Current status of internal hernia after gastrectomy for gastric cancer.

BACKGROUND: Internal hernia is a well-known postoperative complication after Roux-en-Y gastric bypass. However, it has not been considered a recognized complication for gastric cancer. METHODS: We reviewed the literature in the past decade to clarify the current status of internal hernia after gastrectomy including its incidence, high-risk factors, and treatment. RESULTS: The incidence of internal hernia after gastrectomy was found to be between 0.2 and 5.63%, and the median interval time was less than 2 years. High-risk factors include laparoscopic approach, non-closure of all the mesenteric defects, and Roux-en-Y reconstruction. The rate of bowel resection was significantly higher than that of adhesive small bowel obstruction. CONCLUSION: The true incidence of internal hernia after gastrectomy is generally underestimated. Closure of all the mesenteric defects is one of the most effective methods to prevent postoperative internal hernia. Early surgical exploration is necessary when internal hernia is suspected.

Esophagus two-step-cut overlap method in esophagojejunostomy after laparoscopic gastrectomy.

PURPOSE: Esophagojejunostomy is a challenging step in laparoscopic gastrectomy. Although the overlap method is a safe and feasible approach for esophagojejunostomy, it has several technical limitations. We developed novel modifications for the overlap method to overcome these disadvantages. METHODS: Forty-eight consecutive gastric cancer patients underwent totally laparoscopic total gastrectomy or laparoscopic proximal gastrectomy with double-tract reconstruction at our institution from January 2019 to April 2020 using the overlap method with the following modifications. The esophagus was initially rotated by 90° counterclockwise, followed by transection of two-thirds of the esophageal diameter. The unstapled esophagus was then transected with a harmonic ultrasonic scalpel to enable esophagostomy at the posterior side of the esophagus. A side-to-side esophagojejunostomy was then formed at the posterior side of the esophagus using an endoscopic linear stapler through the right lower trocar. The common entry hole was closed via hand sewing method using V-Loc suture. This procedure was termed "esophagus two-step-cut overlap method." RESULTS: Only one patient suffered from esophagojejunal anastomotic leakage but subsequently recovered after conservative treatment. Patients did not experience anastomotic bleeding or stricture. CONCLUSION: Our modified overlap method provides satisfactory surgical outcomes and overcomes several technical limitations, such as entering the false lumen of the esophagus, unnecessary pollution caused by nasogastric tube, and unintended left crus stapling during anastomosis.

MicroRNA-31 triggers G2/M cell cycle arrest, enhances the chemosensitivity and inhibits migration and invasion of human gastric cancer cells by downregulating the expression of zeste homolog 2 (ZH2).

Gastric cancer is the second most leading cause of cancer related mortality across the world over. Although the incidence of GC has declined to some extent but it is still the fourth highly diagnosed cancer across the world. GC generally remains undiagnosed till advanced stages due to unavailability of biomarkers and when diagnosed it becomes difficult to manage due to the lack of therapeutic targets and efficient chemotherapy. There are concrete evidences suggesting that miRNAs may prove important therapeutic targets for the treatment of devastating diseases such as cancer. The study was designed to investigate the tumor suppressive role of miR-31 via regulation of zeste homolog 2 (ZH2). It was found that miR-31 is significantly downregulated in GC cell lines. Overexpression of miR-31 causes significant (P < 0.05) decrease in the viability and colony formation via initiation of G2/M cell cycle arrest of the AGS cancer cells. Moreover, miR-31 overexpression also enhanced the chemosensitivity of miR-31 to the anticancer drug 5-fluorouracil. In silico analysis together with dual luciferase reporter assay indicated zeste homolog 2 (ZH2) to be the potential target of miR-31 in AGS cells. Investigation of ZH2 expression in GC cell lines showed it to be significantly (P < 0.05) upregulated. Nonetheless, overexpression of miR-31 in AGS cells resulted in the suppression of ZH2 expression. Additionally, silencing of ZH2 in the AGS cells also caused inhibition of AGS cell proliferation and colony formation via G2/M arrest. Moreover, overexpression of ZH2 could at least partially reverse the tumor suppressive effects of miR-31 indicating direct involvement of ZH2 in the miR-31 mediated inhibitory effects on AGS cell proliferation. Finally, miR-31 overexpression caused significant (P < 0.05) inhibition of the migration and invasion of the AGS gastric cancer cells. The overexpression of miR-31 also caused downregulation of mesenchymal markers (Vimentin and N-cadherin) and upregulation of epithelial marker (E-cadherin) protein expression was in AGS cells. It is therefore concluded that miR-31 acts as a tumor suppressor and may prove essential in the treatment of GC.

Small bowel metastasis from pulmonary rhabdomyosarcoma causing intussusception: a case report.

BACKGROUND: Rhabdomyosarcoma (RMS), especially primary pulmonary RMS, is an extremely rare type of soft tissue sarcoma in adults. Small bowel is an uncommon site for metastases. CASE PRESENTATION: This report described an unusual case of jejunum metastasis from primary pulmonary RMS causing intussusception in a 75-year-old man. The patient consulted for 2 weeks of continuous dyspnea. Chest computed tomography (CT) demonstrated a large mass involving the left lower lobe. Transthoracic biopsy confirmed the existence of pleomorphic RMS. Immunohistochemical studies showed positive findings about desmin and MyoD1. The results of gastroscopy, colonoscopy and abdominal CT were all negative. Positron emission tomography/CT demonstrated a fluorodeoxyglucose-reactive large lesion in the left lower lobe without metastatic lesions. The patient received synchronous chemoradiotherapy. After 9 months, the patient presented with intermittent upper abdominal pain with nausea and vomiting. CT showed small bowel dilatation secondary to intussusception. The patient subsequently received laparotomy, and the intussuscepted small bowel segment was resected. Histological examination revealed pleomorphic RMS involving the mucosa, submucosa, and muscular tissues. CONCLUSIONS: RMS is highly aggressive and metastatic. The metastatic disease can rapidly progress to cause subsequent complications. The possibility of small bowel metastasis should be considered, although it is extremely rare.

Pylorus-preserving gastrectomy for early gastric cancer.

Pylorus-preserving gastrectomy (PPG) has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer (EGC) with a distal tumor border at least 4 cm proximal to the pylorus. The procedure essentially preserves the function of the pyloric sphincter, which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 cm. The suprapyloric and infrapyloric vessels are usually preserved, as are the hepatic and pyloric branches of the vagus nerve. Compared with distal gastrectomy, PPG has significant advantages in preventing dumping syndrome, body weight loss and bile reflux gastritis. The postoperative complications after PPG have reached an acceptable level. PPG can be considered a safe, effective, and superior choice in EGC, and is expected to be extensively performed in the future.

Identification of lncRNA and mRNA regulatory networks associated with gastric cancer progression.

Gastric cancer is a tumor type characterized by lymph node metastasis and the invasion of local tissues. There is thus a critical need to clarify the molecular mechanisms governing gastric cancer onset and progression to guide the treatment of this disease. Long non-coding RNAs and mRNA expression profiles associated with early and local advanced gastric cancer were examined through microarray analyses, with GO and KEGG analyses being employed as a means of exploring the functional roles of those long non-coding RNAs and mRNAs that were differentially expressed in gastric cancer. In total, 1005 and 1831 lncRNAs and mRNAs, respectively, were found to be differentially expressed between early and local advanced gastric cancer. GO and KEGG analyses revealed several pathways and processes that were dysregulated, including the RNA transport, ECM-receptor interaction, and mRNA splicing pathways. In co-expression networks, E2F1, E2F4, and STAT2 were identified as key transcriptional regulators of these processes. Moreover, thrombospondin-2 was confirmed as being expressed at high levels in more advanced gastric cancer by both the GEO and TCGA databases. RNA-sequencing analyses of SGC-790 cells transfected to express thrombospondin-2 further revealed this gene to enhance NF-kB and TNF pathway signaling activity. These results offer insight into gastric cancer-related regulatory networks and suggest thrombospondin-2 to be an important oncogene that drives the progression of this deadly cancer type.

Suppression of human lung cancer cell proliferation and metastasis in vitro by the transducer of ErbB-2.1 (TOB1).

AIM: To investigate the effects of the transducer of ErbB-2.1 (TOB1) on the proliferation, migration and invasion of human lung cancer cells in vitro. METHODS: Human lung cancer cell lines (95-D, A549, NCI-H1299, NCI-H1975, NCI-H661, NCI-H446, NCI-H1395, and Calu-3) and the normal human bronchial epithelial (HBE) cell line were tested. The expression levels of TOB1 in the cells were determined with Western blot and RT-PCR analyses. TOB1-overexpressing cell line 95-D/TOB1 was constructed using lipofectamine-induced TOB1 recombinant plasmid transfection and selective G418 cell culture. The A549 cells were transcend-transfected with TOB1-siRNA. MTT assay, flow cytometry and Western blot analysis were used to examine the effects of TOB1 on cancer cell proliferation and wound healing. Transwell invasive assay was performed to evaluate the effects of TOB1 on cancer cell migration and invasion. The activity of MMP2 and MMP9 was measured using gelatin zymography assay. RESULTS: The expression levels of TOB1 in the 8 human lung cancer cell lines were significantly lower than that in HBE cells. TOB1 overexpression inhibited the proliferation of 95-D cells, whereas TOB1 knockdown with TOB1-siRNA promoted the growth of A549 cells. Decreased cell migration and invasion were detected in 95-D/TOB1 cells, and the suppression of TOB1 enhanced the metastasis in A549 cells. TOB1 overexpression not only increased the expression of the phosphatase and tensin homolog (PTEN), an important tumor suppressor, but also regulated the downstream effectors in the PI3K/PTEN signaling pathway, including Akt, ERK1/2, etc. In contrast, decreased expression of TOB1 oppositely regulated the expression of these factors. TOB1 also regulates the gelatinase activity of MMP2 and MMP9 in lung cancer cells. CONCLUSION: The results demonstrate that the PI3K/PTEN pathway, which is essential for carcinogenesis, angiogenesis, and metastasis, may be one of the possible signaling pathways for regulation of proliferation and metastasis of human lung cancer cells by TOB1 in vitro.

Mechanical intestinal obstruction in underweight, elderly women due to an incarcerated obturator hernia.

BACKGROUND: Obturator hernia is an infrequent pelvic hernia observed in elderly, emaciated and multiparous women. It often presents with nonspecific clinical symptoms, making it difficult to diagnose. METHODS: We conducted a retrospective descriptive study on 11 patients admitted to our hospital for obturator hernia from 2009 to 2020. RESULTS: All the patients were diagnosed with intestinal obstruction due to incarcerated obturator hernia preoperatively. Eight patients underwent laparotomy with low midline incision. Laparoscopic approach was tried on the other three patients with two patients converting to open surgery because of inadequate visualization, and only one patient received laparoscopic repair. Of the 10 patients receiving laparotomy, seven cases received obturator hernia repair with a match and three cases were subjected to bowel resection (two cases intestinal necrosis and one case intestinal perforation). Simple peritoneal closure was performed on the three contaminated cases. One patient died of septic shock and multiple organ failure. CONCLUSION: The emergent computed tomography allow for early and precise diagnosis of incarcerated obturator hernia. Laparotomy with low midline incision is commonly used to manage obturator hernia in an emergency, whereas laproscopic approach may only apply to some selected cases.

Current status of laparoscopic proximal gastrectomy in proximal gastric cancer: Technical details and oncologic outcomes.

The incidence of proximal gastric cancer has been increasing continuously. This status has prevailed despite the application of laparoscopic proximal gastrectomy as a surgical treatment for early proximal gastric cancer. The widespread adoption and standardization of this surgical procedure as the primary treatment for the abovementioned cancer has been hampered by the lack of consensus on the optimal reconstruction method after proximal gastrectomy. In addition, the oncological safety of proximal gastrectomy for advanced gastric disease remains unclear. We reviewed the English-language literature to clarify the current status of laparoscopic proximal gastrectomy in proximal gastric cancer. Japanese gastric cancer guidelines have suggested three types of reconstructions for proximal gastrectomy, namely, esophagogastrostomy, double-tract reconstruction, and jejunal interposition. Optimal reconstruction methods remain to be determined because of the lack of adequately performed and well-designed randomized controlled trials. The technical complexity and challenging implementation of reconstruction procedures have resulted in several complications with anastomoses. Multicenter randomized controlled trials are necessary to evaluate the various reconstruction methods and the oncological safety of laparoscopic proximal gastrectomy for advanced gastric disease.

Vascular anatomical variation in laparoscopic right hemicolectomy.

Laparoscopic complete mesocolic excision is gradually becoming the standard surgical approach in colon cancer therapy, the core element of which is central vascular ligation. However, this increases the difficulty for surgeons, particularly in the context of right colectomy, which encounters complex vascular anatomy. This study aimed to examine vascular variations that occur during laparoscopic right hemicolectomy through a review of the medical literature. We demonstrated that the ICA and MCA are evident in the majority of patients. The RCA was inconsistently present ranging from 12% to 45%. The ICA passed the SMV anteriorly or posteriorly at average rates. However, the RCA passed anterior to the SMV in most patients. Regarding intravenous, the ICV was consistently present, whereas the RCV was absent in up to 80% of patients. The GTH was present in nearly 80% of patients. We classified the vascular variations by the location of the branches instead of using numerical classification. The GCT and GPCT were common types whilst the GPT was relatively rare. In summary, detailed information on the vascular anatomical variations occurring on the right-side of the colon is vital. Failure to identify variations during surgical procedures can result in unwanted bleeding. Thus, we advocate for the use of the ICV as an anatomic marker during surgery.

Challenges surrounding postoperative adjuvant chemotherapy for T2N0 gastric cancer.

Determining the requirement for adjuvant chemotherapy in patients with stage IB gastric cancer (GC), and particularly for those with stage T2N0 (muscularis propria) disease, remains challenging. Patients with stage II/III disease benefit from postoperative adjuvant therapy; however, the randomized trials examining whether such therapy affords any survival benefit to patients with T2N0 disease are not sufficient. Current evidence suggests that not all patients with T2N0 disease should undergo such treatment, but only those with a high risk. To date, a number of retrospective studies have attempted to identify factors that are predictive of increased risk in an effort to guide adjuvant therapy-related clinical decision making. The National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology have published guidelines regarding factors associated with increased patient risk. As a result, treatment decisions for patients with stage T2N0 disease are currently determined on an individualized basis, in light of risk factors and the potential benefits of treatment. The present review surveyed current evidence related to the treatment of patients with high-risk GC and highlighted the potential avenues for future investigated.

Integrated Profiling Revealed Potential Regulatory Networks Among Long Noncoding RNAs and mRNAs in Mucosal Gastric Cancer.

Gastric cancer is one of the most commonly occurring cancers worldwide. Investigation of long noncoding RNAs is of increasing interest, particularly in relation to their contribution to progression and prognosis of gastric cancers; however, insufficient studies been performed investigating the part of long noncoding RNAs play in gastric cancer carcinogenesis. Patterns of dysregulated long noncoding RNA and messenger RNA between mucosa gastric cancer and adjacent normal tissues were identified using long noncoding RNAs microarray analysis. Quantitative real-time polymerase chain reaction was conducted as a means to verify the obtained data. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes  (KEGG) pathway analyses were subsequently used to investigate the function of dysregulated long noncoding RNAs and messenger RNAs. Cis and trans action was used to predict the possible targets of long noncoding RNAs, and a coexpression network was created to simulate the complex intergenic interactions. Ninety-five dysregulated long noncoding RNAs and 123 messenger RNAs were identified, and quantitative real-time polymerase chain reaction was used to validate 6 filtered long noncoding RNAs. Gene Ontology and KEGG pathway analyses identified several remarkably biological processes and signaling pathways, including spliceosome, RNA transport, and ubiquitin-mediated proteolysis. The transcriptional factors MYC, GABPA, and E2F1 were found to play a central function in the long noncoding RNAs process, as indicated by the coexpression network. This study revealed the dysregulated long noncoding RNA profiles of mucosal gastric cancer. The results shed light on the biological function of long noncoding RNAs in gastric cancer pathogenesis. This provides useful information for exploring potential early screening biomarkers in gastric cancer.

miR-557 inhibits the proliferation and invasion of pancreatic cancer cells by targeting EGFR.

Deregulation of microRNA has been suggested as a critical event in pancreatic cancer development and progression. Thus far, very little is known about the role of miR-557; therefore, the goal of this study was to investigate the potential role of miR-557 in pancreatic cancer. In the present study, we discovered that miR-557 expression was lowered in cancerous pancreatic tissue samples relative to non-cancerous adjacent controls, and when miR-557 was overexpressed we found that this promoted the apoptotic death of pancreatic cancer cells, suppressing their proliferation, invasion, and migration. Using western blotting and luciferase reporter assays, we further found evidence that this miRNA may directly suppress expression of the epidermal growth factor receptor via suppressing its translation through 3'-UTR binding. When EGFR was overexpressed in our pancreatic cancer cells, this was sufficient to reverse the effects of miR-557 inhibition. In summary, miR-557 acts as a tumor suppressor in pancreatic cancer cells, impairing their ability to grow and invade surrounding tissues due at least in part to EGFR inhibition. Harnessing this targeting of EGFR via this miRNA may therefore be a viable strategy useful for patient suffering from this deadly disease.

Small bowel adenocarcinoma in Lynch syndrome: A case report.

Small bowel adenocarcinoma is part of the tumor spectrum of Lynch syndrome, which is caused by germline mutations in the mismatch repair genes. The present study describes the case of a 51-year-old man fulfilling the Amsterdam II criteria for Lynch syndrome, who had a 15-mm early-stage colorectal cancer resected endoscopically from the ascending colon. Due to upper abdominal discomfort after eating and consequent anorexia, a computed tomography scan performed 1 month later showed a tumoral mass of the upper jejunum with local lymphadenopathy. The laparotomy revealed a completely obstructing mass. Intraoperative frozen section showed a small bowel adenocarcinoma. Subsequent genetic testing confirmed the germline mutation of mutL homolog 1. The patient received 6 cycles of an adjuvant folinic acid, fluorouracil and ocaliplatin chemotherapy regimen. The latest CT scan, 16 months after the chemotherapy, did not show any recurrence. This case highlights the importance of considering the possibility of small bowel adenocarcinoma in patients with upper bowel obstruction, particularly for patients with Lynch syndrome.

Primary adenocarcinoma of the small intestine presenting as superior mesenteric artery syndrome: A case report.

Superior mesenteric artery syndrome (SMAS) is an uncommon cause of vomiting and weight loss due to compression of the third part of the duodenum by the superior mesenteric artery. Small bowel adenocarcinoma is an uncommon tumor, which is frequently delayed in diagnosis as its symptoms and signs are non-specific. The present study describes a case of SMAS occurring in a 51-year-old man, caused by intestinal obstruction secondary to a primary adenocarcinoma of the duodenal-jejunal junction. To the best of our knowledge, the present case is the first report of small bowel adenocarcinoma masquerading as SMAS. The present case highlights the importance of considering the possibility of SMAS in patients with upper bowel obstruction caused by intestinal carcinoma.

Atypical presentation of a gastric stromal tumor masquerading as a giant intraabdominal cyst: A case report.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract, accounting for ~1% of gastric malignancies. The present study reports the case of a GIST of the stomach in a 75-year-old man who presented with abdominal distension and anorexia for 1 month. Gastroscopy was unremarkable. Ultrasound and computed tomography (CT) scans showed a giant intraabdominal cystic lesion of unknown origin. The lesion was initially believed to be a duplication cyst, a pancreatic pseudocyst or a liver cyst in the pre-operative diagnosis. Exploratory laparotomy revealed a cystic lesion of the lesser sac originating from the lesser curvature of the stomach. A distal gastrectomy with en bloc resection of the lesion was performed. The intraoperative frozen section showed a spindle-cell GIST and microscopically negative margins. The patient was treated with imatinib for 1 year. The latest CT scan at 14 months post-surgery did not show any recurrence. Although GISTs presenting as predominantly cystic lesions are very rare, they should be considered in the differential diagnosis of cystic lesions of the upper abdomen.

Descending colo-colonic intussusception secondary to signet ring cell carcinoma: A case report.

The incidence of intussusception is low in adults, particularly in the descending colon, due to the anatomical attachment of the descending colon to the retroperitoneum. Signet ring cell histology represents ~1% of colon adenocarcinomas and is associated with young patients and a poor clinical outcome. The present study describes a case of descending colo-colonic intussusception caused by signet ring cell carcinoma in a 27-year-old male. The patient presented with a history of intermittent left upper-quadrant abdominal pain for more than six months without any evident etiology. A computed tomography scan of the abdomen revealed left-sided colo-colonic intussusception. Upon laparotomy, a left hemicolectomy was performed according to intraoperative frozen-section pathology. Post-operative pathological evaluation revealed signet ring cell carcinoma invasion of the serosa, and 31.8% (7/22) of the regional lymph nodes were positive for cancerous cells. The post-operative course was uneventful and the patient was discharged on the tenth post-operative day.

Clinicopathological significance of cytoplasmic transducer of ErbB2. 1 expression in gastric cancer.

The aim of the present study was to investigate the expression of transducer of ErbB2. 1 (TOB1) in gastric carcinoma and to clarify the association between TOB1 expression and the clinical significance of this expression in patients with gastric carcinoma. Western blot analysis was performed to confirm the expression of TOB1 in gastric cancer. Immunohistochemistry (IHC) was performed on a tissue microarray containing 90 pairs of primary gastric cancer and adjacent normal tissue samples. TOB1 expression was evaluated separately with cytoplasmic and nuclear staining. Western blot analysis revealed significantly lower expression levels of TOB1 in gastric cancer tissues than those in adjacent normal tissues in 91.7% of cases. This was confirmed by IHC, which revealed decreased cytoplasmic TOB1 expression in cancer tissues compared with those of normal tissue samples in 84.4% of cases. The IHC data also revealed low cytoplasmic expression of TOB1 in 67.8% of human gastric cancer samples. Nuclear TOB1 expression exhibited no significant association with specific pathological features. However, a significant association was identified between cytoplasmic expression levels of TOB1 and clinicopathological characteristics, including the depth of invasion (P=0.017), differentiation grade (P=0.034) and tumor-node-metastasis stage (P<0.000). In conclusion, cytoplasmic TOB1 expression was suggested to be significant in angiogenesis and cell differentiation in gastric cancer tissues and may be used as a potential prognostic marker.

Transducer of erbB2.1 is a potential cellular target of gefitinib in lung cancer therapy.

Gefitinib, the specific inhibitor of the epidermal growth factor receptor (EGFR), may cause growth delay in cancer cell lines. Thorough understanding of the downstream cellular signaling of gefitinib will facilitate the discovery of biomarkers for predicting outcomes and monitoring anti-EGFR therapies, and provide information for key targets for therapeutic intervention. In this study, we investigated the role of transducer of erbB2.1 (TOB1) in gefitinib therapy. Using the lung carcinoma cell lines A549 and NCI-H1975, the results suggested that gefitinib might mediate cell cycle arrest in lung cancer cells at least by targeting TOB1 expression. Gefitinib treatment caused cell cycle arrest predominantly at the G1 phase, which is associated with TOB1 nuclear translocation and its interaction with cyclin D1. We also showed that knockdown of TOB1 expression by RNAi rescued lung cancer cells from gefitinib-induced cell-proliferative arrest. These results suggest that TOB1 interaction with cyclin D1 and nuclear translocation is directly involved in the gefitinib-induced anti-proliferative cell cycle arrest.