Percutaneous Trans-Esophageal Gastrostomy for Oral Intake in a Case of Anastomotic Obstruction following Total Gastrectomy.

Gastric cancer is one of the most common diseases globally. Total gastrectomy is often performed surgically. However, late-stage anastomotic passage obstruction after total gastrectomy is relatively rare. Here, we report a case involving a 73-year-old male patient who experienced repeated aspiration pneumonia due to anastomotic passage obstruction 22 years after a total gastrectomy for gastric cancer. He was eventually hospitalized in the Department of Gastroenterology at our hospital because of difficulty eating. Computed tomography revealed prominent dilation of the esophagus and the blind end of the elevated jejunum. Upper gastrointestinal endoscopy revealed a poorly extended site on the main side of the elevated jejunum; however, the passage through the scope was good. A percutaneous trans-esophageal gastrostomy was performed for oral intake. The patient experienced decreased nausea and vomiting. He gained weight, and his general condition improved. He did not feel inconvenienced by percutaneous trans-esophageal gastrostomy and had no desire for surgery. Follow-up observations are currently being conducted, with tubes exchanged every 6 months. There are no reports of percutaneous trans-esophageal gastrostomy for oral intake for anastomotic passage obstruction following total gastrectomy; therefore, we report this as a reference when similar cases are encountered.

Distal Gastrectomy for Symptomatic Stage IV Gastric Cancer Contributes to Prognosis with Acceptable Safety Compared to Gastrojejunostomy.

BACKGROUND: The prognostic prolongation effect of reduction surgery for asymptomatic stage IV gastric cancer (GC) is unfavorable; however, its prognostic effect for symptomatic stage IV GC remains unclear. We aimed to compare the prognosis of gastrectomy and gastrojejunostomy for symptomatic stage IV GC. METHODS: This multicenter retrospective study analyzed record-based data of patients undergoing palliative surgery for symptomatic stage IV GC in the middle or lower-third regions between January 2015 and December 2019. Patients were divided into distal gastrectomy and gastrojejunostomy groups. We compared clinicopathological features and outcomes after propensity score matching (PSM). RESULTS: Among the 126 patients studied, 46 and 80 underwent distal gastrectomy and gastrojejunostomy, respectively. There was no difference in postoperative complications between the groups. Regarding prognostic factors, surgical procedures and postoperative chemotherapy were significantly different in multivariate analysis. Each group was further subdivided into groups with and without postoperative chemotherapy. After PSM, the data of 21 well-matched patients with postoperative chemotherapy and 8 without postoperative chemotherapy were evaluated. Overall survival was significantly longer in the distal gastrectomy group (p = 0.007 [group with postoperative chemotherapy], p = 0.02 [group without postoperative chemotherapy]). CONCLUSIONS: Distal gastrectomy for symptomatic stage IV GC contributes to prognosis with acceptable safety compared to gastrojejunostomy.

A liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor.

Duodenal gastrointestinal stromal tumors (dGISTs) are rare, and a lack of consensus exists regarding their treatment, particularly for recurrent disease. We herein report a rare case of liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor. A 45-year-old woman revealed positive fecal occult blood. Upper gastrointestinal endoscopy revealed a submucosal duodenal tumor with ulceration and oozing on the apex. Endoscopic ultrasound showed a hypoechoic mass originating in the submucosa. Contrast-enhanced abdominal computed tomography (CT) revealed a 30-mm hyper-vascular tumor in the duodenal bulb. The patient underwent partial resection of the duodenal bulb with distal gastrectomy, followed by Roux-en-Y reconstruction. Histopathological evaluation revealed a tumor comprised of spindle-shaped cells including 5 mitotic figures per 50 high-power fields. Immunohistochemical evaluation indicated that the tumor cells were positive for c-Kit and CD34 expression. The tumor was diagnosed as low-risk dGIST. Postoperative follow-up was continued, and 7 years later, CT revealed a 39-mm enhanced tumor in liver segment 4. The tumor was diagnosed as a metastatic liver tumor, and the patient underwent S4 partial hepatectomy. As a result of histological and immunohistochemical analysis, the tumor was diagnosed as a liver metastasis from dGIST. The patient has been receiving oral imatinib 400 mg daily and remains free of disease 5 years after her last surgery. Low-risk dGIST can metastasize relatively long after surgery. However, an excellent long-term prognosis may be achieved by combining complete resection and imatinib therapy in patients with recurrent liver metastases.

Clinical Complete Response after Chemotherapy and Palliative Surgery for Unresectable Gastric Cancer.

Gastric cancer incidence is high in several countries, and management of advanced gastric cancer remains a challenge. Chemotherapy for unresectable gastric cancers is still evolving, and achieving a complete cure is difficult. Although a clinical complete response to chemotherapy has been reported in patients with unresectable gastric cancer, the chemotherapy duration for these patients is unclear. Here, we report the case of a 71-year-old man who presented with abdominal discomfort. Upper endoscopy revealed advanced gastric cancer on the upper gastric body. Histopathological examination revealed a poorly differentiated adenocarcinoma. Computed tomography revealed regional lymph node and multiple bilobar hepatic metastases. Radical surgery was not possible; therefore, palliative resection of the primary lesion was planned for symptomatic improvement. Tegafur, 5-chloro-2,4-dihydro-pyrimidine, and potassium oxonate were administered prior to surgery, and proximal gastrectomy was performed. Tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate administration was reinitiated after surgery. A clinical complete response was achieved in the 8th postoperative month, with no hepatic metastases noted on radio imaging. Computed tomography performed in the 1st postoperative year revealed ascites; however, the cytological examination findings were negative. The initial chemotherapy was discontinued, and paclitaxel administration was commenced. Computed tomography performed annually thereafter demonstrated no recurrence, and paclitaxel was discontinued in the 9th postoperative year. The patient remained recurrence free at 12 years postoperatively. For elderly patients like the one presented here, it may be necessary to consider ceasing chemotherapy; however, because it is possible for a complete clinical response over the long term, it should be continued if the patient is well.

A case of duodenal duplication cyst mimicking a pancreatic pseudocyst with intracystic hemorrhage.

BACKGROUND: Duodenal duplication cysts in adults are rare, and a preoperative diagnosis remains difficult because clinical manifestations are nonspecific and variable. We describe a case of a duodenal duplication cyst mimicking a pancreatic pseudocyst with repeated intracystic hemorrhage. CASE PRESENTATION: A 47-year-old male who complained of upper abdominal pain and vomiting was referred to our hospital. He was a heavy drinker and had a past history of hospitalization for alcoholic chronic pancreatitis. Plain abdominal computed tomography (CT) showed a cystic lesion of 7 cm in size in the lumen near the second part of the duodenum. The cystic lesion showed high density inside. Gastrointestinal endoscopy revealed that the lumen of the duodenum was deformed by a submucosal tumor-like mass and the endoscope could not pass through it, but active bleeding was not seen in the lumen of the duodenum. On the fourth day of hospitalization, anemia progressed and contrast-enhanced CT demonstrated a high-density spot on the wall of the cystic lesion. A pancreatic pseudocyst complicated with intracystic hemorrhage was preliminarily considered. Angiography was immediately performed, and a pseudoaneurysm was identified in the branch of the anterior superior pancreaticoduodenal artery (ASPDA). Transcatheter arterial embolization (TAE) was performed. Anemia did not progress after that, and follow-up CT showed reduction in the size of the cystic lesion. Afterward, the same symptoms recurred twice and surgical treatment was performed for the pancreatic pseudocyst with repeated intracystic hemorrhage. Macroscopically, a cystic mass of 5 cm in size was adjacent to the second part of the duodenum on the pancreas side. A pinhole-sized communication was identified between the cyst and the duodenum lumen. Microscopically, the cyst wall was composed of gastric mucosa and shared a common proper muscle layer with the duodenum. Chronic ulcers and erosions were seen in the cyst. Based on these findings, a diagnosis of duodenal duplication cyst was made. CONCLUSIONS: Duodenal duplication cysts in adults have seldom been reported and should be considered as a differential diagnosis for a patient with a cystic lesion adjoining the duodenum.

Hemorrhagic Cholecystitis in a Patient on Maintenance Dialysis.

The present paper describes a case of hemorrhagic cholecystitis in a patient on maintenance dialysis. The patient presented with right upper quadrant abdominal pain. Computed tomography revealed swelling of the gallbladder, high- and isodensity contents of the gallbladder, and high-density stone in the gallbladder neck. He was hospitalized for suspected acute cholecystitis. After hospitalization, his levels of total bilirubin, aspartate aminotransferase, and alanine aminotransferase increased. T2-weighted magnetic resonance imaging showed low-intensity contents expanded to include a wide area from the common bile duct to the cystic duct and gallbladder neck. Endoscopic retrograde cholangiopancreatography revealed clotting from the duodenal papilla. After cannulation of the bile duct, old blood and pus began to flow from the mammary papilla, and an endoscopic nasobiliary drainage tube was placed. After his liver function had improved, the patient underwent laparoscopic cholecystectomy. His sample revealed that the gallbladder was filled with blood clots and stones. His postoperative course was uneventful and he was discharged on day 19 after the procedure. Although hemorrhagic cholecystitis is rare, it should be considered as a differential diagnosis for patients on dialysis who have acute abdominal symptoms.

Successful resection of liver metastasis detected by exacerbation of skin symptom in a patient with dermatomyositis accompanied by rectal cancer: a case report and literature review.

BACKGROUND: Dermatomyositis (DM) is a rare syndrome that belongs to the group of idiopathic inflammatory myopathies. The association between DM and malignancy is well recognized, and the severity of DM symptoms has been linked to the progression of metastatic disease. CASE PRESENTATION: We report the case of a 42-year-old man that was diagnosed with dermatomyositis (DM) and rectal cancer. Proctectomy was performed, and DM symptoms were resolved postoperatively. One year and 9 months after the surgery, liver metastasis occurred accompanied by the exacerbation of DM symptom. Partial resection of the liver was performed, and postoperative course was uneventful. DM symptoms improved postoperatively, and no evidence of cancer recurrence or DM symptoms was observed 2 years after the second surgery. To date, few reports have described recurring cases of DM accompanied by colorectal cancer in detail. We reviewed four similar cases that were reported poor prognoses with treatment resistance. However, our case report demonstrates good long-term results with resection of metastatic lesion. CONCLUSIONS: It is important to check the exacerbation of DM symptoms, as this symptom sometimes preceded cancer relapse during the follow-up of our patient with DM and colorectal cancer.

Prognostic Nutritional Index Predicts Treatment Outcomes following Palliative Surgery for Colorectal Adenocarcinoma.

OBJECTIVES: Palliative surgeries such as stoma creation and bypass are effective for relieving symptoms related to incurable abdominal malignancies; however, these methods are controversial in patients with severe metastatic disease or poor pre-surgical health. The aim of this study was to examine the clinical significance of the prognostic nutritional index (PNI) in evaluations for palliative surgery. METHODS: We retrospectively analyzed data from 37 patients who underwent palliative surgery for histologically-proven colorectal adenocarcinoma from 2009 to 2015. We investigated both risk factors for postoperative complications and prognostic factors. We used a PNI cutoff value of 40, as defined by previous studies. RESULTS: The reason for surgery was stenosis in 18 patients, obstruction in 12, fistula in 5, and bleeding in 2. Bypass was performed in 10 cases, ileostomy in 5, and colostomy in 22. Postoperative morbidity and mortality occurred in 9 and 2 patients, respectively. Median overall survival time was 8.9 months. Only low PNI correlated with postoperative complications at trend-level (p=0.07), and the 2 patients with mortality were classified as PNI-low. The presence of ascites (p=0.003) and PNI (p=0.02) were identified as independent prognostic factors. CONCLUSIONS: PNI could be used as an objective marker for deciding whether to proceed with palliative surgery, independent of the extent of metastatic disease.

Adoptive transfer of allogeneic liver sinusoidal endothelial cells specifically inhibits T-cell responses to cognate stimuli.

Although it is well known that liver allografts are often accepted by recipients, leading to donor-specific tolerance of further organ transplants, the underlying mechanisms remain unclear. We had previously used an in vitro model and showed that mouse liver sinusoidal endothelial cells (LSECs) selectively suppress allospecific T-cells across major histocompatibility complex (MHC) barriers. In the present study, we established an in vivo model for evaluating the immunomodulatory effects of allogeneic LSECs on corresponding T-cells. Allogeneic BALB/cA LSECs were injected intraportally into recombination activating gene 2 γ-chain double-knockout (RAG2/gc-KO, H-2(b)) mice lacking T, B, and natural killer (NK) cells. In order to facilitate LSEC engraftment, the RAG2/gc-KO mice were injected intraperitoneally with monocrotaline 2 days before the adoptive transfer of LSECs; this impaired the host LSECs, conferring a proliferative advantage to the transplanted LSECs. After orthotopic allogeneic LSEC engraftment, the RAG2/gc-KO mice were immune reconstituted intravenously with C57BL/6 splenocytes. After immune reconstitution, mixed lymphocyte reaction (MLR) assay using splenocytes from the recipients revealed that specific inhibition of host CD4(+) and CD8(+) T-cell proliferation was greater in response to allostimulation with irradiated BALB/cA splenocytes rather than to stimulation with irradiated third party SJL/jorllco splenocytes. This inhibitory effect was attenuated by administering anti-programmed death ligand 1 (PD-L1) monoclonal antibody during immune reconstitution in the above-mentioned mice, but not in RAG2/gc-KO mice engrafted with Fas ligand (FasL)-deficient BALB/cA LSECs. Furthermore, engraftment of allogeneic BALB/cA LSECs significantly prolonged the survival of subsequently grafted cognate allogeneic BALB/cA hearts in RAG2/gc-KO mice immune reconstituted with bone marrow transplantation from C57BL/6 mice. In conclusion, murine LSECs have been proven capable of suppressing T-cells with cognate specificity for LSECs in an in vivo model. The programmed death 1/PD-L1 pathway is likely involved in these suppressive effects.

Benign papillary mesothelioma of the peritoneum associated with gastric cancer: report of a case.

Benign papillary mesothelioma of the peritoneum is an uncommon lesion that is usually discovered by chance during a surgical procedure. This lesion resembles metastatic carcinoma in gross appearance; therefore, intraoperative diagnosis can be difficult. This report presents a case of benign papillary mesothelioma concurrent with gastric cancer. The tumor was located on the hepatogastric ligament and resembled a metastatic peritoneal implant. A pathological review confirmed the diagnosis to be benign papillary mesothelioma.

A case of encapsulating peritoneal sclerosis suspected to result from the use of icodextrin peritoneal solution.

Encapsulating peritoneal sclerosis (EPS) is an intestinal obstruction syndrome in which peritoneal deterioration and intraperitoneal inflammation result in intestinal adhesions, which are covered with a fibrin capsule and which cause bowel obstruction. Here, we report the case of a patient with EPS suspected to result from the use of icodextrin peritoneal solution. In this patient, peritoneal permeability to high molecular weight solutes and effluent interleukin-6 (IL-6) levels increased after initiation on-to icodextrin solution. The patient developed symptoms of intestinal obstruction accompanied by intestinal edema 30 months after the start of icodextrin and after a peritoneal dialysis (PD) duration of 78 months. He was then diagnosed as being in a pre-EPS state. The use of icodextrin solution was discontinued, and the symptoms of intestinal obstruction improved after corticosteroid administration. Subsequently, he was managed on a combination of PD using glucose solution low in glucose degradation products and of twice-weekly hemodialysis, but he showed enhanced peritoneal permeability and increases in effluent IL-6. After a PD period of 98 months, severe symptoms of intestinal obstruction developed, and enterolysis was performed. The degeneration of the intestinal wall itself was slight, and the adhesions between the capsule and intestinal surface could be readily removed. In this patient, the degree of peritoneal deterioration and capsule formation differed from that of typical EPS. These findings suggest the promotion of capsule formation by icodextrin solution and the involvement of certain inflammatory reactions.

Successful hepatitis B vaccination in liver transplant recipients with donor-specific hyporesponsiveness.

Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV-related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor-specific hyporesponse with a well-maintained response to the third-party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third-party stimulus were unable to do so. Thus, inducing an anti-donor-specific immunosuppressive status by minimizing immunosuppression should enable post-transplant HBV vaccination to be a promising prophylactic strategy.

Prophylaxis against recurrence of HBV hepatitis after living-donor liver transplantation.

BACKGROUND/AIMS: Although antiviral prophylaxis with the combined high-dose hepatitis B immunoglobulin (HBIg) and lamivudine therapy has effectively reduced post-liver transplantation recurrence of hepatitis B virus infection, its use is limited by cost and availability. METHODOLOGY: Fourteen living-donor liver transplant patients were performed with the mean follow-up of the 23 months (range, 5 to 58 months). We examined the effectiveness of prophylaxis against recurrence of hepatitis B with much lower dose of HBIg. HBIg (10000 IU/day) was two or three times intra- and postoperatively administered and then the serum titers of HBIg was maintained at more than 100 IU/mL. RESULTS: Although two patients were preoperatively HBV-DNA positive (DNA concentrations were 4.4 and 4.7 LGE, respectively) by a transcription-mediated amplification assay (TMA) method, all 14 patients postoperatively became HBV-DNA-negative and HBsAg-negative. CONCLUSIONS: Our protocol of the combination low-dose HBIg and lamivudine therapy prevents the recurrence of hepatitis B and is likely to be more cost-effective than high-dose HBIg regimens. Further study is needed to develop the combination therapy of the optimal dose of HBIg and lamivudine.

Role of invariant natural killer T cells in liver sinusoidal endothelial cell-induced immunosuppression among T cells with indirect allospecificity.

We have previously demonstrated that liver sinusoidal endothelial cells (LSECs) that endocytose portally injected allogeneic cells exert immunosuppressive effects on T cells with indirect allospecificity. In this study, we have demonstrated that invariant natural killer T cells plays a significant role in such immunosuppressive effects induced by LSECs. The endocytic activity of LSECs toward intraportally injected splenocytes from B6 major histocompatibility complex class II-deficient C2ta (C2D) mice was markedly impaired in BALB/c CD1d-deficient mice. The intraportal adoptive transfer of LSECs isolated from BALB/c wild-type mice treated with a portal injection of B6 C2D splenocytes into BALB/c mice significantly prolonged the survival of subsequently transplanted heart allografts; however, the transfer of LSECs isolated from similarly treated BALB/c CD1d-deficient mice did not produce such a survival prolonging effect. These findings indicate that natural killer T cells are required for the LSEC-induced immune modulation of T cells with indirect allospecificity.

Microsurgical hepatic artery reconstruction during living-donor liver transplantation by using head-mounted surgical binocular system.

We have described our experience with arterial reconstruction during living-donor liver transplantation by using Varioscope AF3--a head-mounted surgical binocular system with automatic focusing and continuous zoom magnification from 3.6x to 7.2x. From July 1996 to December 2006, 91 grafts were implanted in 89 living-donor liver transplantation recipients, including two that required retransplantation. For microsurgical reconstruction of the graft hepatic artery, a conventional operating microscope was used in the first 10 transplants and Varioscope, in the subsequent 81. The time required to complete arterial reconstruction while using a conventional operating microscope and Varioscope was 78.6 +/- 44.6 min and 35.5 +/- 15.5 min, respectively. No arterial complications, including hepatic artery thrombosis, occurred in any of the 89 patients during the observation period. In living-donor liver transplantation, successful hepatic artery reconstruction can be safely carried out using Varioscope.

Possible therapeutic effect of lipid supplementation on neurological complications in liver transplant recipients.

Neurological complications (NCs) represent a serious problem following liver transplantation and may develop either because of various peri-operative factors or the toxicity of immunosuppression. Although the causality assessment of NCs can be particularly difficult in the setting of organ transplantation, calcineurin inhibitors (CNIs) might influence NCs to a certain extent, regardless of the etiology. Therefore, minimizing the influence of CNIs could be a reasonable strategy for alleviating NCs. Based on our hypothesis that lipid supplementation prevents lipophilic CNIs from crossing the blood-brain barrier, soybean oil was administered to five liver transplant patients with NCs. In all of these patients, the neurological symptoms improved without discontinuing or reducing the dose of CNIs. Thus, lipid supplementation might be able to reduce the adverse neurological effects of CNIs.

Induction of endotoxin tolerance inhibits alloimmune responses.

It was recently reported that the induction of endotoxin tolerance (ET), which is defined as a reduced response to a lipopolysaccharide (LPS) challenge following the first LPS encounter, inhibits major histocompatibility complex (MHC)-restricted antigen presentation. This raises the question whether alloimmune responses can be inhibited by inducing ET in transplant donors. C57BL/6 mice were treated with a low dose of LPS prior to a challenge with a high dose of LPS to induce ET. Hearts from endotoxin-tolerized C57BL/6 mice were transplanted to BALB/c mice. The survival of the endotoxin-tolerized heart allografts was significantly prolonged. By using irradiated splenocytes from C57BL/6 mice and allogeneic splenocytes from BALB/c mice, a mixed lymphocyte reaction (MLR) assay was performed. The MLR assay used CFSE, and revealed that the splenocytes from the endotoxin-tolerized mice failed to induce the proliferation of allogeneic CD4(+) and CD8(+) T cells. Cytokine analyses of the supernatant of the MLR culture using endotoxin-tolerized stimulators revealed a distinct shift in the Th 1/Th 2 balance toward the Th 2-type response. The induction of ET increased the proportion of myeloid-related dendritic cells (DCs) expressing molecules necessary for antigen presentation, which favor the development of a Th 2 response; however, it reduced the proportion of lymphoid-related DCs expressing those molecules, which favor the development of the Th 1 response. Although the relevance of these findings with regard to the prolonged survival of the endotoxin-tolerized heart allografts remains to be elucidated, this is the first study to demonstrate that the induction of ET in donor animals inhibits alloimmune responses.

Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity.

A portal venous injection of allogeneic donor cells is known to prolong the survival of subsequently transplanted allografts. In this study, we investigated the role of liver sinusoidal endothelial cells (LSECs) in immunosuppressive effects induced by a portal injection of allogeneic cells on T cells with indirect allospecificity. To eliminate the direct CD4+ T cell response, C57BL/6 (B6) MHC class II-deficient C2tatm1Ccum (C2D) mice were used as donors. After portal injection of irradiated B6 C2D splenocytes into BALB/c mice, the host LSECs that endocytosed the irradiated allogeneic splenocytes showed enhanced expression of MHC class II molecules, CD80, and Fas ligand (FasL). Due to transmigration across the LSECs from BALB/c mice treated with a portal injection of B6 C2D splenocytes, the naive BALB/c CD4+ T cells lost their responsiveness to stimulus of BALB/c splenic APCs that endocytose donor-type B6 C2D alloantigens, while maintaining a normal response to stimulus of BALB/c splenic APCs that endocytose third-party C3H alloantigens. Similar results were not observed for naive BALB/c CD4+ T cells that transmigrated across the LSECs from BALB/c FasL-deficient mice treated with a portal injection of B6 C2D splenocytes. Adaptive transfer of BALB/c LSECs that had endocytosed B6 C2D splenocytes into BALB/c mice via the portal vein prolonged the survival of subsequently transplanted B6 C2D hearts; however, a similar effect was not observed for BALB/c FasL-deficient LSECs. These findings indicate that LSECs that had endocytosed allogeneic splenocytes have immunosuppressive effects on T cells with indirect allospecificity, at least partially via the Fas/FasL pathway.

Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice.

Although livers transplanted across MHC barriers in mice are normally accepted without recipient immune suppression, the underlying mechanisms remain to be clarified. To identify the cell type that contributes to induction of such a tolerance state, we established a mixed hepatic constituent cell-lymphocyte reaction (MHLR) assay. Irradiated C57BL/6 (B6) or BALB/c mouse hepatic constituent cells (HCs) and CFSE-labeled B6 splenocytes were cocultured. In allogeneic MHLR, whole HCs did not promote T cell proliferation. When liver sinusoidal endothelial cells (LSECs) were depleted from HC stimulators, allogeneic MHLR resulted in marked proliferation of reactive CD4(+) and CD8(+) T cells. To test the tolerizing capacity of the LSECs toward alloreactive T cells, B6 splenocytes that had transmigrated through monolayers of B6, BALB/c, or SJL/j LSECs were restimulated with irradiated BALB/c splenocytes. Nonresponsiveness of T cells that had transmigrated through allogeneic BALB/c LSECs and marked proliferation of T cells transmigrated through syngeneic B6 or third-party SJL/j LSECs were observed after the restimulation. Transmigration across the Fas ligand-deficient BALB/c LSECs failed to render CD4(+) T cells tolerant. Thus, we demonstrate that Fas ligand expressed on naive LSECs can impart tolerogenic potential upon alloantigen recognition via the direct pathway. This presents a novel relevant mechanism of liver allograft tolerance. In conclusion, LSECs are capable of regulating a polyclonal population of T cells with direct allospecificity, and the Fas/Fas ligand pathway is involved in such LSEC-mediated T cell regulation.

Preservation of peritoneal catheter for prevention of encapsulating peritoneal sclerosis.

We evaluated the usefulness of periodic abdominal irrigation through the peritoneal catheter preserved after termination of peritoneal dialysis (PD) to prevent encapsulating peritoneal sclerosis (EPS). The study group included 8 patients in whom PD had been terminated (mean age: 53.1 +/- 7.1 years; mean PD duration: 119.6 +/- 37.8 months). The abdominal cavity was periodically irrigated through the peritoneal catheter preserved after PD discontinuation. The appearance rate of cancer antigen 125 (CA125-AR), corrected by body surface area, was obtained every 3 months from 4-hour dwells. Based on the creatinine levels in 4-hour dwells and plasma, the dialysate-to-plasma creatinine (D/P Cr) was also obtained. Following abdominal irrigation for more than 12 months, the peritoneal catheter was removed and a biopsy specimen was taken from the peritoneum. The CA125-AR increased 3 months after PD discontinuation, but decreased thereafter. Encapsulating peritoneal sclerosis developed in 3 of 4 patients who lacked parietal mesothelial cells (PMCs) in a peritoneal specimen. In contrast, a good prognosis was obtained in 4 patients who had PMCs. The maximum value of the change in CA125-AR (delta CA125-AR, as compared with the value at PD discontinuation) was significantly greater in the PMC+ group than in the PMC- group (8.0 +/- 2.7 vs. 3.4 +/- 3.1, p < 0.001). The D/P Cr at catheter removal was lower in the PMC+ group than in the PMC- group (0.45 +/- 0.21 vs. 0.85 +/- 0.18, p < 0.05). Our findings suggest that periodic abdominal irrigation through the peritoneal catheter preserved after PD enhances the recovery of peritoneal damage. The CA125-AR value is a useful marker of viability and proliferation of PMCs.