Minimally Invasive Surgery for Colorectal Cancer During the COVID-19 Pandemic in a Tertiary Medical Facility in Japan.

BACKGROUND/AIM: The coronavirus disease 2019 (COVID-19) pandemic has reduced hospital visits due to concerns regarding infection and also resulted in cancer screening delays. These changes may have had an impact on the progression of colorectal cancer (CRC). Therefore, the present study investigated the effects of the COVID-19 pandemic on minimally invasive surgery (MIS) for CRC using a correlation analysis of clinical outcomes before and during the COVID-19 pandemic. PATIENTS AND METHODS: The present study targeted CRC patients who underwent MIS between January 2018 and December 2019 (pre-COVID-19) and between April 2020 and March 2021 (COVID-19). A comparison analysis of clinical, surgical, and pathological findings between the pre-COVID-19 and COVID-19 groups was performed. RESULTS: Ninety-one patients underwent MIS for CRC pre-COVID-19 and 67 during COVID-19. The number of CRC cases detected by fecal occult blood tests was slightly higher in the pre-COVID-19 group than that in the COVID-19 group. Re-evaluations of laparoscopic videos revealed that the number of cases of surgical T4 CRC resected with the combined resection of the adjacent organs was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (16.4 vs. 4.4%, p=0.010). Furthermore, surgical times were significantly longer in the COVID-19 group than those in the pre-COVID-19 group (p<0.001). Pathological findings showed that the number of pT4 cases was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (p=0.026). CONCLUSION: The number of T4 CRC cases was higher during than before the COVID-19 pandemic, with increases in the surgical difficulty of MIS.

The expression and role of TRPV2 in esophageal squamous cell carcinoma.

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). METHODS: Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples. RESULTS: TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/ß-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients. CONCLUSION: The present results suggest that TRPV2 regulates cancer progression by affecting WNT/ß-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.

Effect of low temperature on the regulation of cell volume after hypotonic shock in gastric cancer cells.

Although peritoneal lavage with distilled water performed after surgery prevents peritoneal seeding, cancer cells may avoid rupture under mild hypotonicity through regulatory volume decrease (RVD), which is the homeostatic regulation of ion and water transport. The aim of the present study was to investigate the effect of low temperature on cell volume and cell death under hypoosmolal conditions and determine the underlying molecular mechanisms in gastric cancer (GC). Three human GC cell lines (NUGC4, KATO­III and MKN45) were exposed to hypotonic solutions, and the effects of low temperature on cell volume and viability were examined. Low temperature­induced changes in membrane transporters were evaluated, and knockdown and overexpression experiments were conducted to determine their effects on cell volume during hypotonic stimulation. Low temperature (24˚C) during hypotonic stimulation inhibited RVD and enhanced the cytocidal effects on GC cells. The expression of leucine­rich repeat containing protein A (LRRC8A), a component of a Cl­ channel, was decreased, and aquaporin 5 (AQP5) expression was increased at low temperatures. LRRC8A knockdown markedly slowed the decrease in cell volume following cell swelling by hypotonic shock. AQP5 overexpression enhanced initial cell swelling after hypotonic shock and increased the final cell volume. These results suggest that a hypotonic solution at low temperature increased initial water influx via activation of AQP5 and decreased Cl­ efflux via inhibition of LRRC8A. Therefore, low temperature enhanced the hypotonicity­induced cytocidal effects on GC cells, and these results may contribute to the development of a novel lavage method effective in reducing peritoneal recurrence in GC.

Aquaporin 1 suppresses apoptosis and affects prognosis in esophageal squamous cell carcinoma.

Aquaporin 1 (AQP1) is a membrane protein whose main function is to transfer water across cellular membranes. Recent studies have described important roles for AQP1 in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AQP1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 50 primary tumor samples underwent esophagectomy. AQP1 was primarily located in the cytoplasm and/or the nuclear membrane of carcinoma cells. The 5-year survival rate of patients with the "cytoplasm dominant" expression of AQP1 (47.1%) was significantly lower than other patients (83.2%). The depletion of AQP1 using siRNA induced apoptosis in TE5 and TE15 cells. The results of microarray analysis revealed that Death receptor signaling pathway-related genes were changed in AQP1-depleted TE5 cells. In conclusion, the results of the present study suggested that the cytoplasm dominant expression of AQP1 is related to a poor prognosis in patients with ESCC, and that it activates tumor progression by affecting Death receptor signaling pathway. These results provide insights into the role of AQP1 as a mediator of and/or a biomarker for ESCC.

Anion exchanger 2 suppresses cellular movement and has prognostic significance in esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC). RESULTS: AE2 was strongly expressed in KYSE170 and TE13 cells. The depletion of AE2 in these cells increased cell migration and inhibited the induction of apoptosis. The results of the microarray analysis revealed that various matrix metalloproteinase (MMP) signaling pathway-related genes, such as MMP1, MMP12, and TIMP4, were up- or down-regulated in AE2-depleted KYSE170 cells. Immunohistochemical staining showed that AE2 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its expression pattern at the invasive front of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the invasive front was associated with shorter postoperative survival. CONCLUSIONS: The results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by activating MMP signaling pathways and are related to a poor prognosis in patients with ESCC. METHODS: In human ESCC cell lines, knockdown experiments were conducted using AE2 siRNA, and the effects on cellular movement and survival were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy.

[A Case of Early Duodenal Cancer with Lymph Node Involvement Confirmed by Laparoscopic Lymph Node Sampling].

The patient was a 67-year-old man. A Type 0-Ⅱa+Ⅱc tumor, 20mm in size was observed in the 1st portion of the duodenum under magnifying endoscopy. Mucosal cancer was suspected and endoscopic resection was performed, with pathological findings as follows: Type 0-Ⅱa+Ⅱc, 19×12 mm, tub1, pT1b(SM2: 700 mm), pUL0, Ly0, V0, pHM0, pVM0. He refused subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)because of the high morbidity and mortality rates. Instead, he underwent only laparoscopic sampling of No. 5, 6, 12b, and 13a lymph nodes, and metastasis in a No. 6 node was pathologically confirmed. He eventually underwent SSPPD with D2, but no metastases were found in other lymph nodes. Pancreaticoduodenectomy is currently considered the best treatment option for complete removal of regional lymph nodes in duodenal cancer despite high morbidity and mortality rates. Further studies are needed to determine the pattern and incidence of lymph node metastasis by location and depth of the primary tumor, to establish optimal treatment guidelines for duodenal cancer.

[Two-Stage Reconstruction Surgery with Free Jejunum Graft for Necrosis of the Gastric Tube Following Subtotal Esophagectomy-A Case Report].

The case is a 73-year-old man who underwent esophagectomy and retrosternal gastric conduit reconstruction for esophageal cancer. Reoperation was performed because the oral side of the gastric tube developed necrosis on the 31st postoperative day. The necrotic parts of the gastric tube were resected, and a cervical esophageal stoma was created. The remaining gastric tube was pulled up at the anterosternal subcutaneous location in preparation for the two-stage reconstructive operation. The reconstructive operation with a free jejunum graft through the anterosternal subcutaneous route was performed 35 days after the reoperation. Vascular anastomosis was performed with the right internal thoracic artery and vein by microsurgery. The postoperative course was satisfactory. Necrosis of the gastric tube is a rare and severe complication of esophagectomy. Reconstructive surgery for gastric tube necrosis is generally necessary but difficult to perform because of the severe surgical stress it confers on the patient. In this paper, we showed a new approach for two-stage reconstruction with a free jejunum graft through the anterosternal subcutaneous route. This operative procedure causes relatively less surgical stress than other procedures; hence, it is considered to be a beneficial reconstructive approach for patients with gastric tube necrosis.

Blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects in gastric cancer.

BACKGROUND: Peritoneal lavage with distilled water has been used for surgeries of various cancers to reduce peritoneal recurrence. This study examined whether blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects in gastric cancer (GC). RESULTS: A potassium channel blocker inhibited the occurrence of regulatory volume decrease (RVD) induced by mild hypotonic stimulation, and significantly enhanced cytocidal effects on GC cells. Incubating MKN45 cells with hypotonic solutions containing a potassium channel blocker significantly reduced the formation of peritoneal metastases in nude mice. METHODS: The three human GC cell lines (HGC-27, Kato III, and MKN45) were exposed to mild hypotonic solutions, and the effects of blockade of potassium ion transports during hypotonic stimulation on cell volume changes and cell viabilities were examined. In the in vivo study, MKN45 cells stimulated with mild hypotonic solutions were intraperitoneally injected into nude mice, and the effects of blockade of potassium ion transports during hypotonic stimulation on the formation of peritoneal metastases were evaluated. CONCLUSIONS: Blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects on GC cells, which may contribute to development of a novel lavage method for further reduction of peritoneal recurrence in GC.

[A Case of Intestinal Obstruction Caused by a Bezoar after Pylous-Preserving Gastrectomy].

A 65-year-old woman with a history of pylorus-preserving gastrectomy(PPG)for early gastric cancer visited our hospital because of vomiting. Gastrointestinal endoscopy revealed a large bezoar in the anastomotic site of the stomach. Because the bezoar was too large to be collected orally, the dissolution therapy with taking Coca-Cola®was continued. On the 3rd day after hospitalization, she felt acute abdominal pain with vomiting. Computed tomography revealed intestinal obstruction by a mass with air bubbles inside in the ileum. Emergency operation was performed under a diagnosis of intestinal obstruction due to the bezoar. The black brown bezoar sized 80×35×30mm was extracted through an ileotomy. The delayed gastric empty is considered to involve in the bezoar formation. Therefore, the appropriate education of diet and periodic endoscopic screening are necessary for patients with large amounts of gastric residues especially after PPG. In the dissolution therapy, physicians need to be careful of intestinal obstruction by a bezoar.

[A case report of distal gastrectomy with thrombectomy after NAC for Gastric cancer].

This is a case report of gastric cancer with a tumor embolus in the portal vein of a 76-year-old male. Both computed tomography (CT) and upper gastrointestinal endoscopy were performed. The diagnosis was gastric cancer with an accompanying tumor embolus in the portal vein, specifically in the superior mesenteric vein. After neoadjuvant chemotherapy, a distal gastrectomy, and thrombectomy were performed. Upon pathological examination, the main tumor was diagnosed as adenocarcinoma, and the embolus was confirmed to extend from the main tumor into the superior mesenteric vein. Upon immunostaining examination, neither the embolus nor main tumor expressed alpha-fetoprotein (AFP), but both expressed carcinoembryonic antigen (CEA). Gastric cancer with a tumor embolus in the portal vein is considered an incurable disease. However, with no other non-curative factor than portal vein embolus, it is possible that gastrectomy with thrombectomy can result in a good prognosis. On the other hand, it is extremely difficult to improve the prognosis of gastric cancer with both tumor embolus in the portal vein and liver metastasis.