Pregnancy Complications and Impact on Kidney Allograft After Kidney Transplantation in IgA Nephropathy.

Pregnancy in kidney transplantation (KT) recipients has been challenging because of the high risk of maternal, fetal, and renal complications. Although patients with immunoglobulin A nephropathy (IgAN)-chronic kidney disease (CKD) are at a high risk for hypertension in pregnancy (HIP), the maternal risk in KT recipients with IgAN as the etiology remains unclear. We retrospectively reviewed the medical records of pregnant KT recipients who delivered at our hospital. The incidence of maternal and fetal complications and the impact on kidney allografts between the group with IgAN as the primary kidney disease and the group with other primary diseases were compared. The analysis included 73 pregnancies in 64 KT recipients. The IgAN group had a higher incidence of HIP than the non-IgAN group (69% vs. 40%, p = 0.02). IgAN as primary kidney disease and interval from transplantation to conception were associated with HIP (OR 3.33 [1.11-9.92], p = 0.03, OR 0.83 [0.72-0.96], p < 0.01, respectively). The 20-year graft survival or prevention of CKD stage 5 in group with IgAN was lower than that in the group with other primary disease (p < 0.01). KT recipients should be informed of the risk of HIP and possibility of long-term worsening of postpartum renal function.

Influence of a low-dose tacrolimus protocol on the appearance of de novo donor-specific antibodies during 7 years of follow-up after renal transplantation.

BACKGROUND: Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs). METHODS: A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not. RESULTS: We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P < 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P < 0.001) and showed poor allograft outcome. CONCLUSIONS: There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4-6 ng/mL during the immunosuppression maintenance period.

Single fixed low-dose rituximab as induction therapy suppresses de novo donor-specific anti-HLA antibody production in ABO compatible living kidney transplant recipients.

This study was conducted to evaluate de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA) production leading to antibody-mediated rejection (ABMR) after rituximab induction in non-sensitized ABO-compatible living kidney transplantation (ABO-CLKTx). During 2008-2015, 318 ABO-CLKTx were performed at the Department of Surgery III at Tokyo Women's Medical University Hospital. To reduce confounding factors, we adopted a propensity score analysis, which was applied with adjustment for age, gender, duration of pretransplant dialysis, HLA mismatch count, preformed DSA, non-insulin-dependent diabetes mellitus, immunosuppressive treatment, and estimated glomerular filtration rate (eGFR) on postoperative day 7. Using a propensity score matching model (1:1, 115 pairs), we analyzed the long-term outcomes of 230 ABO-CLKTx recipients retrospectively. Recipients were classified into a rituximab-treated (RTX-KTx, N = 115) group and a control group not treated with rituximab (C-KTx, N = 115). During five years, adverse events, survival rates for grafts and patients, and incidence of biopsy-proven acute rejection (BPAR) and dnDSA production for the two groups were monitored and compared. All recipients in the RTX-KTx group received rituximab induction on preoperative day 4 at a single fixed low dose of 100 mg; the CD19+ B cells were eliminated completely before surgery. Of those recipients, 13 (11.3%) developed BPAR; 1 (0.8%) experienced graft loss. By contrast, of C-KTx group recipients, 25 (21.7%) developed BPAR; 3 (2.6%) experienced graft loss. The RTX-KTx group exhibited a significantly lower incidence of BPAR (P = .041) and dnDSA production (13.9% in the RTX-KTx group vs. 26.9% in the C-RTx group, P = .005). Furthermore, lower incidence of CMV infection was detected in the RTX-KTx group than in the C-KTx group (13.9% in the RTX-KTx group vs. 27.0% in the C-KTx group, P = .014). No significant difference was found between groups for several other factors: renal function (P = .384), graft and patient survival (P = .458 and P = .119, respectively), and the respective incidences of BK virus infection (P = .722) and leukopenia (P = .207). During five-year follow-up, single fixed low-dose rituximab therapy is sufficient for ensuring safety, reducing rejection, and suppressing dnDSA production for immunological low-risk non-sensitized ABO-CLKTx.

Single Graft Utilization From Donors With Severe Acute Kidney Injury After Circulatory Death.

Chronic shortages of organs for transplantation have led to the use of marginal kidneys from donors after circulatory death with acute kidney injury (AKI), but the utilization of kidneys with severe AKI is not well established. We retrospectively analyzed eight kidney transplantation (KTx) cases from donation after circulatory death (DCD) with terminal creatinine (t-Cr) concentrations higher than 10.0 mg/dL and/or oliguria for more than 5 days (AKI network criteria: stage III). Although all patients showed delayed graft function, no cases of primary nonfunction (PNF) were found. Five patients maintained stable renal function for approximately 15.5, 10, 10, 5, and 0.5 years after KTx. Only 1 patient showed biopsy-proven acute rejection. Also, 2 patients developed graft failure: one attributable to chronic antibody mediated rejection at 11.3 years after KTx, and one attributable to recurrence of IgA nephropathy at 4.6 years after KTx. Kidneys with AKI stage III yielded great outcomes without the risk of primary nonfunction and rejection. Although the AKI kidneys were associated with delayed graft function, these results suggest that even the most severe kidneys with AKI stage III from DCD donors can be considered a valid alternative for recipients on a waiting list for KTx.

Longterm renal allograft survival after sequential liver-kidney transplantation from a single living donor.

Combined liver-kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver-kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow-up period of 103.6 months. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor-specific antibody, will be needed. Liver Transplantation 23 315-323 2017 AASLD.

Successful Long-term Graft Survival of a Renal Transplantation Patient with Wiskott-Aldrich Syndrome.

Wiskott-Aldrich syndrome, a rare X-linked hereditary syndrome, is characterized by immunodeficiency, thrombocytopenia, and eczema. The underlying T-cell defect renders renal transplantation and immunosuppressive treatments uncertain. The present case exhibited the mild clinical manifestation, regarded as X-linked thrombocytopenia. He successfully underwent a living-donor ABO-compatible renal transplantation and splenectomy in 2002, and thereafter experiencing no severe rejection, serious infection, or malignancy for more than 10 years. Though IgA nephropathy was detected 8 months after transplantation, the patient's renal function and proteinuria were stable without any treatment. The present case showed a successful long-term graft survival and the importance of splenectomy added to renal transplantation.

Variant on Manifestation of Duodenal Metastasis 26 Years after Initial Diagnosis of Primary Cutaneous Melanoma.

Malignant duodenal neoplasms are relatively rare, and the diagnosis is often delayed because of their vague and nonspecific symptoms. We report the case of a 79-year-old female who had a medical history of malignant melanoma of the cheek that had initially been diagnosed at 53 years of age. Work-up revealed severe stenosis of the duodenum caused by a large mass with ulceration at the tip of its mucosal surface. Tumor biopsy led to a histological diagnosis of extremely poorly differentiated carcinoma, but it was impossible to determine whether the lesion was a primary neoplasm or represented secondary involvement. Pancreatoduodenectomy was performed, and the surgical specimen showed a protuberant tumor in the nonampullary region of the second portion of the duodenum. Final diagnosis of metastatic duodenal melanoma was made by immunohistological examination. She is currently alive without recurrence 28 months after the surgical treatment.

Intractable ascites without mechanical vascular obstruction after orthotopic liver transplantation: etiology and clinical outcome of sinusoidal obstruction syndrome.

Intractable ascites after orthotopic liver transplantation (OLT) is a relatively rare complication. However, it often takes a life threatening course, which requires re-transplantation. In previous studies, several reports gave hepatic sinusoidal obstruction syndrome (SOS) as one of the causes of refractory ascites. However, the detailed etiology of SOS after OLT and its association with clinical consequences remain unclear because there have been few studies to date. We report two recent cases with rapidly progressive refractory ascites associated with SOS, following completely different clinical courses. In case 1, the first episode of acute allograft rejection triggered SOS and subsequent intractable ascites, while the second acute rejection worsened his clinical status. A transjugular intrahepatic portosystemic stent-shunt (TIPS) was placed and this procedure resulted in complete disappearance of ascites and of renal dysfunction. In contrast, refractory ascites in case 2, who had neither rejection nor mechanical outlet obstruction, worsened despite TIPS stent placement, and re-transplantation was necessary. We speculate that the pre-existing diseased liver of the cadaver donor caused this serious complication, necessitating a second graft.

Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene.

While surgical resection is the most effective treatment for gallbladder cancer, most of these cancers are not resectable at the time of diagnosis, and therefore, chemotherapy serves as the primary therapy in many cases. However, to date, there is no standard chemotherapy for this cancer. We report a case of advanced gallbladder cancer for which the anticancer drug S-1 was effective. The patient was a 53-year-old woman who presented with a huge ovarian tumor. On workup, all abdominal images revealed the presence of advanced gallbladder cancer that had invaded the liver. Because the gallbladder formed a relatively hard and swollen mass involving the omentum, as revealed during exploration, the surgical resection of the gallbladder was not possible at that time, and only hysterectomy and bilateral salpingo-oophorectomy were performed. She started on the anticancer drug S-1 just after this operation. S-1 is a prodrug of 5-fluorouracil (5-FU), and contains 5-chloro-2-4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase (DPD) that rapidly degrades 5-FU. Eight months after the first operation, radical cholecystectomy was performed. Pathologically, the tumor was diagnosed as an adenocarcinoma of the gallbladder, and no evidence of liver invasion was found. Intratumoral gene expression analysis of the resected gallbladder revealed significantly elevated DPD expression. We suggest that the rapid degradation of 5-FU mediated by this high DPD in our patient was significantly blocked by the CDHP in S-1, and that the efficacy of 5-FU was consequently maintained at the maximum level.

Xanthogranulomatous cholecystitis expressing high levels of DUPAN-II.

We report a case of xanthogranulomatous cholecystitis (XGC) showing high levels of serum DUPAN-II in a 65-year-old woman. Preoperative radiologic examination showed no abnormal findings except in the gallbladder. Endoscopic ultrasonography was effective for differentiating chronic cholecystitis from gallbladder cancer before the operation. Cholecystectomy was performed by laparotomy, and the diagnosis of XGC was confirmed intraoperatively by examining a frozen section. Histologically, no cancer lesion was observed in the gallbladder, while immunochemical reactivity to DUPAN-II was demonstrated in the brush-border area of the epithelium and in histiocytes in the gallbladder. The half-life of serum DUPAN-II in our patient after cholecystectomy was approximately 1 month, and finally dropped to within the normal range after cholecystectomy.

Systemic inflammatory response syndrome after hand-assisted laparoscopic distal pancreatectomy.

BACKGROUND: Although the clinical benefits of hand-assisted laparoscopic surgery have been shown in several procedures including colorectal resection, splenectomy and gastrectomy, efficacy and invasiveness in pancreatic surgery have not been well investigated. We assessed the clinical benefits and invasiveness of hand-assisted laparoscopic distal pancreatectomy (HALS-DP) in relation to the occurrence of post-operative systemic inflammatory response syndrome (SIRS). METHODS: Subjects comprised 8 patients underwent HALS-DP (with splenectomy, n = 7; without splenectomy, n = 1) for benign or low malignant pancreatic lesions between March 2004 and December 2005. Indications for HALS-DP consisted of mucinous cystadenoma (n = 4), endocrine tumors (n = 2), serous cystadenoma (n = 1) and pancreatic pseudocyst (n = 1). Controls comprised 9 patients who underwent conventional open distal pancreatectomy (Open-DP) for benign or low malignant lesions of the pancreas in the same period. RESULTS: No significant differences were identified between HALS-DP and Open-DP in operation time. However, intra-operative blood loss, CRP on post-operative day (POD) 1 [5.5 mg/dl (1.8-8.1) vs. 9.7 mg/dl (5.9-12.1); p = .006] and POD 3 [8.5 mg/dl (1.7-11.1) vs. 17.7 mg/dl (10.7-21.5); p = .003], occurrence of post-operative SIRS (13% vs. 67%; p < .05, one-sided), duration of SIRS [0 day (0-1) vs. 1 day (0-4); p = .02] and post-operative hospital stay were significantly lower in HALS-DP than in Open-DP. Furthermore, no pancreatic fistula was seen with HALS-DP, as compared to 2 (22%) with Open-DP. CONCLUSION: HALS-DP is safer and less invasive than Open-DP for benign or low malignant pancreatic tumors.

Intrahepatic cholangiocarcinoma mimicking hepatic inflammatory pseudotumor.

A 50-year-old male with hepatitis B was referred for a small intrahepatic nodule. Magnetic resonance images raised strong suspicion of a benign lesion, such as an inflammatory pseudotumor, while the other radiological studies were equivocal. Furthermore, the high-intensity image on diffusion magnified-weighted imaging with a low B value strongly suggested a benign tumor. In spite of the absence of typical clinical or radiological findings, needle biopsy revealed an intrahepatic cholangiocarcinoma (ICC). The diagnosis of peripheral ICC rich in fibrous tissue seems to require needle biopsy for pathological examination with immunohistochemical staining because it frequently mimics other diseases, including benign tumors.

Analysis of bile duct injuries (Stewart-Way classification) during laparoscopic cholecystectomy.

In order to investigate mechanisms underlying the occurrence of bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC), we analyzed results for 34 patients (0.59%; 17 men, 17 women; average age, 57 years) with BDI out of 5750 LCs, based on questionnaire responses from surgical operators, records of direct interviews with these operators, operative reports, and videotapes of the operations. The indications for LC in the 34 patients were chronic cholecystitis in 32 patients and acute cholecystitis in 2. The BDIs in these patients were divided into four classes using the Stewart-Way classification: class I, incision (incomplete transection) of the common bile duct (CBD), n = 6 (17.6%); class II, lateral damage to the common hepatic duct (CHD), n = 9 (26.5%); class III, transection of the CBD or CHD, n = 15 (44.1%); and class IV, right hepatic duct or right segmental hepatic duct injuries, n = 4 (11.8%). In all class III and 3 class I cases (18 in total; incidence 53%), the mistake involved misidentifying the CBD as the cystic duct. Of all types (classes) of injuries, class III injuries showed the mildest gallbladder inflammation, and there was a significant (P = 0.0005) difference in the severity of inflammation between class II and III injuries. We conclude that complete transection of the CBD, which is rare in laparotomy, was the most common BDI pattern occurring during LC and that the underlying factor in the operator making this error was mistaking the CBD for the cystic duct.

Fusion of the planes of the liver: an anatomic entity merging the midplane and the left intersectional plane.

BACKGROUND: Alignment of the gallbladder fossa and the round ligament may be associated with an almost unknown portal vein branching anomaly. STUDY DESIGN: Ultrasonographic imaging allowed detection of this anomaly, which we characterized as fusion of the planes of the liver. When appropriate, additional specific radiologic examinations were performed (CT scanner supplemented with a three-dimensional reconstruction, a biliary cartography, or an angiography). Surgical consequences were studied from this series and from the literature. RESULTS: Seven patients (0.5%) had the following criteria: 1) round ligament, gallbladder fossa, and termination of the portal vein occurring in the same plane; 2) typical portal vein branching, including a right posterior branch, left branches, and a main medial branch terminated by the Rex's recessus; 3) two main hepatic veins without a significant middle hepatic vein; and 4) absence of the horizontal part of the left hepatic duct. Fusion of the planes may have been involved in two cases of iatrogenic bile duct injury and contraindicated a tumor resection and a right-liver donation. A review of the literature revealed that lack of recognition of the fusion of the planes led to a high proportion of surgical iatrogenic injury. Fusion of the planes could result from incomplete development of the central part of the liver, in agreement with embryologic knowledge. CONCLUSIONS: Knowledge of the fusion of the planes by hepato-biliary surgeons is important. This anomaly may lead to serious complications if it remains undetected during liver resection or bile duct surgery.