The prognostic significance of neuroendocrine markers and somatostatin receptor 2 in hepatocellular carcinoma.

Prostatic and colon carcinomas with neuroendocrine differentiation are reported to behave more aggressively than those without such differentiation. In hepatocellular carcinomas (HCCs), however, only a few studies have reported the expression status of neuroendocrine markers and somatostatin receptor 2, the main target of a somatostatin analog. Furthermore, the prognostic significance of the markers in HCCs has not been fully explored. We evaluated the expression of the neuroendocrine makers (chromogranin A, synaptophysin, and CD56) and somatostatin receptor 2 (SSTR2) in 95 HCCs, and investigated the correlation between the expression of these markers and clinicopathological findings. Chromogranin A was immunolocalized in 2 cases, synaptophysin in 15 cases, CD56 in 11 cases, and SSTR2 in 19 cases. Immunoreactivity of synaptophysin and CD56 were the significant unfavorable prognostic factors in terms of 2-year disease-free survival (DFS) and the overall survival (OS) along with a high nuclear mitosis level (>10/10 high-power field), a larger tumor size (>5 cm), the presence of vascular and/or biliary invasion, and high TNM stage (III/IV). Multivariate Cox proportional hazards analysis identified synaptophysin as an independent prognostic factor for 2-year DFS and OS. Synaptophysin expression can be used to predict an unfavorable prognosis in patients with HCC.

Renal Epithelioid Angiomyolipoma Undergoing Aggressive Clinical Outcome: The MDM2 Expression in Tumor Cells of Two Cases.

Epithelioid angiomyolipoma (EAML) has been known as a potentially malignant tumor which occasionally recur and/or metastasize to other organs, and clinically and pathologically recognized as distinct entity. However, the mechanisms of recurrence and/or metastasis (recurrence/metastasis) has still remained unknown. Here, we report two cases of renal EAML associated with recurrence/metastasis, and three cases of EAML in kidney or liver without recurrence/metastasis. According to the previous histological predictive models of EAML, the primary tumor was classified as low risk group in one of the cases with recurrence/metastasis in spite of its malignant behavior. Therefore, we considered that further investigation about the mechanisms of recurrence/metastasis in EAML is required for a malignancy prediction. We focused on some cell-cycle modulators, including mouse double minute 2 homolog (MDM2), which is ubiquitin ligase well-known to promote malignant behaviors by p53 ubiquitination and degradation, and also other cellular processes including genomic instability and epithelial-mesenchymal transition in p53-independent manners in various human malignancies. Immunohistochemical evaluation revealed that MDM2 protein expression increased stepwise throughout every steps of metastasis/recurrence in both cases, although it was negative in primary tumors. In conclusion, this is the first study demonstrating that MDM2 could play an important role in the molecular mechanisms of recurrence/metastasis of EAML. Further analyses focusing on MDM2 pathway could contribute to the identification of novel prognostic factors and/or therapeutic targets in EAML patients.

Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms.

STEROIDOGENESIS IN HEPATIC MUCINOUS CYSTIC NEOPLASM: Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.

Efficacy of intraoperative fluorescence imaging using indocyanine green-containing gauze in identifying the appropriate dissection layer in laparoscopic intersphincteric resection: A case report.

In laparoscopic intersphincteric resection, identifying the dissection layer near the anus is often difficult. We safely proceeded with it, using indocyanine green-containing gauze on the anal side to remove the internal anal sphincter with indocyanine green fluorography.

Living-Donor Kidney Transplantation With Laparoscopic Nephrectomy From a Donor With Horseshoe Kidney: A Case Report.

BACKGROUND: In living-donor kidney transplantation, laparoscopic nephrectomy from a donor has become widespread. However, more careful treatment is required for nephrectomy from a donor with horseshoe kidney. This report presents an interesting surgical case of laparoscopic nephrectomy from a donor with horseshoe kidney. CASE PRESENTATION: A woman aged 53 years was a donor candidate for living-donor kidney transplantation for her husband. She had no medical history and had no problems on preoperative examination, but contrast-enhanced computed tomography revealed that she had horseshoe kidney. As the isthmus was thin and the contrast effect was poor, the isthmus was considered to have poor kidney parenchyma and consisted almost exclusively of fibrous tissue. Therefore, laparoscopic nephrectomy was performed for the donor. On the basis of the 99m Tc-dimercaptosuccinic acid renal scintigraphy results, the right kidney was collected. A laparoscopic nephrectomy with a retroperitoneal approach was performed using GelPort access platforms in a right abdominal incision with an accessory port. We firmly expanded the isthmus and then dissected it just above the aorta using a linear stapling device. Subsequently, we sutured a renal artery and vein with linear stapling devices. The recipient's surgery was also performed without any problems, and the postoperative course of both donor and recipient was good. CONCLUSIONS: We suggest that even if the donor has horseshoe kidney, laparoscopic donor nephrectomy should be actively considered depending on the thickness of the isthmus of the horseshoe kidney.

Surgical strategy for an adult patient with a catecholamine-producing ganglioneuroblastoma and a cerebral aneurysm: a case report.

BACKGROUND: Ganglioneuroblastomas, particularly those that produce catecholamine, are extremely rare in adults. Here, we report an interesting surgical case of an adult patient with a catecholamine-producing ganglioneuroblastomas in her adrenal gland, suspected to be a pheochromocytoma, and with a cerebral aneurysm. CASE PRESENTATION: The patient was a 73-year-old woman under treatment for hypertension. During a health check-up, a cystic retroperitoneal tumor was incidentally found in the superior pole of her right kidney. Her blood adrenaline level was slightly elevated, and her urinary adrenaline, noradrenaline, and dopamine levels were above the upper reference limits. In addition, 24-h urinary excretion of metanephrine, normetanephrine, and vanillylmandelic acid were all increased. 123I-Meta-iodobenzylguanidine scintigraphy showed an abnormal accumulation of the marker in the cyst wall. She was, therefore, diagnosed with a pheochromocytoma and scheduled for tumor resection. However, preoperatively, 8-mm-diameter cerebral aneurysm was incidentally found in her basilar artery. This required careful preoperative discussion. The aneurysm was difficult to approach and treat, and based on its position, shape, and size, the risk of rupture was low. Because hypertension is a major risk factor for aneurysmal rupture, we decided to proceed with the tumor resection. A lumbar catheter was placed to monitor the cerebral aneurysm for intraoperative rupture, and her transcranial motor-evoked potential and somatosensory-evoked potentials were monitored to track her intraoperative neurological function. During surgery, we carefully monitored fluctuations in blood pressure and resected the tumor with minimal mobilization. Postoperatively, head computed tomography confirmed that there was no sign of rupture. Histopathologically, the tumor was diagnosed as a catecholamine-producing ganglioneuroblastoma. The postoperative course was good, and the patient's blood pressure improved. CONCLUSIONS: Careful perioperative management is needed for a patient with both a catecholamine-producing tumor and cerebral aneurysm.

Classical Hodgkin lymphoma-type and monomorphic-type post-transplant lymphoproliferative disorder following liver transplantation: a case report.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication that can be difficult to treat; moreover, determination of the pathophysiological type is difficult. We report a rare case of a patient who developed two types of Epstein-Barr virus (EBV)-negative PTLD following living donor liver transplantation (LDLT). CASE PRESENTATION: A 64-year-old man underwent LDLT for acute fulminant hepatitis B. Sixty-five months later, he developed EBV-negative monomorphic B cell PTLD. Reduction of immunosuppressive therapy and chemotherapy with rituximab resulted in a partial response. He received radioimmunotherapy with yttrium-90-ibritumomab tiuxetan, which was effective for all lesions, except for the splenic hilar lesion, which enlarged and seemed to penetrate the stomach. Therefore, he underwent resection of the pancreatic tail with splenectomy and partial gastrectomy. The pathological diagnosis was EBV-negative classical Hodgkin lymphoma (cHL)-type PTLD. CONCLUSIONS: This patient showed an unexpected course of PTLD, from both a clinical and pathological perspective. There are no prior reports of an adult case of EBV-negative cHL-type PTLD coexisting with EBV-negative monomorphic B cell PTLD. When a strange and refractory lesion persists despite effective therapy for PTLD, we must consider the possibility of another type of PTLD within the residual lesion.

Extrahepatic bile duct hepatocellular carcinoma due to recurrence of hematogenous metastasis 50 months after hepatectomy.

BACKGROUND: Recurrent hepatocellular carcinoma (HCC) in the extrahepatic bile duct is rare with most cases diagnosed after manifesting sudden obstructive jaundice. Here, we report an extremely rare case of recurrent HCC in the common bile duct due to hematogenous metastasis. CASE PRESENTATION: A 66-year-old man underwent an extended left hepatectomy for HCC in the medial segment of the liver. Fifty months later, he presented with sudden obstructive jaundice. Endoscopic retrograde cholangiography showed a space-occupying lesion in the common bile duct, which was suspected as cholangiocarcinoma. Therefore, he underwent extrahepatic bile duct resection and choledochojejunostomy with lymph node dissection. Macroscopically, a polypoid tumor and several nodular tumors were found in the common bile duct, which was obstructed by a tumor thrombus. Histopathologically, the tumors were diagnosed as metastases from the HCC resected 50 months before. Several distinct, nodular tumors were observed in the subepithelium of the common bile duct and had invaded some blood vessels. These findings support the conclusion that the HCC metastasized hematogenously to the extrahepatic bile duct. CONCLUSIONS: Recurrent HCC in the extrahepatic bile duct due to hematogenous metastasis is rare, and it is difficult to diagnose. Further similar cases should be accumulated for clarifying the pathological mechanism.

Renoportal Anastomosis in Left Lateral Lobe Living Donor Liver Transplantation: A Pediatric Case.

In adult liver transplantation, renoportal anastomosis (RPA) has been introduced as a useful technique for patients with grade 4 portal vein thrombosis and a splenorenal shunt. Here, we report a pediatric case in which RPA allowed a left lateral lobe living donor liver transplantation (LDLT) despite portal vein thrombosis and a large splenorenal shunt. At 36 days old, the patient underwent a Kasai operation for biliary atresia. At 17 months old, she underwent LDLT because of repetitive cholangitis. Pretransplant examinations revealed a large splenorenal shunt and portal vein thrombosis. Simple end-to-end portal reconstruction and clamping of the collateral route after removing the thrombosis were unsuccessful. Thus, RPA was performed using a donor superficial femoral vein as an interpositional graft. The portal vein pressure was 20 mm Hg after arterial reperfusion. Ligation of the splenic artery reduced the portal vein pressure. Although she developed severe acute cellular rejection and chylous ascites, there were no signs of portal vein complications. She was discharged 73 days after transplantation without any signs of renal dysfunction. The patient's condition was good at her last follow-up, 22 months after transplantation. To our knowledge, this is the youngest case of RPA in pediatric left lateral lobe LDLT. Additionally, this is the first case of RPA with splenic artery ligation and using the donor's superficial femoral vein as the venous graft for RPA. Although long-term follow-up is necessary, RPA could be a salvage option in LDLT in infants if other methods are unsuccessful.