Incidence, risk factors, and management options for portal vein thrombosis after hepatectomy: a 14-year, single-center experience.

BACKGROUND: Portal vein thrombosis (PVT) after hepatectomy is rare; however, it increases mortality and morbidity. Few studies have been conducted that focused on PVT following major hepatectomy. METHODS: Patients who underwent hepatectomy at a single institution were retrospectively reviewed, and risk factors and management options were evaluated. RESULTS: Of the 1,193 patients undergoing hepatectomy, 25 patients developed PVT. Right-sided hepatectomy, caudate lobectomy, splenectomy, and postoperative bile leakage were independent risk factors for PVT following hepatectomy. PVT occurred more frequently after major hepatectomy compared with minor hepatectomy. Increased instability and reduced portal venous flow caused by kinking was the reason for increasing the risk of PVT after right-sided hepatectomy with caudate lobectomy. The new operative procedure, suturing the posterior wall of the portal vein with the anterior wall of the inferior vena cava, was effective for reducing the risk of PVT following right-sided hepatectomy. Operative thrombectomy showed significant benefits for PVT detected within 5 days after hepatectomy. CONCLUSIONS: PVT frequently occurs following major hepatectomy. Urgent operative thrombectomy is strongly recommended for PVT with early detection.

Increased coagulation and suppressed generation of activated protein C in aged mice during intra-abdominal sepsis.

Sepsis is a life-threatening clinical condition that is particularly serious among the elderly who experience considerably higher mortality rates compared with younger patients. Using a sterile endotoxemia model, we previously reported age-dependent mortality in conjunction with enhanced coagulation and insufficient levels of anti-coagulant factor activated protein C (aPC). The purpose of the present study was to further investigate the mechanisms for age-dependent coagulation and aPC insufficiency during experimental sepsis. Intra-abdominal sepsis was induced by cecal ligation and puncture (CLP) using 21 or 16 gauge (G) needles (double-puncture) on young (4 to 6 mo old) and aged (20 to 25 mo old) male C57BL/6 mice. When compared with young mice, aged mice showed significantly increased mortality (92% vs. 28%), systemic inflammation, and coagulation in the lung and kidney after 21G CLP. Young mice with more severe CLP (16G) showed a mortality rate and inflammation equivalent to aged mice with 21G CLP; however, enhanced coagulation and kidney dysfunction were significant only in the aged. In young mice, increased levels of aPC after CLP were coupled with reduced levels of protein C (PC), suggesting the conversion of PC to aPC; however, PC and aPC levels remained unchanged in aged mice, indicating a lack of PC to aPC conversion. Activation of fibrinolysis, determined by plasma d-dimer levels, was similar regardless of age or CLP severity, and plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, showed severity-dependent induction independent of age. These results suggest that enhanced coagulation in aged mice during sepsis is due to dysfunction of the PC activation mechanism.

[Surgical Resection for Mediastinal Lymph Node Metastasis of Combined Hepatocellular and Cholangiocarcinoma--A Case Report].

We report the case of a 77-year-old woman with mediastinal lymph node metastasis of combined hepatocellular and cholangiocarcinoma who was successfully treated with S8 segmentectomy and lymphadenectomy. A hepatic nodule was detected in segment 8 during follow-up computed tomography (CT) after left iliac arterial aneurysm repair. The patient was diagnosed with a hepatocellular carcinoma (HCC), and transcatheter arterial chemoembolization (TACE) was selected for HCC because of the patient's condition. The levels of tumor markers did not change after TACE was performed twice. Therefore, TACE treatment was considered to be ineffective for HCC, and the patient was admitted to our hospital for surgical resection. In addition to the primary lesion, a lymph node with a diameter of 20 mm was detected in the anterior mediastinum using CT and magnetic resonance imaging(MRI). We did not find any other metastases, and therefore, S8 segmentectomy and lymphadenectomy in the anterior mediastinum were performed. Recovery was uneventful, and the patient was discharged from the hospital on postoperative day 12. Based on histopathologic findings, combined hepatocellular and cholangiocarcinoma with mediastinal lymph node metastasis was confirmed. Levels of tumor markers normalized, and the patient survived without recurrence for 6 months.

[A Case of R0 Resection of Locally Advanced Pancreatic Cancer Following Chemoradiation Therapy].

Patients with borderline resectable pancreatic cancer have a poorer prognosis than patients with resectable pancreatic cancer, but some cases treated with neoadjuvant chemoradiation therapy and radical surgery (R0 surgery) show long-term survival. A 72-year-old woman presented with a history of back pain and weight loss. Computed tomography revealed a cancer of the pancreatic body encasing the celiac trunk, common hepatic artery, and portal vein. After neoadjuvant chemotherapy ( S-1) and carbon-ion radiotherapy, the tumor was considered to be resectable. Distal pancreatectomy with en bloc celiac trunk resection (DP-CAR), portal vein resection, and reconstruction was performed. The histopathologic findings showed that the effect of NACRT was gradeⅡa (Evens' classification), and the surgical margins were histologically clear. S-1 was administered again for half a year as postoperative chemotherapy. With post-operative follow-up of 1 year and 1 month after surgery, the patient shows no signs of recurrent disease.

[Two Cases of Pancreatic Neuroendocrine Tumor with Liver Metastases Successfully Treated with Multidisciplinary Therapy including Multiple Surgical Resections].

UNLABELLED: We report 2 cases of pancreatic neuroendocrine tumor with liver metastases successfully treated with multidisciplinary therapy, including multiple surgical resections. Case 1: A 63-year-old man underwent distal pancreatectomy and portal vein resection for a pancreatic body tumor. Histological analysis revealed the tumor was a pancreatic neuroendocrine tumor (p-NET), classified as NET G2. His metachronous liver metastases were treated with lateral sectionectomy and 2 rounds of transcatheter arterial chemoembolization (TACE). He is being treated with everolimus for para-aortic lymph node metastases and is alive 90 months after the primary operation. Case 2: A 64-year-old man underwent distal gastrectomy for a duodenal ulcer and distal pancreatectomy for a pancreatic tumor. The histological diagnosis was gastrinoma classified as NET G2. Hepatectomy (segmentectomy of segment 8 and partial hepatectomy) was performed twice for metachronous liver metastases. Everolimus has been administered for liver and para-aortic lymph node metastases, and the patient is alive 108 months after the primary operation. CONCLUSION: Multidisciplinary treatment should be considered for patients with p-NETs with multiple metastases.

[Surgical Resection of Metachronous Hepatic Metastasis from Pancreatic Acinar Cell Carcinoma after Total Pancreatectomy].

Pancreatic acinar cell carcinoma is rare. There is no consensus on a treatment strategy for metastatic lesions to the liver. We report of a 68-year-old man who received total pancreatectomy for pancreatic acinar cell carcinoma. One year after surgery, abdominal enhanced CT showed a small liver tumor in segment 8. We diagnosed this tumor as hepatic metastasis of pancreatic acinar cell carcinoma, and we resected it via partial liver resection. Pathological studies indicated a metastasis from pancreatic acinar cell carcinoma. The patient has been alive without recurrence for 7 months after the hepatectomy. There is no consensus on surgery for hepatic metastasis of acinar cell carcinoma, but if surgical resection is possible and safe, we consider it an appropriate treatment option.

Tips and tricks of surgical technique for pancreatic cancer: portal vein resection and reconstruction (with videos).

Surgical resection is the only hope for cure in patients with pancreatic cancer. To improve the resectability and achieve better prognosis of this lethal disease, extended resection for pancreatic cancer has been applied. We have performed portal vein resection aggressively for pancreatic cancer with portal vein invasion. We also established a method of portal vein reconstruction using the left renal vein graft for tumors widely extended to the portal vein. Our data show similar survival between patients with portal vein obstruction and those without invasion. We also show that portal vein reconstruction using the left renal vein graft can be performed safely without severe liver damage. With video, we introduce our surgical technique for portal vein resection and reconstruction, especially focusing on the usage of the left renal vein graft, providing several tips for a safe and successful procedure.

[A case of curative resection after downsizing chemotherapy in initially unresectable locally advanced intrahepatic cholangiocarcinoma].

This case report describes an 83-year-old man with intrahepatic cholangiocarcinoma who was referred by a local hospital. Abdominal computed tomography (CT) showed a large tumor in hepatic segments 4, 5, and 8 involving the right hepatic vein and inferior vena cava, which is normally indicative of an unresectable locally advanced tumor. After systemic chemotherapy with gemcitabine and cisplatin, the observed decrease in the level of tumor marker suggested that the cancer was responding to treatment, while radiological findings showed the main tumor shrunk without the presence of distant metastases. Thus, hepatic left trisectionectomy with bile duct resection was performed after portal vein embolization. Pathological examination revealed negative margins (R0). Eighteen months after surgery, the patient is free of disease and shows no signs of recurrence. An initially unresectable, locally advanced biliary tract cancer may be down sized by chemotherapy, which makes radical resection possible, at least in a proportion of patients. This approach provides longer survival and may have a potential for disease eradication as a new multidisciplinary approach for patients with unresectable locally advanced biliary tract cancer.

[Hepatic inferior vena cava resection and vascular prosthesis reconstruction for locally advanced intrahepatic cholangiocarcinoma - a case report].

A 61-year-old woman was referred to our hospital because of jaundice and general itching. Computed tomography (CT) scan demonstrated that the tumor was located in the caudate lobe of the liver with hilar invasion and involved the hepatic inferior vena cava (IVC) and the right renal artery and vein. The patient was diagnosed with locally advanced intrahepatic cholangiocarcinoma, for which she underwent right hemihepatectomy with right caudate lobectomy, portal vein resection, hepatic IVC resection, extrahepatic bile duct resection, and right nephrectomy. IVC was reconstructed using vascular prosthesis by expanded polytetrafluoroethylene (ePTFE)-ringed graft. The patient's postoperative course was uneventful. The patient was treated with gemcitabine for postoperative chemotherapy, and 3 years after the operation, she died due to recurrence resulting from peritoneal dissemination. Although the thrombosis-related vascular prosthesis obstruction had occurred 2 years after the operation, no clinical symptom were noted, such as lower leg edema or renal dysfunction, during the postoperative course. Hepatic IVC prosthesis reconstruction for locally advanced cancer with extensive IVC invasion can be a useful surgical procedure for improving the resection rate and maintaining quality of life (QOL) in such cases.

[Prophylactic portal vein stenting in a patient with local recurrence of cholangiocarcinoma without clinical symptoms of portal vein stenosis - a case report].

A 70-year-old man was diagnosed with local recurrence 1 and half years after pancreatoduodenectomy for extrahepatic cholangiocarcinoma. Progression of the recurrent tumor involved the portal vein, even though the patient had received chemotherapy (gemcitabine). Although no clinical symptoms caused by portal venous stenosis were found at the time, we performed percutaneous transhepatic portal vein stenting to avoid interrupting chemotherapy. Eighteen months after this procedure, the patency of the portal vein stent was well maintained, and the patient was treated with S-1 chemotherapy continuously without any symptoms related to portal venous stenosis reported. Prophylactic portal vein stenting without clinical symptoms of portal vein stenosis is a useful procedure, not only for palliative care but for improving the prognosis of patients with cholangiocarcinoma by continuous chemotherapy.

[A case of main-duct IPMN with multicentric invasive carcinoma].

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas often contains multifocal lesions, and total pancreatectomy is sometimes needed for curative resection. We report here our experience with a case of IPMN with multiple invasive carcinoma foci that was successfully treated with total pancreatectomy. A 66-year-old man had jaundice, and a computed tomography (CT) scan revealed a hypovascular mass in the pancreas head in conjunction with calcification and dilation of the entire main pancreatic duct. He was diagnosed with pancreas head cancer and chronic pancreatitis, and a pancreaticoduodenectomy was planned. Intraoperative pathological examination revealed papillary growth of high grade dysplasia in the main and branch duct epithelium and perineural invasion of the atypical glands. After 2 additional resections, we performed a total pancreatectomy. Pathological findings showed that the pancreas head tumor was an invasive carcinoma derived from main-duct IPMN of the pancreas. It was a mucinous carcinoma with calcification. Moreover, we found other multiple, discontinuous invasive foci in the body and tail of the pancreas which were undetectable by preoperative imaging. This case was highly suggestive for preoperative diagnosis for pancreas tumor and developmental pattern of main-duct IPMN.

Repeat pancreatectomy for pancreatic ductal cancer recurrence in the remnant pancreas after initial pancreatectomy: is it worthwhile?

BACKGROUND: The clinical implications of repeat completion pancreatectomy for recurrent pancreatic cancer in the remnant pancreas after initial pancreatectomy have not been clarified. We retrospectively analyzed our patients and evaluated the clinical implications of repeat pancreatectomy for isolated local recurrence in the remnant pancreas after initial resection for pancreatic cancer. METHODS: One-hundred seventy patients who had recurrence of pancreatic cancer out of 326 patients who had initially undergone resection for pancreatic cancer were included in this study. Sixty-seven of 170 recurrent patients were diagnosed as having isolated local recurrence of pancreatic cancer. Eleven of these 67 patients with isolated local recurrence only in the remnant pancreas underwent repeat pancreatectomy. Characteristics and operative outcomes for these 11 patients with repeat pancreatectomy were analyzed and evaluated in comparison with other recurrent patients. RESULTS: Among 170 patients with recurrence after initial resection for pancreatic cancer, the median survival time was 78.2 and 20.3 months after initial resection, in the repeat pancreatectomy group and the unresectable group, respectively (P < .001), and the 2- and 5-year survival probability rates after initial resection were 91%, and 82% vs 42%, and 13%, respectively. Among 67 patients with isolated local recurrence, the median survival time after repeat resection or diagnosis of recurrence was 25.0 and 9.3 months, and the 2- and 5-year survival probability rates after repeat resection or diagnosis of recurrence were and 61% and 46% vs 19% and 6.2% in the repeat pancreatectomy group and the unresectable group, respectively (P < .01). There was no difference in survivals between the unresectable isolated local recurrence group and the unresectable nonlocal recurrence group. CONCLUSION: Repeat pancreatectomy might bring about beneficial effects on prognosis in selected patients with isolated local recurrence in the remnant pancreas after initial pancreatectomy for pancreatic cancer without increased operative morbidity or mortality.

Cytoskeleton-associated protein 2 is a potential predictive marker for risk of early and extensive recurrence of hepatocellular carcinoma after operative resection.

BACKGROUND: De principe transplantation is an attractive strategy for the treatment of patients with hepatocellular carcinoma (HCC). The most important issue for this strategy is how to predict the risk of early and extensive recurrence. The present study aimed to identify a molecule associated with early and extensive recurrence of HCC after resection. METHODS: Differentially expressed genes were screened by DNA microarray analysis with the use of 12 HCC samples from patients who had different clinical courses based on the timing and extent of recurrence after operative resection. Furthermore, the obtained results were validated in 60 independent samples by quantitative real-time reverse transcription-polymerase chain reaction. Immunohistochemistry was performed to assess gene expression at the protein level. RESULTS: Microarray analysis and quantitative reverse transcription-polymerase chain reaction revealed cytoskeleton-associated protein 2 (CKAP2) as a candidate gene associated with early and extensive recurrence of HCC after resection. This observation was confirmed through examination of independent set samples, in which patients with greater-level CKAP2 mRNA expression exhibited shorter recurrence-free survival. Immunohistochemistry showed CKAP2 protein expression was associated with early (≤3 years) and extensive recurrence (beyond Milan criteria) after operative resection. CONCLUSION: Immunohistochemical CKAP2 expression might be a potential biologic marker for identifying HCC patients at risk of early and extensive recurrence after operative resection.

Protective effects of simultaneous splenectomy on small-for-size liver graft injury in rat liver transplantation.

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small-for-size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)-1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET-1 mRNA and hepatic protein levels of ET-1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET-1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET-1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET-1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET-1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.

Left hepatic trisectionectomy for hepatolithiasis with occluded left and right anterior branches of the portal vein: report of a case.

A 64-year-old male was admitted to a local hospital with epigastric pain. Diagnostic imaging revealed hepatolithiasis in the atrophic left lobe. However, endoscopic intervention was impossible because of the presence of many large stones. He was referred to our hospital for surgical treatment. Enhanced multidetector-row computed tomography revealed that the right posterior portal vein (PV) was branched from the portal trunk as a first-order branch, and the bile duct of segment 3 ran caudally to the umbilical portion of the left PV. Furthermore, the umbilical portion of the left PV, which was located between the dilated bile ducts of segment 2 and segment 3, and also the right anterior PV, was occluded with thrombus. Based on these findings, he underwent left hepatic trisectionectomy. Although the indications for left hepatic trisectionectomy for hepatolithiasis are limited, it is therefore extremely important to determine the most appropriate surgical procedure based on the anatomy and findings of hepatic hilus in individual cases.

Inflammatory cytokine gene expression in mesenteric adipose tissue during acute experimental colitis.

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1ß, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.

Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis.

The severity and mortality rates of acute pancreatitis (AP) are significantly elevated in the elderly population. However, due to a lack of appropriate animal models, the underlying mechanisms for this age-dependent vulnerability remain largely unknown. The purpose of this study was to characterize a murine model of AP, which displays age-associated severity, and to use this model to identify pathophysiologies that are distinctive of the aged with AP. AP was induced in young (4-5 months), middle-aged (12-13 months), and aged (23-25 months) C57BL/6 mice by repeated injection of caerulein, a homologue of the gastrointestinal hormone cholecystokinin. Approximately 10% of aged mice died during AP, while young and middle-aged mice showed no mortality. Although both young and aged mice exhibited early signs of edema and inflammation in the pancreas, kidney, and lung, young mice showed signs of recovery within 24 h, while aged mice exhibited increasingly severe tissue damage and cell death. There was a significant age-dependent increase in pancreatic neutrophil activation and systemic inflammation as assessed by pancreatic myeloperoxidase and plasma interleukin-6 (IL-6) concentration, respectively. Importantly, aged but not young mice with AP showed significantly elevated thrombosis in the lung and kidney as well as a marked increase in plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of the fibrinolytic system. These results demonstrate that aging is associated with increased severity of AP characterized by augmented and prolonged pancreatic inflammation and the presence of multiple extra-pancreatic sequelae including thrombosis.

Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma.

BACKGROUND: Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC. METHODS: We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of FGF19 and FGFR4 to regulate their concentrations. RESULTS: We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (P < 0.05). Univariate and multivariate analyses revealed that the tumor FGF19 mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (P < 0.01, n = 12) and invasion (P < 0.01, n = 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (P < 0.01, n = 12). Inversely, decreasing FGF19 and FGFR4 expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (P < 0.01, n = 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (P < 0.01, n = 29). CONCLUSIONS: FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.