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Background Hepatocellular carcinoma (HCC) patients with metastases to the cervical lymph nodes are extremely rare, and its clinical course is characterized by rapidly progressive disease. Hence, there have been no reports of metastatic cervical lymph node recurrence indicated after a long postoperative surveillance period. Case presentation The patient was a 63-year-old male who underwent right hepatectomy for HCC of the right upper lobe. Three years after resection, metastatic lymph node recurrence was detected in the subdiaphragm, superior mediastinum, and right cervical lymph nodes. The patient underwent excisional biopsy of the cervical lymph node, followed by molecular-targeted therapy and radiation therapy. Lenvatinib reduced the size of all metastatic lymph nodes and the patient survived for a relatively long period of 43 months after the recurrence was detected. Conclusions After resection of HCC in the right upper lobe, there is the possibility of metastatic lymph node recurrence in unusual sites, including the cervical region, and lenvatinib may be effective in those recurrences.

Background Perivascular epithelioid cell neoplasm (PEComa) in a child is very rare. We herein report the first malignant case of PEComa developing in the liver of a pediatric patient. Case presentation A 10-year-old boy visited a private clinic with prolonged fever of unknown etiology. Abdominal ultrasonography was performed to evaluate the fever’s origin, revealing a large tumor in the liver. He was thus referred to a nearby hospital to investigate the tumor further. Enhanced computed tomography (CT) showed a 6.8 × 5.9 × 10.5-cm solid lesion on S4 and S5. On magnetic resonance imaging (MRI), the tumor had a low signal intensity on T1 imaging and high signal intensity on T2 imaging, with partial diffusion restriction. 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a marked uptake in the mass lesion with no evidence of metastasis. The patient was negative for all tumor markers, including AFP, CEA and PIVKA-II. The results of a needle biopsy suggested hepatocellular carcinoma. The tumor’s rapid growth suggested malignancy. Hepatic segmentectomy (S4 + S5 + S8) was performed. The tumor was resected en bloc with a margin. Microscopically, the tumor showed atypical spindle, polygonal or oval-shaped cells with a high nuclear grade, and vascular invasion. Immunohistochemistry was positive for alpha-smooth muscle antigen (α-SMA), human melanin black-45 (HMB-45) and melan A. The pathological diagnosis was malignant PEComa. In the 6 months after surgery, the patient complained of shoulder pain. MRI showed a dumbbell-shaped tumor at the 2nd thoracic vertebrae, which was confirmed to be bone metastasis of PEComa. After chemotherapy, including ifosfamide and doxorubicin, vertebrectomy was performed. Two years later, thoracoabdominal CT showed a 10-cm solid mass occupying the pelvis and a 15-mm nodule in the middle lobe of the right lung. Under a diagnosis of peritoneal and lung metastases, they were surgically removed and metastasis of PEComa was pathologically confirmed. Four months after the 2nd relapse, pelvic metastasis appeared again and mTOR (mammalian target of rapamycin) inhibitor was initiated. To our knowledge, this is the first report of malignant hepatic PEComa in a pediatric patient. Conclusion Although extremely rare, malignant hepatic PEComa can develop in a child.

BackgroundThis study aimed to examine the prognostic relevance of glucose transporter type 1 (GLUT-1), which is a key regulator of the glucose metabolism. In particular, the study aimed to examine the association between GLUT-1 expression and the therapeutic effect of chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC).MethodsPatients with PDAC were enrolled in the study. Patients with distant metastases and those who received only chemotherapy as treatment were excluded from the study. Specimens for immunohistochemical evaluations were obtained through surgical resection and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the primary tumor before any treatment.ResultsThis study included 197 patients. Of these 197 patients, 100 underwent upfront surgery, and 97 received neoadjuvant CRT (NACRT), which was performed mainly for patients with locally advanced tumors. Of the 97 patients who received NACRT, 21 later underwent surgical resection. For the patients who underwent upfront surgery, low GLUT-1 expression was an independent factor for a better prognosis. For the patients who underwent NACRT, low GLUT-1 expression was significantly associated with greater tumor size reduction, a higher resection rate, and a better prognosis. Additionally, GLUT-1 expression was significantly increased after NACRT treatment.ConclusionsAmong the patients with PDAC, those with low GLUT-1 expression in the primary tumor had a better prognosis those with high GLUT-1 expression. Moreover, the patients with low GLUT-1 expression displayed a better therapeutic response to NACRT.

Background While recent research has shown that expression of ZEB-1 in a variety of tumors has a crucial impact on patient survival, there is little information regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study investigated the co-expression of ZEB-1 and E-cadherin in HCC by immunohistochemistry and evaluated its association with clinical factors, including patient prognosis. Methods A total of 108 patients with primary HCC treated by curative hepatectomy were enrolled. ZEB-1 expression was immunohistochemically categorized as positive if at least 1% cancer cells exhibited nuclear staining. E-cadherin expression was divided into preserved and reduced expression groups and correlations between ZEB-1 and E-cadherin expression and clinical factors were then evaluated. Results With respect to ZEB-1 expression, 23 patients were classified into the positive group and 85 into the negative group. Reduced E-cadherin expression was seen in 44 patients and preserved expression in the remaining 64 patients. ZEB-1 positivity was significantly associated with reduced expression of E-cadherin (p = 0.027). Moreover, significant associations were found between ZEB-1 expression and venous invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p = 0.025). Reduced E-cadherin expression was significantly associated with intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients with both ZEB-1 positivity and reduced E-cadherin expression had a poorer prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a significant prognostic factor by multivariate analysis. There was no statistical difference in overall survival when E-cadherin expression was reduced in the ZEB-1 positive group (p = 0.24). Conclusions Positive ZEB-1 expression and loss of E-cadherin expression are correlated with poor prognosis in HCC patients and malignancy of ZEB-1 positive tumors involves EMT.

Background A metabolic shift to glycolysis is reportedly involved in radioresistance. We examined whether pretreatment 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect enhanced glucose uptake, was able to predict the therapeutic response to chemoradiotherapy (CRT) in patients with pancreatic cancer (PC). Methods Of 125 PC patients (75 unresectable and 50 borderline resectable), 37 and 26 underwent induction chemotherapy before CRT and surgical resection after CRT, respectively. FDG-PET was performed at three different institutions. Results Of the 88 patients who underwent upfront CRT, 31 (35%), 34 (39%), and 23 (26%) showed a partial response (PR), stable disease, and progressive disease, respectively. The tumor PR rate was an independent factor associated with longer overall survival (OS) on multivariate analysis. We evaluated the optimal cut-off of maximum standardized uptake values (SUV max ) at initial diagnosis to detect the tumor PR rate at the three institutions separately. The SUV max was independently associated with tumor response rate on multivariate analysis. In the low SUV max group, induction chemotherapy had no significant impact on OS. In contrast, induction chemotherapy was significantly associated with longer OS in the high SUV max group. Conclusions FDG-PET SUV max was significantly associated with the therapeutic response to CRT in PC patients. Moreover, induction chemotherapy may improve the prognosis of patients with a high SUV max tumor.

Aim We examine the impact of interferon (IFN)‐based and IFN‐free treatment on the prognosis of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) sustained virological response (SVR). Methods Clinical information was collected on 311 cases of HCC after HCV‐SVR from 16 facilities affiliated with the Kyushu Liver Surgery Study Group. Clinical factors and the tumor microenvironment of HCC after SVR treatment with IFN‐based and IFN‐free treatments were analyzed. Results No statistically significant differences were observed in the recurrence rate and overall survival (OS) between the two groups. Propensity score–matched analysis similarly showed no statistically significant differences in recurrence and OS. In the IFN‐based treatment group, OS time was significantly shorter for the programmed death‐ligand 1(PD‐L1)‐positive HCC than the PD‐L1‐negative HCC group (p = 0.0183). No significant difference was observed in the recurrence rate between PD‐L1‐positive and PD‐L1‐negative HCC groups. In the IFN‐based treatment group, the recurrence rate in the cluster of differentiation (CD) 8‐positive group was significantly lower than in the CD8‐negative group (p = 0.0292). There was no difference in OS time between the CD8‐positive and CD8‐negative groups. In the IFN‐free treatment group, PD‐L1 and CD8 were not associated with recurrence rate or OS. Conclusions No statistically significant differences were observed in recurrence or OS rate after HCC resection in the IFN‐free treatment group compared with the IFN‐based treatment group. In the IFN‐based treatment group, PD‐L1 and CD8 expression on cancer cells might be prognostic factors.

Background: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). Methods: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. Results: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. Conclusions: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB.

Background Pancreatic hamartoma is an extremely rare benign disease of the pancreas. Only 30 cases have been reported to date. Case presentation A 68-year-old man presented with an asymptomatic solid and multi-cystic lesion in the uncus of the pancreas, incidentally detected on abdominal enhanced computed tomography. The tumor was found to be a well-demarcated solid and multi-cystic lesion without any enhancement, measuring 4 cm in diameter. After 28 months of follow-up, the tumor enlarged. At 31 months after initial diagnosis, the patient underwent surgical resection because it was difficult to clinically determine whether the tumor was malignant or not. Macroscopically, the solid tumor consisted of yellow adipose tissue with a smooth thin capsule confined to the pancreatic uncus. The inner structure of the tumor consisted of multiple cysts with a white nodule between the cysts. Histologically, the solid part and the multi-cystic portion consisted of mature adipose tissue and colonization of dilated pancreatic ducts with mild fibrosis, respectively. Immunohistochemical findings revealed cytokeratin 7 and 19 positive staining in the epithelial cells of the ducts. Adipose tissue showed positive staining for S-100 protein and there were only a few MIB-1 positive cells. The tumor was then diagnosed as a pancreatic hamartoma. Conclusion Beside on the above findings, we suggest that the term “well-demarcated solid and cystic lesion with chronological morphological changes” could be a clinical keyword to describe pancreatic hamartomas.

High mobility group box-1 (HMGB1) induces the release of proinflammatory cytokines and chemokines as a late-acting mediator of inflammation. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer. However, little is known about the relationship between HCC and HMGB1 and its receptor RAGE (receptor for advanced glycation end products). This study analyzes the clinicopathological relevance of HMGB1 expression level and the effect of HMGB1 expression on the characteristics of HCC. Samples from 75 HCC patients including 13 with positive hepatitis B surface antigen and 36 with hepatitis C antibody were studied. The expression of HMGB1 in paired cancer and non-cancerous tissues from patients with HCC was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. Quantitative RT-PCR data were analyzed in association with the clinicopathological factors of patients with HCC. The expression of HMGB1 mRNA in HCC was high in well-differentiated tumors, but declined as tumors dedifferentiated to moderately and poorly differentiated HCC. The levels of HMGB1 mRNA showed a negative correlation with the presence of portal invasion (p=0.005) and the rise of serum PIVKA-II (p=0.034). There was no clear correlation between HMGB1 expression and proliferation activity of HCC using Ki-67 staining. In HCC, HMGB1 expression level correlated inversely with tumor differentiation. The RAGE-HMGB1 interaction may play a greater role in the early stages of HCC tumorigenesis than during cancer development.

PurposeExtrahepatic bile duct (EHBD) resection is performed as part of radical cholecystectomy for gallbladder (GB) cancer. However, the indication for EHBD resection is still controversial. The aim of the present study was to evaluate the prognostic value of this procedure.MethodsPatients who underwent surgical resection for GB cancer with curative intent were enrolled. We divided GB cancer into two categories based on the tumor location: proximal-type and distal-type tumors. The former refers to tumors involving the neck or cystic duct, while the latter comprises tumors located between the body and fundus.ResultsThis study included 80 patients, 40 each with proximal- and distal-type tumors. Proximal tumor location, lymph node metastasis, and a serum carcinoembryonic antigen level > 5.0 ng/mL were independent predictors of poor prognosis. The 5-year survival rates of patients with proximal-type and distal-type tumors were 33.3 and 73.5%, respectively. Patients with proximal-type tumors showed significantly lower rates of R0 resection, more frequently had ≥ 3 metastatic lymph nodes, and exhibited a higher rate of perineural invasion. EHBD resection improved prognoses only in patients with proximal-type tumors but not in those with distal-type tumors. In the former group, EHBD resection significantly reduced the rate of local or regional lymph node recurrence.ConclusionsExtended cholecystectomy with EHBD resection should be performed for patients with GB cancer involving the neck and cystic duct to reduce local and regional lymph node recurrence and achieve better prognosis.