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Abstract Aim We conducted a multicenter study on classical laparoscopic and endoscopic cooperative surgery (LECS) and LECS‐related procedures to retrospectively clarify the safety, problems, and mid‐term outcomes of these methods after their coverage by the national health insurance. Methods A total of 201 patients who underwent classical LECS/LECS‐related procedures for gastric submucosal tumors (G‐SMTs) in 21 institutions affiliated with the Laparoscopy Endoscopy Cooperative Surgery Study Group from April 2014 to March 2016 were included. Data was retrospectively obtained from the patients' charts. Results The most common surgical procedure was classical LECS (155 patients, 77.1%), non‐exposed endoscopic wall inversion surgery (22 patients, 11.4%), a combination of laparoscopic and endoscopic approaches to neoplasia with non‐exposure technique (16 patients, 8%), and closed LECS (two patients, 1%). Only six (3%) patients underwent LECS with gastrostomy. The mean operative time and blood loss were 188.4 (70–462) minutes and 23.3 (0–793) g, respectively. Ten (5%) patients developed postoperative complications (Clavien–Dindo classification grade II or higher). Two patients needed reoperation due to postoperative bleeding or anastomotic leakage. All tumors were resected with negative margins. A total of 127 (63.2%) patients underwent follow‐up observations for over 36 months, one of whom had a recurrence of peritoneal dissemination and one had poor oral intake. Conclusion Classical LECS and LECS‐related procedures for G‐SMTs have favorable short/mid‐term outcomes.

Abstract Introduction Complexities of robotic distal gastrectomy (RDG) give reason to assess physician's surgical skill. Varying levels in surgical skill affect patient outcomes. We aim to investigate how a novel artificial intelligence (AI) model can be used to evaluate surgical skill in RDG by recognizing surgical instruments. Methods Fifty‐five consecutive robotic surgical videos of RDG for gastric cancer were analyzed. We used Deeplab, a multi‐stage temporal convolutional network, and it trained on 1234 manually annotated images. The model was then tested on 149 annotated images for accuracy. Deep learning metrics such as Intersection over Union (IoU) and accuracy were assessed, and the comparison between experienced and non‐experienced surgeons based on usage of instruments during infrapyloric lymph node dissection was performed. Results We annotated 540 Cadiere forceps, 898 Fenestrated bipolars, 359 Suction tubes, 307 Maryland bipolars, 688 Harmonic scalpels, 400 Staplers, and 59 Large clips. The average IoU and accuracy were 0.82 ± 0.12 and 87.2 ± 11.9% respectively. Moreover, the percentage of each instrument's usage to overall infrapyloric lymphadenectomy duration predicted by AI were compared. The use of Stapler and Large clip were significantly shorter in the experienced group compared to the non‐experienced group. Conclusions This study is the first to report that surgical skill can be successfully and accurately determined by an AI model for RDG. Our AI gives us a way to recognize and automatically generate instance segmentation of the surgical instruments present in this procedure. Use of this technology allows unbiased, more accessible RDG surgical skill.

Peritoneal tumor dissemination and subsequent malignant tumor ascites (MTA) occur unexpectedly and repeatedly in patients with gastrointestinal (GI) cancers, and worsen quality of life and prognosis of the patients. Various treatments have been clinically developed for these patients, while most of the MTA cases are refractory to the treatments. Thus, effective treatments are urgently needed to improve the clinical outcomes. In this study, we identified α-synuclein (SNCA) as an immunological determinant of MTA progression in GI cancer through translational research using mouse tumor models and clinical specimens collected from gastric cancer patients. We found that the SNCA+ subsets were significantly increased in CD3+ T cells, CD56+ NK cells, and CD11b+ myeloid cells within MTA and peripheral blood cells (PBCs) of MTA cases, albeit almost absent in PBCs of healthy donors, and spleen of naive mice. Of note, the SNCA+ T-cell subset was rarely seen in patients that intraperitoneal lavage fluid without tumor cells was collected before surgery as a tumor-free control, suggesting a possible cancer-induced product, especially within the peritoneal cavity. In vivo treatment with anti-SNCA blocking mAb significantly induced anti-tumor effects in mouse MTA models, and synergistically improved anti-PD1 therapeutic efficacy, providing a significantly better prognosis. These suggest that SNCA is involved in severe immunosuppression in the MTA cases, and that blocking SNCA is effective in dramatically improving the immune status in the hosts. Targeting SNCA will be a promising strategy to improve clinical outcomes in the treatment of GI cancer patients, especially with MTA.

Abstract Background There are two methods of Roux‐en‐Y (RY) reconstruction after gastrectomy: the antecolic route (ACR) and retrocolic route (RCR). There is no evidence to support that the ACR achieves comparable long‐term survival. Methods This was a multi‐center historical cohort study. Patients diagnosed with clinical T3/4a and any N stage who underwent open gastrectomy and R0 resection for gastric adenocarcinoma between January 2006 and December 2012 were enrolled. The primary outcome was the hazard ratio of ACR for overall survival, with adjustment for confounding factors by propensity score matching, and a Cox proportional hazards model. Results A total of 1758 eligible patients were identified from the database. After matching, 410 patients in the ACR and RCR groups were included in the final analysis. The adjusted hazard ratio (95% CI) for ACR was 1.148 (0.870–1.492). The five‐year survival rates in the ACR and RCR groups were 74.3% (69.5–78.4) and 77.3% (72.3–81.2), respectively. The short‐term surgical outcomes of the two groups did not differ to a statistically significant extent. Conclusion The route used to lift the jejunum in RY reconstruction did not affect the incidence of long‐term survival or postoperative complications. The ACR and RCR are both acceptable options for RY reconstruction during gastric cancer surgery.

Abstract The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol‐voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol‐voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC.

Abstract Background The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG. Methods Enrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared. Discussion Surgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG. Trial registration This trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022–00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022.

Patients with pancreatic neuroendocrine tumors (pNETs) have limited access to effective targeted agents and invariably succumb to progressive disease. MUC1-C is a druggable oncogenic protein linked to driving pan-cancers. There is no known involvement of MUC1-C in pNET progression. The present work was performed to determine if MUC1-C represents a potential target for advancing pNET treatment. We demonstrate that the MUC1 gene is upregulated in primary pNETs that progress with metastatic disease. In pNET cells, MUC1-C drives E2F- and MYC-signaling pathways necessary for survival. Targeting MUC1-C genetically and pharmacologically also inhibits self-renewal capacity and tumorigenicity. Studies of primary pNET tissues further demonstrate that MUC1-C expression is associated with (i) an advanced NET grade and pathological stage, (ii) metastatic disease, and (iii) decreased disease-free survival. These findings demonstrate that MUC1-C is necessary for pNET progression and is a novel target for treating these rare cancers with anti-MUC1-C agents under clinical development.

Abstract Background C–C chemokine receptor type 7 (CCR7) participates in chemotactic and metastatic responses in various cancers, including in esophageal squamous cell carcinoma (ESCC). The microRNA (miRNA) let-7a suppresses migration and invasion of various types of cancer cells by downregulating CCR7 expression. Methods The expression levels of CCR7 and let-7a were measured in the cell lines, tumor, and peritumoral tissues of ESCC patients. KYSE cell lines were transfected with synthetic let-7a miRNA and a let-7a miRNA inhibitor, and their CCR7 expression levels as well as invasive ability were evaluated. A highly invasive cell line was established via an invasion assay, and CCR7 expression level along with let-7a level was subsequently evaluated. Cancer cells overexpressing CCR7 were injected subcutaneously into mice, and the animals were monitored for tumor growth along with lymph node metastasis. Results A negative correlation between CCR7 and let-7a expression was observed in the ESCC cell lines as well as in tissue samples from patients. Synthetic let-7a decreased CCR7 expression level, while the let-7a inhibitor increased it. In vitro, the established highly invasive cancer cells with high and low levels of CCR7 and let-7a expression, respectively, exhibited a greater invasive ability than the wild-type cell line. The cells were associated with tumor growth and lymph node metastasis in mice. Patients in the high-CCR7/low-let-7a group had the worst prognosis, with a five-year recurrence free survival (5-RFS) rate of 37.5%, followed by the high-CCR7/high-let-7a (5-RFS: 60.0%) and low-CCR7 (5-RFS: 85.7%; p = 0.038) groups. Conclusions The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients. Trial registration. Retrospectively registered.

Introduction Surgical site infections (SSIs) are among the most common nosocomial infections in surgery patients. Two types of preparations, povidone-iodine and chlorhexidine-alcohol, are commonly used in preoperative antiseptic procedures worldwide. However, there are inconsistencies among international guideline recommendations concerning skin antiseptics. This trial aimed to evaluate the superiority of olanexidine, which reduced SSI rates more than povidone-iodine in our previous randomised trial, over chlorhexidine-alcohol in clean-contaminated surgery.Methods and analysis This multicentre randomised controlled clinical trial will compare two antiseptics (1.5% olanexidine and 1.0% chlorhexidine-alcohol) to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. On providing consent, patients aged

Abstract Background Organ/space surgical site infection (SSI) is a significant clinical problem. The postdiagnosis course of organ/space SSIs and the impact of its early diagnosis on clinical outcomes are yet to be clarified. Thus, we aimed to investigate the association between the timing of diagnosis and the clinical outcome of organ/space SSI. Methods This retrospective, single‐center cohort study evaluated patients who underwent elective gastrointestinal or hepatopancreatobiliary surgery between 2016 and 2020. Clinical outcomes were compared between the early group (ie, SSI diagnosed until postoperative day [POD] 4) and normal‐late group (ie, SSI diagnosed after POD 5). The primary outcome was the final C‐reactive protein (CRP) level within 14 d after organ/space SSI diagnosis. Results In total, 110 patients were evaluated. The median time of diagnosis was 7 d postoperatively (interquartile range, 5–9 d postoperatively). Compared with the normal‐late group, the early group included a higher proportion of patients with Clavien–Dindo grade ≥IIIb (8/21 vs 11/89, P = .01), higher final CRP value within 14 d after SSI diagnosis (mean, 4.49 mg/dL vs 2.27 mg/dL, P = .01), longer postoperative length of hospitalization (median, 45.0 d vs 33.0 d; P = .028), and worse 1‐y overall survival rate (74.8% vs 89.3%, P = .08). Conclusion Early diagnosed organ/space SSI are originally severe and may therefore be detected earlier. Importantly, early diagnosed organ/space SSI is likely to be severe and refractory.

Background and Aims: Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. Methods: This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. Results: LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). Conclusion: Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Abstract Background and Aim Percutaneous endoscopic gastrostomy (PEG) has been used in patients with dysphagia and inadequate food intake via an oral route. Despite being a procedure with a high success rate, complications and death have been reported. The aim was to identify the factors related to major complications and mortality, as well as PEG removal prognostic factors due to improvement of their general condition. Methods Patient characteristics, comorbidities, laboratory data, concomitant medication, sedation, and indication for PEG placement were collected. Major complications, mortality, and PEG removal factors were assessed. Results A total of 388 patients were enrolled. There were 15 (3.9%) cases of major complications, with major bleeding being the most frequent in 6 (1.5%) patients. Corticosteroids were the independent variable associated with major complications (odds ratio [OR] 5.85; 95% confidence interval [CI] 1.71–20; P =

Abstract Aim We have previously reported the existence of lymph nodes surrounding the thoracic duct ( TDLN) and transthoracic esophagectomy (TTE) with thoracic duct (TD) resection increased the number of lymph nodes (LNs) retrieved. The current study aims to evaluate the prognostic impact of TDLN metastasis in esophageal cancer patients subdivided by its location and comparing the patients’ survival with those with extra‐regional LN metastasis. Methods Patients who underwent TTE with TD resection for esophageal squamous cell carcinoma (ESCC) were reviewed. Patients were classified into those with or without TDLN metastasis, and clinicopathological factors were compared between groups. TDLN was further divided into TDLN‐Ut/Mt/Lt based on the location in the mediastinum. The relapse‐free survival (RFS) and overall survival (OS) were compared between groups. Results Of 232 patients, TDLN metastasis was observed in 17 (7%). RFS and OS were significantly worse in the TDLN metastasis group. TDLN metastasis was shown to be an independent prognostic factor for RFS and OS in the multivariate analysis. The negative prognostic impact of TDLN metastasis was evident in TDLN‐Mt/Lt. The RFS and OS of patients with TDLN metastasis were almost identical to those with positive LN metastasis in extra‐regional LNs. Conclusion TDLN metastasis was proven to be a strong prognostic indicator. Although the TDLN has been included in the classification of regional LN in the current staging systems, it could be independently classified from the current regional LNs. Given that neoadjuvant therapy has been a standard, we might need to introduce adjuvant therapy when TDLN metastasis is observed.

Abstract Background In Japan, the prevalence of synchronous multiple intramucosal gastric carcinoma is reported to be 5–15%. Here is a case of a synchronous small gastric carcinoma fulfilling the definite indication and curative criteria for endoscopic submucosal dissection with multiple lymph node metastases. Case presentation A Japanese woman in her fifties with a history of endoscopic resection for mucosal poorly differentiated adenocarcinoma was evaluated, with the UICC TNM classification stage being cT1aN0M0 cStageIA. She had undergone total gastrectomy with D1 + lymph node dissection. Histopathological examination revealed 16 individual sporadic lesions in the gastric body, with maximum diameter 3 mm and localization in the lamina propria. Twenty-seven nodes were resected, and metastasis of the carcinoma was revealed in 24 nodes. Conclusions Undifferentiated intramucosal gastric cancer has a relatively high probability of lymph node metastasis; however, synchronous early lesions are often overlooked. Frequent follow-up examinations may increase the detection of multiple gastric cancers.

Abstract Perioperative and surgical management of gastric cancer have been changing as pivotal phase II trials and landmark phase III trials offer new insights to the existing knowledge. The results of many landmark trials have been published or presented in the past year, many of which have changed or will change current clinical practice. For example, FLOT4 has completely changed the regimen of perioperative chemotherapy in Europe. Furthermore, evidence for minimally invasive surgery for clinical Stage I was firmly established by KLASS‐01 and JCOG0912 for distal gastrectomy and CLASS‐02, KLASS‐03, and JCOG1401 for total gastrectomy. Moreover, promising results were provided by CLASS‐01 and KLASS‐02 for locally advanced gastric cancer. For adjuvant chemotherapy, JACCRO GC‐07 (START‐2) has provided a new doublet regimen for pathological Stage III, which is often refractory to chemotherapy. Conversely, JCOG0501 poses a significant challenge for advanced tumors, such as large type 3 and scirrhous (type 4) tumors. In this review, we briefly review recent updates and discuss future perspectives of gastric cancer treatment.

Abstract Background Gastric cancer that mimics a submucosal tumor (SMT) is infrequently encountered in routine clinical settings, and histopathological analysis is often negative for malignant cells. In such cases, excisional biopsy of the entire tumor may be necessary to make a definitive pathological diagnosis, and laparoscopic and endoscopic cooperative surgery (LECS) is a viable method of excisional biopsy. Case presentation An 80-year-old male patient diagnosed with stomach wall irregularities at routine medical check-up was referred to our facility, and consequent endoscopic examination detected a 20-mm protruded lesion in the greater curvature at the middle third of the stomach. Endoscopic ultrasound (EUS) showed a thick, low echoic lesion with an irregular margin in the second layer of the gastric wall. Further, a nodular part of the lesion had infiltrated into the submucosa, with an appearance similar to that of linitis plastica of the stomach. The lesion was highly suspected to be a gastric carcinoma with submucosal invasion. However, mucosal-incision-assisted biopsy revealed no malignant cells. Computed tomography (CT) identified no metastatic lymph nodes. Therefore, an excisional biopsy using LECS was performed, and to avoid peritoneal dissemination, we used a modified version, namely, combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET). The procedure ended without any complications, and post-operative course was uneventful. As histopathology returned a diagnosis of adenocarcinoma pT4a, we performed radical gastrectomy and D2 lymphadenectomy. Post-operative course was unremarkable and the patient underwent follow-up examinations without adjuvant chemotherapy because of old age. Conclusions Local resection using LECS for gastric tumors with a high suspicion of malignancy is useful and feasible. LECS could be used in similar cases.

Primary rhabdomyosarcoma (RMS) of the diaphragm, especially alveolar RMS, is extremely rare. Because of its rarity, no treatment for it has yet been established, but previous studies have reported long-term survival in recipients of a combination therapy with local control, including a total resection and/or radiation therapy concomitant with multiagent chemotherapy. We experienced a case of primary alveolar rhabdomyosarcoma of the diaphragm surrounding the gastric cardia in a 15-year-old, female patient. After administering chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide (VAC) to shrink the tumor, tumor resection was performed with a proximal gastrectomy and partial resection of the diaphragm, pericardium, and left lung. After receiving postoperative adjuvant chemotherapy with VAC and radiotherapy at a total of 41.4 Gy, the patient has been relapse-free for 18 months. The tumor-induced stenosis at the hilum was corrected, allowing oral intake and markedly improving the patient's nutritional status. Tumor resection with a proximal gastrectomy for primary diaphragmatic RMS surrounding the lower esophagus is recommended both for its efficacy in local control and for allowing the preservation of postoperative gastrointestinal function.

Intraperitoneal (i.p.) tumor dissemination and the consequent malignant ascites remain unpredictable and incurable in patients with gastrointestinal (GI) cancer, and practical advances in diagnosis and treatment are urgently needed in the clinical settings. Here, we explored tumor biological and immunological mechanisms underlying the i.p. tumor progression for establishing more effective treatments.We established mouse tumor ascites models that murine and human colorectal cancer cells were both i.p. and subcutaneously (s.c.) implanted in mice, and analyzed peritoneal exudate cells (PECs) obtained from the mice. We then evaluated anti-tumor efficacy of agents targeting the identified molecular mechanisms using the ascites models. Furthermore, we validated the clinical relevancy of the findings using peritoneal lavage fluids obtained from gastric cancer patients.I.p. tumor cells were giant with large nuclei, and highly express AURKA, but less phosphorylated TP53, as compared to s.c. tumor cells, suggesting polyploidy-like cells. The i.p. tumors impaired phagocytic activity and the consequent T-cell stimulatory activity of CD11b+Gr1+PD1+ myeloid cells by GDF15 that is regulated by AURKA, leading to treatment resistance. Blocking AURKA with MLN8237 or siRNAs, however, abrogated the adverse events, and induced potent anti-tumor immunity in the ascites models. This treatment synergized with anti-PD1 therapy. The CD11b+PD1+ TAMs are also markedly expanded in the PECs of gastric cancer patients.These suggest AURKA is a determinant of treatment resistance of the i.p. tumors. Targeting the AURKA-GDF15 axis could be a promising strategy for improving clinical outcome in the treatment of GI cancer.

Abstract Multimodal treatment combining surgery with chemotherapy and/or radiotherapy is necessary to improve the chances of survival in patients with locally advanced thoracic esophageal cancer. Based on the results of the Japan Clinical Oncology Group 9907 (JCOG9907) trial, neoadjuvant chemotherapy, two courses of cisplatin and 5‐fluorouracil (5‐FU), followed by esophagectomy with D2 lymphadenectomy is the recommended treatment in Japan. Alternatively, neoadjuvant chemoradiotherapy (NACRT) typified by carboplatin and paclitaxel plus concurrent radiotherapy with 41.4 Gy (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study [CROSS]) has shown promising outcomes in some Western countries. Currently, several clinical trials are being conducted within and outside of Japan to confirm the best neoadjuvant treatment regimen. For instance, a three‐arm phase III randomized controlled trial (JCOG1109) is ongoing in Japan. The three arms comprise a doublet regimen (two courses of cisplatin 80 mg/m2 day 1 and 5‐FU 800 mg/m2 days 1‐5; repeated every 3 weeks) versus a triplet regimen (three courses of docetaxel, 70 mg/m2 day 1; cisplatin 70 mg/m2 day 1; and 5‐FU 750 mg/m2 days 1‐5; repeated every 3 weeks) versus a chemoradiotherapy (CRT) regimen (radiotherapy of 41.4 Gy/23 fractions with two courses of cisplatin 75 mg/m2 day 1 and 5‐FU 1000 mg/m2 days 1‐4; repeated every 4 weeks). Development of a multimodal strategy for neoadjuvant therapy is expected to receive the continuous focus of research in the hope of achieving better outcomes from treatment of patients with advanced thoracic esophageal cancer.

Abstract Background Oesophageal cancer has a high metastatic potential and poor prognosis, with a significant risk of recurrence after radical resection. However, resected pancreatic metastasis from oesophageal cancer is rare. Case presentation Eleven years prior, a seventy-year-old woman had been treated with transthoracic radical oesophagectomy for oesophageal squamous cell carcinoma. Four years prior, she had undergone chemotherapy for lymph node recurrence at the splenic hilum and achieved a partial response. She had also received chemoradiotherapy for lymph node recurrence at the splenic hilum 3 years prior; a complete response was achieved. However, routine follow-up with abdominal computed tomography recently revealed a tumour at the pancreatic tail and swollen lymph nodes. The patient underwent distal pancreatectomy on the basis of a pre-operative diagnosis of primary pancreatic cancer, although a histological examination of the surgical specimen revealed metastatic squamous cell carcinoma that was compatible with metachronous pancreatic metastasis from oesophageal squamous cell carcinoma. The patient has been undergoing clinical follow-up without adjuvant therapy and has been disease-free for 24 months after resection of the pancreatic metastasis. Conclusions Resection of pancreatic metastasis may improve prognosis and should be considered when treating patients with solitary metastasis from oesophageal squamous cell carcinoma.

Abstract Background Endoscopic resection (ER) has come to be recognized as a standard treatment for early gastric cancer (EGC). While its adoption is expanding, ER remains restricted to cases of EGC without lymph node metastasis for the treatment of local resection. On the other hand, histopathological analyses of surgically resected specimens of EGC have revealed the presence of lymph node (LN) metastasis in some cases of mucosal gastric cancer (MGC) and undifferentiated MGC (UD-MGC) is considered to have higher risk of nodal metastases than differentiated MGC (D-MGC). To evaluate the risk factors for LN metastasis in MGC, we investigated the characteristics of UD-MGC associated with LN metastasis. Methods Among all UD-MGC patients who underwent surgery as initial treatment, between January 2000 and March 2016, we reviewed the clinicopathological data, including the preoperative endoscopic findings and histopathological findings in the resected specimens, of the 11 UD-MGC patients who were identified as having lymph node metastasis. Furthermore, in comparison with cases without lymph node metastasis, we examined the possibility of expansion of the indication for local treatment. Results In most of the cases of UD-MGC with LN metastasis, the lesions were relatively large (> 20 mm in diameter) and of the clearly depressed type with faded color and apparent border, and histopathology revealed a high percentage of cases with lymphatic invasion and a predominance of signet ring cell carcinomas. No cases with LN metastasis without depressed macroscopic type nor signet ring cell carcinoma component existed. A degree of invasion of lamina propria (LP) or muscularis mucosae (MM) had same relation to the risk of LN metastasis. Conclusions In this study, none of the cases of undifferentiated-type mucosal cancer (UD-MGC) with LN metastasis satisfied the current adoption criteria for ER. We suggested significant risk factors for LN metastasis in UD-MGC cases as depressed tumor type, presence of a signet ring cell carcinoma component, presence of lymphatic tumor invasion, and a large tumor size. More detailed analyses of the endoscopic and histopathological findings may allow further risk classification for LN metastasis in cases of UD-MGC.

We report a patient with highly advanced gastric carcinoma who was treated successfully with chemoradiotherapy (CRT) comprising S-1 and cisplatin. The patient was a 71-year-old male who was diagnosed with advanced gastric carcinoma by esophagogastroduodenoscopy (EGD) by medical examination. EGD demonstrated type 3 advanced gastric carcinoma in the posterior wall of the upper gastric body. An abdominal computed tomography (CT) scan showed that the gastric wall was thickened due to gastric primary tumor, and large lymph nodes (LNs) including the lesser curvature LN, anterosuperior LN along the common hepatic artery and some para-aortic LNs were detected. The patient was diagnosed with stage IV advanced gastric carcinoma according to the Japanese classification of gastric carcinoma (cT4a, cN3, cM1 [para-aortic LN], cStage IV). Preoperative CRT was carried out in an attempt to downstage the disease. Remarkable reduction of the primary tumor and metastatic LNs was observed after initial CRT, and radiological examination determined that a partial response had been achieved. Adverse effects included grade 2 anorexia and grade 3 ALP elevation (919 U/ml). No grade 4 or more severe adverse event was observed. After CRT, although we recommended curative surgery, the patient refused surgical treatment and opted for conservative treatment. Thus, we continued S-1 oral administration for 1 year. Five months after beginning CRT, upper endoscopy showed that the tumor had maintained regression and scar formation, in which no cancer cells were detected by endoscopic biopsy. The patient is doing well and has maintained a clinical complete response for more than 42 months without curative surgery. CRT could be considered as an option for treatment of patients with locally advanced gastric carcinoma diagnosed as unresectable, or for those who refuse surgical treatment.

Abstract Background Inflammatory myofibroblastic tumor is an uncommon soft tissue neoplasm rarely reported in the stomach. Case presentation We identified a tumor highly suggestive of poorly differentiated gastric adenocarcinoma in the lesser curvature of the stomach of a 53-year-old female during screening endoscopy. Although the patient’s gastric biopsy did not reveal cancer, the tumor configuration was strongly suspicious for malignancy, and we performed a gastric wedge resection using a combined laparoscopic and endoscopic method. The lesion was diagnosed as inflammatory myofibroblastic tumor based on its morphological and immunohistological features. Conclusions Inflammatory myofibroblastic tumor should be considered in the differential diagnosis of soft tissue tumors in the stomach. We present a case of inflammatory myofibroblastic tumor safely treated with combined laparoscopic and endoscopic gastric wedge resection.

Alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians. We invented a health risk appraisal (HRA) model for predicting the risk of ESCC based on drinking, smoking, dietary habits, and alcohol flushing, i.e., past or present facial flushing after drinking a glass of beer, a surrogate marker for inactive ALDH2.Prospective follow-up examinations (median follow-up time, 50.3 months) were performed in 278 Japanese men after endoscopic mucosectomy for early ESCC (UMIN Clinical Trials Registry ID: UMIN000001676).Sixty-four subjects developed metachronous ESCC. A receiver operating characteristic curve showed that HRA scores ≥12 best predicted the development of metachronous ESCC. The ESCC detection rate per 100 person-years was 9.8 in the high-HRA-score group (n = 104) and 4.5 in the low-HRA-score group (n = 174), and the risk of development of metachronous ESCC was higher in the high-HRA-score group than in the low-HRA-score group (adjusted hazard ratio: 2.00 [95% CI: 1.12-3.30]). Multiple LVLs was a very strong predictor of the development of metachronous SCC, but high HRA scores predicted it independently. The cumulative incidences of metachronous ESCC decreased after drinking cessation in the high-HRA-score drinker group (adjusted hazard ratio: 0.37 [0.14-0.97]).Both the HRA model that included alcohol flushing and the multiple LVL grade predicted the development of metachronous ESCC in Japanese men after endoscopic mucosectomy for ESCC. Drinking cessation in the high-HRA-score drinker group reduced the rate of metachronous ESCC.