Long-term prognosis and DNA damage status after oral mucosal epithelial cell sheet transplantation following esophageal endoscopic submucosal dissection for squamous cell carcinoma: A case series.

Autologous oral mucosal epithelial cell sheet (AOMECS) transplantation has recently been applied in human patients to prevent postprocedural stenosis following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma. However, the long-term safety of AOMECS transplantation remains unclear. We evaluated the long-term outcomes of 10 patients who participated in a clinical trial of AOMECS transplantation after esophageal ESD. Additionally, we assessed the local DNA damage response in the esophageal epithelium using p53 binding protein 1 (53BP1) immunofluorescence in post-AOMECS biopsy specimens. The median follow-up period was 118.5 months (range: 46-130 months). Two patients developed primary esophageal cancer near the AOMECS site and successfully underwent additional ESD. One patient developed lymph node metastasis and underwent chemotherapy. None of the patients died from the original disease, although one patient died from unrelated causes. The rate of abnormal 53BP1 nuclear foci, indicative of increased genome instability, increased with the progression of neoplasia in patients post AOMECS. Our case series suggests that AOMECS transplantation provides an acceptable long-term prognosis and 53BP1 foci may serve as a useful marker for assessing DNA instability in the post-AOMECS esophageal epithelium.

A prospective randomized controlled study evaluating efficacy of Daikenchuto in the treatment of postoperative abdominal pain and bloating following hepatectomy.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of TJ-100 TSUMURA Daikenchuto (DKT) Extract Granules in preventing post-hepatectomy digestive symptoms and the effects on small intestinal mucosal atrophy. METHODS: Eligible patients were randomly assigned to the DKT therapy and usual care groups in a 1:1 ratio. The DKT therapy group was administered DKT for 14 days after surgery or until the day of discharge if the patient left the hospital before 14 days, and the usual care group did not receive DKT. We used the numeric rating scale to measure abdominal pain and bloating after surgery and compared the results between the two groups to determine the efficiency of DKT. We also evaluated postoperative small intestinal mucosal atrophy using diamine oxidase (DAO) and glucagon-like peptide-2 (GLP-2) activities in the serum, and postoperative complications. RESULTS: No adverse effects were observed in the DKT group. No significant difference was observed in the area under the curve for postoperative abdominal pain or bloating throughout the study period. No differences were observed in DAO2, GLP2, and other nutrition assessment indicators. Four postoperative infections were observed in three patients (two with intra-abdominal surgical site infections [SSIs] and two with pneumonia). All cases of infection occurred in the control group. CONCLUSIONS: Although DKT did not significantly improve postoperative symptoms, such as abdominal pain or bloating, it is widely used in Japan to improve bowel movement and is safely prescribed for patients undergoing hepatectomy with a tendency toward less postoperative infection.

Generation of human hepatobiliary organoids with a functional bile duct from chemically induced liver progenitor cells.

BACKGROUND: Liver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine. METHODS: In this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs). hCLiPs were induced in mature cryo-hepatocytes using a small-molecule cocktail of TGF-ß inhibitor (A-83-01, A), GSK3 inhibitor (CHIR99021, C), and 10% FBS (FAC). HBOs were then formed by seeding hCLiPs into ultralow attachment plates and culturing them with a combination of small molecules of Rock-inhibitor (Y-27632) and AC (YAC). RESULTS: These HBOs exhibited bile canaliculi of MHs connected to BD structures, mimicking bile secretion and transportation functions of the liver. The organoids showed gene expression patterns consistent with both MHs and BD structures, and functional assays confirmed their ability to transport the bile analogs of rhodamine-123 and CLF. Functional patient-specific HBOs were also successfully created from hCLiPs sourced from cirrhotic liver tissues. CONCLUSIONS: This study demonstrated the potential of human HBOs as an efficient model for studying hepatobiliary diseases, drug discovery, and personalized medicine.

Chemotherapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer. MATERIALS AND METHODS: This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6 months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. RESULTS: Eighteen women were included in the study (median age: 57 years; range: 55-62 years). At 6 months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01; -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09; -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline. CONCLUSION: Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6 months after chemotherapy.

18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters are associated with histological outcomes in superficial esophageal squamous cell carcinoma.

Endoscopic submucosal dissection is a standard treatment for early esophageal squamous cell carcinoma. However, submucosal or lymphovascular invasion increases the risk of lymph node metastasis. Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters are associated with prognosis in patients with advanced esophageal squamous cell carcinoma, the utility of FDG PET/CT in diagnosing superficial esophageal carcinoma remains unclear. This study aimed to investigate the association between FDG PET/CT parameters and histopathological findings in superficial esophageal carcinoma. Fifty-three patients with superficial esophageal cancer who underwent FDG PET/CT scans before undergoing interventions were retrospectively analyzed. The maximal standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis were significantly higher in the cases with submucosal invasion (T1b) compared with those confined to the muscularis mucosa (T1a). In contrast, classification of intrapapillary capillary loops patterns with magnifying endoscopy did not yield statistical differences between T1a and T1b. Multivariable analysis revealed that SUVmax was the only independent predictor of submucosal and lymphovascular invasion. This study demonstrated that SUVmax may be useful in predicting submucosal and lymphovascular invasion. Thus, the value of SUVmax may guide clinical decision-making in superficial esophageal squamous cell carcinoma.

Minimally invasive pancreaticoduodenectomy for circumportal pancreas: literature review and report of two type IIIA cases.

BACKGROUND: Circumportal pancreas is a rare morphological variant with clinical significance due to the high risk of postoperative pancreatic fistula in patients undergoing pancreaticoduodenectomy. Type IIIA (suprasplenic anteportal) is the most common type of circumportal pancreas. We present two cases of type IIIA treated with minimally invasive pancreaticoduodenectomy, and review the literature on patients with circumportal pancreas who underwent pancreatic surgery. CASE PRESENTATION: Case 1: Laparoscopic Pancreaticoduodenectomy for Non-functioning Pancreatic Neuroendocrine Neoplasm with Circumportal Pancreas. A 69-year-old female with no prior medical history presented with a pancreatic head mass detected during routine ultrasound. CT revealed a 20 mm hypervascular tumor in pancreas head and a suprasplenic circumportal pancreas with an anteportal duct. The main pancreatic duct (MPD) was not in the parenchyma on the dorsal side of the portal vein (PV). Laparoscopic pancreaticoduodenectomy was performed. The anteportal side was resected with an ultrasonic device, and the retroportal side with a mesh-reinforced stapler. Pancreaticojejunostomy was performed without complications. Case 2: Robot-assisted Pancreaticoduodenectomy for Pancreatic Head Cancer and Non-functioning Pancreatic Neuroendocrine Neoplasm in the pancreatic tail with Circumportal Pancreas. A 72-year-old male with no prior medical history presented with a dilated main pancreatic duct on ultrasound. Diagnosed with pancreatic head cancer (Stage IIA), he underwent neoadjuvant chemotherapy. Contrast-enhanced CT revealed pancreatic cancer in the head and a tumor in the tail with unknown pathology. Robot-assisted pancreaticoduodenectomy was performed, and pancreatectomy on the left side of the tail tumor was planned. Intraoperative findings revealed a circumportal pancreas with the MPD not running through the dorsal parenchyma. After resected the parenchyma on the left side of the tail tumor, parenchyma on the dorsal side of the PV was dissected using SynchroSeal®. Pancreaticojejunostomy was performed without complications. The postoperative course was uneventful. CONCLUSIONS: The optimal location and method of pancreatic resection should be selected according to the type of circumportal pancreas and the location of the lesion to be resected to minimize the risk of pancreatic fistula. Minimally invasive surgery for circumportal pancreas remains challenging even for surgical teams with sufficient experience and skills, and careful consideration are necessary for its application.

Multicenter retrospective analysis of complications and risk factors in endoscopic resection for esophageal cancer across Japan.

BACKGROUND: Endoscopic resection (ER) is a minimally invasive treatment for esophageal cancer that sometimes causes complications. To understand the real-world incidence and risk factors for these complications, a nationwide survey was conducted across Japan. METHODS: This retrospective multicenter study included patients who underwent ER for esophageal cancer from April 2017 to March 2018 (2017 complication analysis) and April 2021 to March 2022 (2021 complication analysis). The study assessed the complication rates and conducted risk factor analyses for endoscopic submucosal dissection (ESD) using data for these patients, with exclusions based on specific criteria to ensure data accuracy. RESULTS: In the 2021 complication analysis, there were two mortalities highly likely attributable (0.03%) to ER and one mortality possibly attributable (0.01%) to ER. Intraoperative perforation, delayed bleeding, and pneumonia occurred in 137 cases (1.8%), 44 cases (0.6%), and 130 cases (1.7%), respectively. In the multivariate analysis for complications after ESD, low ER volume of the facility was an independent risk factor for perforation, while lesion location in the cervical or upper thoracic esophagus was an independent factor for reduced risk of perforation. Age ≥ 80 years was a risk factor for pneumonia, while use of traction techniques was a factor for reduced risk of pneumonia. Lesions located in the middle thoracic esophagus had a lower risk of stricture, and the risk of stricture increased as the circumferential extent of the lesion increased. CONCLUSIONS: This large-scale study provided detailed insights into the complications associated with esophageal ER and identified significant risk factors.

DCLK1 Expression and its Functional Significance in Intrahepatic Cholangiocarcinoma and Bil-IN Stage.

BACKGROUND/AIM: Although several studies in some neoplasms have reported correlation between the expression levels of Doublecortin-like kinase1(DCLK1) and carcinogenesis, its role in cholangiocarcinoma remains unknown. MATERIALS AND METHODS: DCLK1 expression in normal epithelium (NE), biliary intraepithelial neoplasia (BilIN)1∼3, and intrahepatic cholangiocarcinoma (ICC) were investigated immuno-histochemically. The molecular effects of DCLK1 were investigated by gene silencing using RNAi [DCLK1-tagrgeting (siDCLK1)]. The human ICC cell lines HuCCT1 and HuH28 were transfected with these siRNAs, and used for assays in the presence or absence of DCLK1 inhibitors. RESULTS: The positive ratio of DCLK1 expression in ICC was higher than that in NE, and equally distributed among BilIN1∼3 (NE: BilIN1: BilIN2: BilIN3: ICC=62%: 91%: 97%: 100%: 95%, p<0.05). In the wound healing assay, the migration of the siDCLK1-treated cells was significantly inhibited compared to the NT-treated cells (p<0.05). In the cell invasion assay, the invasion of the siDCLK1-treated cells was significantly inhibited compared to the NT-treated cells (p<0.05). In the presence of the DCLK1 inhibitor, cell proliferative capacity at 24 hours was decreased in a concentration-dependent manner. CONCLUSION: DCLK1 was highly expressed in the early stage of ICC carcinogenesis. Human ICC cell growth was suppressed in vitro by siRNA silencing of DCLK1 or after treatment with the DCLK1 inhibitor, indicating DCLK1 may be molecular target for ICC therapy.

A first-in-human clinical study of laparoscopic autologous myoblast sheet transplantation to prevent delayed perforation after duodenal endoscopic mucosal dissection.

BACKGROUND: The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD. METHODS: To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period. RESULTS: Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient's postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis. CONCLUSIONS: This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future. TRIAL REGISTRATION: jRCT, jRCT2073210094. Registered November 8 2021, https://jrct.niph.go.jp/latest-detail/jRCT2073210094 .

High serum alpha-fetoprotein and positive immunohistochemistry of alpha-fetoprotein are related to poor prognosis of gastric cancer with liver metastasis.

Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.

Serum wisteria floribunda agglutinin-positive human Mac-2 binding protein is unsuitable as a diagnostic marker of occult hepatocellular carcinoma in end-stage liver cirrhosis.

BACKGROUND AND PURPOSE: Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a marker of liver fibrosis and hepatocellular carcinoma (HCC). In this study, we aimed to evaluate the diagnostic ability of WFA+-M2BP for occult HCC, which current diagnostic imaging tests fail to detect. METHODS: Patients who underwent hepatectomy for liver transplantation (LT) and whose whole liver could be sliced and subjected to histological examination between 2010 and 2018 were eligible for this study (n = 89). WFA+-M2BP levels were measured in samples collected before the LT. Comparison of the postoperative histological test results with the preoperative imaging data grouped the patients into histologically no group (N), histologically detected group (D), histologically increased group (I), and histologically decreased or same group (DS), and the results were compared with the WFA+-M2BP values. In addition, comparisons were made between each data with and without HCC, including occult HCC, and total tumor diameter. RESULTS: Irrespective of underlying hepatic disease conditions, there were 6 patients in the N group, 10 in the D group, 41 in the I group, and 32 in the DS group. The median of the serum WFA+-M2BP level for each group was as follows: N group, 8.05 (1.25-11.9); D group, 11.025 (1.01-18.21); I group, 9.67 (0.29-17.83); and DS group, 9.56 (0.28-19.44) confidence of interval. We found no significant differences between the pairings. Comparison of underlying hepatic diseases revealed that liver cirrhosis due to hepatitis B and C and non-B and -C liver cirrhosis had no significant differences. AFP levels, on the other hand, had significant relationships in comparison between the presence or absence of histological HCC, in correlation between total tumor diameter, and in the ROC analysis for the diagnosis of HCC including occult HCC. CONCLUSION: Serum WFA+-M2BP cannot help diagnose occult HCC that is already undetected using imaging tests in decompensated liver cirrhosis patients requiring LT.

EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Three-dimensional human bile duct formation from chemically induced human liver progenitor cells.

Background: The intrahepatic bile ducts (BDs) play an important role in the modification and transport of bile, and the integration between the BD and hepatocytes is the basis of the liver function. However, the lack of a source of cholangiocytes limits in vitro research. The aim of the present study was to establish three-dimensional BDs combined with human mature hepatocytes (hMHs) in vitro using chemically induced human liver progenitor cells (hCLiPs) derived from hMHs. Methods: In this study, we formed functional BDs from hCLiPs using hepatocyte growth factor and extracellular matrix. BDs expressed the typical biliary markers CK-7, GGT1, CFTR and EpCAM and were able to transport the bile-like substance rhodamine 123 into the lumen. The established three-dimensional BDs were cocultured with hMHs. These cells were able to bind to the BDs, and the bile acid analog CLF was transported from the culture medium through the hMHs and accumulated in the lumen of the BDs. The BDs generated from the hCLiPs showed a BD function and a physiological system (e.g., the transport of bile within the liver) when they were connected to the hMHs. Conclusion: We present a novel in vitro three-dimensional BD combined with hMHs for study, drug screening and the therapeutic modulation of the cholangiocyte function.

Feasibility of Organ Transportation by a Drone: An Experimental Study Using a Rat Model.

BACKGROUND: Recently, the successful delivery of organs for transplantation using drones was reported. We investigated the influence of transportation by drones on the quality of liver grafts using a rat model. METHODS: Livers of 12 rats (8 and 32 weeks old) were divided into 2 groups of six. Livers were split into 2 parts and allocated to the drone or control groups (both n = 12). The drone experiment was conducted between islands in Nagasaki Prefecture, Japan. The distance between the islands was 12 km. Livers of the drone group were transported by a multicopter at a speed of 30 km-40 km/h over 60 m above sea level. Transported liver quality was analyzed by histology, and biochemistry data were compared between groups. RESULTS: Cold ischemia time did not differ between groups (902 min and 909 min, respectively). There were no differences in macroscopic findings regarding coloration and damage between groups. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in preservation fluid were graft weight-corrected and compared, and no significant differences were found between groups: AST/g (4.61 vs 4.81 IU/L), ALT/g (2.78 vs 2.92 IU/L), and ALP/g (39.1 vs 37.0 IU/L). Immunochemical staining showed no significant difference between groups for terminal deoxynucleotidyl transferase dUTP nick and labeling staining (141 vs 113 cells), CD163 (818 vs 870 cells), and TNF-α (1.25 vs 1.41 scores). CONCLUSIONS: The simulation experiment of organ transport for transplantation by drones was successfully conducted. There were no differences in the quality of livers transported by drones or other means. Further studies including large-animal experiments could lead to future clinical applications.

Association of quantitative analysis of intratumoral reduced E-cadherin expression with lymph node metastasis and prognosis in patients with breast cancer.

Loss of E-cadherin expression is a poor prognostic factor in patients with breast cancer. Breast cancer cells co-cultured with adipocytes reportedly promote E-cadherin attenuation and tumor progression. The current study aimed to investigate the association of reduced E-cadherin expression with adipose tissue invasion (ATI) and prognosis in breast cancer. Surgical specimens were collected from 188 women with invasive ductal carcinoma of the breast who had undergone surgery without neoadjuvant treatment. We compared E-cadherin expression in ATI and invasive front (IF) using immunohistochemistry with ImageJ. Reduced E-cadherin expression was detected not only in the ATI area but also in the IF, and the degree of reduced E-cadherin expression was positively correlated with both areas. In patients with lymph node metastasis compared to those without, E-cadherin expression was reduced and this reduction was associated with poor recurrence-free survival. We concluded that E-cadherin expression is reduced not only at the ATI area but also at the IF of the tumor. Reduced E-cadherin expression is a clear prognostic factor for breast cancer. Hence, future research is warranted for establishing an objective and quantitative E-cadherin staining assay that will allow clinical use of E-cadherin as a prognostic factor.

Therapeutic effect and mechanism of Daikenchuto in a model of methotrexate-induced acute small intestinal mucositis.

BACKGROUND: Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. METHODS: Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. RESULTS: The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-ß1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. CONCLUSION: DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.

Double vision approach applied by two teams for retrosternal gastric conduit for gastric tube cancer.

Gastric tube cancer is classically treated with resection through a midline sternal incision. However, because of its invasiveness and limited reconstructive potential, transdiaphragmatic laparoscopic or thoracoscopic dissection of the gastric tube has been investigated. As resection from only the abdominal or thoracic cavity is difficult, we performed surgery with a thoracic surgeon approaching from the thoracic cavity and an abdominal surgeon simultaneously approaching from the cervical and abdominal regions. The gastric tube may be tightly adhered to the back of the sternum, cervicothoracic transition or thoracoabdominal transition. Dissection can be safely performed by operating from two directions simultaneously, the neck and chest or chest and abdomen, to successfully withdraw the gastric tube from the abdominal cavity. We performed this surgery in four cases. This collaborative operation provided a good surgical view and allowed for safe dissection of the gastric tube without requiring sternotomy.