A case of intrahepatic mass-forming portal biliopathy mimicking intrahepatic cholangiocarcinoma.

A 75-year-old man was referred to our department because of an enlarging intrahepatic mass detected on magnetic resonance imaging (MRI) follow-up for another disease. MRI showed hypointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging in liver segment 4. Abdominal plain computed tomography (CT) indicated a low-density lesion with an unclear boundary, measuring approximately 4 cm × 3 cm in liver segment 4. Dynamic CT showed early rim enhancement and gradual central enhancement. Contrast-enhanced CT also showed occlusion of the portal vein in segment 4. As the possibility of intrahepatic cholangiocarcinoma could not be excluded on imaging studies, we performed laparoscopic left medial sectionectomy. Histologically, the lesion showed diminished numbers of hepatocytes with increased collagen fibers compared with normal, with no patent portal vein. We considered this lesion a reactive lesion caused by collapse of the liver parenchyma owing to localized obstruction and loss of the portal vein. This lesion was pathologically diagnosed as portal biliopathy. We experienced an extremely rare case of intrahepatic mass-forming portal biliopathy that mimicked a hepatic tumor, which was diagnosed by laparoscopic resection. Portal biliopathy rarely forms intrahepatic mass lesions and must be distinguished from a malignant hepatic tumor.

Robotic spleen-preserving distal pancreatectomy using the first domestic surgical robot platform (the hinotori™ Surgical Robot System): a case report.

BACKGROUND: Robotic pancreatectomy has been performed worldwide mainly using the da Vinci® Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Recently, because of the death of some patents related to the da Vinci® system, new surgical robot systems have been introduced that are characterized by unique technical refinements. In Japan, the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan) was approved for use in gastroenterological surgery in October 2022. Since then, we have attempted complicated procedures using this robot. In this report, we report our first experience performing spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein using this first Japanese domestic surgical robot. CASE PRESENTATION: The patient was a 58-year-old woman with a mass in the pancreatic tail identified during medical screening. Further examinations resulted in a diagnosis of a pancreatic neuroendocrine tumor. The patient consented to surgical resection, and we planned robotic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein, using the hinotori™. Five trocars, including one port for the assistant surgeon, were placed in the upper abdomen. The operating unit was rolled in from the patient's right side. The pivot position was set for each robotic arm, and this setting was specific to the hinotori™. The cockpit surgeon performed all surgical procedures, excluding port placement and pancreatic transection. There were no unrecoverable device errors during the operation. The operation time was 531 min, and blood loss was 192 ml. The postoperative course was uneventful. We were able to safely perform this highly complicated surgery for a pancreatic tumor using the first Japanese domestic surgical robot platform. CONCLUSIONS: The first Japanese domestic surgical robot platform, hinotori™, has different features from those of the da Vinci® and performed sufficiently as a surgical robot system in highly advanced pancreatic surgery.

Laparoscopic liver resection for local recurrence after carbon­ion radiotherapy for hepatocellular carcinoma: A case report.

Numerous potentially curative treatments have become available for patients with hepatocellular carcinoma (HCC) on the basis of the individual patient and tumor characteristics. Carbon-ion radiotherapy (C-ion RT) is a novel treatment option to reduce the physical burden in patients with HCC. However, the long-term outcomes and the clinical and pathological features of locoregional recurrence after initial C-ion RT are unclear. The present study reports the case of a patient who underwent a curative laparoscopic liver resection for the local recurrence of HCC after C-ion RT. A 73-year-old man was diagnosed with chronic hepatitis C and achieved a sustained virological response. During subsequent surveillance, a solitary HCC of 2.3 cm in diameter appeared in liver segment 7 (S7). While surgical resection was considered the best option, the patient chose C-ion RT as the initial HCC treatment. Although C-ion RT appeared to be successful for the primary lesion, enhanced computed tomography revealed that a hypervascular tumor had reappeared in the same area 16 months later. As HCC recurrence was suspected, several different examinations were performed. Computed tomography and magnetic resonance imaging showed that the recurrent tumor had irregular margins, and communication was suspected with the intrahepatic portal vein. A laparoscopic partial liver resection of S7 was planned. Histopathological examination of the excised specimen revealed proliferation of viable moderately to poorly differentiated HCC, with marked invasive growth and numerous portal vein infiltrations. To the best of our knowledge, this is the first report of surgery for locally recurrent HCC after C-ion RT. Oncological outcomes following C-ion RT for HCC remain unclear. Notably, there are cases of unusual recurrence with massive vascular invasion after C-ion RT. In the present case, the histological features were confirmed after C-ion RT for HCC. This case may raise concerns about the true efficacy of C-ion RT and warns against the easy choice of C-ion RT in spite of a resectable HCC.

A surgical case of inflammatory pseudotumor by hepatic anisakiasis.

Anisakiasis is a parasitic infection caused by the ingestion of raw or undercooked seafood infected with Anisakis larvae. It generally affects the gastrointestinal tract, particularly the stomach, but very rare cases have been reported in which infection of the liver leads to the formation of inflammatory pseudotumors. We herein report an extremely rare case of an inflammatory pseudotumor induced by hepatic anisakiasis that was laparoscopically resected for the purpose of both diagnosis and treatment. A 51-year-old woman underwent a routine medical checkup by ultrasound examination, which incidentally detected a 15-mm mass on the surface of S6 of the liver. Because a malignant tumor could not be ruled out on several preoperative imaging studies, laparoscopic partial resection of the liver was performed. Histopathological examination revealed Anisakis larva in the inflammatory pseudotumor, suggesting hepatic anisakiasis. This report describes an extremely rare case of an inflammatory pseudotumor induced by hepatic anisakiasis. Because the preoperative diagnosis could not be obtained by several imaging modalities, laparoscopic liver resection with a sufficient margin might be suitable for diagnosis and treatment of this disease.

Treatment strategy for lymph node metastasis of hepatocellular carcinoma using an ICG navigation system: a case report.

BACKGROUND: Since indocyanine green (ICG) accumulates selectively in hepatocellular carcinoma (HCC) cells, it can be used to detect metastatic lesions. Lymph node metastasis of HCC is rarely observed, both simultaneously and metachronously. Therefore, it is sometimes difficult to identify metachronous lymph nodes during salvage surgery because of prior surgery. Herein, we report a case in which lymph node metastasis of HCC was successfully resected using an ICG navigation system. CASE PRESENTATION: The patient was a 62-year-old man who had undergone radical liver resection for HCC 8 years ago. During surveillance, contrast-enhanced computed tomography (CT) revealed a mass in the hepatic hilum. Various diagnostic modalities suggested that the patient had a solitary metastatic lymph node of HCC, and extirpation of the tumor was planned. Intraoperative ICG fluorescence imaging allowed surgeons to clearly identify the target lesion. Histopathologically, the tumor was confirmed to be a lymph node metastasis of HCC. The patient's postoperative course was uneventful, and he remains alive without recurrence 2 years after the second surgery. CONCLUSION: Intraoperative navigation surgery by ICG fluorescence imaging was useful for the safe resection of extrahepatic metastasis of HCC in a complicated situation.

A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells.

BACKGROUND: A hypoxic environment often persists within solid tumors, including hepatocellular carcinoma (HCC). Hypoxia-inducible factor-1α (HIF-1α) can accelerate cancer malignancy by inducing hypoxia-dependent expression of various genes. Tumor hypoxia can also induce metabolic reprogramming of fatty acid (FA) metabolism, through which HIF-1α plays an essential role in diminishing fatty acid ß-oxidation (FAO) in hypoxic cancer cells. METHODS: We aimed to investigate potential new drug therapy options for targeting hypoxic cancer cells within HCC tumors, specifically through combining HIF-1α inhibition with palmitic acid (PA) + L-carnitine (LC) treatment to effectively induce apoptosis in hypoxic HCC cells. To test this hypothesis, in vitro and in vivo studies were performed. RESULTS: We first demonstrated that hypoxia-dependent apoptosis was induced by an overload of PA in two HCC cell lines (HepG2 and Hep3B) via excessive production of reactive oxygen species (ROS). Moreover, this observed PA-induced apoptosis was enhanced by HIF-1α knockdown (KD) in these cells under hypoxia. In addition, the combination of PA with FAO activator LC increased FAO activity and led to stronger cell death than PA alone in hypoxic HIF-1α KD cells, specifically through further ROS generation. To clarify the mechanism of hypoxia-induced FA metabolism reprogramming, expression levels of the genes encoding FAO enzymes CPT1A, ACSL1, MCAD, and LCAD, FA transporter CD36, and FA esterification enzymes DGAT and APGAT were analyzed using HIF-1α KD and scramble control (SC) cells. The results suggested that HIF-1α could repress mRNA expression of the FAO-related enzymes and CD36, while it upregulated FA esterification gene expression. This suggested a central role for HIF-1α in hypoxia-induced reprogramming of FA metabolism in HCC cells. Using a nude mouse model, PA administration was found to induce apoptosis from ROS overproduction in HIF-1α KD tumors compared with SC tumors. Additional LC treatment synergistically enhanced the PA-induced apoptosis in HIF-1α KD tumors. Finally, in vivo therapy composed of HIF-1α inhibitor YC-1 with PA + LC could induce ROS-mediated apoptosis in HepG2 tumors without significant toxicity. CONCLUSIONS: A combination therapy of YC-1 with PA + LC may be a unique anti-tumor therapy for targeting hypoxic HCC cells, specifically by ROS overproduction leading to forced FAO activation.

The Oncological Effect of Mutant p53 on the Metastatic Phenotype of Gastric Cancer Cells.

BACKGROUND/AIM: P53 is the most frequently mutated tumor suppressor gene among all cancers. In human cancers, specific residues of p53 are mutated at a high frequency, and those mutations are known as hotspot mutations. Mutant p53 promotes tumor progression through the gain-of-function (GOF) mechanism. However, its biological characteristics, especially its metastatic potential, owing to different hotspot mutations in gastric cancer remain unclear. In the present study, we investigated the p53-depended metastatic phenotype. MATERIALS AND METHODS: This study examined the differences in the metastatic potential of wild-type, mutant-p53-R175H, and mutant-p53-R273H NUGC-4 gastric cancer cells in vitro and in vivo. RESULTS: NUGC-4-mutant-p53-R175H cells showed significant cell proliferation, healing and invasive abilities in proliferation, wound healing and invasion assay, respectively, compared to wild-type and mutant-p53-R273H cells. Both NUGC-4-mutant-p53 cell types expressed epithelial-mesenchymal transition (EMT)-related proteins. Furthermore, NUGC-4-mutant-p53-R175H cells showed less attachment to the extracellular matrix and greater expression of EMT-related proteins than NUGC-4-mutant-p53-R273H cells. Regarding the peritoneal dissemination model, NUCG-4-mutant-p53-R175H and NUCG-4-mutant-p53-R273H cells demonstrated less frequent formation of dissemination nodules than NUGC-4-empty cells. In contrast, liver metastases were more frequent and greater in number in NUCG3-mutant-p53-R175H than in the other cell lines. CONCLUSION: Our results suggest that differences in the p53 status, even in the hotspot mutation site, affect not only the characteristics of the cells but also the metastatic ability of gastric cancer.

Robotic distal pancreatectomy using a docking-free system (the hinotori™ Surgical Robot System).

BACKGROUND: Although robotic surgery has rapidly spread in pancreatectomy [1], the procedure is performed by the da Vinci™ Surgical System (Intuitive Surgical Inc., CA), the most common surgical robot in the world [2]. We herein present our first experience of robotic distal pancreatectomy using a new Japanese surgical robot named the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan). METHODS: A 68-year-old man who was found to have the mass lesion in the pancreatic tail in a medical examination. Investigations, including various imaging studies suggested a diagnosis of pancreatic cancer (Fig. 1). The patient was considered for robotic pancreatectomy. RESULTS: Five trocars, including one port for the assistant surgeon, were placed at the upper abdomen. The operation unit was rolled in from the right side (Fig. 2). The patient successfully underwent robotic distal pancreatectomy combined with dissection of the regional lymph nodes using the hinotori™ system. The cockpit surgeon performed all procedures, excluding port placement, vessel clipping, and transection of the pancreas. There were no unrecoverable device errors in this operation. The total operation time was 473 minutes, and the estimated blood loss was 182 ml. The postoperative course was uneventful, and hospital length of stay was 10 days. Pathological diagnosis was pancreatic cancer, T1N1M0, Stage ⅡB. Adjuvant chemotherapy using S-1 was administered, and he has survived without recurrence for 3 months after the curative resection. CONCLUSIONS: This is the first report of robotic pancreatectomy using the hinotori™ system, which showed the favorable perioperative results. The accumulation of experience and further studies are required to confirm its clinical benefits.

Suppression of NASH-Related HCC by Farnesyltransferase Inhibitor through Inhibition of Inflammation and Hypoxia-Inducible Factor-1α Expression.

Inflammatory processes play major roles in carcinogenesis and the progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But, there are no therapies for NASH-related HCC, especially focusing on these critical steps. Previous studies have reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In hepatoblastoma and HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed the expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed the expression of phosphorylated nuclear factor-κB and transforming growth factor-ß. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high-fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

A Case of Multicystic Biliary Hamartoma with a Marked Peribiliary Gland Component Successfully Treated by Purely Laparoscopic Anatomical Liver Resection.

BACKGROUND: Multicystic biliary hamartoma (MCBH) is an extremely rare benign liver lesion characterized by a gross well-circumscribed multicystic honeycomb appearance. This report presents a MCBH case with a marked peribiliary gland component which showed unusual histology. CASE PRESENTATION: A 63-year-old Japanese male was admitted to our hospital for a detailed examination of a hepatic cystic lesion, which was originally detected 14 years ago and had slowly enlarged. A preoperative imaging study revealed a well-demarcated multicystic lesion without communication to the biliary tracts. The possible clinical diagnoses were mucinous cystic neoplasm (MCN) or MCBH. The lesion was successfully resected by purely laparoscopic right anterior sectionectomy. The cut surfaces of resected specimens grossly exhibited a well-circumscribed multicystic lesion with a thick septum. Histologically, the cyst wall was covered by cuboidal epithelial cells resembling epithelium of the bile duct while abundant small ducts, which morphologically resembled peribiliary glands, were observed among the fibrous stroma of the thick septum. Although possible pathological diagnosis varied, including intrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the bile duct, biliary adenofibroma, MCN and MCBH, the lesion was finally diagnosed as MCBH with a marked peribiliary gland component. CONCLUSIONS: MCBH can contain abundant peribiliary glands in the fibrous stroma. A pathologist should be careful not to diagnose such peribiliary glands in MCBH as neoplastic glands.