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.

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.

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.

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.

Cytological Comparison between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Image Analysis Software Using Touch Smear Samples of Surgically Resected Specimens.

To investigate useful cytological features for differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), this study cytologically compared HCC to ICC using image analysis software. Touch smear specimens of surgically resected specimens were obtained from a total of 61 nodules of HCC and 16 of ICC. The results indicated that the major/minor axis ratio of ICC is significantly larger than that of HCC (1.67 ± 0.27 vs. 1.32 ± 0.11, p < 0.0001) in Papanicolaou staining. This result means that the nucleus of HCC is close to round and the nucleus of ICC is close to an oval. This significant difference in the major/minor axis ratio between ICC and HCC was consistently observed by the same analyses using clinical samples of cytology (4 cases of HCC and 13 cases of ICC) such a fine-needle aspiration, brushing and ascites (ICC: 1.45 ± 0.13 vs. HCC: 1.18 ± 0.056, p = 0.004). We also confirmed that nuclear position center-positioned nucleus (p < 0.0001) and granular cytoplasm (p < 0.0001) are typical features of HCC tumor cells compared to ICC tumor cells. The research study found a significant difference in the nuclear morphology of HCC (round shape) and ICC (oval shape) in Papanicolaou-stained cytology specimens. This simple and objective finding will be very useful for the differential cytodiagnosis of HCC and ICC.

Matrix metalloproteinase­1 expression is regulated by HIF­1­dependent and epigenetic mechanisms and serves a tumor­suppressive role in gastric cancer progression.

The matrix metalloproteinase (MMP) family is associated with degradation of the extracellular matrix and is known to promote cancer invasion. The present study aimed to investigate the biological role of MMP­1 in gastric cancer cells and analyze the association between MMP­1 expression and the clinical outcomes of gastric cancer patients. In the present study, hypoxia accelerated invasion, accompanied by elevated MMP­1 expression in the gastric cancer cell line 58As9. Additionally, hypoxia­inducible factor­1α (HIF­1α) knockdown in 58As9 cells reduced MMP­1 expression under hypoxic conditions. Treatment with 5­aza­2­deoxycytidine and trichostatin A restored MMP­1 expression in the MMP­1­deficient cell lines MKN45 and MKN74. These results indicated that MMP­1 expression was controlled by both HIF­1α­dependent and epigenetic mechanisms in gastric cancer cell lines. In addition, MMP­1 knockdown impaired the hypoxia­induced invasiveness of 58As9 cells, implicating MMP­1 in the elevated invasion. By contrast, knockdown enhanced the proliferative ability of 58As9 cells, whereby expression of cell cycle­related genes was subsequently altered. In nude mouse models, the knockdown accelerated the growth of xenograft tumor and the development of peritoneal dissemination. In an immunohistochemical study using 161 surgically resected cancer tissues, the Ki67 score was significantly higher in the group with low MMP­1 expression (P<0.001). Disease­free survival (DFS) and disease­specific survival (DSS) were both significantly reduced in patients with low MMP­1 expression (log­rank test; DFS: P=0.005; DSS: P=0.022). Multivariate analysis demonstrated that MMP­1 expression was an independent prognostic factor for DFS and DSS [DFS: HR=2.11 (1.22­3.92) P=0.005, DSS: HR=2.90 (1.23­8.50) P=0.012]. In conclusion, the present study indicated that MMP­1 may serve as a tumor­suppressive factor that inhibits gastric cancer progression, although it promoted invasion in vitro.

Antitumor effects of low-dose tipifarnib on the mTOR signaling pathway and reactive oxygen species production in HIF-1α-expressing gastric cancer cells.

Farnesyltransferase inhibitors (FTIs) suppress tumor aggressiveness in several malignancies by inhibiting Ras signaling. However, treatment of cells with a low dose of the FTI tipifarnib suppresses the expression of hypoxia-inducible factor-1α (HIF-1α) and results in antitumor effects without inhibiting the Ras pathway. Although we previously reported that elevated HIF-1α expression is associated with an aggressive phenotype in gastric cancer (GC), little is known about the antitumor effects of FTIs on GC. In this study, we examined the relationship between the antitumor effects of low-dose tipifarnib and HIF-1α expression in GC cells. Under normoxic conditions, HIF-1α was expressed only in MKN45 and KATOIII cells. The inhibitory effect of tipifarnib on HIF-1α was observed in HIF-1α-positive cells. Low-dose tipifarnib had antitumor effects only on HIF-1α-positive cells both in vitro and in vivo. Furthermore, low-dose tipifarnib inactivated ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) signaling and decreased intracellular reactive oxygen species (ROS) levels in HIF-1α-positive GC cells. Our results that the antitumor effects of low-dose tipifarnib are at least partially mediated through suppression of mTOR signaling and HIF-1α expression via inhibition of Rheb farnesylation and reduction in ROS levels. These findings suggest that low-dose tipifarnib may be capable of exerting an antitumor effect that is dependent on HIF-1α expression in GC cells. Tipifarnib may have potential as a novel therapeutic agent for HIF-1α-expressing GC exhibiting an aggressive phenotype.

Modification of the Thermal Spread by the Blade Shape of an Ultrasonically Activated Device.

BACKGROUND: Few studies have focused on the spread of thermal damage from different blade shapes of ultrasonically activated devices (USADs) used during minimally invasive surgery. METHODS: In vivo experiments using pig arteries, nerves, and mesentery were used to compare the thermal spread of two different blade types of USADs, non-tapered and tapered, under the same conditions. The tissue temperatures were monitored using a high-resolution infrared thermographic camera and calculated using an image analysis program. The spread of heat denaturation was measured histologically. RESULTS: The temperature was greater at the sides with greater curvature when non-tapered USADs were activated (artery, 1 s, 2 mm: - 0.92 ± 0.5 °C vs. - 0.44 ± 0.5 °C, P = 0.022). This effect was more prominent in the tapered type (artery, 1 s, 0/1/2 mm: 9.14 ± 3.7 °C vs. 28.3 ± 16.2 °C/0.5 ± 1.4 °C vs. 9.76 ± 6.2 °C/ - 0.12 ± 0.9 °C vs. 1.44 ± 1.9 °C, P = 0.044/0.016/0.038, respectively). The temperatures in the tapered USAD were significantly higher at some time- and distance-points than those in a non-tapered USAD (artery, 1 s, 0 mm, Less/1 s, 1 mm, Gre: 4.2 ± 2.9 °C vs. 9.14 ± 3.7 °C /0.36 ± 0.5 °C vs. 9.76 ± 6.2 °C, P = 0.047/0.027; nerve, 2 s, 0 mm, Gre: 6.54 ± 3.9 °C vs. 17.66 ± 6.2 °C, P = 0.012). A three-directional study revealed the thermal spread of the mesentery was greatest at the tip side of the non-tapered type USAD (4.55 ± 2.53 °C vs. 12.43 ± 4.03 °C/12.43 ± 4.03 °C vs. 5.04 ± 1.91 °C, P = 0.003/0.005). CONCLUSIONS: The thermal spread changed according to the blade shape of the USAD. This knowledge can be applied to more meticulous and complicated procedures, reducing surgical morbidity.

Feasibility of purely laparoscopic right anterior sectionectomy.

BACKGROUND: Right anterior sectionectomy is complex in comparison to other liver resections. Thus, the operation has not been widely performed via a laparoscopic approach. We herein present a purely laparoscopic method for right anterior sectionectomy using the standardized techniques. METHODS: Between May 2017 and December 2018, ten pure laparoscopic right anterior sectionectomies were performed for hepatic malignancy. To perform laparoscopic anatomical liver resection safely and securely, we developed an original surgical procedure based on the isolation of the targeted Glissonean pedicle at the hilum, with appropriate transection planes built sequentially according to anatomical landmarks. The extrahepatic right anterior Glissonean pedicle was isolated without parenchymal destruction by utilizing a unique view in the laparoscopic approach. The selective right anterior segment inflow was temporary occluded, consequently liver parenchymal transection consisted of four planes according to the demarcation line, middle hepatic vein (MHV), right anterior Glissonean pedicle, and right hepatic vein (RHV), which were used as anatomical landmarks. Transection was started between the demarcation line and ventral of the MHV (plane 1). Transection of the parenchyma was then performed from dorsal of the MHV to the right anterior Glissonean pedicle (plane 2). Parenchyma was then transected from dorsal of the RHV to the right anterior Glissonean pedicle (plane 3). We subsequently divide the right anterior Glissonean pedicle with a linear stapler. Finally, the resection plane was completed by performing parenchymal transection between the demarcation line and ventral of the RHV (plane 4). RESULTS: The mean operation time was 446 min with 334 ml of estimated blood loss. No cases required conversion to open surgery. Bile leakage occurred as a postoperative complication in one patient. There was no mortality. CONCLUSION: Isolating the extrahepatic Glissonean pedicle at the hilum and transection along four planes determined according to anatomical landmarks made purely laparoscopic right anterior sectionectomy feasible.

Immunohistochemical analysis of the aggregation of CD1a-positive dendritic cells in resected specimens and its association with surgical outcomes for patients with gallbladder cancer.

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis. Antigen-presenting dendritic cells (DCs) play a central role in antitumor immunity. DCs expressing CD1a (CD1a-DCs) are considered immature DCs. The aim of this study was to evaluate the clinical impact of CD1a-DC infiltration into GBC tissue. Seventy-five patients with GBC (excluding non-invasive and intramucosal cancer) were enrolled. Immunohistochemistry for CD1a, S100 and CD8 was performed using representative surgically resected specimens. The cases were divided into a high CD1a-DC group (27 cases, 36%) and low CD1a-DC group (48 cases, 64%) according to the degree of CD1a-DC infiltration/aggregation. The high CD1a-DC group contained fewer patients with distant metastasis (P = 0.039) and more patients given postoperative chemotherapy (P = 0.038). The high CD1a-DC group had significantly longer overall survival (P = 0.001) and disease-specific survival (P = 0.002) than the low CD1a-DC group. In contrast, S100-DC and CD8+ tumor-infiltrating lymphocyte statuses were without effect on OS or DSS. The results of multivariate analyses indicated that the degree of infiltration/aggregation of CD1a-DCs was an independent prognostic factor associated with a favorable prognosis after surgery.

Postoperative hiatal hernia after minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: Minimally invasive esophagectomy (MIE) can reduce various complications compared with conventional thoracotomic esophagectomy. However, several reports suggested that MIE promoted incidence of post-operative hiatal hernia (HH). In current reports, we retrospectively analyzed incidence and risk factors of HH development after MIE. METHODS: A total of 113 patients undergoing MIE (McKeown esophagectomy) at our institute from April 2009 to December 2015 were included in this study. Patients with clinical stage II and III received neoadjuvant chemotherapy (NAC). RESULTS: Eleven of 113 patients (9.7%) undergoing MIE developed HH. Four of them were female and the ratio of female among the patient with HH was higher than that among the patient without HH after MIE (36.4% vs. 13.7%, P=0.05). Sixty-six patients (58.4%) during the study period were administered NAC and 10 of 11 patients with HH (90.9%) received NAC according to the clinical stage, which was significantly more than in the non-HH group (P=0.02). Type and route of graft organ were not related to HH development. Moreover, the fixation of the conduit organ at the hiatus does not contribute to post-operative HH. CONCLUSIONS: In the current study, we showed that NAC was a major risk factor of HH development after MIE.

Predictive value of the ratio of 8­hydroxydeoxyguanosine levels between cancerous and normal tissues in patients with stage II/III colorectal cancer.

Reactive oxygen species (ROS) accumulation is known to induce carcinogenesis and accelerate cancer progression. 8­Hydroxydeoxyguanosine (8­OHdG) is a specific marker of ROS­mediated DNA damage. Therefore, we analysed 8­OHdG levels in cancerous and normal tissue DNA via enzyme­linked immunosorbent assay (ELISA) using 97 tissue specimens obtained from surgically­treated patients with stage II/III colorectal cancer (CRC). Additionally, 8­OHdG levels in these tissues were also assessed via quantitative immunohistochemistry (qIHC). To eliminate individual background variables, the ratio of 8­OHdG levels between cancerous and normal tissues was calculated using both techniques. A comparative analysis demonstrated that the 8­OHdG ratio in DNA was significantly correlated with both lymph node metastasis and lymphatic invasion. Multivariate analysis revealed that a high 8­OHdG ratio in DNA was independently correlated with poor prognosis. These results suggest that the 8­OHdG ratio in DNA reflects ROS­induced cancer progression. Conversely, a low 8­OHdG ratio as estimated via qIHC was an independent factor for poor prognosis. In Kaplan­Meier analysis, the combination of a high 8­OHdG ratio in DNA (ELISA) and a low 8­OHdG ratio in cytoplasm (qIHC) was associated with markedly worse patient prognosis than other combinations. Combined evaluation of the 8­OHdG ratio using ELISA and qIHC may be pivotal for predicting surgical outcomes for patients with stage II/III CRC.

Mieap-induced accumulation of lysosomes within mitochondria (MALM) regulates gastric cancer cell invasion under hypoxia by suppressing reactive oxygen species accumulation.

Mitochondrial quality control (MQC) protects against potentially damaging events, such as excessive generation of mitochondrial reactive oxygen species (mtROS). We investigated the contribution of the two major MQC processes, namely, mitophagy and Mieap-induced accumulation of lysosomes within mitochondria (MALM), to the response to hypoxia of two human gastric cancer (GC) cell lines. We found that hypoxia increased mtROS generation and cell invasion in 58As9, but not in MKN45, although the transcription factor hypoxia-inducible factor 1α was induced in both cell lines. Colocalisation of lysosomes with mitochondria was found only in hypoxic MKN45 cells, suggesting that hypoxia-induced MQC functions normally in MKN45 but may be impaired in 58As9. Hypoxia did not lead to decreased mitochondrial mass or DNA or altered appearance of autophagosomes, as judged by electron microscopy, suggesting that mitophagy was not induced in either cell line. However, western blot analysis revealed the presence of the MALM-associated proteins Mieap, BNIP3 and BNIP3L, and the lysosomal protein cathepsin D in the mitochondrial fraction of MKN45 cells under hypoxia. Finally, Mieap knockdown in MKN45 cells resulted in increased mtROS accumulation and cell invasion under hypoxia. Our results suggest that hypoxia-induced MALM suppresses GC cell invasion by preventing mtROS generation.