Small Intestinal Adenocarcinoma Arising at the Anastomotic Site after Kasai Operation for Biliary Atresia: A Case Report and Literature Review.

Biliary atresia is an obliterative cholangiopathy of unknown etiology. Hepatic portoenterostomy, in which obliterated extrahepatic bile ducts are resected and bile flow is restored, known as Kasai operation, is performed within 3 months after birth. While this operation enhances long-term survival of patients, the occurrence of primary malignant hepatic tumors has been increasing. We report a case of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation. A 49-year-old man, who underwent Kasai operation for biliary atresia when he was 2 months old, experienced rapidly progressive jaundice and liver dysfunction. Deceased-donor liver transplantation was performed for liver failure. Macroscopically, there was a white-yellow tumor located at the anastomotic site of hepatic portoenterostomy of the resected liver. Pathological examination revealed a well-differentiated adenocarcinoma with some Paneth cells in the neoplastic lesion. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) but positive for cytokeratin 20 (CK20) and a homeobox domain-containing transcription factor (CDX2). Mucin expression in tumor cells was negative for mucin 1 (MUC1) and mucin 6 (MUC6) and positive for mucin 2 (MUC2) and mucin 5AC (MUC5AC). The pathological diagnosis was small intestinal adenocarcinoma originating from the jejunum. The patient was discharged 48 days after the operation. The patient had not experienced recurrence at 10 months after the operation. This is the first report of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation for biliary atresia. Special care should be taken for the patients after Kasai operation with acute progressive jaundice and liver dysfunction because there is a possibility of malignancy in their native liver.

Tumor-to-Tumor Metastasis of Medullary Thyroid Carcinoma to Paraganglioma in a Multiple Endocrine Neoplasia Type 2B Patient: A Case Report and Literature Review.

Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize to other tumors. Herein, we report an extremely rare case of tumor-to-tumor metastasis of medullary thyroid carcinoma to a paraganglioma in a patient with multiple endocrine neoplasia type 2B. Based on genetic examination, a 36-year-old woman was diagnosed with multiple endocrine neoplasia type 2B when she was 24 years old. She had a history of total thyroidectomy for medullary thyroid carcinoma and bilateral adrenalectomy for pheochromocytomas, which were performed when she was 15 years and 29 years old, respectively. Follow-up computed tomography demonstrated a retroperitoneal tumor of 30 mm in diameter beside the left kidney and a liver tumor of 16 mm in diameter located in segment 6. The retroperitoneal and liver tumors were surgically resected and examined by a pathologist. Histological examination revealed the classic Zellballen pattern in the retroperitoneal tumor, rendering the diagnosis of a paraganglioma recurrence. Inside the tumor, a white nodule positive for carcinoembryonic antigen, weakly positive for calcitonin, and negative for tyrosine hydroxylase, was identified and diagnosed as a metastatic medullary thyroid carcinoma with high malignant potential. The liver lesion was diagnosed as a metastasis of the medullary thyroid carcinoma. This is the first report of tumor-to-tumor metastasis of medullary thyroid carcinoma to paraganglioma in a patient with multiple endocrine neoplasia type 2B twenty years after total thyroidectomy.

Ideal Duration of Pretreatment Using a Gelatin Hydrogel Nonwoven Fabric Prior to Subcutaneous Islet Transplantation.

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment in comparison with intraportal islet transplantation. We herein investigated whether the duration of pretreatment using GHNF affected the outcome of subcutaneous islet transplantation. A silicone spacer with GHNF was implanted into the subcutaneous space of healthy mice at 2, 4, 6, or 8 weeks before transplantation, and then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, inflammatory mediators, and gene expression were evaluated. The 6-week group showed significantly better blood glucose changes than the other groups (P < 0.05). The cure rate of the 6-week group (60.0%) was the highest among the groups (2-week = 0%, 4-week = 50.0%, 8-week = 15.4%). The number of von Willebrand factor (vWF)-positive vessels in the 6-week group was significantly higher than in the other groups at pre-islet and post-islet transplantation (P < 0.01 [vs 2-and 4-week groups] and P < 0.05 [vs all other groups], respectively). Notably, this beneficial effect was also observed when GHNF was implanted into diabetic mice injected with streptozotocin 7 days before GHNF implantation. The positive rates for laminin, collagen III, and collagen IV increased as the duration of pretreatment became longer and were significantly higher in the 8-week group (P < 0.01). Inflammatory mediators, including interleukin (IL)-1b, granulocyte colony-stimulating factor (G-CSF), and interferon (IFN)-γ, were gradually downregulated according to the duration of GHNF pretreatment and re-elevated in the 8-week group. Taken together, the duration of GHNF pretreatment apparently had an impact on the outcomes of subcutaneous islet transplantation, and 6 weeks appeared to be the ideal duration. Islet graft revascularization, extracellular matrix compensation of the islet capsule, and the inflammatory status at the subcutaneous space would be crucial factors for successful subcutaneous islet transplantation.

A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation.

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be removed when transplanting islets. We herein investigated whether a novel bioabsorbable gelatin hydrogel nonwoven fabric (GHNF) could improve subcutaneous islet engraftment. A silicon spacer with or without GHNF was implanted into the subcutaneous space of diabetic mice. Syngeneic islets were transplanted into the pretreated space or intraportally (Ipo group). Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, CT angiography and gene expression were evaluated. The cure rate and glucose tolerance of the GHNF group were significantly better than in the control and Ipo groups (p < 0.01, p < 0.05, respectively). In the GHNF group, a limited increase of vWF-positive vessels was detected in the islet capsule, whereas laminin (p < 0.05), collagen III and IV were considerably enhanced. TaqMan arrays revealed a significant upregulation of 19 target genes (including insulin-like growth factor-2) in the pretreated space. GHNF markedly improved the subcutaneous islet transplantation outcomes, likely due to ECM compensation and protection of islet function by various growth factors, rather than enhanced neovascularization.

Clinical Significance of the Mac-2 Binding Protein Glycosylated Isomer as a Surrogate Marker of Graft Fibrosis After Pediatric Liver Transplantation.

BACKGROUND: After pediatric liver transplantation, liver fibrosis may occur during long-term follow-up. Noninvasive markers for assessing this liver fibrosis are desired. Mac-2 binding protein glycosylated isomer (M2BPGi) has recently been reported as a useful biomarker for liver fibrosis. However, its usefulness in the pediatric population is yet to be established. This study investigated the clinical significance of M2BPGi levels as a surrogate marker of graft fibrosis after pediatric liver transplantation. METHODS: We retrospectively identified 96 patients who underwent pediatric liver transplantation at our institution between 1991 and 2015. The association between M2BPGi levels and other fibrosis markers was analyzed in 60 patients in whom fibrosis markers were measured. The association between fibrosis marker levels and graft fibrosis was assessed in 42 patients who underwent biopsies between 2016 and 2022. RESULTS: The M2BPGi levels were statistically correlated with the hyaluronic acid and type-IV collagen levels. None of the fibrosis markers were significantly associated with liver graft fibrosis, although the levels of these markers were slightly higher in patients with severe liver fibrosis than in those with mild fibrosis. CONCLUSIONS: The M2BPGi levels had a limited ability to assess liver graft fibrosis after pediatric liver transplantation, similar to other fibrosis markers. Further studies with larger cohorts are required to validate these findings externally.

A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats.

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.

Development of a novel method for measuring tissue oxygen pressure to improve the hypoxic condition in subcutaneous islet transplantation.

Subcutaneous tissue is a promising site for islet transplantation, but poor engraftment, due to hypoxia and low vascularity, hinders its prevalence. However, oxygen partial pressure (pO2) of the subcutaneous space (SC) and other sites were reported to be equivalent in several previous reports. This contradiction may be based on accidental puncture to the indwelling micro-vessels in target tissues. We therefore developed a novel optical sensor system, instead of a conventional Clark-type needle probe, for measuring tissue pO2 and found that pO2 of the SC was extremely low in comparison to other sites. To verify the utility of this method, we transplanted syngeneic rat islets subcutaneously into diabetic recipients under several oxygenation conditions using an oxygen delivery device, then performed pO2 measurement, glucose tolerance, and immunohistochemistry. The optical sensor system was validated by correlating the pO2 values with the transplanted islet function. Interestingly, this novel technique revealed that islet viability estimated by ATP/DNA assay reduced to less than 75% by hypoxic condition at the SC, indicating that islet engraftment may substantially improve if the pO2 levels reach those of the renal subcapsular space. Further refinements for a hypoxic condition using the present technique may contribute to improving the efficiency of subcutaneous islet transplantation.

Usefulness of Thiel-Embalmed Cadavers for Training in Organ Procurement.

BACKGROUND: The number of brain-dead donors has been increasing; however, the opportunity for young surgeons to experience deceased donor surgeries is extremely limited, especially in many Asian countries including Japan. Deceased donor surgeries require unique surgical skills and knowledge; however, it is difficult to provide on-the-job guidance and education. Therefore, cadaver training is meaningful and suitable for the training of deceased donor surgeries. Thiel's embalming method (TEM) provides natural coloration, flexibility, and tissue plasticity, and is widely used for cadaver surgical training. In this study, we evaluated the usefulness of Thiel's embalmed cadaver training for organ procurement surgery. MATERIAL AND METHODS: Each trainee performed hepatectomy, pancreatectomy, and nephrectomy using conventional open techniques. Faculty experts of transplantation surgery and organ procurement took attendees through surgical steps. After the procedure, all participants were asked to complete a voluntary, anonymous survey, consisting of a 10-point satisfaction scale, to evaluate their perceptions of the training. RESULTS: A total of 33 gastrointestinal surgeons participated in the training program for procuring the liver, pancreas, and kidneys. In the questionnaire administered to the participants, the evaluation was generally satisfactory, with an average of 9.1 points on the 10-point scales. Some participants expressed that Thiel-embalmed cadavers are more suitable for training on organ procurement compared with animals used in wet-lab training. CONCLUSION: We conclude that organ procurement training in human cadavers preserved by TEM is useful and suitable for practicing deceased donor organ procurement, especially in countries where deceased donors are not common, as in Japan.

Laparoscopic liver cyst fenestration with real-time indocyanine green fluorescence-guided surgery: a case report.

Laparoscopic fenestration (LF) has recently been considered a standard procedure for nonparasitic symptomatic liver cysts. Here, we report a case of LF that was safely performed using real-time indocyanine green (ICG) fluorescence-guided surgery. A 74-year-old woman presented with right upper abdominal pain and poor dietary intake. The patient was diagnosed with symptomatic liver cysts and underwent LF. One hour before surgery, ICG (2.5 mg) was intravenously administered to the patient. ICG fluorescence imaging clearly showed the biliary ducts and distinguished the cysts from the liver parenchyma. We could resect only the cyst walls as wide as possible under the guidance of both white light and fluorescence imaging. There were no signs of postoperative symptom recurrence. Detection of ICG fluorescence in the liver parenchyma is as important as ICG cholangiography for fenestration. Laparoscopic liver cyst fenestration with real-time ICG fluorescence-guided surgery is safe and can be used as a standard procedure.