Preoperative Chemotherapy Followed by Hepatectomy for Potentially Resectable UICC7 Stage IIIA, IIIB Hepatocellular Carcinoma; A Phase II Clinical Trial.

BACKGROUND: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. AIM: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. DISCUSSION: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

Prognostic Factors for Distal Bile Duct Carcinoma After Surgery.

BACKGROUND: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data.

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

Impact of Interferon on the Prognosis of Hepatitis C Virus-Related Hepatocellular Carcinoma Patients with a Sustained Virological Response -An Additional Comparison Between Preoperative and Postoperative Sustained Virological Response.

BACKGROUND: Several studies have reported that interferon (IFN) therapy improves the prognosis of patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), especially for patients who have achieved a sustained virological response (SVR). We retrospectively evaluated the clinicopathological outcomes of patients who acquired an SVR through IFN therapy pre- or post-hepatectomy for treatment naïve HCC. METHOD: Among the 305 HCV-related HCC patients entered in this study, 59 patients (SVR group) achieved an SVR after IFN therapy and received hepatectomy either after or before achieving an SVR (n=36 and n=23, respectively), while the remaining 179 patients (control group) did not receive IFN therapy, or did not achieve an SVR through IFN therapy (n=67). RESULTS: In the SVR group, the overall survival (OS) and disease-free survival (DFS) rates were significantly higher than in the control group. We evaluated the prognosis of patients with an SVR achieved pre- or post-hepatectomy separately. There were no significant differences in OS and DFS. CONCLUSION: This result suggests that the prognosis of naïve HCC may be improved by additional INF therapy to achieve SVR status after hepatectomy.

Fatty Liver Does Not Increase the Risk of Postoperative Liver Damage Following Hepatectomy.

BACKGROUND/AIM: The number of patients with fatty liver due to alcohol consumption, metabolic syndrome, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis is increasing. Since there is no consensus on the risk of hepatectomy for patients with fatty liver, this study examined the clinical outcomes of hepatectomy for fatty liver patients via evaluation of transaminase. PATIENTS AND METHODS: Patients (n=164) who underwent hepatectomy for primary liver tumors from January 2014 to March 2019 were included in the study. Patients were divided into steatohepatitis (n=19), steatosis (n=20), and control (n=30) groups. Serum values of aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TB), prothrombin time (PT), white blood cells, and platelets were compared before and immediately after surgery, and on postoperative days 1-5, 7, and 10. And their rates of change were compared using the preoperative value as a reference value. RESULTS: Overall, AST and ALT elevation rates were higher in the control group than in the steatosis and steatohepatitis groups from postoperative days 2-7. There was no difference in postoperative hepatic dysfunction between the steatosis and steatohepatitis groups. Univariate analysis revealed significant differences in liver stiffness, operative time, mobilization, and Pringle time. Multivariate analysis indicated low liver stiffness and longer Pringle time as independent risk factors. Postoperative change in TB, PT, and albumin levels did not differ between the groups. There was no difference in postoperative complications and hospital stay between the groups. CONCLUSION: Fatty liver does not increase the risk of postoperative liver damage following hepatectomy.

Hematogenous Dissemination of Tumor Cells in Hepatocellular Carcinoma: Comparing Anterior and Non-anterior Approach Hepatectomy.

BACKGROUND/AIM: Studies have indicated that liver mobilization during hepatectomy could cause the dissemination of tumor cells. However, the data are still limited in terms of the relationship between circulating tumor cells (CTCs) and surgical procedures. PATIENTS AND METHODS: Fifteen patients who underwent hepatectomy for primary hepatocellular carcinoma (HCC) were included in the study. Blood samples were collected from the portal vein, central vein, and peripheral artery at three time points, namely, before mobilization (BM) of the liver, during transection (DT) of parenchyma, and after resection (AR) of the tumor. To detect CTCs, a real-time PCR assay was performed using primers for the epithelial cell adhesion molecule, cytokeratin 18, and glypican 3. Patients were divided into anterior approach (AA) and non-AA (NA) groups. In the AA group, patients underwent an initial hilar vascular dissection followed by a liver hanging maneuver during transection. RESULTS: Seven patients were allocated to the AA group, and eight to the NA group. In the NA group, CTC levels in the portal vein were significantly increased at DT and AR compared to BM. In cases with large HCC (>70 mm), CTC levels in central venous blood were significantly increased at DT and AR in the NA group. CONCLUSION: The AA liver resection technique may minimize CTC dissemination, improving the prognosis of patients with HCC.

Assessing the incidence of complications and malignancies in the long-term management of benign biliary strictures with a percutaneous transhepatic drain.

ABSTRACT: Percutaneous drainage catheters (PDCs) are required for the management of benign biliary strictures refractory to first-line endoscopic treatment. While biliary patency after PDC placement exceeds 75%, long-term catheterization is occasionally necessary. In this article, we assess the outcomes of patients at our institution who required long-term PDC placement.A single-institution retrospective analysis was performed on patients who required a PDC for 10 years or longer for the management of a benign biliary stricture. The primary outcome was uncomplicated drain management without infection or complication. Drain replacement was performed every 4 to 12 weeks as an outpatient procedure.Nine patients (three males and six females; age range of 48-96 years) required a long-term PDC; eight patients required the long-term PDC for an anastomotic stricture and one for iatrogenic bile duct stenosis. A long-term PDC was required for residual stenosis or patient refusal. Drain placement ranged from 157 to 408 months. In seven patients, intrahepatic stones developed, while in one patient each, intrahepatic cholangiocarcinoma or hepatocellular carcinoma occurred.Long-term PDC has a high rate of complications; therefore, to avoid the need for using long-term placement, careful observation or early surgical interventions are required.

Predictive Factors for Local Recurrence after Intraoperative Microwave Ablation for Colorectal Liver Metastases.

This study aimed to clarify local recurrence (LR) predictive factors following intraoperative microwave ablation (MWA) for colorectal liver metastases. The data from 195 patients with 1392 CRLM lesions, who were preoperatively diagnosed by gadolinium-enhanced MRI with diffusion-weighted imaging and dynamic CT and treated with intraoperative MWA (2450 MHz) with or without hepatectomy, from January 2005 to December 2019, were retrospectively reviewed and analyzed using logistic regression. In addition, the margins were measured on contrast-enhanced CT 6 weeks post-ablation. Overall, 1066 lesions were ablated. The LRs occurred in 44 lesions (4.1%) among 39 patients (20.0%). The multivariate analysis per patient showed that tumor size > 20 mm and ablation margin < 5 mm were significant predictors for LR. Furthermore, multivariate analysis per lesion revealed that segments 1, 7, and 8 and tumor size > 15 mm, ablation margin < 5 mm, tumor size > 20 mm, and proximity to the Glisson were significant LR predictors. Finally, the outcome of this study may help determine indications for MWA.

Hepatic Epithelioid Hemangioendothelioma Presenting Synchronously with Hepatocellular Carcinoma.

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor with unknown pathogenesis. Herein, we report a case of a hepatic EHE presenting synchronously with a hepatocellular carcinoma (HCC). To the best of our knowledge, this is the second case report of synchronous hepatic EHE and HCC. An 84-year-old man presented with back pain. During examination, a tumor in liver segment 3 was coincidentally detected. Tumor marker (carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II) levels were elevated. Contrast-enhanced computed tomography revealed perinodular enhancement in the arterial and portal phases. Another tumor was detected in liver segment 2, which was homogeneously enhanced in the arterial phase, followed by washout in the portal and late phases. Based on these imaging findings, we diagnosed the tumor in segment 3 as a solitary cholangiocellular carcinoma and the tumor in segment 2 as a solitary HCC. Lateral sectionectomy of the liver was performed. Microscopically, spindle-shaped and epithelioid cells were present in the tumor in segment 3. On immunohistochemistry, the tumor cells were positive for CD31 and CD34, focally positive for D2-40, and negative for AE1/AE3. Therefore, the tumor in segment 3 was ultimately diagnosed as an EHE and the tumor in segment 2 as a well-differentiated HCC. Preoperative diagnosis of EHE is difficult owing to the lack of specific findings. Intratumoral calcification, halo sign, and lollipop sign are occasionally found in EHE and are useful imaging findings for diagnosis. Clinical behavior is unpredictable, ranging from indolent growth to rapid progression. Clinical or pathological predictors of the course of EHE are urgently required.

Laparoscopic left hepatectomy for a patient with intrahepatic cholangiocarcinoma metastasis in the falciform ligament: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is primary cancer of the liver with poor prognosis because of its high potential for recurrence and metastasis. We experienced a rare case of ICC with hematogenous metastasis to the falciform ligament. We aimed to clarify the route of metastasis to the mesentery by increasing the accuracy of preoperative imaging and establish a hepatectomy to control cancer. CASE PRESENTATION: An 85-year-old woman was referred to our hospital for a detailed study of progressively increasing liver tumors. She had no subjective symptoms. Her medical history showed hypertension, aneurysm clipping for cerebral hemorrhage, and gallstones. A detailed physical examination and laboratory data evaluation included tumor markers but did not demonstrate any abnormalities. On computed tomography scan, contrast-enhanced ultrasound, and magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid, the tumor appeared to be located in liver segment IV, protruding outside the liver. It appeared to contain two distinct components; we suspected ICC in the intrahepatic tumor component. Laparoscopic observation revealed that the extrahepatic lesion was an intra-falciform ligament mass; laparoscopic left hepatectomy was performed. Microscopically, the main tumor in segment IV was 15 mm in diameter and was diagnosed as moderately and poorly differentiated ICC. The tumor of the intra-falciform ligament was not continuous with the main intrahepatic nodule and was also diagnosed as ICC with extensive necrosis. There were no infiltrates in the round ligament of the liver, and several tumor thrombi were found in the small veins of the falciform ligament. CONCLUSIONS: To date, there have been a few reports of metastases of primary liver cancer to the falciform ligament. At the time of preoperative imaging and pathological diagnosis, this case was suggestive of considering that the malignant liver tumor might be suspected of metastasizing to the falciform ligament. Our case improves awareness of this pathology, which can be useful in the future when encountered by hepatic specialists and surgeons.

Successful nonoperative management by endoscopic and percutaneous drainage for penetrating pancreatic duct injury: a case report.

BACKGROUND: Pancreatic trauma is a rare condition with a wide presentation, ranging from hematoma or laceration without main pancreatic duct involvement, to massive destruction of the pancreatic head. The optimal diagnosis of pancreatic trauma and its management approaches are still under debate. The East Association of Surgery for Trauma (EAST) guidelines recommend operative management for high-grade pancreatic trauma; however, several reports have reported successful outcomes with nonoperative management (NOM) for grade III/IV pancreatic injuries. Herein, we report a case of grade IV pancreatic injury that was nonoperatively managed through endoscopic and percutaneous drainage. CASE PRESENTATION: A 47-year-old Japanese man was stabbed in the back with a knife; upon blood examination, both serum amylase and lipase levels were within normal limits. Contrast-enhanced computed tomography (CT) showed extravasation of the contrast medium around the pancreatic head and a hematoma behind the pancreas. Abdominal arterial angiography revealed a pseudo aneurysm in the inferior pancreatoduodenal artery, as well as extravasation of the contrast medium in that artery; coil embolization was thus performed. On day 12, CT revealed a wedge-shaped, low-density area in the pancreatic head, as well as consecutive pseudocysts behind the pancreas; thereafter, percutaneous drainage was performed via the stab wound. On day 22, contrast radiography through the percutaneous drain revealed the proximal and distal parts of the main pancreatic duct. The injury was thus diagnosed as a grade IV pancreatic injury based on the American Association for the Surgery of Trauma guidelines. On day 26, an endoscopic nasopancreatic drainage tube was inserted across the disruption; on day 38, contrast-enhanced CT showed a marked reduction in the fluid collection. Finally, on day 61, the patient was discharged. CONCLUSIONS: Although the EAST guidelines recommend operative treatment for high-grade pancreatic trauma, NOM with appropriate drainage by endoscopic and/or percutaneous approaches may be a promising treatment for grade III or IV trauma.

Laparoscopic Liver Resection Using a Silicone Band Retraction Method (With Video).

BACKGROUND: The success of laparoscopic liver resection (LLR) depends on stable and full exposure of the parenchymal transection plane. We evaluated the efficacy of LLR using a silicone band retraction method for lesions in the anterolateral and posterosuperior segments. METHODS: We retrospectively analyzed 189 consecutive patients who had undergone LLR in our hospital between July 2010 and July 2020. They were divided into 2 groups according to whether LLR was performed before (conventional group; n=64) or after (silicone band group; n=125) the introduction of the silicone band retraction method. RESULTS: The silicone band group demonstrated significantly less blood loss than that by the conventional group. The mean operative time and the hospital stay in the silicone band group were obviously shorter than that in the conventional group. The open conversion rate and the major complication rate were significantly lower in the silicone band group than that in the conventional group. CONCLUSION: The silicone band retraction method is a useful approach that results in a safe LLR.

[Laparoscopic Extirpation of Peritoneal Dissemination of Hepatocellular Carcinoma Using ICG Imaging].

A 71-year-old man who underwent laparoscopic partial liver resection for local recurrence hepatocellular carcinoma (HCC)in segment 4 one year after percutaneous radiofrequency ablation(RFA)for HCC. About 3 years after treatment, the patient showed elevation of serum level of tumor marker and a mass lesion in the round ligament on CT and EOB-MRI. We made a diagnosis of peritoneal dissemination of HCC. Laparoscopic extirpation of peritoneal dissemination using indocyanine green(ICG)imaging was performed and no other tumors were observed in the peritoneal cavity. A lesion was diagnosed as peritoneal dissemination of HCC, and postoperative course was uneventful. This patient underwent repeated RFA and partial resection for recurrence of HCC. The patient was died for intrahepatic multiple recurrence of HCC without peritoneal dissemination 25 months after extirpation of peritoneal dissemination. In the field of hepatobiliary surgery, ICG imaging can be used for the intraoperative real-time visualization of hepatic malignancies. The ICG imaging is restricted to detection of fluorescence for liver tumors 5-10 mm from the liver surface. In the detection of peritoneal dissemination, however, there are no such limitations. Laparoscopic extirpation using ICG imaging is useful for the detection of peritoneal dissemination of HCC and may improve the prognosis in selected patients.

Quercetin Suppresses Proliferation of Liver Cancer Cell Lines In Vitro.

BACKGROUND/AIM: We investigated the anti-proliferative effect of quercetin on liver cancer cell lines. MATERIALS AND METHODS: Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 µM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin. RESULTS: The addition of quercetin resulted in a dose- and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle. CONCLUSION: Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.

[A Case of Pancreatoduodenectomy for Pancreatic Head Cancer with Invasion to the Hepatic Artery from the Pancreatic Arcade].

This case pertained a 53-year-old man who underwent nab-PTX plus GEM therapy for BR-A pancreatic head cancer. He achieved a partial response and underwent pancreatoduodenectomy. Dynamic CT showed blockage of the original common hepatic artery branching from the celiac artery. Hepatic blood flow was maintained by a pancreatic arcade branching from the superior mesenteric artery which ran along the ventral side of the pancreatic head. The cancer had invaded the same location; therefore, the hepatic artery and portal vein were both resected and reconstructed. The patient had no complications, such as postoperative pancreatic fistula, and was discharged 45 days postoperatively. Currently(5 months postoperatively), postoperative S-1-based adjuvant chemotherapy is being administered, and the patient had a recurrence-free survival.

Differences in the immunosurveillance pattern associated with DNA mismatch repair status between right-sided and left-sided colorectal cancer.

Tumor location and immunity play important roles in the progression of colorectal cancer (CRC). This study aimed to investigate the differences in the immunosurveillance pattern between right- and left-sided CRC and analyze their association with clinicopathologic features, including mismatch repair (MMR) status. We included surgically resected stage II/III CRC cases and evaluated the immunohistochemical findings of HLA class I, HLA class II, programmed cell death-ligand 1 (PD-L1), PD-1, CTLA-4, CD3, CD4, CD8, TIA-1, T-bet, GATA3, RORγT, Foxp3, and CD163. A total of 117 patients were included in the analyses; of these, 30 and 87 had right- and left-sided cancer, respectively. Tumor immunity varied according to the tumor location in the overall cohort. Analysis of the tumors excluding those with DNA mismatch repair (MMR) deficiency also revealed that tumor immunity differed according to the tumor location. In right-sided colon cancer (CC), high expression of Foxp3 (P = .0055) and TIA-1 (P = .0396) were associated with significantly better disease-free survival (DFS). High CD8 (P = .0808) and CD3 (P = .0863) expression tended to have better DFS. Furthermore, in left-sided CRC, only high PD-L1 expression in the stroma (P = .0426) was associated with better DFS. In multivariate analysis, high Foxp3 expression in right-sided CC was an independent prognostic factor for DFS (hazard ratio, 7.6445; 95% confidence interval, 1.2091-150.35; P = .0284). In conclusion, the immunosurveillance pattern differs between right- and left-sided CRC, even after adjusting for MMR deficiency.

A case of reactive lymphoid hyperplasia of the liver in a patient with autoimmune hepatitis.

BACKGROUND: Reactive lymphoid hyperplasia (RLH) of the liver is a benign disorder. It is usually observed in the skin, orbit, thyroid, lung, breast, or gastrointestinal tract, but rarely in the liver. Since the first report of RLH of the liver in 1981, only 75 cases have been described in the past literature. Herein, we report a case of RLH of the liver in a patient with autoimmune hepatitis (AIH), which was misdiagnosed as hepatocellular carcinoma (HCC) preoperatively and resected laparoscopically. CASE PRESENTATION: A 43-year-old Japanese woman with autoimmune hepatitis was followed up for 5 years. During her medical checkup, a hypoechoic nodule in segment 6 of the liver was detected. The nodule had been gradually increasing in size for 4 years. Abdominal ultrasound (US) revealed a round, hypoechoic nodule, 12 mm in diameter. Contrast-enhanced computed tomography (CT) demonstrated that the nodule was slightly enhanced in the arterial dominant phase, followed by perinodular enhancement in the portal and late phases. A magnetic resonance imaging (MRI) scan showed low signal intensity on the T1-weighted image (T1WI) and slightly high signal intensity on the T2-weighted image (T2WI). The findings of the Gd-EOB-DTPA-enhanced MRI were similar to those of contrast-enhanced CT. Tumor markers were all within the normal range. The preoperative diagnosis was HCC and a laparoscopic right posterior sectionectomy was performed. Pathological examination revealed that the nodular lesion was infiltrated by small lymphocytes and plasma cells, and germinal centers were present. Immunohistochemistry was positive for B cell and T cell markers, indicating polyclonality. The final diagnosis was RLH of the liver. CONCLUSIONS: The pathogenesis of RLH of the liver remains unknown, and a definitive diagnosis based on imaging findings is extremely difficult. If a small, solitary nodule is found in female patients with AIH, the possibility of RLH of the liver should be considered.

[A Case Report of Duodenal Ampullary Carcinoma with Annular Pancreas].

Annular pancreas is a rare congenital anomaly that rarely occurs in parallel with malignancy. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 76-year-old woman presented with abdominal pain and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla. Preoperative computed tomography confirmed the presence of an ampullary tumor. During surgery, we found an anomaly consisting of a ring-like band of pancreatic tissue encircling the second part of the duodenum. Transduodenal papillectomy with preservation of the annular pancreas was subsequently performed. The patient was discharged without any postoperative morbidity.

Histological changes in patients who developed hepatocellular carcinoma after hepatitis C virus eradication by interferon-based therapy.

Although the incidence of hepatocellular carcinoma (HCC) occurring after hepatitis C virus (HCV) eradication has decreased, there are still reports of hepatocarcinogenesis. The present study investigated the histological changes of non-cancerous liver tissue obtained prior to interferon (IFN) therapy and after HCC development. A total of 669 HCV-infected Japanese patients who achieved sustained virological response (SVR) by IFN-based therapy were retrospectively enrolled. Of these, the present study investigated 18 patients who developed HCC after IFN-based SVR. Specimens from 9 of 18 patients were available for histological comparisons prior to IFN therapy and following HCC development. Of these 9 patients, the specimens of 5 individuals were compared via immunohistochemical staining [CD3, CD4, CD8, CD20, forkhead box P3 (FOXP3), transforming growth factor-ß1 and granzyme B]. The current study included 6 control patients with HCV-associated chronic liver disease who subsequently developed HCC (non-SVR-HCC group). Mann-Whitney and Wilcoxon tests were used to compare groups. Bonferroni correction was used for multiple comparisons. P<0.05 was used as a critical P-value, and following Bonferroni's correction, P<0.017 was considered to indicate a statistically significant difference. In the 9 patients examined, continuous inflammation and fibrosis were observed after HCC development. There was also a significant decrease in the positive rate of FOXP3 in all 5 patients at the time of HCC development compared with that prior to IFN therapy (P=0.0084). Additionally, there was a significant difference in the positive rate of FOXP3 between the 5 patients after HCC development and the control individuals (P=0.0022). In patients who developed HCC after IFN-based SVR, the frequency of FOXP3 decreased, but inflammation and fibrosis remained. The extent of the reduction of FOXP3 differed in patients who developed HCC in the presence of HCV. Inflammation and fibrosis remained for a long duration after SVR, which may be associated with hepatocarcinogenesis.

Expression of Matrix Metalloproteinases in Intraductal Papillary Mucinous Neoplasm of the Pancreas.

BACKGROUND/AIM: Intraductal papillary mucinous neoplasm (IPMN) has a variety of histological and morphological appearances. Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. The aim of this study was to elucidate the molecular basis of IPMN variation in different types of lesions. MATERIALS AND METHODS: The expression of MMP-1,2,7,9 in 51 cases of IPMN were investigated. The MMP score was calculated as the sum of the score of staining distribution and the score of the intensity staining. RESULTS: MMP scores were correlated with histological grade, histological subtype, and type of invasion. MMP high expression groups (MMP score ≥5) had worse prognosis than low-expression groups. CONCLUSION: MMP expression varied between different types of IPMN, a result supporting differences in molecular basis of malignancies. These considerations may be helpful for optimal management or treatment according to various types of IPMN.