Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy.

Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.

The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines.

We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.

[A Case of Transverse Colon Cancer with Gastrointestinal Amyloidosis Prevented from Anastomotic Leakage by Multidimensional Approach].

The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage Ⅲc). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.

"Role-sharing surgery": a new surgical education system that gives beginner surgeons more chances to operate while ensuring the surgical quality of robotic surgery.

It has been pointed out that robotic surgery is more time-consuming than laparoscopic surgery, and a major challenge for the future is educating young surgeons while maintaining the surgical quality. To solve these problems, we report a role-sharing surgery (RSS) approach in which the surgery is divided into several areas and timetabled, with roles shared by several operators. We performed RSS for 19 standard colorectal cancer surgeries. The surgery was completed within + 28 min of the scheduled operation time, and a beginner robotic surgeon (BRS) was able to perform approximately 66% of the total surgery. There were no statistically significant differences in the short-term outcomes between the RSS and conventional surgery groups. Based on these findings, RSS has the potential to be the best practice for educating BRSs in robotic surgery, the use of which is expected to increase steadily in the future.

Severe esophageal stricture after perforation and necrotizing esophagitis: unusual presentation of a duodenal gastrinoma.

Gastrinomas are pancreatic or duodenal endocrine tumors that secrete excess gastrin, which causes gastroesophageal reflux disease, peptic ulcers, and chronic diarrhea. Due to the rarity of the disease, nonspecific symptoms, and the outstanding effect of proton pump inhibitors, diagnosing gastrinomas is difficult. Here, we present the case of a 58-year-old woman who had a duodenal gastrinoma that caused rare but critical events, including esophageal perforation, necrotizing esophagitis, and severe esophageal stricture. She presented with a non-malignant severe lower esophageal stricture, which was resistant to endoscopic dilatation. During esophagectomy, a duodenal mass was excised and diagnosed as gastrinoma. This was considered the main cause of all events. Gastrinomas are rarely encountered in clinical practice, but early diagnosis is necessary to avoid serious conditions. Therefore, whenever we encounter a patient with gastroesophageal reflux disease requiring long-term treatment or is refractory, we must not forget to screen for gastrinomas.

Upregulation of integrin­linked kinase enhances tumor progression in gemcitabine­resistant pancreatic cancer.

Pancreatic cancer (PaCa) tends to be resistant to chemotherapy and is associated with a very poor prognosis. It has been previously reported by the authors that integrin­linked kinase (ILK) is a prognostic factor in PaCa. ILK expression was examined in a newly established gemcitabine (Gem)­resistant (Gem­R) PaCa cell line and it was demonstrated that ILK expression was upregulated compared with that in Gem­sensitive (Gem­S) cells. In the present study, the effects of increased ILK expression in Gem­R PaCa cells were evaluated and it was examined whether compound 22 (Cpd22), an ILK inhibitor, exerted antitumor effects not only in Gem­S cells but also in Gem­R cells. Reverse transcription­quantitative polymerase chain reaction and western blotting revealed that ILK expression was higher in Gem­R PaCa cells than in Gem­S PaCa cells. Cpd22 inhibited the growth of PaCa cells in a concentration­dependent manner. Cpd22 also inhibited the growth of Gem­R PaCa cells. The invasive and angiogenic potential of Gem­R PaCa cells was enhanced compared with that in Gem­S cells; however, ILK small interfering RNA and Cpd22 treatment suppressed this enhancement of invasive potential compared with that in Gem­S cells. The addition of Cpd22 to Gem also improved the sensitivity of Gem­R cell lines to Gem. Furthermore, enhanced Akt signaling was associated with increased malignancy in Gem­R cell lines. In conclusion, ILK was upregulated with resistance and may be involved in tumor angiogenesis, invasive potential, and chemotherapy resistance, which were all suppressed by Cpd22 treatment. Thus, Cpd22 may be a novel therapeutic agent for the treatment of PaCa.

Girdin regulates both migration and angiogenesis in pancreatic cancer cell lines.

Girdin, an actin­binding protein, is reportedly involved in the invasion and angiogenesis of various cancers. It has been suggested that the flavonoid Scutellarin (SCU) inhibits Girdin signaling. In the present study, the function and therapeutic applications of Girdin in pancreatic cancer (PaCa) were investigated. Immunohistochemical staining of Girdin in resected PaCa specimens from the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science showed that high Girdin expression was associated with poor overall survival and relapse­free survival, as well as with T factor, indicating invasion into the surrounding tissues. On the other hand, Girdin was highly expressed in almost all PaCa cell lines, and the migration ability of Girdin­knockdown cell lines was decreased even under epidermal growth factor (EGF) stimulation. In addition, SCU suppressed PaCa cell migration by inhibiting the phosphorylation of Girdin. The expression and production of vascular endothelial growth factor A (VEGF­A) was significantly decreased in Girdin­knockdown cell lines. Furthermore, in Matrigel tube formation assays performed using culture supernatant, the lumen­forming ability of vascular endothelial cells was also decreased in Girdin­knockdown cell lines. However, SCU treatment did not significantly alter the expression or production of VEGF­A. These results suggested that Girdin is involved in EGF signaling­mediated migration of PaCa cells, that SCU inhibits PaCa invasion by suppressing Girdin activity, and that Girdin is also involved in angiogenesis via an activation pathway different from the action site of SCU. Girdin may be a prognostic biomarker, and the development of a novel molecular­targeted drugs for Girdin may improve the prognosis of PaCa in the future.

[A Case of Surgical Resection of Advanced Gallbladder Cancer with Adult Annular Pancreas].

An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.

Spontaneous regression of advanced transverse colon cancer with deficient mismatch repair: a case report.

BACKGROUND: Spontaneous regression (SR) of cancer occurs in 1 in 60,000-100,000 patients. This phenomenon has been reported in almost all cancer types, most commonly neuroblastoma, renal cell carcinoma, malignant melanoma, and lymphoma/leukemia. However, SR in colorectal cancer (CRC) is extremely rare, particularly in advanced cases. Hence, this report describes a very rare case of spontaneous regression of advanced transverse colon cancer. CASE PRESENTATION: A 76-year-old female with anemia was diagnosed with a type II well-differentiated adenocarcinoma in the middle transverse colon. Two months later, a second colonoscopy examination was performed for preoperative marking, and it revealed tumor shrinkage and a shift to type 0-IIc morphology. Endoscopic tattooing was then performed, followed by a laparoscopic partial resection of the transverse colon with D3 lymph node dissection. However, the resected specimen contained no tumor, and colonoscopy showed no tumor remnants in the remaining colon. Histopathological examination revealed mucosal regeneration and a mucus nodule in between the submucosal and muscular layers, with no cancer cells detected. Immunohistochemical analysis revealed the loss of MutL homolog 1 (MLH1) and postmeiotic segregation increased 2 (PMS2) expression in the cancer cells of biopsied specimens, suggesting deficient mismatch repair (dMMR). The patient continues to be followed up until 6 years postoperatively, and no recurrence has been observed. In this study, we also reviewed similar reported cases of spontaneous regression of cancer involving dMMR. CONCLUSION: This study presents a rare case of spontaneous regression of advanced transverse colon cancer wherein dMMR is strongly involved. However, further accumulation of similar cases is needed to elucidate this phenomenon and to develop new treatment strategies for CRC.

Simultaneous robotic distal gastrectomy and distal pancreatectomy: Avoiding total gastrectomy using indocyanine green fluorescence imaging.

Remnant gastric ischemia is the most significant complication in distal pancreatectomy (DP) after distal gastrectomy (DG). Some studies have reported the safety of asynchronous DP in patients who underwent DG. We report a case of simultaneous robotic DG and DP. A 78-year-old man was diagnosed with gastric and pancreatic cancer. We preoperatively confirmed the absence of anomalies in the left inferior phrenic artery. Robotic simultaneous DG and DP was performed; subtotal resection of the stomach was carried out, enabling the left inferior phrenic artery to maintain perfusion of the remnant stomach, even after ligation of the splenic artery. The remnant stomach was preserved as scheduled, and indocyanine green fluorescence imaging confirmed sufficient remnant stomach tissue perfusion. Robotic surgery using the da Vinci surgical system (with a fluorescence imaging system and technology enabling surgical precision) is suitable for this surgical procedure because it considers tumor radicality and allows for function preservation.

The cisplatin-induced acute kidney injury is a novel risk factor for postoperative complications in patients with esophageal cancer: a retrospective cohort study.

BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer. METHODS: In this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models. RESULTS: Among 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3-31.9) and 43.8 days (26.5-61.2), respectively, mean difference (95%CI) 16.2 days (4.4-28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30-13.18) and 3.87 (1.35-11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%). CONCLUSION: c-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.

Robotic gastrectomy for remnant gastric cancer after pancreaticoduodenectomy.

The utility of robotic surgery for remnant gastric cancer remains unclear. We report a case of a robotic gastrectomy for remnant gastric cancer after pancreaticoduodenectomy and Child reconstruction with Braun enteroenterostomy. Adhesiolysis, lymphadenectomy, and gastrectomy were robotically performed. Indocyanine green fluorescence imaging confirmed the tissue perfusion of the reconstructive tract. The patient's postoperative course was uneventful. Robotic surgery facilitates safety for gastrectomy after pancreaticoduodenectomy because of its precise manipulation; its advantages can be further exploited by maximizing usage of the assistant's forceps. Indocyanine green fluorescence imaging capability of the da Vinci Xi Surgical System allows timely evaluation of tissue perfusion at the site of interest, leading to a more reliable procedure.

AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells.

Ataxia telangiectasia and Rad3­related (ATR) is a kinase that repairs DNA damage. Although inhibitors that selectively target ATR have been developed, their effectiveness in colorectal cancer has not been widely reported. The present study hypothesized that anticancer agents that effectively act in the S phase before the G2/M checkpoint may be ideal agents for concomitant use with ATR inhibitors, which act at the G2/M checkpoint. Therefore, the present study examined the combined effects of AZD6738, an ATR inhibitor, and trifluridine (FTD), which acts in the S phase and has a high DNA uptake rate. In vitro cell viability assays, flow cytometry and western blotting were performed to evaluate cell viability, and changes in cell cycle localization and protein expression. The results revealed that in colorectal cancer cells, the combination of AZD6738 and FTD inhibited cell viability, cell cycle arrest at the G2/M checkpoint and Chk1 phosphorylation, and increased apoptotic protein expression levels more than that when treated with FTD alone. HT29, a BRAF­mutant cell line known to be resistant to anticancer drugs, was used to induce tumors in vivo. Since FTD does not have sufficient efficacy when administered orally, it was mixed with tipiracil to prevent degradation; this mixture is known as TAS­102. TAS­102 alone exerted minimal tumor suppressive effects; however, when used in combination with AZD6738, tumor suppression was observed, suggesting that AZD6738 may increase the effectiveness of a weakly effective drug. Although ATR inhibitors are effective against p53 mutants, the present study demonstrated that these inhibitors were also effective against the p53 wild­type HCT116 colorectal cancer cell line. In conclusion, combination therapy with AZD6738 and FTD enhanced the inhibition of tumor proliferation in vitro and in vivo. In the future, we aim to investigate the potentiating effect of AZD6738 on 5­fluouracil­resistant cell lines that are difficult to treat.

[A Case Report of Hepatic Angiosarcoma Developed against the Background of Hepatic Hemochromatosis].

A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.

Benefits of laparoscopic trans-hiatal approach with Heller-Dor surgery in a case of mid-esophageal diverticulum.

Compared to the more common epiphrenic diverticula, those located at the central section of the esophagus are quite rare. Minimally invasive approaches for mid-esophageal diverticula have lacked standardization. Certain mid-esophageal diverticula, like epiphrenic diverticula, have been attributed to esophageal motility disorders. Thus, we believe that surgery for esophageal diverticula requires preoperative evaluation of esophageal function, with additional surgery being performed in case of abnormalities. The laparoscopic trans-hiatal approach has been a common technique for managing epiphrenic diverticula but can also be used for mid-esophageal diverticula located far from the esophagogastric junction provided that the port location is carefully considered. Laparoscopic surgery is also preferable given that it is a minimally invasive procedure and allows for diverticulum resection and Heller myotomy and Dor surgery to prevent reflux in the same field of view. Hence, laparoscopic surgery may be a beneficial alternative to the traditional thoracic or thoracoabdominal techniques.

Incomplete lymphatic sealing around the inferior mesenteric artery is a risk factor for chylous ascites in robotic rectal cancer surgery.

INTRODUCTION: Compared with laparoscopic surgery (LS), robotic surgery (RS) is considered to have acceptable outcomes in rectal cancer, but few reports have focused on chylous ascites in RS. The aim of this study was to investigate the incidence and etiology of chylous ascites after RS. METHODS: This retrospective study included 291 patients with rectal cancer who underwent RS (n = 165) or LS (n = 126) with high ligation of the inferior mesenteric artery (IMA). Propensity score matching (PSM) was performed to compare the two groups. RESULTS: \Dissection around the IMA was achieved using ultrasonic coagulating shears in most LS cases, and monopolar scissors in most RS cases, sometimes using bipolar vessel sealing device or bipolar forceps. The incidence of chylous ascites was 12.2% in RS and 4.1% in LS after PSM (P = .037). When limited to the RS group, multivariate analysis identified absence of lymphatic sealing at the left side of the IMA and shorter operative time as independent risk factors for chylous ascites. Except for duration of drain placement, no outcomes differed significantly with or without chylous ascites. One patient with chylous ascites developed later infection and required antibiotic treatment. CONCLUSION: The incidence of chylous ascites is significantly higher in RS than in LS, and RS with incomplete lymphatic sealing around the IMA is a risk factor for chylous ascites in rectal cancer. Although outcomes for patients with chylous ascites were acceptable, adequate lymphatic sealing during dissection around the IMA is crucial to prevent chylous ascites in RS.

[An Intraductal Papillary Mucinous Neoplasm of the Pancreas with Metachronous Quadruple Cancers].

The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).

[A Case of Intrahepatic Cholangiocarcinoma in Contact with the Gastroduodenal Anastomosis in Which Proton Beam Therapy Was Performed after Placement of an Absorbable Spacer].

Chemotherapy is the standard therapy for unresectable intrahepatic cholangiocarcinoma(ICC), but chemotherapy is not efficacious. Proton beam therapy(PBT)has been covered by Japanese health insurance for ICC since 2022, and the number of cases is expected to increase. In some cases, irradiation is difficult due to the close proximity of the gastrointestinal tract to the tumor. We report our management of a patient with ICC close to the gastrointestinal tract. The patient was a 69-year- old woman with a history of distal gastrectomy and Billroth-Ⅰ reconstruction for gastric cancer. A CT scan showed a tumor in liver S3; a biopsy revealed ICC. Because the tumor was in contact with the gastroduodenal anastomosis, we placed an absorbable spacer and performed PBT. After the treatment, the tumor shrank slightly. Although the liver is anatomically adjacent to the digestive tract, the placement of absorbable spacers facilitates performing PBT without adverse events, and is thus considered a useful treatment.

Potential Role of TRPV4 in Stretch-Induced Ghrelin Secretion and Obesity.

Obesity is an important health problem, which can be prevented through appetite control. Ghrelin is an appetite-stimulating hormone considered to promote obesity. Thus, we examined whether gastric stretching affects ghrelin secretion. We investigated the role of transient receptor potential vanilloid 4 (TRPV4) in gastric glands in the regulation of ghrelin secretion. TRPV4 immunostaining was performed in tissue samples from 57 patients who underwent gastrectomy. TRPV4 expression was compared between patients with (body mass index (BMI) ≥ 30) and without (BMI <30) obesity. For in vitro experiments, we used MGN3-1 cells, a ghrelin-producing cell line derived from mice. To investigate the bioactivity of TRPV4, MGN3-1 cells were treated with TRPV4 agonists and antagonists, and changes in intracellular Ca2+ concentration were confirmed. The concentration of ghrelin in the cell supernatant was measured using the ELISA with and without 120% stretch stimulation. TRPV4 expression was significantly higher in patients with obesity than in those without at all sites, except the fornix. Immunostaining confirmed the expression of TRPV4 in MGN3-1 cells. TRPV4 agonist administration increased intracellular Ca2+ concentration and ghrelin secretion in MGN3-1 cells, whereas the administration of the agonist combined with the antagonist decreased intracellular Ca2+ concentration and ghrelin secretion. Ghrelin secretion significantly increased in response to a 120% stretch in MGN3-1 cells. However, secretion was not increased by stretch when cells were treated with a TRPV4 antagonist. TRPV4 regulates ghrelin secretion in response to stretch in the stomach, which may affect body weight.

Robotic distal gastrectomy for gastric cancer in a patient with situs inversus totalis and a vascular anomaly.

Situs inversus totalis is defined as a complete mirror-image transposition of the thoracic and abdominal viscera. Cancer surgery in patients with situs inversus totalis can be more difficult than in patients without situs inversus totalis; however, robotic surgery using the da Vinci Surgical System allows for intuitive operation with its multi-articular function and stereopsis effect. In addition, prevention of shaking and the motion scale allows for efficient surgical procedures. We evaluated a 64-year-old man who had gastric cancer, and situs inversus totalis and a blood-vessel variation. To facilitate intuitive handling of the robot in this patient with organs reversed from the norm, we arranged the instruments and ports in such a way that the Maryland bipolar forceps could be used with the surgeon's right hand. We performed a successful robotic distal gastrectomy with lymph node dissection. The operative time was 286 min, and the blood loss was 44 mL. There were no intra- or post-operative complications. The patient was discharged on postoperative day 7 and has had no evidence of a recurrence for 18 months. We conclude that robotic surgery is an efficient tool for operating on patients with gastric cancer, and situs inversus totalis and vessel variations.