Clinicopathological characteristics of clinical early gastric cancer in the upper-third stomach

AIM: To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions.METHODS: A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach(U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography(CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower-third stomach(ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth.RESULTS: Patients in the U group were older(P = 0.029), had a higher ratio of males to females(P = 0.015), and had more histologically differentiated tumors(P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients(8.3%), and was more frequent in the U group than in the ML group(16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group(P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors(P = 0.094) and in those larger than 4 cm(P = 0.024). The medianfollow-up period after surgery was 56 mo(range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group(P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study.CONCLUSION: Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with larger or undifferentiated tumors.

Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer

AIM: To assess the clinical features of hepatoduodenal lymph node(HDLN) metastasis and to clarify the optimal indication of HDLN dissection.METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy,including HDLN dissection,for gastric cancer between 1999 and 2012. Of these,26 patients(9.4%) had HDLN metastasis. First,we investigated the clinicopathological characteristics,their perioperative clinical outcomes,such as postoperative complications,and prognostic outcomes between patients with and without HDLN metastasis. Second,we detected the prognostic factors,particularly in patients with HDLN metastasis. Third,we assessed the therapeutic value of HDLN dissection to determine its optimal indication.RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location(the middle or lower stomach [P = 0.005,OR = 5.88(95%CI: 1.61-38.1)] and p T category [T3 or T4,P = 0.017,OR = 4.45(95%CI: 1.28-21.3)] were independent risk factors for HDLNmetastasis. Cox proportional hazard analysis identified p N3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021,HR = 5.17(95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection,HDLN metastasis was a prognostic indicator in p N3 gastric cancer(P < 0.0001),but not p N1-2(P = 0.602). Furthermore,the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0,respectively.CONCLUSION: We suggest that HDLN dissection should be indicated for p N1 or p N2 gastric cancers located at the middle or lower stomach.

Surgery for gastric cancer patients of age 85 and older: Multicenter survey

AIM To investigate the surgical therapies for gastric cancer(GC) patients of age 85 or older in a multicenter survey.METHODS Therapeutic opportunities for elderly GC patients have expanded in conjunction with extended life expectancy. However, the number of cases encountered in a single institution is usually very small and surgical therapies for elderly GC patients have not yet been standardized completely. In the present study, a total of 134 GC patients of age 85 or older who underwent surgery in 9 related facilities were retrospectively investigated. The relationships between surgical therapies and clinicopathological or prognostic features were analyzed.RESULTS Eighty-nine of the patients(66%) presented with a comorbidity, and 26(19% overall) presented with more than two comorbidities. Radical lymphadenectomy was performed in 59 patients(44%), and no patient received pre- or post-operative chemotherapy. Forty of the patients(30%) experienced perioperative complications, but no surgical or perioperative mortality occurred. Laparoscopic surgery was performed in only 12 of the patients(9.0%). Univariate and multivariate analyses of the 113 patients who underwent R0 or R1 resection identified the factors of p T3/4 and limited lymphadenectomy as predictive of worse prognosis(HR = 4.68, P = 0.02 and HR =2.19, P = 0.05, respectively). Non-cancer-specific death was more common in c Stage Ⅰ patients than in c Stage Ⅱ or Ⅲ patients. Limited lymphadenectomy correlated with worse cancer-specific survival(P = 0.01), particularly in c Stage Ⅱ patients(P < 0.01). There were no relationships between limited lymphadenectomy and any comorbidities, except for cerebrovascular disease(P = 0.07). CONCLUSION N o n- c a n c e r- s p e c i f i c d e a t h w a s n o t n e g l i g i b l e, particularly in c Stage Ⅰ, and gastrectomy with radical lymphadenectomy appears to be an effective treatment for cS tage Ⅱ elderly GC patients.

Laparoscopic and endoscopic co-operative surgery for nonampullary duodenal tumors

AIM To assess the safety and feasibility of laparoscopic and endoscopic co-operative surgery(LECS) for early nonampullary duodenal tumors.METHODS Twelve patients with a non-ampullary duodenal tumor underwent LECS at our hospital. One patient had two mucosal lesions in the duodenum. The indication for this procedure was the presence of duodenal tumors with a low risk for lymph node metastasis. In particular, the tumors included small(less than 10 mm) submucosal tumors(SMT) and epithelial mucosal tumors, such as mucosal cancers or large mucosal adenomas with malignant suspicion. The LECS procedures, such as full-thickness dissection for SMT and laparoscopic reinforcement after endoscopic submucosal dissection(ESD) for epithelial tumors, were performed for the 13 early duodenal lesions in 12 patients. Here we present the short-term outcomes and evaluate the safety and feasibility of this new technique.RESULTS Two SMT-like lesions and eleven superficial epithelial tumor-like lesions were observed. Seven and Six lesions were located in the second and third parts of the duodenum, respectively. All lesions were successfully resected en bloc. The defect in the duodenal wall was manually sutured after resection of the duodenal SMT. For epithelial duodenal tumors, the ulcer bed was laparoscopically reinforced via manual suturing after ESD. Intraoperative perforation occurred in two out of eleven epithelial tumor-like lesions during ESD; however, they were successfully laparoscopically repaired. The median operative time and intraoperative estimated blood loss were 322 min and 0 mL, respectively. Histological examination of the tumors revealed one adenoma with moderate atypia, ten adenocarcinomas, and two neuroendocrine tumors. No severe postoperative complications(Clavien-Dindo classification grade Ⅲ or higher) were reported in this series, but minor leakage secondary to pancreatic fistula occurred in one patient.CONCLUSION LECS can be a safe and minimally invasive treatment option for non-ampullary early duodenal tumors.

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland(HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery(LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor(SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm intothe submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG.

Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett's esophagus

Barrett's esophagus(BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE(LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach(LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of thearch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 m L of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis.

Discrepancies in the histologic type between biopsy and resected specimens:A cautionary note for mixed-type gastric carcinoma

AIM: To evaluate discrepancies between biopsy and resected specimens using the Japanese Classification of Gastric Carcinoma(JCGC) and tumor-node-metastasis(TNM) classification.METHODS: A total of 376 consecutive paired samples from biopsy and resected gastric specimens, which were derived from curative gastrectomy for gastric cancer between 2008 and 2011, were retrospectively analyzed.RESULTS:(1) Discrepancies in the histologic type were observed between biopsy and resected specimens; 11.7%(44/376) in the JCGC and 18.1%(68/376) in TNM. In specimens diagnosed as the differentiated type from biopsy specimens, 14.4%(28/195) in the JCGC and 41.1%(67/163) in TNM were finally diagnosed as the undifferentiated type from resected specimens; and(2) the incidence of mixed-type gastric cancer was significantly higher in specimens with discrepancies than in those without in both the JCGC and TNM(both P < 0.0001); 93.2%(41/44) of specimens with discrepancies in the JCGC and 97.1%(66/68) of specimens with discrepancies in TNM were mixed-type gastric cancers. CONCLUSION: Mixed-type gastric cancer was associated with a high incidence of histologic discrepancies between biopsy and resected specimens in both the JCGC and TNM definitions. Care should be taken in deciding treatments based on diagnosis of the histologic typefor mixed-type gastric cancer from biopsy specimens.

Anoctamin 5 regulates the cell cycle and affects prognosis in gastric cancer

BACKGROUND Anoctamin 5(ANO5)/transmembrane protein 16E belongs to the ANO/transmembrane protein 16 anion channel family.ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types.Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types.However,it remains unclear whether ANO5 acts as a plasma membrane chloride channel,and its expression and functions in gastric cancer(GC)have not been investigated.AIM To examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC.METHODS Knockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines,and changes in cell proliferation,cell cycle progression,apoptosis,and cellular movement were assessed.The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis.Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department.RESULTS Reverse transcription-quantitative polymerase chain reaction(PCR)and western blotting demonstrated high ANO5 mRNA and protein expression,respectively,in NUGC4 and MKN45 cells.In these cells,ANO5 silencing inhibited cell proliferation and induced apoptosis.In addition,the knockdown of ANO5 inhibited G1-S phase progression,invasion,and migration.The results of the microarray analysis revealed changes in the expression levels of several cyclin-associated genes,such as CDKN1A,CDK2/4/6,CCNE2,and E2F1,in ANO5-depleted NUGC4 cells.The expression of these genes was verified using reverse transcription-quantitative PCR.Immunohistochemical staining revealed that high ANO5 expression levels were associated with a poor prognosis.Multivariate analysis identified high ANO5 expression as an independent prognostic factor for 5-year survival in patients with GC(P=0.0457).CONCLUSION ANO5 regulates the cell cycle progression by regulating the expression of cyclin-associated genes and affects the prognosis of patients with GC.These results may provide insights into the role of ANO5 as a key mediator in tumor progression and/or promising prognostic biomarker for GC.

Artificial intelligence in gastrointestinal cancer:Recent advances and future perspectives

Artificial intelligence(AI)using machine or deep learning algorithms is attracting increasing attention because of its more accurate image recognition ability and prediction performance than human-aid analyses.The application of AI models to gastrointestinal(GI)clinical oncology has been investigated for the past decade.AI has the capacity to automatically detect and diagnose GI tumors with similar diagnostic accuracy to expert clinicians.AI may also predict malignant potential,such as tumor histology,metastasis,patient survival,resistance to cancer treatments and the molecular biology of tumors,through image analyses of radiological or pathological imaging data using complex deep learning models beyond human cognition.The introduction of AI-assisted diagnostic systems into clinical settings is expected in the near future.However,limitations associated with the evaluation of GI tumors by AI models have yet to be resolved.Recent studies on AI-assisted diagnostic models of gastric and colorectal cancers in the endoscopic,pathological,and radiological fields were herein reviewed.The limitations and future perspectives for the application of AI systems in clinical settings have also been discussed.With the establishment of a multidisciplinary team containing AI experts in each medical institution and prospective studies,AI-assisted medical systems will become a promising tool for GI cancer.

Early thrombomodulin-α administration outcome for acute disseminated intravascular coagulopathy in gastrointestinal surgery

AIM To investigate the efficacy of thrombomodulin(TM)-α for treatment of disseminated intravascular coagulopathy(DIC) in the field of gastrointestinal surgery. METHODS Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the ini-tiation of TM-α and patient demographics were also evaluated. RESULTS Abscess formation or bacteremia was the most frequent cause of DIC(33%), followed by digestive tract perforation(31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk(81%). TM-α was most often administered within 1 d of the DIC diagnosis(72%) and was continued for more than 3 d(64%). Although bleeding tendency was observed in 7 patients(19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome(SIRS) scores, quick-sequential organ failure assessment(qS OFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk(P < 0.05, for all). The overall survival rate at 28 d was 71%. The duration of TM-α administration(≥ 4, ≤ 6) and improvements in DIC-associated scores(DIC, SIRS and q SOFA) at 1 wk were significantly better prognostic factors for 28-d survival(P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qS OFA scores, sepsis, shock or high lactate values(P < 0.05, for all). CONCLUSION Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.