patients underwent DG. The median %DI loss of the overall study population at 1 and 3 months after surgery was -9.3% and -3.6%. The median %DI loss at 1 and 3 months postoperatively was -15.6% and -5.3% in TG group, -8.9% and -3.3% in DG group (p=0.10 and 0.49, respectively). Conclusion The patients experienced DI loss of approximately 10% at 1 month after gastrectomy. Patients who received TG tended to show a greater %DI loss at 1 month postoperatively.

Background: We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on the pancreatic cancer survival and recurrence after curative surgery followed by adjuvant chemotherapy. Patients and Methods: This study included 155 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. Results: An ACCI of 8 was regarded as the optimum critical point of classification considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 25.7% and 19.0% in the ACCI-low group, respectively, and 7.6% and 0% in the ACCI-high group, which amounted to a statistically significant difference (P = 0.019). The RFS rates at 3 and 5 years after surgery were 17.3% and 13.8% in the ACCI-low group, respectively, and 7.1% and 0% in the ACCI-high group, which amounted to a marginally statistically significant difference (P = 0.104). A multivariate analysis showed that the ACCI was a significant independent risk factor for both the OS and RFS. Conclusions: The ACCI was a risk factor for the OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. An effective plan is needed for determining the optimum surgical strategy according to the ACCI.

Objectives The multidrug regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is widely used for recurrent pancreatic cancer after pancreatic resection. However, there are concerns about severe toxicities and poor tolerability of FOLFIRINOX in these patients because some suffer from surgery-associated malnutrition, weight loss, and diabetes mellitus. We evaluated the toxicity and tolerability of FOLFIRINOX in these patients. Methods This study was conducted as a secondary analysis of the Japan Adjuvant Study Group of Pancreatic Cancer 06 study, which was a multicenter observational study of FOLFIRINOX for pancreatic cancer in Japan. The toxicity and tolerability of FOLFIRINOX in recurrent disease correlated with those of both the locally advanced and the metastatic disease group. Results The major grades 3 and 4 toxicities observed in the recurrent and locally advanced or metastatic disease groups were neutropenia (68% vs 63%), febrile neutropenia (4% vs 15%, P = 0.007), thrombocytopenia (4% vs 3%), diarrhea (4% vs 8%), and sensory neuropathy (0% vs 2%). The dose modification and relative dose intensity did not differ markedly between the groups. Conclusions The toxicity and tolerability of FOLFIRINOX for recurrence after pancreatic resection were similar to those for locally advanced or metastatic disease with appropriate patient selection and dose modifications.