Radiopaque biodegradable stent for duct-to-duct biliary reconstruction in pigs.

BACKGROUND: Biliary stricture is a common cause of morbidity after liver transplantation. We previously developed a duct-to-duct biliary anastomosis technique using a biodegradable stent tube and confirmed the feasibility and safety of biliary stent use. However, the duration and mechanism of biliary stent absorption in the common bile duct remain unclear. MATERIALS AND METHODS: Radiopaque biodegradable biliary stents were created using a copolymer of L-lactide and ε-caprolactone (70: 30) and coated with barium sulfate. Stents were surgically implanted in the common bile duct of 11 pigs. Liver function tests and computed tomography (CT) scans were performed postoperatively, and autopsies were conducted 6 months after biliary stent implantation. RESULTS: After the surgery, all 11 pigs had normal liver function and survived without any significant complications such as biliary leakage. A CT scan at 2 months post-procedure showed that the biliary stents were located in the hilum of the liver. The stents were not visible by CT scan at the 6-month follow-up examination. CONCLUSIONS: The surgical implantation of radiopaque biodegradable biliary stents in biliary surgery represents a new option for duct-to-duct biliary reconstruction. This technique appears to be feasible and safe and is not associated with any significant biliary complications. The advantage of coated biliary stent use is that it may be visualized using abdominal radiography such as CT.

Fatty liver creates a pro-metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells.

Fatty liver (FL) is associated with development of hepatocellular carcinoma (HCC). However, whether FL itself promotes the progression of HCC is unclear. We recently found that hepatic stellate cells (HSCs) were prominently activated in the steatotic liver. Here, we investigated whether steatotic livers promote HCC progression and whether HSCs of steatotic liver are associated with HCC progression. We implanted rat HCC cells into diet-induced steatotic livers in rats via portal vein injection. Thereafter, HSCs and HCC cells were co-implanted subcutaneously into nude rats. Migration and proliferation of HCC cells were measured, and activation of ERK and Akt in these cells was determined by western blotting. Chemokines secreted from HSCs and HCC cells were also evaluated by ELISA. Steatotic livers significantly promoted HCC metastasis compared with non-steatotic livers. Additionally, co-implantation of HCC cells with HSCs from steatotic livers produced significantly larger tumors in recipient rats as compared to those induced by HCC cells co-implanted with HSCs from normal livers (NLs). HSCs isolated from steatotic livers, compared with HSCs isolated from NLs, secreted greater amounts of interleukin-1α, vascular endothelial growth factor, and transforming growth factor-ß. These cytokines may enhance the proliferation and migration of HCC cells by increasing the phosphorylation of ERK and Akt in HCC cells. Moreover, we noted that the Rho-kinase inhibitor deactivated activated HSCs and attenuated HCC progression. In conclusion, the rat steatotic liver microenvironment favors HCC metastasis, and this effect appears to be promoted by activated HSCs in the steatotic liver.

Rho-kinase inhibitor targeting the liver prevents ischemia/reperfusion injury in the steatotic liver without major systemic adversity in rats.

Rho-kinase (ROCK) inhibitors improve liver blood flow after ischemia/reperfusion (IR) injury, especially in the setting of steatosis, by decreasing the resistance of intrahepatic microcirculation through hepatic stellate cell (HSC) relaxation. However, the systemic administration of ROCK inhibitors causes severe hypotension; therefore, liver-specific ROCK inhibition is required. Here, we tested vitamin A (VA)-coupled liposomes carrying the ROCK inhibitor Y-27632 for targeted HSCs in steatotic rats. Rat livers with steatosis induced by a choline-deficient diet were subjected to IR injury. The delivery site and effect of the ROCK inhibitor were investigated. After liposomal Y-27632 injection, the survival rate after IR, the liver blood flow, the portal perfused pressure, and the hemodynamics were investigated. Immunohistochemical studies showed VA-coupled liposome accumulation in livers. Liposomal Y-27632 was 100-fold more effective in inhibiting HSC activation than free Y-27632. Liposomal Y-27632 improved the survival rate after IR injury, the liver blood flow, and the portal perfusion pressure without severe hypotension. In contrast, untargeted Y-27632 elicited severe systemic hypotension. We conclude that VA-coupled liposomes carrying the ROCK inhibitor yield enhanced drug accumulation in the liver and thus mitigate IR injury in the steatotic liver and reduce major systemic adversity.

Administration of antithrombin III attenuates posthepatectomy liver failure in hepatocellular carcinoma.

BACKGROUND/AIMS: Coagulopathy can cause disseminated intravascular coagulation and posthepatectomy liver failure. Posthepatectomy liver failure predicts a poor prognosis after hepatectomy for hepatocellular carcinoma. Although antithrombin III reduces hypercoagulation, the impact of postoperative antithrombin III administration remains unknown. The aim of this study was to determine whether postoperative antithrombin III administration protects against the development of coagulation disorders. METHODS: Data from 164 patients who received antithrombin III and 169 who did following curative hepatectomy for hepatocellular carcinoma were retrospectively collected and analyzed. To overcome bias due to different distributions of covariates for the two groups, a one-to-one match was created using propensity score analysis. After matching, patient outcomes were analyzed. RESULTS: A multivariate analysis of the whole group revealed that antithrombin III activity of <50% on postoperative day 1 was an independent risk factor for posthepatectomy liver failure. After one-to-one matching, the rate of posthepatectomy liver failure was significantly lower in the AT-III-treated group than in the non-AT-III-treated group (16.3% (7/43) vs. 44.2% (19/43), p < 0.01). CONCLUSIONS: Antithrombin III may attenuate posthepatectomy liver failure in hepatocellular carcinoma, possibly by suppressing coagulopathy.

Clinicopathological features of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease.

PURPOSE: The incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD) is increasing. However, the clinicopathological features of HCC in these patients are little known. Thus, we investigated the differences in the clinical and pathological characteristics of HCC between NAFLD patients and hepatitis-C virus (HCV) patients. METHODS: Data from 21 HCC patients with NAFLD and 645 HCC patients with HCV who underwent curative hepatectomy were collected and analyzed. To overcome bias due to differences in the distribution of covariates between the two groups, propensity score matching was performed, and clinicopathological features and outcomes were compared. RESULTS: In propensity score analysis, the rate of microscopic vascular invasion was significantly higher in the NAFLD group than in the HCV group (65 vs. 30%; P = 0.027). However, overall survival and disease-free survival did not differ between the two matched groups. CONCLUSIONS: NAFLD may have permissive microenvironment for HCC progression.

Ischemia­reperfusion injury in patients with fatty liver and the clinical impact of steatotic liver on hepatic surgery.

Hepatic steatosis is one of the most common hepatic disorders in developed countries. The epidemic of obesity in developed countries has increased with its attendant complications, including metabolic syndrome and non-alcoholic fatty liver disease. Steatotic livers are particularly vulnerable to ischemia/reperfusion injury, resulting in an increased risk of postoperative morbidity and mortality after liver surgery, including liver transplantation. There is growing understanding of the molecular and cellular mechanisms and therapeutic approaches for treating ischemia/reperfusion injury in patients with steatotic livers. This review discusses the mechanisms underlying the susceptibility of steatotic livers to ischemia/reperfusion injuries, such as mitochondrial dysfunction and signal transduction alterations, and summarizes the clinical impact of steatotic livers in the setting of hepatic resection and liver transplantation. This review also describes potential therapeutic approaches, such as ischemic and pharmacological preconditioning, to prevent ischemia/reperfusion injury in patients with steatotic livers. Other approaches, including machine perfusion, are also under clinical investigation; however, many pharmacological approaches developed through basic research are not yet suitable for clinical application.

Desmoid tumor occurrence following gastric cancer surgery: A report of two cases.

INTRODUCTION AND IMPORTANCE: While rare, desmoid tumors can develop after abdominal surgery and are difficult to differentiate from recurrent tumors following cancer resection. In this report, we describe two cases of desmoid tumors that occurred following gastric cancer procedures and were successfully treated with surgical resection. CASE PRESENTATION: In Case 1, a 77-year-old woman underwent open distal gastrectomy for gastric cancer followed by Roux-en-Y reconstruction. The pathological diagnosis was stage IIB T3N1M0 disease. Four years postsurgically, computed tomography (CT) revealed a 2.4 cm tumor lesion in the upper abdomen. Desmoid tumor was the most suspected tumor, for which a resection with partial resection of the jejunum was performed. In case 2, a 60-year-old man underwent open distal gastrectomy for gastric cancer and Billroth I reconstruction; the pathological diagnosis was T1aN0M0 stage IA. Two years later, CT revealed a 4.0 cm tumor lesion in the upper abdomen. As in Case 1, desmoid tumor was most suspected, a tumor resection with partial resection of the jejunum was performed. Based on the pathological findings, the tumors were diagnosed as desmoid tumor. There had been no recurrence of either gastric cancer or the desmoid tumor in both cases. CLINICAL DISCUSSION: Although active surveillance has been recommended for desmoid tumors recently, surgical resection is appropriate when recurrence cannot be ruled out. CONCLUSIONS: Desmoid tumors should be included in the differential diagnosis when intra-abdominal tumors occur after surgery for gastric cancer. Complete resection with adequate margins can prevent desmoid recurrence.

Surgical resection of a retroperitoneal liposarcoma producing insulin-like growth factor II: a case report.

BACKGROUND: Tumor-produced high molecular weight insulin-like growth factor-II (big insulin-like growth factor-II) is considered to cause non-islet cell tumor hypoglycemia. This paper presents a case of surgically resected retroperitoneal liposarcoma that produced big insulin-like growth factor-II. CASE PRESENTATION: Here, we report the case of a 62-year-old woman who presented with an abdominal mass and hypoglycemia. Non-islet cell tumor hypoglycemia due to retroperitoneal liposarcoma was suspected. After complete resection of the tumor, the patient's hypoglycemia improved and big insulin-like growth factor-II disappeared in the molecular weight analysis of serum insulin-like growth factor-II by western blotting. The patient had no tumor recurrence or reappearance of hypoglycemia 16 months after the operation without any adjuvant therapy. CONCLUSIONS: Although insulin-like growth factor-II-producing tumors are generally large and difficult to operate on, surgical resection is currently the most effective and only treatment; thus, it is essential to attempt resection aggressively.

Prognostic significance of antithrombin III levels for outcomes in patients with hepatocellular carcinoma after curative hepatectomy.

BACKGROUND: Although several studies have shown that serum antithrombin III (ATIII) has anti-inflammatory effects, the prognostic value of ATIII in HCC is unknown. We investigated the influence of preoperative ATIII levels on the outcome of patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: Data from 440 patients (314 patients with ATIII ≥ 70 % and 126 patients with ATIII <70 %) who underwent curative hepatectomy for HCC were retrospectively collected and analyzed. To overcome bias due to the different distribution of covariates for the 2 groups, propensity score matching was performed on the patients, and outcomes were compared. RESULTS: The propensity score analysis revealed that 65 patients with ATIII of ≥ 70 % (group 1) and 65 patients with ATIII of <70 % (group 2) had the same preoperative and operative characteristics (excluding the ATIII level). The overall survival rate and the disease-free survival rate was significantly higher in group 1 than in group 2 (P = 0.005 and 0.011, respectively). Multivariate analysis showed that ATIII was a significant favorable factor for overall survival and disease-free survival of patients with HCC after curative hepatectomy. CONCLUSIONS: The prognosis of patients with HCC was found to be associated with preoperative antithrombin III levels. ATIII may be useful for predicting outcomes of patients with HCC after curative hepatectomy.

Changes in Physical Function and Effects on QOL in Patients after Pancreatic Cancer Surgery.

This study examined the changes in physical function and quality of life (QOL) of postoperative patients with pancreatic cancer for 3 months after surgery and examined the factors affecting the QOL at the 3 months after surgery. METHODS: This study comprised 32 pancreatic cancer patients who underwent surgery at our hospital. Among these patients, 20 patients for whom data was measured before surgery to 3 months after surgery were selected for statistical analyses: 8 males and 12 females, 69.8 ± 7.4 years. The preoperative and postoperative rehabilitation was given to patients under the guidance of a physiotherapist. Nutritional status, body composition, physical function, gait assessments, and QOL were investigated. RESULTS: Body weight, body fat mass, body fat percentage, body mass index (BMI), and muscle mass significantly decreased 3 months after surgery compared with their respective preoperative values. The mean grip strength at the time of 3 months after the surgery had decreased significantly from 27.3 kg to 24.5 kg. The mean skeletal muscle mass index (SMI) had decreased significantly from 6.3 kg before surgery to 5.9 kg after the surgery. The QOL scores for global health status, physical, and role showed significant decreases 2 weeks after surgery compared with the respective preoperative scores. Significant improvements in these scores were observed 3 months after surgery compared with the respective scores 2 weeks after surgery. Physical function assessments after surgery were associated with QOL 3 months after surgery. CONCLUSION: Recovery of patients after pancreatic cancer surgery in body weight, BMI, body fat percentage, body fat percentage, muscle mass, SMI, and grip strength was not sufficient at the time of 3 months after surgery. It has been observed that physical function of patients has affected the improvement of QOL.

Rare pancreatic metastasis of undifferentiated pleomorphic sarcoma originating from the pelvis: A case report.

INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) is a reclassification of malignant fibrous histiocytoma by the World Health Organization in 2002. UPS, the most common soft tissue sarcoma reported in adults, mostly recurs as lung disease. Pancreatic metastasis of UPS is extremely rare. We present a rare case of pelvic UPS with pancreatic metastasis. PRESENTATION OF CASE: A 69-year-old man was identified as having mediastinal lymphadenopathy on follow-up computed tomography (CT), 2 years after undergoing surgery for gastric adenocarcinoma (pT4aN3M0/IIIC). Subsequent positron emission tomography-CT (PET/CT) indicated pelvic lesions and magnetic resonance imaging (MRI) showed multiple tumors of the left pubis and femur. Histopathology of diagnostic thoracoscopic lymph node dissection and CT-guided needle biopsy of the left pubic lesion showed UPS. Systemic chemotherapy and targeted molecular therapy reduced multiple pelvic and metastatic tumors. Left pubic primary lesion contraction was achieved with intensity-modulated radiation therapy. CT performed 4 years after treatment initiation showed a 40-mm pancreatic head mass. Lesions other than the pancreatic tumor were in remission, and a pancreatoduodenectomy was performed. Histological analysis confirmed pancreatic metastasis of anaplastic pleomorphic sarcoma. DISCUSSION: Reports of pelvic UPS with pancreatic metastasis, as that of the present case, are extremely rare. UPS is malignant potential tumor, and complete excision is the first treatment option, while the usefulness of chemotherapy or radiation therapy remains uncertain. CONCLUSIONS: Complete resection is vital for local control in pancreatic metastasis of UPS. Sites of recurrence are rare; hence, patients must be carefully followed up.

Viability of Airborne Tumor Cells during Excision by Ultrasonic Device.

Background. Laparoscopic surgery has become more widely used, but peritoneal dissemination and port-site metastasis have been reported to occur in these surgeries. One reason for these problems is the ultrasonically activated scalpel (UAS) used for laparoscopic surgery. This study aimed to investigate the viability of airborne cells released during cancer dissection using a UAS. Methods. Flank tumors measuring about 2 cm were induced in male NOD-Cg-Rag1tm1MomIL2rgtm1wjl/SzJ mice by subcutaneous injection of 1 × 106 HepG2 cells. Dissection was performed with UAS (in high or low power modes) and PowerStar bipolar scissors. The mist of released tissue was collected in cell culture medium. The viability of the cellular material was assessed with trypan blue exclusion cell counting, counting after immunofluorescence staining, and flow cytometric analysis. Results. Large quantities of cellular debris were trapped in the tissue dispersed by both devices. In all experiments, there were significantly more viable cells produced by the UAS in high power mode. By using suction at the excision site, the number of viable cancer cells was reduced. Conclusions. This study demonstrates that viable cancer cells can be released into the nearby environment during tumor ablation with a UAS.

Application of endobronchial ultrasonography in laparoscopic liver segmentectomy in an animal model.

INTRODUCTION: This study investigated whether laparoscopic ultrasound-guided segment staining and real-time ultrasound-guided hepatectomy, with endobronchial ultrasonography equipped with a guide sheath, would be useful for laparoscopic liver segmentectomy in a porcine model. MATERIAL AND SURGICAL TECHNIQUE: The abdominal cavity (in two pigs) was reached via a 12-mm umbilical trocar. An artificial tumor was created by radiofrequency ablation within the intended resection area. Portal vein puncture and staining were performed by the endobronchial ultrasonography-guided method. The targeted portal branch was successfully visualized and punctured with a needle through an equipped guide sheath. After targeted segment staining, the liver parenchyma was resected with a bipolar energy device; the regional Glisson's sheath was ligated and cut, and a surgical specimen was extracted. Real-time endobronchial ultrasonography from the cut surface provided information vital for preserving the surgical margin. All procedures were performed laparoscopically. DISCUSSION: This study demonstrated the technical feasibility of laparoscopic ultrasound-guided portal vein staining and safe surgical resection during laparoscopic liver segmentectomy.

A Low-Grade Fibromyxoid Sarcoma of the Internal Abdominal Oblique Muscle.

A low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor, with a benign histologic appearance but malignant behavior. This report describes a 74-year-old man with an internal abdominal oblique muscle mass. The tumor appeared as a well-defined ovoid mass on computed tomography, with mild uptake on fluorine-18-fluorodeoxyglucose positron-emission tomography images. Radical resection with wide safe margins was performed. Histologically, the tumor was composed of spindle-shaped cells in a whorled growth pattern, with alternating fibrous and myxoid stroma. MUC4 expression, a highly sensitive and specific immunohistochemical marker for LGFMS, was detected. Therefore, we diagnosed the tumor as LGFMS. At the 3-month follow-up, there was no sign of recurrence or metastasis. We report the first case of LGFMS arising from the internal abdominal oblique muscle.

Acute acalculous cholecystitis due to breast cancer metastasis to the cystic duct.

BACKGROUND: Acute acalculous cholecystitis (AAC) is a relatively rare disorder of the gallbladder. Breast cancer recurrence more than 10 years after curative surgery is also infrequent. CASE PRESENTATION: Here, we report a case of a 59-year-old woman who presented with right flank pain. Her medical history included a lumpectomy for cancer of the left breast 12 years prior. Laboratory tests showed a severe inflammatory reaction and mild liver function abnormalities. Ultrasonography and computed tomography revealed an enlarged gallbladder and inflammation of the surrounding tissues; however, no gallstone was present. She was diagnosed with AAC. We performed an emergency laparoscopic cholecystectomy, and histopathological examination revealed a poorly differentiated adenocarcinoma in the cystic duct. Both metastatic and primary tumor cells were positive for estrogen and progesterone receptors on immunohistochemistry. The final pathological diagnosis was acute cholecystitis due to breast cancer metastasis to the cystic duct. CONCLUSION: Although AAC secondary to metastatic breast cancer is rare, it should be included in the differential diagnosis for abdominal pain in patients with a previous history of breast cancer.

Hepatocellular carcinoma and focal nodular hyperplasia of the liver in a glycogen storage disease patient.

Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.