Clinical Course of Nonresponders With Recurrent Focal Segmental Glomerulosclerosis After Pediatric Kidney Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. METHODS: We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. RESULTS: Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1-2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add-on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. CONCLUSIONS: Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders.

Pancreatic Ductal Adenocarcinoma Encapsulated by a Tumor-Forming Type 1 Autoimmune Pancreatitis Located at the Pancreatic Tail: A Case Report.

Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications.

A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence.

Possible roles of anti-nephrin antibodies in post-transplant recurrent focal segmental glomerulosclerosis (FSGS) have been reported recently. To confirm these preliminary results, we performed a multi-institutional study of 22 Japanese pediatric kidney transplant recipients with FSGS including eight genetic FSGS and 14 non-genetic (presumed primary) FSGS. Eleven of the 14 non-genetic FSGS patients had post-transplant recurrent FSGS. Median (interquartile range) plasma levels of anti-nephrin antibodies in post-transplant recurrent FSGS measured using ELISA were markedly high at 899 (831, 1292) U/mL (cutoff 231 U/mL) before transplantation or during recurrence. Graft biopsies during recurrence showed punctate IgG deposition co-localized with nephrin that had altered localization with increased nephrin tyrosine phosphorylation and Src homology and collagen homology A expressions. Graft biopsies after remission showed no signals for IgG and a normal expression pattern of nephrin. Anti-nephrin antibody levels decreased to 155 (53, 367) U/mL in five patients with samples available after remission. In patients with genetic FSGS as in those with non-genetic FSGS without recurrence, anti-nephrin antibody levels were comparable to those of 30 control individuals, and graft biopsies had no signals for IgG and a normal expression pattern of nephrin. Thus, our results suggest that circulating anti-nephrin antibodies are a possible candidate for circulating factors involved in the pathogenesis of post-transplant recurrent FSGS and that this may be mediated by nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding.

Risk-Adjusted Assessment of the Learning Curve for Pure Laparoscopic Donor Hepatectomy for Adult Recipients.

BACKGROUND: Studies on pure laparoscopic donor hepatectomy (PLDH) have been reported. However, only few studies have reported on the learning curve of PLDH. In this report, we aimed to determine the learning curve of PLDH in adult patients using cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) analyses. METHODS: The data of donors who underwent PLDH at a single center between December 2012 and May 2022 were retrospectively reviewed. The learning curve was evaluated using the CUSUM and RA-CUSUM methods based on surgery duration. RESULTS: Forty-eight patients were finally included in the present study. The mean operation time was 393.6 ± 80.3 min. PLDH was converted to laparotomy in three cases (6.3%). According to the Clavien-Dindo classification, nine cases (18.8%) had higher-than-grade III postoperative complications and the most frequent complications were biliary complications. The CUSUM graph shows two peaks, at the 13th and 27th case. The multivariate analysis revealed that a body mass index ≥ 23 kg/m2 and intraoperative cholangiography were the only factors that were independently associated with longer operation time. Based on these results, an RA-CUSUM analysis was performed to assess the learning curve, which showed a decrease in the learning curve after 33 to 34 PLDH procedures. CONCLUSIONS: A learning curve effect was demonstrated in this study after 33 to 34 PLDH procedures. There are relatively many biliary complications, and it is necessary to further examine the method of bile duct transection.

Safety and Feasibility of Laparoscopic Parenchymal-Sparing Hepatectomy for Lesions with Proximity to Major Vessels in Posterosuperior Liver Segments 7 and 8.

Laparoscopic parenchymal-sparing hepatectomy (PSH) for lesions with proximity to major vessels (PMV) in posterosuperior segments (PSS) has not yet been sufficiently examined. The aim of this study is to examine the safety and feasibility of laparoscopic PSH for lesions with PMV in PSS 7 and 8. We retrospectively reviewed the outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) for PSS lesions and focused on patients who underwent laparoscopic PSH for lesions with PMV in PSS. Blood loss was lower in the LLR group (n = 110) than the OLR group (n = 16) (p = 0.009), and no other short-term outcomes were significantly different. Compared to the pure LLR group (n = 93), there were no positive surgical margins or complications in hand-assisted laparoscopic surgery (HALS) (n = 17), despite more tumors with PMV (p = 0.009). Regarding pure LLR for one tumor lesion, any short-term outcomes in addition to the operative time were not significantly different between the PMV (n = 23) and no-PMV (n = 48) groups. The present findings indicate that laparoscopic PSH for lesions with PMV in PSS is safe and feasible in a matured team, and the HALS technique still plays an important role.

A novel second-stage surgical strategy for severely obese patient with pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Severely obese patients can have other diseases requiring surgical treatment. In such patients, bariatric surgeries are considered a precursor to operations targeting the original disease for the purpose of reducing severe perioperative complications. Pancreatic ectopic fat deposition increases pancreas volume (PV) and thickness, which can worsen insulin resistance and islet ß cell function. To address this problem, we present a novel two-stage surgical strategy performed on a severely obese patient with pancreatic neuroendocrine tumor (PNET) consisting of laparoscopic sleeve gastrectomy (LSG) as a metabolic surgery followed by laparoscopic spleen-preserving distal pancreatectomy (LSPDP). CASE PRESENTATION: A 56-year-old man was referred to our hospital for further investigation of a pancreatic tumor. His initial body weight and body mass index (BMI) were 94.0 kg and 37.2 kg/m2, respectively. Contrast computed tomography revealed an enhanced tumor measuring 15 mm on the pancreatic body. The pancreas thickness and PV were 32 mm and 148 mL, respectively. An endoscopic ultrasonographic fine needle aspiration identified the tumor as PNET-G1. We first performed LSG, the patient's body weight and BMI had decreased dramatically to 64.0 kg and 25.3 kg/m2 at 6 months after LSG. The pancreas thickness and PV had also decreased to 17 mm and 99 mL, respectively, with no tumor growth. Since LSG has been shown to reduce the perioperative risk factors of LSPDP, and to improve insulin resistance and recovery of islet ß cell function, we performed LSPDP for PNET-G1 as a second-stage surgery. The postoperative course was unremarkable, and the patient was discharged on postoperative day 14 without symptomatic postoperative pancreatic fistula (POPF). He was followed without recurrence or type 2 diabetes (T2D) onset for 6 months after LSPDP. CONCLUSIONS: We present a novel two-stage surgical strategy for a severely obese patient with PNET, consisting of LSG as a metabolic surgery for severe obesity, followed by LSPDP after confirmation of good weight loss and metabolic effects. LSG before pancreatectomy may have a potential to reduce pancreas thickness and recovery of islet ß cell function in severely obese patients, thereby reducing the risk of clinically relevant POPF and post-pancreatectomy T2D onset.

Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of steroid-resistant nephrotic syndrome.

BACKGROUND: Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. METHODS: Seventy patients aged 1-15 years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post-transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A. RESULTS: Data from 36 kidney transplant recipients were analyzed. Twenty-two (61%) patients experienced post-transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p = .01). CONCLUSION: This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A may predict post-transplant SRNS recurrence.

Laparoscopic Left Hepatectomy with Middle Hepatic Vein Resection for Hepatocellular Carcinoma with Extrahepatic Portal Vein Obstruction.

BACKGROUND Extrahepatic portal vein obstruction (EHPVO) is one of the most important diseases that causes pre-hepatic portal hypertension, and EHPVO sometimes develops cavernous transformation to maintain hepatopetal flow. In this report, we describe the first case of hepatocellular carcinoma (HCC) with EHPVO having underwent pure laparoscopic left hepatectomy with middle hepatic vein (MHV) resection. CASE REPORT A 70-year-old woman with a diagnosis of mixed-type HCC or cholangiocarcinoma located in segment 4b was referred to our hospital, and computed tomography revealed EHPVO with cavernous transformation. We successfully performed pure laparoscopic left hepatectomy with MHV resection by using the individual hilar approach, frequent intraoperative sonography, and indocyanine green imaging. In this case, the routine Glissonian approach was impossible due to cavernous transformation growth and the absence of a portal vein. Therefore, frequent confirmation of intrahepatic flow was crucial to avoid intraoperative complications. The patient was discharged with no complications on postoperative day 7. A histopathological examination revealed that the moderately differentiated HCC formed a pseudoglandular pattern and cord-like structures, thereby defined as type II according to Edmondson's classification. CONCLUSIONS Currently, difficulty scoring systems for laparoscopic liver resection (LLR) usually contain the procedure and location of the hepatic tumor, but they do not contain the variety of anatomical abnormality due to its rarity. However, the false recognition of hilar vessels and biliary ducts in patients with an anatomical abnormality, including EHPVO, leads to severe injury; therefore, anatomical variety and abnormality are also important factors increasing the difficulty of LLR.

Valganciclovir prophylaxis for cytomegalovirus infection in pediatric kidney transplant recipients: a single-center experience.

BACKGROUND: There are two approaches for treating cytomegalovirus (CMV) infection occurring after kidney transplantation (KTx). One is preemptive therapy in which treatment is started after confirming positive CMV antigenemia using periodic antigenemia assay. The other approach is prophylactic therapy in which oral valganciclovir (VGCV) is started within 10 days after KTx and continued for 200 days. The Transplantation Society guidelines recommend prophylactic therapy for high-risk (donor's CMV-IgG antibody positive and recipient's negative) pediatric recipients. However, the adequate dose and side effects of VGCV are not clear in children, and there is no sufficient information about prophylaxis for Japanese pediatric recipients. METHODS: A single-center retrospective analysis was conducted on case series of high-risk pediatric patients who underwent KTx and received oral VGCV prophylaxis at the Department of Pediatric Nephrology, Tokyo Women's Medical University, between August 2018 and March 2019. Data were collected using medical records. RESULTS: The dose of administration was 450 mg in all the study patients (n = 5). Reduction or discontinuation was required in four of five patients due to adverse events, which included neutropenia in one patient, anemia in two patients, and neutropenia and digestive symptoms in one patient. Late-onset CMV disease occurred in all patients. No seroconversion was observed during prophylaxis. CONCLUSIONS: Our preliminary study suggests that the dosage endorsed by The Transplantation Society may be an overdose for Japanese pediatric recipients. Further studies are required to examine the safety and efficacy of VGCV prophylaxis in Japanese pediatric recipients.

Indocyanine green fluorescence imaging via endoscopic nasal biliary drainage during laparoscopic deroofing of liver cysts.

Laparoscopic deroofing of liver cysts is widely accepted as the treatment of symptomatic huge liver cysts. As bile leakage is a common complication of this procedure, indocyanine green (ICG) imaging has played an active role in detecting intrahepatic biliary tract. However, infusion ICG imaging needs time rag after injection due to moving from bloodstream to bile, and also, additional injection is needed when the fluorescent imaging is not clear. To cover this weakness of ICG imaging, we first applied ICG imaging via 5-Fr endoscopic nasal biliary drainage (ENBD) during laparoscopic deroofing of liver cysts. This technique promptly gives us ICG imaging after ICG injection from ENBD; in addition, direct ICG imaging sometimes reveals minor leakage from sealing line and staple lines; therefore, we believe that direct ICG imaging via ENBD helps us to prevent post-operative bile leakage.

Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis.

Background: The development of glomerulosclerosis in FSGS is associated with a reduction in podocyte number in the glomerular capillary tufts. Although it has been reported that the number of urinary podocytes in FSGS exceeds that of minimal-change nephrotic syndrome, the nature of events that promote podocyte detachment in FSGS remains elusive. Methods: In this study, we provide detailed, morphologic analysis of the urinary podocytes found in FSGS by examining the size of the urinary podocytes from patients with FSGS, minimal-change nephrotic syndrome, and GN. In addition, in urinary podocytes from patients with FSGS and minimal-change nephrotic syndrome, we analyzed podocyte hypertrophy and mitotic catastrophe using immunostaining of p21 and phospho-ribosomal protein S6. Results: The size of the urinary podocytes was strikingly larger in samples obtained from patients with FSGS compared with those with minimal-change nephrotic syndrome and GN (P=0.008). Urinary podocytes from patients with FSGS had a higher frequency of positive immunostaining for p21 (P<0.001) and phospho-ribosomal protein S6 (P=0.02) than those from patients with minimal-change nephrotic syndrome. Characteristic features of mitotic catastrophe were more commonly observed in FSGS than in minimal-change nephrotic syndrome urinary samples (P=0.001). Conclusions: We posit that the significant increase in the size of urinary podocytes in FSGS, compared with those in minimal-change nephrotic syndrome, may be explained by hypertrophy and mitotic catastrophe.

Portal bifurcation reconstruction using own hepatic vein grafts due to portal vein anomaly of the living donor for the patient with portal vein thrombosis.

A 57-year-old Japanese female was considered for living donor liver transplantation (LDLT) due to end-stage liver cirrhosis caused by primary biliary cholangitis with portal vein thrombosis (PVT) formation. A 26-year-old daughter of the patient was selected as a living donor; however, a computed tomography examination revealed trifurcated-type portal vein anomaly (PVA). Preoperative liver volumetry showed that the right lobe graft was necessary for the recipient; therefore, reconstruction of the portal vein bifurcation during LDLT was necessary. We planned to extract the recipient's own hepatic vein grafts after total hepatectomy, and these would be attached with anterior and posterior portal branches as jump grafts. We performed laparoscopic donor hepatectomy as usual, and the recipient's hepatic vein grafts were anastomosed on the bench. Then, the liver graft was inserted, and the hepatic vein reconstruction was routinely performed. We confirmed the alignment between the recipient's portal vein and the bridged hepatic vein graft of the liver graft's posterior branch, and anastomosed these two vessels. Moreover, we confirmed the front flow and expansion of the reconstructed posterior branch by declamping only the suprapancreatic side of the portal vein. The decision regarding the punch-out location was crucial. We confirmed the alignment between the reconstructed posterior branch and the bridged hepatic vein graft of the anterior branch, and anastomosed these two vessels employing the punched-out technique. In LDLT, liver transplant surgeons occasionally encounter living donors with PVA or recipients with PVT. Our contrivance may be useful when the liver graft needs reconstruction of portal vein bifurcation.

Identifying Cystic Vein Perfusion Area Employing Indocyanine Green Fluorescence Imaging during Laparoscopic Extended Cholecystectomy for Clinical T2 Gallbladder Cancer.

We present an original surgical technique for identifying the perfusion area of the cystic vein with indocyanine green (ICG) fluorescence imaging and laparoscopic extended cholecystectomy with lymphadenectomy for a 56-year-old woman with diagnosis of clinical T2 gallbladder cancer (GBC). First, we encircled Calot's triangle using the Glissonean approach from the ventral side of the gallbladder plate and then taped the hilar Glissonean pedicles; these were temporally clamped, and ICG was injected into the vein. The perfusion area of the cystic vein was scrutinized, specifically the stained area of the hepatic parenchyma was marked, and extended cholecystectomy was performed along the resection line. Subsequently, we performed lymphadenectomy of the hepatoduodenal ligament to complete the operation. A postoperative histopathological examination revealed moderately differentiated adenocarcinoma with pathological T1bN0M0. Although extended cholecystectomy is currently recommended for clinical T2 GBC, there is no consensus on the definition of the gallbladder bed, and the ideal extent of hepatic resection has, therefore, not yet been determined. In addition, gallbladder bed resection with 2-3 cm of surgical margin is an empirical procedure that lacks scientific verification. Regarding anatomical features, the cystic vein sometimes drains directly into the anterior branch of the portal vein, penetrating the gallbladder plate and Laennec's capsule of the anterior Glissonean pedicle. To address this background, we have developed a technique to identify the perfusion area of the cystic vein to determine the extent of hepatic parenchyma that should be resected during laparoscopic extended cholecystectomy for clinical T2 GBC.

Nonosmotic secretion of arginine vasopressin and salt loss in hyponatremia in Kawasaki disease.

BACKGROUND: The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports. METHODS: Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels <135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by >3% was defined as hypervolemia and a decrease in body weight by >3% was defined as hypovolemia. RESULTS: The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH. CONCLUSIONS: Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.

Pancreas volume reduction and metabolic effects in Japanese patients with severe obesity following laparoscopic sleeve gastrectomy.

This study aimed to assess the relationship between the metabolic effect after laparoscopic sleeve gastrectomy (LSG) in morbidly obese Japanese patients, with or without type 2 diabetes mellitus (T2DM), and improved pancreatic steatosis (PS). The study enrolled 27 morbidly obese Japanese patients who were undergoing LSG. Their clinical and metabolic effects were evaluated at baseline and six months after LSG. Pancreas volume (PV), pancreatic attenuation (PA), and splenic attenuation (SA) were measured using a 64-row computed tomography (CT). Changes in PV, PA-SA, and PA/SA were evaluated. The mean body-weight loss, body mass index loss, and percentage of excess weight loss (%EWL) were -34.4 kg (p < 0.001), -11.0 kg/m2 (p < 0.001), and 43.7%, respectively. The mean PV was 96.7 mL at baseline, and it decreased six months after LSG (-16.3mL, p < 0.001). The mean PA significantly increased six months after LSG (9.5 HU, p < 0.001). PA-SA (-23.2 HU vs. -13.3 HU, p = 0.003), and PA/SA (0.54 vs. 0.73, p < 0.001) also significantly increased six months after LSG. In T2DM patients, decreased PV correlated with decreased fasting blood sugar, decreased insulin, and reduced liver volume. In conclusion, PV significantly decreased after LSG in morbidly obese Japanese patients, and that decrease correlated with improvements in PS. In addition, PS plays an important role of development and progression of insulin resistance and T2DM.

Effects of dielectric planar interface on tight focusing coherent beam: direct comparison between observations and vectorial calculation of lateral focal patterns.

We report direct observation of lateral focal patterns through an acrylic material to investigate the effects of aberrations caused by a planar dielectric interface. Numerical analyses based on vectorial Huygens-Fresnel diffraction theory were also performed to examine the behavior of three-dimensional point spread functions. Experimental and numerical results showed agreement of the behavior of the peak position in the focal patterns with changes in the interface position. Our approach has the potential to predict the effects of aberrations in confocal laser scanning microscopes and super-resolution applications.

High-quality generation of a multispot pattern using a spatial light modulator with adaptive feedback.

We propose and demonstrate high-quality generation of a uniform multispot pattern (MSP) by using a spatial light modulator with adaptive feedback. The method iteratively updates a computer generated hologram (CGH) using correction coefficients to improve the intensity distribution of the generated MSP in the optical system. Thanks to a simple method of determining the correction coefficients, the computational cost for optimizing the CGH is low, while maintaining high uniformity of the generated MSP. We demonstrate the generation of a 28×28 square-aligned MSP with high uniformity. Additionally, the proposed method could generate an MSP with a gradually varying intensity profile, as well as a uniform MSP consisting of more than 1000 spots arranged in an arbitrary pattern.