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.

Optimal treatment strategy for patients with pancreatic cancer having positive peritoneal cytology: A nationwide multicenter retrospective cohort study supervised by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: The aim of this study was to determine the optimal treatment for patients with pancreatic cancer (PaCa) having positive peritoneal cytology (PPC). METHODS: This multicenter retrospective study included patients with PPC treated at 78 high-volume centers between January 2012 and December 2020. Prognoses after resection (S-group) and initiation of nonsurgical treatment (N-group) were compared. Prognostic factors for survival in both groups were analyzed. Detailed characteristics of conversion surgery (CS) in the N-group were evaluated. RESULTS: In total, 568 enrolled patients were classified into an S-group (n = 445) or an N-group (n = 123). Median survival times (MSTs) were 19.0 months and 19.3 months, respectively, with no significant difference in prognosis (p = .845). The intervenable prognostic factors for survival were adjuvant treatment in the S-group (p < .001) and CS in the N-group (p < .001). Following CS, the MST was prolonged to 45.6 months, and peritoneal or liver recurrence decreased considerably. CS can be expected if PPC is diagnosed before neoadjuvant treatment and when combination treatment is initiated. CONCLUSION: Surgical resection may not be beneficial for improving survival when PPC is evident. Chemotherapy aiming for CS may be the optimal treatment for such patients.

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.

Fully-Covered Self-Expandable Metal Stent for Hepaticojejunostomy Anastomotic Stricture After Living Donor Liver Transplantation: A Case Series.

INTRODUCTION: We prospectively evaluated 3 cases regarding the usefulness of fully-covered self-expandable metal stents (FCSEMSs) for hepaticojejunostomy anastomotic stricture (HAS) after living donor liver transplantation (LDLT), which could not be resolved with conventional treatment using a plastic stent. CASE REPORT: All patients underwent LDLT with Roux-en-Y reconstruction; therefore, a short-type double-balloon enteroscope was used for the endoscopic procedures. HAS was observed on enteroscopic view of endoscopy in patients 1 and 2, and cholangiography revealed dilatation of the intrahepatic bile duct. The FCSEMS was successfully placed without the report of adverse events. The FCSEMS was removed after 16 weeks, and the HAS improved in both patients. In addition, stone clearance was also achieved in patient 2. On the other hand, FCSEMS was not placed in patient 3 because there was no indication of FCSEMS placement due to the multiple segmental biliary strictures (pruned-tree appearance on cholangiography). Subsequent deceased-donor liver transplantation confirmed recurrent primary sclerosing cholangitis. In this case, magnetic resonance cholangiopancreatography (MRCP) was not performed prior to cholangiography to rule out PSC recurrence. CONCLUSION: FCSEMS placement may be effective and safe for HAS after LDLT, which is not resolved with conventional treatment using a plastic stent. MRCP should be used to identify HAS prior to invasive cholangiography.

A case of acute appendicitis caused by obstruction due to caecal cancer.

Acute appendicitis supposedly results from appendix obstruction caused by various conditions, including caecal cancer. Here, we report an adenocarcinoma found in the specimen of a 65-year-old man diagnosed with acute appendicitis. The adenocarcinoma was detected in the appendix stump after emergency laparoscopic appendectomy. The patient was diagnosed with caecal cancer based on post-operative lower endoscopy findings, and an additional laparoscopic right hemicolectomy was performed. Acute appendicitis can occur at any age and may require emergency surgery. It is a benign disease that can be cured entirely by appendectomy in most cases but may result from an underlying malignant disease in some cases, especially in patients >40 years of age. Thus, clinicians should consider the possibility of a malignancy while diagnosing and treating acute appendicitis.

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.

Well-leg compartment syndrome after laparoscopic low anterior resection in the lithotomy position: a case report and literature review.

Well-leg compartment syndrome (WLCS) develops in healthy lower limbs because of surgical factors such as operative position, lower limb compression, and long operative time during abdominopelvic surgery. WLCS can lead to irreversible muscle and nerve damage if a prompt diagnosis and appropriate treatment are not provided. We report the case of a 57-year-old male who developed rectal cancer immediately after laparoscopic low anterior resection and was successfully treated with fasciotomy without sequelae. Patients who undergo surgery in the lithotomy position for a prolonged period are at risk of WLCS. Therefore, when determining the differential diagnosis of postoperative lower leg pain, it is necessary to consider WLCS because it is a complication caused by the intraoperative position.

Analysis of the Clinical Course in a Population of Patients with Biliary Tract Cancer Diagnosed as Unresectable After Portal Vein Embolization: A Case Series.

Portal vein embolization (PVE) is recommended as a preoperative procedure for patients with biliary tract cancer scheduled to undergo hepatic resection of more than 50%-60% of the liver. However, details and/or information regarding the follow-up of unresectable cases are often lacking, and the clinical course of unresectable cases is not well analyzed and reported. This study aimed to clarify the clinical prognosis of patients with unresectable biliary tract cancer after PVE. We retrospectively analyzed the clinical backgrounds of patients with biliary tract cancer who underwent PVE without subsequent resection between January 2011 and October 2022. Of the 21 patients with biliary tract cancer who underwent PVE during the study period, eight (38%) cases were unsuitable for resection after PVE for the following reasons: intraoperatively detected dissemination (n=2), para-aortic lymph node metastasis (n=1), liver metastasis (n=1), decreased liver function (n=2), development of liver metastasis while waiting (n=1), and insufficient residual liver volume (n=1). All patients received subsequent chemotherapy, including gemcitabine plus S-1 therapy in three cases, gemcitabine plus cisplatin plus S-1 in three cases, and gemcitabine plus cisplatin or S-1+cisplatin in one case each. As there is currently no curative treatment for biliary tract cancer other than surgery, multidisciplinary management and treatment of patient factors, including tumor factors and liver function, are essential to reducing the number of unresectable cases after PVE.

A case of indirect inguinal bladder hernia treated with laparoscopic transabdominal preperitoneal repair with high peritoneal incisional approach.

BACKGROUND: Inguinal herniation of the urinary bladder is uncommon and those descending into the scrotum are even rarer. Although open anterior repair has been used for inguinal bladder hernia, the efficacy of laparoscopic herniorrhaphy has been reported in recent years. CASE PRESENTATION: A 63-year-old man presented with an irreducible right groin and scrotal bulge associated with voiding difficulty. Abdominal ultrasonography showed a dislocation of the urinary bladder descending into the right scrotum. Abdominal CT imaging revealed that a part of the bladder and small intestine was herniating into the scrotum through the internal inguinal ring and running laterally to the inferior epigastric artery. Under the diagnosis of indirect inguinal bladder hernia, the patient underwent trans-abdominal preperitoneal hernia repair (TAPP). The bladder herniated into the scrotum through the internal inguinal ring was replaced to the original position. Then the myopectineal orifice was exposed and covered with polypropylene mesh, where a horizontal peritoneal incision 4 cm above the hernia orifice, i.e., the high peritoneal incision approach (HPIA), allowed an easy peeling of the peritoneum and hernia sac. The patient's postoperative course was uneventful and the voiding difficulty resolved. The patient continued to do well without recurrence at 20 months after surgery. CONCLUSION: Preoperative evaluation with abdominal ultrasonography and CT scan allowed a precise diagnosis of a groin hernia with voiding difficulty. TAPP with HPIA was useful in the treatment of inguinal bladder hernia because this technique facilitated a quick confirmation of the hernia contents, secure dissection of the whole protruded bladder, and adequate replacement of the bladder to the original position without any injury.

Outcomes of living donor liver transplant recipients receiving grafts with the graft-to-recipient weight ratio less than 0.6%: A matched pair analysis.

We sometimes experience living donor liver transplantation (LDLT) involving very small grafts with graft-to-recipient weight ratio (GRWR) < 0.6% when the actual graft size is smaller than predicted. The outcomes in this situation have not been fully investigated. The present study aimed to determine the graft outcomes of LDLT with GRWR < 0.6%. We retrospectively reviewed 280 cases of adult LDLT performed at our institution between January 2000 and March 2021. In our institution, the lower limit for graft volume/standard liver volume ratio was 30%. The patients were divided into 2 groups according to the cutoff value of 0.6% for actual GRWR. Graft survival and surgical outcomes, including small-for-size syndrome (SFSS), were compared between the groups using propensity score matching analysis. Risk factors associated with SFSS in recipients with GRWR < 0.6% were also evaluated. Fifty-nine patients received grafts with GRWR < 0.6%. After propensity score matching, similar graft survival rates were observed for GRWR < 0.6% (n = 53) and GRWR ≥ 0.6% (n = 53) ( p = 0.98). However, patients with GRWR < 0.6% had a significantly worse 3-month graft survival rate (86.8% vs. 98.1%, p = 0.03) and higher incidence of SFSS ( p < 0.001) than patients with GRWR ≥0.6%. On multivariate analysis, Model for End-Stage Liver Disease score and donor age were associated with SFSS in patients with GRWR < 0.6%. The same factors were also associated with graft survival. In conclusion, although similar overall graft survival rates were observed for LDLT with GRWR < 0.6% and GRWR ≥ 0.6%, GRWR < 0.6% was associated with an increased risk of SFSS. Appropriate donor and recipient selection is important for successful LDLT with very small grafts.

Modulatory effects of supplementation of Lentinula edodes mycelia extract and l-arginine on the therapeutic efficacy of immunogenic chemotherapy in colon cancer-bearing mice.

Some chemotherapeutic drugs can induce cancer cell death and enhance antitumor T-cell immunity in cancer-bearing hosts. Immunomodulatory reagents could augment such chemotherapy-induced effects. We previously reported that oral digestion of Lentinula edodes mycelia (L.E.M.) extract or  l-arginine supplementation can augment antitumor T-cell responses in cancer-bearing mice. In this study, the effects of L.E.M. extract with or without  l-arginine on the therapeutic efficacy of immunogenic chemotherapy by 5-fluorouracil (5-FU)/oxaliplatin (L-OHP) and/or cyclophosphamide (CP) are examined using two mouse colon cancer models. In MC38 and CT26 cancer models, therapy with 5-FU/L-OHP/CP significantly suppressed tumor growth, and supplementation with L.E.M. extract halved the tumor volumes. However, the modulatory effect of L.E.M. extract was not significant. In the CT26 cancer model, supplementation with L.E.M. extract and  l-arginine had no clear effect on tumor growth. In contrast, their addition to chemotherapy halved the tumor volumes, although the effect was not significant. There was no difference in the cytotoxicity of tumor-specific cytotoxic T cells generated from CT26-cured mice treated by chemotherapy alone versus chemotherapy combined with L.E.M. extract/ l-arginine. These results indicate that the antitumor effects of immunogenic chemotherapy were too strong to ascertain the effects of supplementation of L.E.M. extract and  l-arginine, but these reagents nonetheless have immunomodulatory effects on the therapeutic efficacy of immunogenic chemotherapy in colon cancer-bearing mice.

[Role of peritoneovenous shunt therapy in end-of-life care of refractory malignant ascites cases].

The short- and long-term outcomes of 34 patients with refractory malignant ascites who underwent peritoneovenous shunt (PVS) therapy were retrospectively reviewed. The primary disease was gastrointestinal cancer in 31 patients and gynecologic cancer in 3 patients. Regarding performance status, 21 patients had Eastern Cooperative Oncology Group Performance Status (PS) 2 and 13 patients were PS 3;thus, many were in a poor general condition. After treatment, abdominal distention disappeared in 79.4% of patients, and appetite improved in 60.9%. The median postoperative survival time was 38 days (range, 1-294 days), and 18 patients (52.9%) were discharged. Disseminated intravascular coagulation with clinical symptoms was observed in 3 patients (8.8%), and heart failure was observed in 7 patients (20.6%). PVS therapy was useful in improving the subjective symptoms of patients with refractory malignant ascites and in enabling them to receive care at home. However, serious postoperative complications are a concern, and appropriate preoperative evaluation is necessary.

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.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report.

BACKGROUND: Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. CASE REPORT: The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications-including intra-abdominal hemorrhaging and ischemic changes in the intestine-her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. CONCLUSIONS: To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Open Gastrostomy by Mini-Laparotomy: Our Method.

When percutaneous endoscopic gastrostomy (PEG) is not feasible owing to anatomical obstacles, laparotomic or laparoscopic gastrostomy (LAG) is an alternative. At our institution, LAG has been the first choice for patients who are unable to undergo PEG; however, we have introduced a small open gastrostomy through a 2-cm-long transverse incision since 2020. By December 2022, 12 patients had undergone this procedure without complications. In one case where the stomach was located cephalad to the rib arch and the patient had a round dorsum, the incision wound was extended, and a lengthy operation was required. We believe that our small-incision gastrostomy is a useful option in addition to LAG for cases in which PEG is difficult to perform. Further studies are required to determine the indications for this procedure.

Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-Of-Concept Study.

Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

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.

Preliminary Observations of An Ex Vivo Normothermic Whole Blood Machine Perfusion in An Experimental Liver Transplant Porcine Model.

BACKGROUND: Even though transplantation is an essential treatment with no viable alternatives, a significant worldwide donor shortage persists. In this study, we assessed the metabolism of livers that underwent extended periods of circulatory death and subsequently conducted functional validation through transplantation to explore the feasibility of using livers from an uncontrolled donor after circulatory death (u-DCD). METHODS: A donor model simulating u-DCD was constructed using pigs. The prolonged warm ischemia time (WIT) was set to 60, 120, and 180 minutes, and the liver function was evaluated after 24 hours of perfusion using an originally developed normothermic perfusion system. Based on the results, functional confirmation by transplantation was performed on the 2 groups with prolonged WIT of 60 and 180 minutes. RESULTS: Based on the 24-hour perfusion of the liver alone, we evaluated the function by transplanting the WI 60-minute model and 180-minute model (N = 3 each). Warm ischemia was 73.5 ± 3.7 minutes and 188 ± 3 minutes in the 60-minute model and 180-minute model, respectively. In the model with 60 minutes of WI, one case survived until the endpoint, and 2 cases survived between 8 and 12 hours, whereas, in the model with 180 minutes of WI, they died within 6 hours. CONCLUSION: We constructed a completely uncontrolled circulatory arrest model without anticoagulation and showed the possibility of using u-DCD livers by ex vivo machine perfusion and transplantation.