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A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino-acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium β-hydroxy-β-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥ III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight were significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p < 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino-acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

Purpose: Distant metastasis develops in approximately one-third of patients with colorectal cancer (CRC) who undergo radical surgery, and colorectal liver metastasis (CRLM) is the most common form of distant metastasis in CRC. Hepatectomy is the only potentially curative treatment for CRLM, but few patients with metastatic CRC meet the criteria for this radical resection, and the 5-year survival rate is poor. Identifying risk factors for CRLM is critical. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for CRC. However, the effect of NAFLD on CRC liver metastasis after radical surgery remains unclear. Therefore, we examined the impact of NAFLD-associated hepatic fibrosis on liver metastasis after radical surgery for CRC., Methods: We retrospectively analyzed data from 388 patients who underwent curative surgery for CRC at our hospital between April 2008 and March 2015. The patients' clinical results, surgical procedures, postoperative course, and pathological and survival data were collected from the hospital records. The NAFLD fibrosis score was calculated and used to divide the patients into two groups (NAFLD and non-NAFLD)., Results: Recurrence was observed in 83/388 (21.4%) patients after a mean follow-up of 65.6 ± 15.1 months. Twenty-five patients had liver metastasis: 8 in the NAFLD group (8/45; 17.8%) and 17 in the non-NALFD group (17/343; 5.0%) (p = 0.004). Liver metastasis-free survival was significantly worse in the NAFLD than non-NAFLD group (p < 0.001). NAFLD and cancer stage were independent risk factors for liver metastasis recurrence., Conclusion: NAFLD may be a risk factor for liver metastasis in patients with CRC who undergo curative surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: This study aimed to evaluate the prognostic factors in T4b gastric cancer (GC) in order to improve future therapeutic strategies., Methods: We retrospectively analyzed the medical records of 43 patients with advanced GC who underwent surgery and were surgically or pathologically diagnosed with T4b GC. The overall survival (OS) rate of patients with T4b GC was analyzed, and univariate and multivariate analyses were performed to identify clinicopathological factors that were independently associated with OS. In addition, we assessed the relationship between postoperative chemotherapy and laboratory parameters 4 weeks post-surgery., Results: The proportion of patients with invasion of cancer in organs, including the pancreas, transverse colon, and liver, were 58.1%, 18.6%, and 14.0%, respectively. The proportion of patients who exhibited distant metastases was 44.2%, and R0 resection was achieved in 30.2% of patients. A total of 69.8% of patients underwent postoperative chemotherapy. The median survival rate was 12.3 months. Upon multivariate analysis, the presence of distant metastases (P = 0.01, HR; 3.48), the use of postoperative chemotherapy (P = 0.0004, HR; 0.12), and R0 resection (P < 0.0001, HR; 0.14) were significantly correlated with OS. Patients who did not undergo postoperative chemotherapy showed significantly higher levels of inflammatory parameters and lower levels of nutritional parameters 4 weeks after surgery than those who did., Conclusions: We evaluated that the presence of distant metastases was significantly associated with a poor prognosis, and the use of postoperative chemotherapy and R0 resection was significantly associated with a better prognosis in patients with T4b GC. It would be more important for a T4b GC treatment to balance between therapeutic tolerance for postoperative chemotherapy and surgical therapeutic effect., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Cancer cells at the invasive front are believed to be responsible for invasion/metastasis. This has led to examining various morphological features and protein expressions at the invasive front. However, accurate assessment of the pathological section requires long-time training, and inter-observer disagreement is problematic. Immunohistochemistry and digital imaging analysis may mitigate these problems; however, the choice of which proteins to stain and the best analysis method remains controversial. We used the "go-or-grow" hypothesis to select markers with the greatest prognostic relevance. Importantly, nonproliferating cells can migrate. We used Ki67 as a proliferation marker, with p16 and p21 designating nonproliferating cells. We established a semi-automated quantification workflow to study protein expression in serial pathological sections. A total of 51 patients with completely resected colorectal cancer (stages I-IV) were analyzed, and 44 patients were followed up. Patients with cancer cells with p16-high/p21-low or p21-low/Ki67-low at the deepest invasive front demonstrated a significantly worse prognosis than those who did not display these characteristics. These results suggest that the nonproliferating cancer cells at the invasion front possess invasion/metastatic property with heterogeneity of senescence., (© 2022 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

A 62-year-old male presented with right intercostal muscle pain. Clinical examination revealed muscular defense in the same area. Abdominal ultrasonography revealed a distended gallbladder and ascites effusion, but no gallstones or polyps were present. Contrast-enhanced computerized tomography was performed, which revealed luminal obstruction due to arterial dissection of the celiac artery and intrinsic hepatic artery. This finding suggested gangrenous cholecystitis; thus, urgent cholecystectomy was performed. Only a few cases of celiac artery dissection and only one case of gangrenous cholecystitis without stones have been reported. We report here an extremely rare case of celiac artery dissection.

Background/aim: This study aimed to evaluate the relationship between clinical outcomes and intra-tumoral fibroblast growth factor receptor 2 (FGFR2) expression in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) patients who had undergone HER2-targeted chemotherapy., Patients and Methods: A retrospective analysis was performed in 22 patients with HER2-positive GC, who had undergone systemic chemotherapy. We performed immunohistochemistry staining of FGFR2 expression using surgically resected specimens or biopsied samples and evaluated clinicopathological characteristic and overall survival (OS) in the FGFR2-negative and -positive GC groups., Results: A total of 8 and 14 patients were placed in the FGFR2-negative and -positive group, respectively. The median OS rates were 56.2 and 16.0 months in the FGFR2-negative and -positive groups, respectively. The FGFR2-negative group had a significantly better prognosis after HER2-targeted chemotherapy [p=0.027 (log-rank test)]. The univariate analysis revealed that performing gastrectomy, response to combination chemotherapy with trastuzumab, and FGFR2 positivity were significantly correlated with OS. In a multivariate analysis, the response to combination chemotherapy with trastuzumab (p=0.008) was significantly correlated with OS. In addition, the proportions of patients who showed CR or PR in response to chemotherapy were 87.5 and 42.9% in the FGFR2-negative and -positive groups, respectively (p=0.031)., Conclusion: HER2-positive GC patients, without overexpression of FGFR2, exhibited an improved prognosis and response rate to trastuzumab combination chemotherapy. Assessment of intra-tumoral FGFR2 expression could be helpful in predicting the prognosis and response to trastuzumab in HER2-positive GC patients., Competing Interests: The Authors declare no competing interest in connection with this study., (Copyright 2022, International Institute of Anticancer Research.)

Background/aim: Following oxaliplatin-based chemotherapy, approximately half of all colorectal cancer patients develop sinusoidal obstruction syndrome (SOS). SOS can be monitored by measuring splenic volume; however, obtaining this measurement is not a simple process. In this study, we evaluated changes in hyaluronic acid (HA) concentrations as a simpler marker of SOS., Patients and Methods: We measured splenic volume and laboratory data, including hyaluronic acid concentration, liver enzymes, and platelet counts, in 34 patients with colorectal cancer who underwent radical resection and who received capecitabine plus oxaliplatin (CapeOx) chemotherapy., Results: A strong correlation was identified between ≥30% increase in splenic volume and significantly elevated HA concentrations. Affected patients also had persistent thrombocytopenia and liver dysfunction compared to patients without elevated HA concentration., Conclusion: HA concentration may predict SOS in patients who receive CapeOx adjuvant chemotherapy., Competing Interests: The Authors declare they have no financial or other conflicts of interest., (Copyright 2022, International Institute of Anticancer Research.)

We investigated the effect of chemoradiotherapy(CRT)on pancreatic cancer and the significance of preoperative chemoradiotherapy( NACRT)on resectable pancreatic cancer. The subjects were 36 patients who underwent CRT for locally advanced pancreatic cancer experienced in our department in the past 12 years(. 1)Regarding the antitumor effect of CRT, tumor diameter, tumor marker, and FDG for PET examination were reduced in 72%, 81%, and 96% of cases, respectively. In addition, the effect of Grade 1b plus 2 was observed in 10 of 16 patients who were resected after CRT(response rate 63%). In these successful cases, irradiation of 40 Gy or more and oral administration of S-1 1,500 mg or more were performed during this period. In addition, the survival rate of the NACRT plus S group(16 cases)was the same as that of the SF group (20 cases)of cStage ⅡA or lower at the same time, 50% survival was longer, and local recurrence was less. Based on the above, preoperative chemoradiotherapy combined with S-1 for resectable pancreatic cancer may be a promising preoperative treatment in the future.

Background/aim: A significant predictive factor for the occurrence of complications after gastrectomy in elderly gastric cancer patients is yet to be determined. We aimed to evaluate the clinical factors associated with overall complications including remote infection after gastrectomy in elderly gastric cancer patients., Patients and Methods: We retrospectively analyzed data of 101 patients aged over 80 years, who underwent curative gastrectomy. We analyzed the clinicopathological factors that were independently associated with the occurrence of overall complications or remote infection by a logistic regression model., Results: The overall complication rate was 24.8%. We identified pneumonia as a remote infection, and the occurrence rate of remote infections was 5.9%. On multivariate analysis, hemoglobin (<11 g/dl) and operation time (>240 min) were significantly correlated with the occurrence of overall complications. Regarding the occurrence of remote infection, performing total gastrectomy and a hemoglobin level <11 g/dl were identified as significant risk factors., Conclusion: Preoperative anemia and intraoperative factors, including the surgical procedure, could affect the occurrence of postoperative complications in elderly patients., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG., Methods: We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups., Results: Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006)., Conclusions: We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG., (© 2021. The Author(s).)

Introduction: In patients with gastric cancer, 6-27% of patients are diagnosed with T4b disease that invades adjacent organs, and curative resection can improve the prognosis of these patients., Case Presentation: A 70-year-old Japanese man presented with an abdominal tumor and was diagnosed with advanced gastric cancer (L-Circ type 3 T4b N2 M0 H0 stage IVA, based on the 15th edition of the Japanese Classification of Gastric Carcinoma) with extensive abdominal wall invasion. We performed open gastrojejunal bypass for gastric obstruction and initiated a chemotherapeutic regimen comprising S-1 (120 mg/day) and oxaliplatin (100 mg/m 2 ). Upper gastrointestinal endoscopy performed after the administration of six courses of the S-1 and oxaliplatin regimen revealed a persistent primary lower gastric wall lesion; however, the diameter of the abdominal wall invasion and metastatic lymph nodes was significantly reduced, in addition to decreased serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Subsequently, the patient underwent distal gastrectomy with D2 lymphadenectomy combined with transverse colon and abdominal wall resection. We performed radical en bloc resection and achieved a tumor-free resection margin. Simple abdominal wall closure was performed without mesh or musculocutaneous flap placement. Histopathological examination of the resected tumor specimen showed direct invasion of the mesocolon and rectus abdominis muscle. The patient was postoperatively diagnosed with L Gre-Ant type5 T4b (SI: rectus abdominis muscle) N2 PM0 DM0 Stage IIIA R0 Grade 2a gastric cancer based on histopathological findings and received S-1 as adjuvant chemotherapy, 2 months postoperatively. No recurrence was detected 6 months postoperatively., Conclusions: We report a case of advanced gastric cancer with extensive abdominal wall invasion that was successfully treated with gastrectomy combined with resection of adjacent organs showing tumor invasion after effective systemic chemotherapy. A therapeutic approach comprising curative surgery combined with perioperative chemotherapy is useful in patients with T4b gastric cancer.

Background: /Objective: We evaluated the risk of acute cholangitis and/or cholecystitis while waiting for cholecystectomy for gallstones., Methods: We retrospectively enrolled 168 patients who underwent cholecystectomy for gallstones after conservative therapy. We compared clinical data of 20 patients who developed acute cholangitis and/or cholecystitis while waiting for cholecystectomy (group A) with 148 patients who did not develop (group B). We investigated surgical outcomes and risk factors for developing acute cholangitis and/or cholecystitis., Results: Preoperatively, significant numbers of patients with previous history of acute grade II or III cholecystitis (55.0% vs 10.8%; p < 0.001) and biliary drainage (20.0% vs 2.0%; p = 0.004) were observed between groups A and B. White blood cell counts (13500/μL vs 8155/μL; p < 0.001) and C-reactive protein levels (12.6 vs 5.1 mg/dL; p < 0.001) were significantly higher in group A than in group B; albumin levels (3.2 vs 4.0 g/dL; p < 0.001) were significantly lower in group A. Gallbladder wall thickening (≥5 mm) (45.0% vs 18.9%; p = 0.018), incarcerated gallbladder neck stones (55.0% vs 22.3%; p = 0.005), and peri-gallbladder abscess (20.0% vs 1.4%; p = 0.002) were significantly more frequent in group A than in group B. A higher conversion rate to open surgery (20.0% vs 2.0%; p = 0.004), longer operation time (137 vs 102 min; p < 0.001), and higher incidence of intraoperative complications (10.0% vs 0%; p = 0.014) were observed in group A, compared with group B., Conclusion: A history of severe cholecystitis may be a risk factor for acute cholangitis and/or cholecystitis in patients waiting for surgery; it may also contribute to increased surgical difficulty., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Taiwan LLC.)

We investigated 34 cases of preoperative chemoradiotherapy(CRT)for locally advanced pancreatic cancer including resectable pancreatic cancer in our department during the past 11 years. For resectable(R)or borderline resectable(BR)pancreatic cancer, survival curves were generally higher in the CRT plus S-1 group treated after CRT than in the CRT group treated with post-CRT chemotherapy, but there was no statistically significant difference. In non-resected cases, local exacerbation was observed, which was one of the causes of a decline in terminal QOL. From the above, at present, it is desirable to remove R or BR pancreatic cancer after CRT, but the significance of surgery may change in the future due to the improvement of multidisciplinary treatment.

Background: Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC)., Methods: This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses., Results: Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4-60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group., Conclusions: Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial., Clinical Trial Registration: UMIN000010638.

Background: Nivolumab has been approved for use in advanced gastric cancer (GC) after third-line chemotherapy in Japan. However, it remains difficult to predict favorable nivolumab response before treatment., Methods: We evaluated the clinical course with a focus on the chronological changes in neutrophil/lymphocyte ratio (NLR) throughout the chemotherapy and assessed the relationship between nivolumab response and chronological changes in NLR before nivolumab administration., Results: We experienced nine cases who received nivolumab monotherapy for unresectable advanced or postoperative recurrent GC. Nivolumab was used as third-line chemotherapy in all patients, and partial response (PR) and stable disease (SD) were observed in two patients each. Nivolumab treatment resulted in progressive disease (PD) in five patients. In patients with PR or SD, changes in the NLR tended to correspond to the response of target metastatic lymph nodes to first- and second-line chemotherapy. In the four cases with PR or SD following nivolumab, ∆NLRresponses that was the difference in the degree of decline during the most effective pretreatment chemotherapy were 1.39, 0.73, 1.62, and 1.22. However, the patients with PD showed lower ∆NLRresponses, at 0.66, 0.66, 0.25, 0.13, and -0.05 in the five cases. Mean ∆NLRresponses in the patients with PR or SD and patients with PD were 1.17 and 0.33, respectively (P = 0.0008)., Conclusions: We experienced nine GC cases treated with nivolumab and assessed the association between chronological NLR changes throughout chemotherapy and tumor response to nivolumab. Changes in NLR during pretreatment chemotherapy might predict tumor response to nivolumab monotherapy in patients with advanced GC., .

It has previously been suggested that postgastrectomy syndrome (PGS) is more severe in patients after surgery for advanced gastric cancer than in patients with early gastric cancer. Using the postgastrectomy syndrome assessment scale-45 (PGSAS-45), the present study aimed to determine whether PGS for postgastrectomy patients, in Kanazawa Medical University Hospital, with advanced gastric cancer was more severe than for patients with early gastric cancer. A questionnaire survey was conducted using PGSAS-45 for curative gastric cancer gastrectomy cases at Kanazawa Medical University Hospital. The questionnaire data were combined with patient background data, anonymized and moved to an unlinked file for patient privacy. Using this dataset, non-recurrent cases of distal partial gastrectomy were extracted and divided into two groups, stage IA or IB patients (group E), and stage IIA or higher (group A). The main outcome measures (MOMs) of PGSAS-45 were compared between the two groups. The participants in the present study included 35 cases in group E and 22 cases in group A. The results of a univariate analysis to compare the MOMs between the two groups showed that only the dumping subscale was significantly different in group A and was judged to be caused by the underlying bias of the background factor. There were no MOMs with significant differences in the pathological stage based on multiple regression analyses. In cases of distal partial gastrectomy, the PGS and quality of life (QoL) of patients following advanced gastric cancer surgery were similar to those of patients with early gastric cancer. The standardized treatment for advanced gastric cancer did not induce notable postoperative failures, and QoL was not impaired. In contrast, for early-stage gastric cancer cases, the present study suggests that it is necessary to distinguish metastasis-negative cases to indicate an appropriate, function-preserving curative gastrectomy., (Copyright: © Kinami et al.)

A 66-year-old man was diagnosed with advanced gastric cancer(L, Less, Type 2, T4a[SE], N2, M1[LYM], H0, P0, cStage Ⅳ)and received treatment with S-1/cisplatin as first-line chemotherapy. This treatment resulted in partial response(PR) after 3 months, with reduction in the sizes of metastatic lymph nodes surrounding the pancreatic head and paraaortic lesion. However, the sizes of metastatic lymph nodes increased after 7 months of chemotherapy. Ramucirumab/nab-paclitaxel was then administered as second-line chemotherapy, and the diameter of the metastatic lymph nodes subsequently decreased after 4 months of the regimen. However, progressive disease was observed at 7 months, and blood transfusion was required because of bleeding from the primary gastric tumor. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the first treatment. After nivolumab administration, a 28% reduction in metastatic lymph nodes was achieved within 3 months, together with the regression of the primary gastric tumor and improvement in anemia within 6 months. PR was achieved after 12 months of nivolumab administration, and effective disease control was maintained for 16 months without any adverse reaction to nivolumab.

Background: There is an increased need for accurate staging for gastric cancer treatment. Consequently, it is necessary to carefully examine all dissected lymph nodes for precise staging. Recently, the fat-dissociation method has been developed as a quick and accurate method for harvesting dissected lymph nodes of colorectal cancer cases., Aim: To investigate the usefulness of the fat-dissociation method for harvesting dissected lymph nodes of gastric cancer cases., Methods: Fifty-six resected specimens from gastric cancer patients who underwent standard curative gastrectomy and lymph node dissection at our hospital were used. Group 2 lymph nodes were separated from each specimen, and the remaining adipose tissue containing the group 1 lymph nodes was used. Some resected specimens were subjected to the fat-dissociation method. One vial of Imofully ® was dissolved in 50 mL of saline and injected into the tissue. The tissue was incubated for 1 h and the dissolved fat was removed. Subsequently, the nodes were identified, picked up with scissors, and mapped. The number of nodes in each lymphatic compartment and duration of lymph node harvest and mapping were compared., Results: The fat-dissociation method was used for 24 samples, while the conventional dissection method was used for 32 samples. The total number of harvested lymph nodes was 45.9 in the fat dissociation group and 44.3 in the control group, and there was no significant difference between the two groups. There were also no significant differences in the number of lymph nodes between the two groups based on a comparison of the lymphatic compartments. However, the total median duration of the fat-dissociation method was 38.2 min, reflecting a reduced duration of approximately 60 min compared to the control group., Conclusion: Based on our results, the fat-dissociation method is effective in shortening the duration of lymph node harvest in gastric cancer surgery., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Peripheral neuropathy (PN) is an intractable side effect of oxaliplatin, with no effective prophylaxis so far. Ninjin'yoeito (NYT), a Kampo medicine, is protective against oxaliplatin-induced neuronal cell injury in vitro and ameliorates oxaliplatin-induced PN in vivo. Thus, this randomized controlled trial was aimed at clarifying NYT's prophylactic effect for oxaliplatin-induced cumulative PN., Methods: 52 patients with colorectal cancers of pathological stage 3 received postoperative adjuvant chemotherapy with the CapeOX regimen: eight cycles of capecitabine (2400 mg/m 2 ) plus oxaliplatin (130 mg/m 2 ) at 3-week intervals. They were randomly assigned to NYT administration and non-administration groups. NYT (9.0 g/day) was administered from day 1 of cycle 1 in the NYT group. The NYT was administered orally daily throughout each cycle. The primary endpoint was the grade of cumulative PN at the end of eight cycles. The secondary endpoints included relative dose intensity (RDI) of oxaliplatin, recurrence-free survival (RFS), and overall survival (OS)., Results: 40 patients (n = 20 in both groups) completed 8 chemotherapy cycles. The incidence of grade 2 or greater cumulative PN at the 8th chemotherapy cycle was significantly lower in the NYT group (2/20, 10.0%) than in the control group (11/20, 55.0%, P < 0.01). RDI of oxaliplatin was significantly higher in the NYT group than in the control group (P = 0.02). RFS and OS were better in the NYT group than in the control group, but the difference was not significant., Conclusions: NYT may reduce the incidence of oxaliplatin-induced cumulative PN and facilitate maintenance of the CapeOX dosing regimen.

Background/aim: We evaluated whether splenic volume (SV) predicts sinusoidal obstruction syndrome (SOS) in colorectal cancer (CRC) patients receiving capecitabine plus oxaliplatin (CapeOX) therapy., Patients and Methods: In this retrospective study, we measured SV in 41 patients receiving adjuvant CapeOX for CRC at five different time points. We compared the clinical data of the 18 patients who experienced ≥30% increases in SV immediately after vs. before CapeOX (group A) with data for the remaining 23 patients (group B)., Results: Platelet numbers decreased and the levels of hepatobiliary enzymes increased significantly 1 year after CapeOX compared with before CapeOX in group A. However, in group B, significantly decreased platelet numbers and significantly increased aspartate transaminase levels were confirmed only immediately after CapeOX, with no significant subsequent changes., Conclusion: SV was significantly associated with thrombocytopenia and liver dysfunction in CRC patients, and predicted SOS., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Conversion surgery (CS) following a response to chemotherapy occasionally leads to prolonged survival in patients with stage IV gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the success of CS in patients with stage IV GC., Methods: We retrospectively analyzed data of 50 patients with stage IV GC who received systemic chemotherapy between January 2009 and December 2017 at the Kanazawa Medical University Hospital. The successful CS group included the patients who underwent R0 or R1 resection with CS, and the failed CS group included the patients who did not undergo CS after chemotherapy or those who, despite undergoing CS, had to additionally undergo R2 resection. Clinicopathological characteristics were examined in both groups. Univariate and multivariate analyses were performed to identify pretherapeutic parameters that were independently associated with the achievement of successful CS., Results: The number of patients in the successful and failed CS groups were 12 and 38, respectively. On univariate analysis, gender (P = 0.01), NLR (P = 0.003), albumin levels (P = 0.004), and absence of peritoneal metastasis (P = 0.004) were found to be significantly correlated with a successful CS. On multivariate analysis, NLR < 4 and absence of peritoneal metastasis were independently correlated with a successful CS (P = 0.02 and P = 0.002, respectively). In patients without peritoneal metastasis, successful CS rates in patients with NLR < 4 were significantly higher than those in patients with NLR ≥ 4 (61.1% vs. 10.0%, P = 0.005)., Conclusions: The NLR was a significant independent predictor of the achievement of successful CS in stage IV GC patients, especially among the patients without peritoneal metastasis. Patients with a low NLR could have higher possibility of achieving successful CS.

Background: The reliability of preoperative nodal diagnosis of advanced gastric cancer by multi-detector spiral computed tomography (MDCT) is still unclear., Aim: To examine the diagnostic ability of MDCT more precisely by using data on intranodal pathological metastatic patterns., Methods: A total of 108 patients with advanced gastric cancer who underwent MDCT and curative gastrectomy at Kanazawa Medical University Hospital were enrolled in this study. The nodal sizes measured on computed tomography (CT) images were compared with the pathology results. A receiver-operating characteristic curve was constructed, from which the critical value (CV) was calculated by using the data of the first 69 patients retrospectively. By using the CV, sensitivity and specificity were calculated with prospectively collected data from 39 consecutive patients. This enabled a more precise one-to-one correspondence of lymph nodes between CT and pathological examination by using the size data of lymph node mapping. The intranodal pathological metastatic patterns were classified into the following four types: Small nodular, peripheral, large nodular, and diffuse., Results: Although all the cases were clinically suspected as having metastasis, 81 had lymph node metastasis and 27 had no metastasis. The number of dissected, detected on CT, and metastatic nodes were, 4241, 897, and 801, respectively. The CV obtained from the receiver-operating characteristic was 7.6 mm for the long axis. The sensitivity was 91.4% and the specificity was 47.3% in the prospective phase. The large nodular and diffuse metastases were easy to diagnose because metastatic nodes with a large axis often exhibit these forms., Conclusion: The ability of MDCT to contribute to a nodal diagnosis of advanced gastric cancer was examined prospectively with precise size data from node mapping, using a CV of 7.6 mm for the long axis that was calculated from the retrospectively collected data. The sensitivity was as high as 91%, and would be improved when referring to the enhanced patterns. However, its specificity was as low as 47%, because most of metastatic nodes in gastric cancer being small in size. The small nodular or peripheral type metastatic nodes were often small and considered difficult to diagnose., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Multicellular structures, such as tumor buddings and poorly differentiated clusters (PDC), exist at the invasive front of colorectal cancers (CRC). Although it has been reported that CRC with PDC showed frequent lymph node metastases with a worse prognosis, the molecular markers of PDC that are responsible for prognosis have not been identified. We here noticed for the first time that Ezrin, a regulator of the actin cytoskeleton, is expressed in the corner cells of PDC. We then aimed to verify whether heterogeneous Ezrin expression in PDC predicts the prognosis of CRC patients. We immunohistochemically analyzed Ezrin expression in PDC of 184 patients with completely resected stages I-III CRC. We established the Ezrin corner score (ECS), which quantifies the tendency of Ezrin-positive cells to accumulate at the corners of PDC. On the basis of ECS values, 2 indices, the mean ECS and the number of PDC with high ECS, were obtained. Both indices were significantly higher in CRC with lymphatic invasion, higher PDC grade, and presence of micropapillary (MP) PDC. The mean ECS-high group showed shorter recurrence-free survival than the mean ECS-low group but without significance. The other index, the number of ECS-high PDC, was significantly associated with recurrence-free survival. These results suggest that Ezrin is involved in PDC progression and lymphatic invasion, and that ECS may be a marker for aggressive PDC., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The use of staging laparoscopy (SL) has become widespread in patients with advanced gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the presence of peritoneal metastasis during staging laparoscopy in patients with advanced GC., Methods: This retrospective analysis was performed in 35 patients with advanced GC who underwent SL at Kanazawa Medical University Hospital between January 2009 and December 2017. Clinicopathological characteristics were examined and multivariate analyses were performed to identify preoperative laboratory parameters that were independently associated with the presence of peritoneal metastasis or cytological malignancy (P/CY positive) during SL., Results: A P/CY-positive result was confirmed during SL in 16 patients (45.7%). Patients with type 4 or diffuse type 3 tumors showed a significantly higher P/CY-positive rate than those with other tumor types (58.3% vs. 18.2%, P = 0.02). In the univariate analysis for preoperative laboratory parameters, NLR (P < 0.0001) and total protein (P = 0.03) and albumin (P = 0.04) levels were significantly correlated with a P/CY-positive result. On multivariate analysis, NLR was significantly correlated with a P/CY-positive result (P = 0.0002). In patients with type 4 or diffuse type 3 tumors, a high NLR (> 3.5) was associated with a significantly higher P/CY-positive rate than a low NLR (≤ 3.5) (83.3% vs. 33.3%, P = 0.01). Moreover, in patients without type 4 or diffuse type 3 tumors, the P/CY-positive rates were 100% and 0% in patients with NLR > 3.5 and NLR ≤ 3.5, respectively., Conclusions: The preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis during SL. Regardless of tumor type, patients with a high NLR could be reasonable candidates for SL. On the other hand, non-diffuse type tumor accompanied by a low NLR may not need to undergo SL.

The gravest prognostic factor in early gastric cancer is lymph-node metastasis, with an incidence of about 10% overall. About two-thirds of early gastric cancer patients can be diagnosed as node-negative prior to treatment based on clinic-pathological data. Thus, the tumor can be resected by endoscopic submucosal dissection. In the remaining third, surgical resection is necessary because of the possibility of nodal metastasis. Nevertheless, almost all patients can be cured by gastrectomy with D1+ lymph-node dissection. Laparoscopic or robotic gastrectomy has become widespread in East Asia because perioperative and oncological safety are similar to open surgery. However, after D1+ gastrectomy, functional symptoms may still result. Physicians must strive to minimize post-gastrectomy symptoms and optimize long-term quality of life after this operation. Depending on the location and size of the primary lesion, preservation of the pylorus or cardia should be considered. In addition, the extent of lymph-node dissection can be individualized, and significant gastric-volume preservation can be achieved if sentinel node biopsy is used to distinguish node-negative patients. Though the surgical treatment for early gastric cancer may be less radical than in the past, the operative method itself seems to be still in transition., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest related to the publication of the study.

A 49-year-old man underwent sigmoidectomy for the diagnosis of type 2 sigmoid cancer. Pathological findings showed a tumor 3.5×4.0cm in size, type 2, pSS, ly2, v1, pN0, cH0, cP0, cM0, pStageⅡ, R0. Asynchronistic metastases to the liver and lungs were subsequently found. Left hepatectomy was performed for 1 liver metastasis, and 4lung metastases were resected through 3 surgeries. A subcutaneous tumor in an abdominal wall scar was also resected in the 4th surgery for metastasis resection. All pathological diagnoses were metastases from sigmoid cancer, and complete curative resection was possible. The final surgery was performed 1 year and 1 month prior, and the patient has now survived without recurrence for 10 years and 2 months after sigmoidectomy. Chemotherapy was not administered during the whole course. This case shows that longterm survival is possible with repeated resection of recurrent metastasis of sigmoid cancer.

A 73-year-old man presented to a clinic complaining of upper abdominal pain with nausea and diarrhea. The patient was subsequently diagnosed with progressive gastric cancer: cT4a(SE), N3M1(H1P1), Stage IV . For first-line therapy, SP: S-1(120 mg, 3 weeks)and CDDP(90 mg, 8 days iv) were selected. Though the patient had Grade 3 thrombocytopenia and renal dysfunction, 13 courses were performed over 1 year 6 months. The primary lesion in the stomach showed complete response, while the metastatic foci in the liver reduced in size. Because of renal dysfunction and thrombocytopenia, 19 courses of SOX: S-1(80 mg, 2 weeks)and oxaliplatin(100 mg, 3 weeks)were administered for 1 year. Thereafter, S-1(80 mg, 4 weeks) was continued for 6 months. Appropriate administration of chemotherapy led to complete radiographic resolution of the gastric tumor, with survival currently approaching 3 years 6 months.

Background: We evaluated the efficacy of surgical resection following response to primary chemotherapy for prospective registered Stage IV gastric cancer patients., Patients and Methods: We analyzed the details and prognosis of 6 patients having advanced gastric cancer clinically diagnosed as resectable following primary chemotherapy between 2011 and 2015., Results: The reason for being diagnosed as unresectable before chemotherapy was metastasis to distant sites, including paraaortic lymph node metastasis in 3 cases, peritoneal metastasis in 2 cases, and liver metastasis in 1 case.Two patients were able to undergo R0 resection, and the remaining 4 patients were unable to undergo complete resection.The median survival time (MST)of the patients who underwent R0 resection was 567.5 days, and the MST of the patients who could not undergo R0 resection was 474 days., Conclusion: Careful consideration of conversion gastrectomy may be important in inducing longterm survival in clinical Stage IV gastric cancer patients.

A 49-year-old man was referred to a neighboring hospital with a chief complaint of abdominal pain.He was diagnosed with locally advanced body-tail pancreatic cancer that had invaded the celiac artery and SMA.He came to our department after undergoing radiotherapy, 2.5 Gy×22 Fr, and chemotherapy with gemcitabine(GEM)and S-1.The same chemotherapy was continued for 15 months until DIC occurred.He was subsequently treated with GEM only and then S-1 only in sequence for 6 years.We decided to stop the chemotherapy because the original lesion had been stable for a long time.After 1 month, a hard nodule appeared in the subcutaneous layer of the navel.Although resection was performed and he received chemotherapy, he died after surviving a total of 7 years and 10 months.This case is important when considering whether to discontinue chemotherapy with a stable long-term pancreatic cancer patient.

The local resection of the stomach is an ideal method for preventing postoperative symptoms. There are various procedures for performing local resection, such as the laparoscopic lesion lifting method, non-touch lesion lifting method, endoscopic full-thickness resection, and laparoscopic endoscopic cooperative surgery. After the invention and widespread use of endoscopic submucosal dissection, local resection has become outdated as a curative surgical technique for gastric cancer. Nevertheless, local resection of the stomach in the treatment of gastric cancer in now expected to make a comeback with the clinical use of sentinel node navigation surgery. However, there are many issues associated with local resection for gastric cancer, other than the normal indications. These include gastric deformation, functional impairment, ensuring a safe surgical margin, the possibility of inducing peritoneal dissemination, and the associated increase in the risk of metachronous gastric cancer. In view of these issues, there is a tendency to regard local resection as an investigative treatment, to be applied only in carefully selected cases. The ideal model for local resection of the stomach for gastric cancer would be a combination of endoscopic full-thickness resection of the stomach using an ESD device and hand sutured closure using a laparoscope or a surgical robot, for achieving both oncological safety and preserved functions.

Background: The prognosis after neoadjuvant chemotherapy(NAC)is expected to improve in patients with resectable advanced gastric cancer who are at high risk of recurrence or those with unfavorable prognostic factors., Patients and Methods: This retrospective study examined treatment outcomes and survival of 25 patients with advanced gastric cancer who received NAC with S-1 and cisplatin(CDDP)between October 2008 and December 2015., Results: Among patients with clinical Stage II (4 patients)and III (21 patients)tumors, 13 had partial response(PR)and 12 had stable disease(SD). Neither complete response(CR)nor progressive disease(PD)was noted. CR of lymph node metastases was observed in 6 patients, PR in 9 patients, and SD in 7 patients. R0 resection was performed in 16 patients, R1 in 3 patients, and R2 in 6 patients. Histologic grades of primary tumors were Grade 0(1 patient), Grade 1a(16 patients), Grade 1b(5 patients), Grade 2(3 patients), and Grade 3(none). The 3-year survival rate after R0 resection was 46%, 3-year progression-free survival rate was 68%, and 3-year recurrence-free survival rate was 69%. Significant differences were observed for pathologic stages ypN0/1, 2, and 3(p=0.04), tumor down-stage(p=0.02), and overall tumor fStage I , II / III , and IV (p<0.01)., Conclusion: It is conceivable that R0 resection and downstaging after NAC will improve prognosis.

The following is a case report of moderately differentiated tubular adenocarcinoma of the stomach with widespread thrombosis of the portal vein, for which chemotherapy proved effective. A 75-year-old man presented to the clinic with a new onset ofmalaise. The patient had anemia, elevation ofliver and biliary enzymes, and significantly elevated CA19-9 levels at 43,581 U/mL and CEA levels at 2,560 ng/mL. An upper endoscopy revealed a mass lesion extending from the fundus to the pylorus as well as to the duodenum along the smaller curvature of the stomach. A biopsy revealed moderately differentiated tubular adenocarcinoma. Abdominal CT showed a mass lesion extending from the body of the stomach and penetrating through the gastric wall, and extensive lymphadenopathy in the surrounding areas. In addition, multiple thromboses were identified in the portal vein and its tributaries, including the inferior mesenteric vein, splenic vein, and intrahepatic capillaries. The patient subsequently received a single round ofS -1 and CDDP. The tumor demonstrated a marked response; the tumor size and lymphadenopathy showed a significant improvement and the CA19-9 level decreased. Because the patient's condition deteriorated, this chemotherapy regimen was discontinued. The patient was switched to S-1 monotherapy and is still alive today, 2 years 10 months after the initial diagnosis.

We report a case of a radical resection of cT3a gallbladder cancer after neoadjuvant chemotherapy(NAC). A 68-year-old man was referred to our hospital with a chief complaint of right hypochondralgia.Imaging findings were consistent with acute cholecystitis with a stone at the neck of the gallbladder, and advanced gallbladder cancer with infiltration into segments 4 and 5 from the fundus of the gallbladder, Gfb, cT3a(liver), cN1(8a), cM0, cStage III B, was diagnosed on staging laparoscopy. The patient received 3 courses of GEM plus CDDP NAC.The response to the treatment included reduction of the main tumor by 35%, diminished accumulation of FDG at the 8a lymph node, and decrease in serum CA19-9, from 163 U/mL to 75 U/mL. Cholecystectomy with the gallbladder bed and regional lymphadenectomy were performed.The histologic examination revealed extensive necrosis and degeneration of cancer cells in the infiltrating lesions, and the therapeutic effect was judged as Grade I b.The patient has now survived for 11 months without recurrence.

Indocyanine green (ICG) fluorescence imaging represents a promising method for sentinel node (SN) biopsy in laparoscopic gastric surgery due to its signal stability. In the present study, the suitability and optimal settings of ICG fluorescence imaging for SN biopsy in early gastric cancer were determined. Patients with single primary superficial-type adenocarcinoma of the stomach, lesions <5 cm in diameter, and no evident nodal metastasis and out of indication for endoscopic submucosal dissection were enrolled. The day prior to surgery, ICG solution was endoscopically injected into four quadrants of the submucosal layer of the tumor. The Photodynamic Eye was used to detect ICG fluorescence. Bright nodes were defined as clearly fluorescent nodes. A total of 72 patients were enrolled; 11 cases presented with metastasis, and of these, 10 could be diagnosed by bright node biopsy. The adequate concentration and injection volume of ICG was determined to be 50 µg/ml (×100) and 0.5 mlx4 points, respectively. There was 1 false-negative case, and this was attributed to the failure of the frozen section diagnosis. These results suggested that ICG fluorescence imaging for SN biopsy in laparoscopic surgery for early gastric cancer is feasible. However, a weakness of ICG fluorescence imaging is the subjectivity of bright node evaluation.

Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%-20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions., Patients and Methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of hypersensitivity reactions., Results: Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%., Conclusion: The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned.

Background: Esophageal bypass surgery is palliative surgery for unresectable esophageal cancer with esophageal stenosis, which often leads to poor nutrition. We investigated the clinical characteristics, nutritional status, and outcomes of patients who underwent esophageal bypass surgery., Patients and Methods: We reviewed 11 cases of esophageal bypass surgery for unresectable esophageal cancer performed in our hospital between 1992 and 2015, and we examined the surgical outcome along with preoperative nutritional assessment., Results: There were 1, 9, and 1 cases of cStage Ⅲ, Ⅳa, and Ⅳb, respectively. For the bypass, a gastric tube was used in 8 cases and colon reconstruction in 3. Postoperative complications were 1 case of recurrent laryngeal nerve palsy (9%), 4 cases of anastomotic leakage (36%), and 4 cases of pneumonia (36%). The preoperative nutritional status (total protein, albumin, and cholinesterase levels) in the esophageal bypass group (n=11) was significantly worse than that in the esophagectomy group (n=40). The median survival of all patients (n=11) was 5.7 months. Patients receiving induction chemoradiotherapy followed by bypass surgery (n=7) had a median survival of 15.2 months., Conclusion: Since patients undergoing esophageal bypass surgery often present with malnutrition, attention to anastomotic leakage and infectious complications is necessary.

A 57-year-old woman was diagnosed with a pancreatic tumor. Abdominal computed tomography showed cStage Ⅳa pancreatic cancer with a 20×16 mm tumor near the base of the celiac artery. Since the tumor contacted the SMA at an angle of 90 degrees, it was judged as a borderline resectable tumor. In addition, cStage ⅠB gastric cancer was found in the corpus ventriculi. Since the patient had a respiratory complication, a distal pancreatectomy with celiac axis resection in combination with a total gastrectomy was considered too aggressive for this patient. Therefore, she received chemoradiotherapy prior to the surgery. Distal pancreatectomy with D2 lymphadenectomy and subtotal gastrectomy with lower left phrenic artery preservation was performed. This case involved a considerable extension of the disease and radical surgery; however, currently the patient's prognosis and QOL are good.

We present a successful case of treatment of colonic metastasis and peritoneal recurrence of type 4 gastric cancer by using colectomy and chemotherapy. A 70-year-old woman with a diagnosis of type 4 advanced gastric cancer underwent distal gastrectomy. The final pathological diagnosis was LM, circ, type 4, sig, pT4a (SE), ly1, v1, pN1, M0, P0, CY0, pStage Ⅲa. Adjuvant chemotherapy was conducted with oral administration of S-1, though regrettably the chemotherapy was interrupted because of diarrhea, an adverse effect of S-1. Metastatic recurrence occurred on the transverse colon, for which she underwent transverse colectomy 2.9 years after the initial surgery. Another colonic metastasis in the ascending colon along with peritoneal recurrence was diagnosed 3.11 years after the initial surgery, and the patient underwent a palliative colostomy and received chemotherapy with S-1 plus docetaxel. She was successfully treated up to a clinical CR with chemotherapy, and she died 5.10 years after the initial surgery. In this case, a good prognosis was obtained through the combination of resection of the recurrence sites, palliative surgery for avoiding obstruction, and chemotherapy using S-1 plus docetaxel for metachronous multiple metastases.

A woman in her 70s was referred for examination of liver dysfunction. A cystic lesion with irregular contrast was observed at the pancreas head. The bile and pancreatic ducts were obstructed by the lesion. Part of the branch of the pancreatic duct at the pancreas head, continuous with the main pancreatic duct, was observed to be extended by using pancreatography. Pancreaticoduodenectomy was performed, and a diagnosis of invasive carcinoma from an intraductal papillary-mucinous neoplasm (IPMN) was made. Postoperative pathological diagnosis showed 16b1 inter-node metastasis. Liver and lung metastases were also detected after surgery; nevertheless, long-term survival was achieved for 5 years and 2 months by using various treatment modalities.