Gastrointestinal stromal tumor coexisting with disseminated peritoneal leiomyomatosis.

BACKGROUND: A case of gastrointestinal stromal tumor (GIST) coexisting with disseminated peritoneal leiomyomatosis (DPL) is rare. We report a case of GIST coexisting with DPL. CASE PRESENTATION: A 50-year-old woman underwent exploratory laparoscopy under a preoperative diagnosis of gastric GIST with an ovarian tumor or peritoneal dissemination in the pelvic space. Laparoscopy showed multiple peritoneal masses in the pelvic space. Intraoperative frozen sectioning of the pelvic tumors showed multiple spindle cells, suggesting leiomyomas or retroperitoneal tumors; however, it was difficult to rule out peritoneal dissemination from GIST. No disseminated lesion was noted near GIST, and hence, we believed that GIST and pelvic lesions had different origins. We achieved R0 resection by partial resection of the stomach, total hysterectomy, and bilateral salpingo-oophorectomy. The postoperative immunohistopathological examination confirmed the final diagnosis of GIST and DPL. The patient has been recurrence free for 10 years. CONCLUSIONS: Immunohistochemical examination is essential for correct diagnosis for GIST and DPL. R0 curative resection should be scheduled after immunohistochemical examination of specimens obtained from exploratory laparoscopy.

Bivalent property of intra-platelet VWF in liver regeneration and HCC recurrence: A prospective multicenter study.

BACKGROUND AND AIMS: A striking difference has been observed in structure and functional properties between plasma and platelet von Willebrand factor (VWF). While the existing evidence has revealed a clinical relevance of plasma VWF-Ag in liver regeneration (LR) and different cancers, this study was designed to explore the properties of intra-platelet (IP) and serum VWF-Ag in patients with hepatocellular carcinoma (HCC) undergoing partial hepatectomy. METHODS: A total of 40 patients undergoing partial hepatectomy were prospectively recruited from 3 institutions. VWF-Ag concentrations were evaluated mainly in serum and platelet extracts. Patients were followed-up for postoperative liver dysfunction and HCC recurrence. RESULTS: We observed a post-resection increase in the concentration of VWF-Ag in serum and platelet. Patients with postoperative liver dysfunction had substantially reduced serum and IP VWF-Ag concentrations. After a 2-year follow-up, patients with higher post-resection serum and IP VWF-Ag concentrations were found to develop early HCC recurrence. Likewise, IP VWF-Ag was able to independently predict post-resection early HCC recurrence. CONCLUSION: This multicenter, prospective, pilot study demonstrates a bivalent property of IP VWF in LR and oncological outcome; low preoperative VWF appeared to have a negative association on post-resection liver dysfunction, whereas, patients with higher post-resection VWF-Ag concentrations were found to have early HCC recurrence.

Predictive Value of Diminished Serum PDGF-BB after Curative Resection of Hepatocellular Cancer.

PURPOSE: Platelet derived growth factor-BB (PDGF-BB) has emerged as one of the key cytokines in malignant transformation of different cells. PDGF-BB also exhibits a potent mitogenic effect on liver cells; studies have advocated clinical implications of monitoring serum PDGF-BB (sPDGF-BB) in patients with liver disease. We thus investigated the predictive relevance of perioperative sPDGF-BB after curative resection of hepatocellular carcinoma (HCC). METHODS: We evaluated perioperative sPDGF-BB in a prospective homogenous cohort of 40 patients diagnosed with HCC. During the first two-year follow-up, patients were evaluated every three months for postresection HCC recurrence. RESULTS: Patients who developed recurrence during two-year follow-up were found to have lower concentration of sPDGF-BB than those without recurrence in both pre- and postoperative settings (P < 0.05 and P < 0.001, resp.). We validated that the reduced postoperative sPDGF-BB (< 2133.29 pg/mL) was associated with an increased incidence of postresection HCC recurrence [area under curve (AUC) > 0.8, 95% confidence interval (CI) = 0.68 - 0.94, P < 0.001]; furthermore, we were able to demonstrate that postoperative sPDGF-BB was an independent predictor of HCC recurrence (hazard ratio = 5.64, 95% CI = 1.56 - 20.30, P < 0.01). CONCLUSIONS: These findings provide a new insight into an association between diminished perioperative sPDGF-BB and HCC recurrence. Patients with low perioperative sPDGF-BB progressed early HCC recurrence. Therefore, evaluating perioperative sPDGF-BB may provide useful clinical information to characterize patients with postresection HCC recurrence.

Deciphering Platelet Kinetics in Diagnostic and Prognostic Evaluation of Hepatocellular Carcinoma.

Liver pathophysiology can, directly and indirectly, impose morphological or biochemical abnormalities of the platelets. Conversely, platelets are also able to regulate the promitogenic and profibrotic signals on liver pathobiology. Platelet contribution to the liver pathophysiology is typically facilitated by the platelet-derived growth factors that are sequestered in different subsets of alpha and dense granules, and the release of these growth factors is synchronized according to the stage and type of liver disease or injury. Thus, platelets harbor clinically relevant information with potential diagnostic and prognostic implications in liver diseases. Hepatocellular carcinoma (HCC) largely influences the platelet kinetics, and a growing body of evidence has recognized its association with HCC occurrence or prognosis. This narrative review summarizes the progress made on implicating platelet as a diagnostic and prognostic tool for HCC; the review also dissects the contradictory results from earlier studies and reflects how combining platelet-based information may enable more reliable test for diagnostic and prognostic evaluation of HCC.

[A case of postoperative recurrent gastric cancer resembling esophageal achalasia diagnosed by staging laparoscopy].

A 65-year-old man underwent subtotal gastrectomy for advanced gastric cancer. The histological type of the cancer was signet-ring cell carcinoma, and the clinical stage was stage IB (T2N0M0). Three years after surgery, the patient had the following symptoms:dysphagia, odynophagia, and weight loss. Esophageal endoscopy and esophagography revealed a circular stenosis covered with the normal mucosa between the middle esophagus and the esophagogastric junction. Histologically, the samples obtained by staging laparoscopy revealed signet-ring cell carcinoma. Tucker's criteria are an important tool for differentiating secondary achalasia from primary achalasia with clinical value. Therefore, we suggest that staging laparoscopy is useful for the histological diagnosis of recurrent gastric cancer.

Therapeutic implication of platelets in liver regeneration -hopes and hues.

INTRODUCTION: Mounting evidence highlights platelet involvement in liver regeneration via interaction with liver cells, growth factors release, and signaling contributions. Existing research suggests a compelling biological rationale for utilizing platelet biology, with the goal of improving liver function and accelerating its regenerative potential. Despite its expanding application in several clinical areas, the contribution of the platelet and its therapeutic implementation in liver regeneration so far has not yet fulfilled the initial high expectations. Areas covered: This review scrutinizes the progress, current updates, and discusses how recent understanding - particularly in the clinical implications of platelet-based therapy - may enable strategies to introduce and harness the therapeutic potential of the platelet during liver regeneration. Expert commentary: Several clinical and translational studies have facilitated a platform for the development of platelet-based therapy to enhance liver regeneration. While some of these therapies are effective to augment liver regeneration, the others have had some detrimental outcomes. The existing evidence represents a challenge for future projects that are focused on directly incorporating platelet-based therapies to induce liver regeneration.

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

Purpose: Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth stimulatory effect on several types of carcinoma and tumor cells. Since a large portion of 5-HT is stored and transported by platelets, the aim of this study was to assess the influence of platelet-sequestered 5-HT on post-resection hepatocellular carcinoma (HCC) recurrence. Methods: This pilot study was conducted in a cohort of forty patients diagnosed with HCC undergoing partial hepatectomy. 5-HT levels in serum, plasma and intra-platelet (IP) were monitored preoperatively and four weeks after liver resection. The patients were followed every three months after the surgery. Results: Follow-up was standardized to a fixed length of time. Fifteen patients (37.5%) developed HCC recurrence during 18 months follow-up. Patients with recurrence had significantly reduced serum and IP 5-HT levels at four weeks of liver resection (P = 0.003 and P = 0.014 respectively). Accordingly, in the Cox regression hazard model, serum and IP 5-HT were able to independently predict the recurrence (hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.75 and hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.89 respectively). The optimal cut-off value of 42.77 ng/ml for serum [area under the curve (AUC): 0.78, P = 0.003] and 0.3117 ng per 106 platelets (AUC: 0.733, P = 0.015), on receiver operating characteristic (ROC) curve corresponded to maximum sensitivity and specificity of prediction. The disease free interval was significantly worse in patients with low serum and IP 5-HT (P = 0.001 and P = 0.029 respectively). Conclusion: IP 5-HT monitored during early follow-up, after liver resection may represent a useful marker of early HCC recurrence.

A surgical case of mycotic aneurysm with Staphylococcus lugdunensis endocarditis.

A 74-year-old man with a history of mitral valve repair was referred to our hospital with fever and diagnosed with mitral valve endocarditis involving occlusion of the superior mesenteric artery. Bacterial cultures showed Staphylococcus lugdunensis. Despite antibiotic therapy, orthopnea ensued due to valve destruction. Emergency mitral valve replacement was performed. Computed tomography on postoperative day 10 revealed a rapidly expanding mycotic aneurysm of the superior mesenteric artery. Aneurysmectomy was undertaken. Mycotic aneurysms of the superior mesenteric artery have not been reported previously in association with Staphylococcus lugdunensis. A rapid diagnosis and prompt surgical intervention are necessary for rescue.

A Switch in the Dynamics of Intra-Platelet VEGF-A from Cancer to the Later Phase of Liver Regeneration after Partial Hepatectomy in Humans.

BACKGROUND: Liver regeneration (LR) involves an early inductive phase characterized by the proliferation of hepatocytes, and a delayed angiogenic phase distinguished by the expansion of non-parenchymal compartment. The interest in understanding the mechanism of LR has lately shifted from the proliferation and growth of parenchymal cells to vascular remodeling during LR. Angiogenesis accompanied by LR exerts a pivotal role to accomplish the process. Vascular endothelial growth factor (VEGF) has been elucidated as the most dynamic regulator of angiogenesis. From this perspective, platelet derived/Intra-platelet (IP) VEGF-A should be associated with LR. MATERIAL AND METHODS: Thirty-seven patients diagnosed with hepatocellular carcinoma and undergoing partial hepatectomy (PH) were enrolled in the study. Serum and IP VEGF-A was monitored preoperatively and at four weeks of PH. Liver volumetry was determined on computer models derived from computed tomography (CT) scan. RESULTS: Serum and IP VEGF-A was significantly elevated at four weeks of PH. Preoperative IP VEGF-A was higher in patients with advanced cancer and vascular invasion. Postoperative IP VEGF-A was higher after major liver resection. There was a statistically significant correlation between postoperative IP VEGF-A and the future remnant liver volume. Moreover, the soluble vascular endothelial growth factor receptor-1 (sVEGFR1) was distinctly down-regulated suggesting a fine-tuned angiogenesis at the later phase of LR. CONCLUSION: IP VEGF-A is overexpressed during later phase of LR suggesting its implications in inducing angiogenesis during LR.

Impact of chemotherapy on eosinophilia-associated advanced rectal cancer: A case report and review of the literature.

The present study reports a case of eosinophilia-associated rectal cancer that was successfully stabilized using chemotherapy, and reviews the mechanisms of eosinophilia and the importance of chemotherapy. A 65-year-old man, who had previously been diagnosed with suspected rectal cancer, presented with the chief complaint of melena. Eosinophilia, abnormal blood coagulation, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 tumor marker levels were observed, and the patient was subsequently diagnosed with advanced rectal cancer accompanied by multiple lymph node metastases that extended from the para-aortic lymph nodes to the left axillary lymph nodes. The complication of deep vein thrombosis was also observed. Tumor hemorrhage was exacerbated, and thus, Hartmann's procedure was performed. Pathological findings included poorly- to moderately-differentiated adenocarcinoma; however, no eosinophil infiltration was observed within the tumor. Following surgery, the eosinophilia and lymph node metastasis were exacerbated, and an oxaliplatin plus capecitabine chemotherapy regimen was initiated. The patient's eosinophil count and tumor marker levels normalized, and the lymph nodes decreased in size; however, re-enlargement of the lymph nodes was observed 6 months after surgery. The patient was then administered a chemotherapeutic regimen of irinotecan/fluorouracil/folinic acid + bevacizumab, and stable disease was maintained until pleural and peritoneal dissemination were observed at 22 months post-surgery. Following a rapid deterioration in condition, the patient succumbed to the disease at 23 months post-surgery. The present case indicates that although eosinophilia-associated colon cancer exhibits a poor prognosis, early chemotherapeutic intervention may improve this.

First jejunal artery, an alternative graft for right hepatic artery reconstruction.

Common bile duct cancer invading right hepatic artery is sometimes diagnosed intraoperatively. Excision and safe reconstruction of the artery with suitable graft is essential. Arterial reconstruction with autologous saphenous vein graft is the preferred method practiced routinely. However the right hepatic artery reconstruction has also been carried out with several other vessels like gastroduodenal artery, right gastroepiploic artery or the splenic artery. We report a case of 63-year-old man presenting with history of progressive jaundice, pruritus and impaired appetite. Following various imaging modalities including computed tomography, endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography, intraductal ultrasound extrahepatic bile duct cancer was diagnosed; however, none of those detected vessel invasion. Intraoperatively, right hepatic artery invasion was revealed. Right hepatic artery was resected and reconstructed with a graft harvested from the first jejunal artery (JA). Postoperative outcome was satisfactory with a long-term graft patency. First JA can be a reliable graft option for right hepatic artery reconstruction.

Middle-preserving pancreatectomy with reversed pancreaticogastrostomy: report of a case.

Parenchyma-sparing pancreatic resections have been reported increasingly in recent years; however, for multifocal diseases involving the head and the tail of the pancreas, total pancreatectomy is still the preferred procedure. The possible consequence of this procedure is loss of normal pancreatic parenchyma, resulting in insufficiency of pancreatic exocrine and endocrine functions. Various types of limited resection have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor. Even for multifocal diseases, if the pancreatic body is spared, a middle-preserving pancreatectomy (MPP) can be performed to assure maximal pancreatic function and uncompromised quality of life. Yet, few papers have introduced the feasibility of MPP for a better outcome. This report describes a new surgical technique for MPP using an alternative approach for the remnant pancreas anastomosis. We used this technique successfully to remove a bifocal neoplasm: adenocarcinoma of the distal bile duct and mucinous cyst adenoma in the tail of the pancreas.

Intrahepatic biliary strictures after liver transplantation.

Biliary complication has been one of the most common complications after liver transplantation. Nonanastomotic strictures and dilatations involving the intrahepatic biliary tree have been recognized as biliary complications. These lesions were reported to be associated with hepatic artery thrombosis; prolonged preservation time; ABO-incompatible organs; and immunological injury, including injuries to vascular endothelial cells (chronic rejection) and the bile duct (primary sclerosing cholangitis). However, the etiology of these lesions appeared to be mostly related to ischemic injury. Anatomical research on the arterial supply of the bile duct has provided further insights into bile duct blood supply and its surgical implications. The biliary tract is supplied with arterial blood by a vasculature called the peribiliary vascular plexus. Any injury to the peribiliary vascular plexus may contribute to ischemic death of the biliary system mucosa. At many points, the process of liver transplantation exposes the endothelial cells and peribiliary vascular plexus to ischemic injury. The majority of intrahepatic biliary strictures (IHBS) are diffuse or bilateral. A percutaneous or an endoscopic approach has been used as the initial treatment. However, a low threshold for surgical intervention (retransplantation) should be adopted, because these patients demonstrate high mortality. The aim of this article is to review the anatomy, etiology, clinical picture, diagnosis, management, and prognosis of IHBS after liver transplantation.

Porcine model of auxiliary partial orthotopic liver transplantation for acute liver failure.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has been an effective alternative in acute liver failure (ALF), but clinically several problems remain to be resolved. Thus, we attempt to establish an APOLT model for ALF using a large animal and demonstrate the validity of our model. METHODS: In experiment 1, we created an animal model of ALF using pig. ALF was induced by resection of 70% of the whole liver under total hepatic vascular exclusion (THVE). The duration of ischemia was 90 minutes. In experiment 2, we tried to make an APOLT model by using this ALF model as a recipient. That is, during 90 minutes of THVE, 70% hepatectomy and subsequent partial orthotopic transplantation was completed. RESULTS: In experiment 1, six of seven pigs died within three days with jaundice and massive ascites. Based on microcirculatory disturbance of the remnant liver and hepatocellular necrosis, 70% hepatectomy with 90 minutes of THVE was considered a proper model of ALF. In experiment 2, six out of seven APOLT model animals survived more than four days. T. Bil levels in the APOLT model remained consistently within the normal range throughout the observation period. In immunohistochemistry, several labeled nuclei stained with Ki67 were identified in native liver of the APOLT model. CONCLUSIONS: This APOLT procedure provided temporary liver function support and enabled the recipient to survive until the failing native liver had regenerated. Our APOLT model could be suitable and useful for understanding the role of APOLT in ALF.

99mTc-DTPA-galactosyl-human-serum-albumin liver scintigraphy for evaluating hepatic functional reserve before hepatectomy in a patient with indocyanine green excretory defect: report of a case.

A 78-year-old woman with indocyanine green (ICG) excretory defect underwent left hepatectomy for cystadenocarcinoma. The retention rate of ICG at 15 min (ICGR(15)) was high, at 79.3%, despite all other liver function tests showing normal values. Conversely, 99mTc-DTPA-galactosyl-human-serum-albumin (GSA) liver scintigraphy showed a reduced accumulation of GSA in the left lateral lobe, the hepatic uptake ratio of the GSA scintigraphy was 0.96, and the arterial ketone body ratio was 1.67. Based on these results, we judged that the hepatic functional reserve of this patient was adequate for left hepatectomy, which was subsequently performed uneventfully. Histopathological examination of the resected liver showed neither fibrosis nor inflammatory cell infiltration. Thus, we consider that GSA liver scintigraphy is the best diagnostic modality for evaluating hepatic functional reserve in a patient with ICG excretory defect.

Advantage of ischemic preconditioning for hepatic resection in pigs.

BACKGROUND: Ischemic preconditioning (IP) and intermittent inflow occlusion (IO) have provided beneficial outcomes in hepatic resection. However, comparison of these two procedures against warm hepatic ischemia-reperfusion injury has not been studied enough. MATERIALS AND METHODS: Pigs that had undergone 65% hepatectomy were subjected to Control (120 min continuous ischemia, n = 6), IP (10 min ischemia and 10 min reperfusion, followed by 120 min continuous ischemia, n = 6), and IO (120 min ischemia in the form of eight successive periods of 15 min ischemia and 5 min reperfusion, n = 6). We evaluated hepatocyte injury by aspartate aminotransferase, lactate dehydrogenase and hepaplastin test, hepatic microcirculation by hepatic tissue blood flow (HTBF) and endothelin (ET)-1, inflammatory response by tumor necrosis factor-alpha (TNF-alpha), and histopathology after reperfusion. RESULTS: IP prevented hepatocyte injury, HTBF disturbance, and hepatocyte necrosis in histopathology as well as IO. These two groups showed significantly better outcomes than Control. IP produced significantly less ET-1 and TNF-alpha than IO. CONCLUSIONS: IP ameliorated hepatic warm ischemia-reperfusion injury. Furthermore, IP gained more advantages in preventing chemokine production such as ET-1 and inflammatory response over IO. IP could take the place of IO for hepatectomy.

Cystic duct directly joining the main pancreatic duct.

A unique anomaly of the direct union between the cystic duct and the main pancreatic duct is presented. A 19-year-old man with a history of repeated epigastralgia underwent endoscopic retrograde cholangiopancreaticography that showed a direct union between the cystic duct and the main pancreatic duct. No pancreaticobiliary maljunction was noticed. Cholecystectomy accompanied by resection of the long cystic duct was performed. The excised gallbladder showed cholesterolosis, chronic cholecystitis, and hyperplasia of the pseudopyloric glands microscopically. The patient has been well for 3 years since surgery.

Carcinosarcoma of the extrahepatic bile duct.

A rare case of a carcinosarcoma of the extrahepatic bile duct demonstrating interesting features is described. A 75-year-old woman with a history of choledocholithotomy presented with acute obstructive suppurative cholangitis. Ultrasonography and computed tomography showed a thickened choledochal wall, with calcification. Percutaneous transhepatic and endoscopic retrograde cholangiography revealed a round filling defect accompanied by an irregular obstruction in the common bile duct. Carcinosarcoma was diagnosed from a protruding lesion in the common bile duct obtained by intraoperative frozen sectioning, and pylorus-preserving pancreatoduodenectomy was performed. Histological examination by light microscopy showed a transition between the carcinomatous and sarcomatous components and positive immunoreactivity for epithelial markers in the sarcomatous component. The patient died of a local recurrence 2 years after the surgery. Polypoid growth and ossification in the tumor could be representative features of carcinosarcoma of the extrahepatic bile duct.

Gastroduodenal artery steal syndrome during liver transplantation: intraoperative diagnosis with Doppler ultrasound and management.

Arterial steal syndrome (ASS) after liver transplantation has been reported. ASS causes arterial hypo-perfusion of the graft liver and devastating consequences. However, the diagnosis tends to be delayed. We present the recognized case of a gastroduodenal artery (GDA) steal syndrome that was diagnosed with intraoperative Doppler ultrasound and treated with GDA ligation during the liver transplantation. The patient had variation of hepatic artery anatomy (low bifurcation of the hepatic artery). Graft liver had the common hepatic artery and aberrant left hepatic artery. Doppler ultrasound of the liver was performed after the arterial reconstruction between the donor common hepatic artery and recipient right hepatic artery. It showed low hepatic arterial flow. There is no backflow bleeding from the donor aberrant left hepatic artery stump. After ligating big GDA, hepatic arterial waveform inside the liver drastically improved and strong backflow bleeding was recognized from the donor left aberrant hepatic artery stump. The current case should show the efficacy of intraoperative Doppler ultrasound of the liver on ASS and alert clinician to ligate GDA to prevent ASS if hepatic arterial flows are suboptimal.

A rare case of gastric lipoma with early gastric cancer.

An 84-year-old man was admitted to our hospital with a 1-month history of epigastralgia. Upper gastrointestinal endoscopy revealed gastric cancer and a gastric submucosal tumor (SMT) on the greater curvature of the gastric body. By endoscopic ultrasonography, SMT was demonstrated as a well-circumscribed, smooth-bordered and hypoechoic mass localized in the submucosal layer. Total gastrectomy was performed. The histology of the resected specimen revealed a gastric lipoma and an early gastric cancer widespread to the surface on the lipoma. Two lesions were present in the same lesion, but not linked. We report a rare case of gastric lipoma complicated with early gastric cancer.