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.

Novel method for classification of prion diseases by detecting PrPres signal patterns from formalin-fixed paraffin-embedded samples.

Prion disease is an infectious and fatal neurodegenerative disease. Western blotting (WB)-based identification of proteinase K (PK)-resistant prion protein (PrPres) is considered a definitive diagnosis of prion diseases. In this study, we aimed to detect PrPres using formalin-fixed paraffin-embedded (FFPE) specimens from cases of sporadic Creutzfeldt-Jakob disease (sCJD), Gerstmann-Sträussler-Scheinker disease (GSS), glycosylphosphatidylinositol-anchorless prion disease (GPIALP), and V180I CJD. FFPE samples were prepared after formic acid treatment to inactivate infectivity. After deparaffinization, PK digestion was performed, and the protein was extracted. In sCJD, a pronounced PrPres signal was observed, with antibodies specific for type 1 and type 2 PrPres exhibited a strong or weak signals depending on the case. Histological examination of serial sections revealed that the histological changes were compatible with the biochemical characteristics. In GSS and GPIALP, prion protein core-specific antibodies presented as PrPres bands at 8-9 kDa and smear bands, respectively. However, an antibody specific for the C-terminus presented as smears in GSS, with no PrPres detected in GPIALP. It was difficult to detect PrPres in V180I CJD. Collectively, our findings demonstrate the possibility of detecting PrPres in FFPE and classifying the prion disease types. This approach facilitates histopathological and biochemical evaluation in the same sample and is safe owing to the inactivation of infectivity. Therefore, it may be valuable for the diagnosis and research of prion diseases.

Chemoradiotherapy and Lymph Node Metastasis Affect Dendritic Cell Infiltration and Maturation in Regional Lymph Nodes of Laryngeal Cancer.

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

Accumulation Area of a Japanese PRNP P102L Variant Associated With Gerstmann-Sträussler-Scheinker Disease: The Ariake PRNP P102L Variant.

BACKGROUND AND PURPOSE: The coast of Kyushu Island on Ariake Sea in Japan is known to be an accumulation area for patients with a proline-to-leucine substitution mutation at residue 102 (P102L) of the human prion protein gene (PRNP), which is associated with Gerstmann-Sträussler-Scheinker disease. We designated this geographical distribution as the "Ariake PRNP P102L variant." The purpose of this study was to characterize the clinical features of this variant. METHODS: We enrolled patients with the PRNP P102L variant who were followed up at the Saga University Hospital from April 2002 to November 2019. The clinical information of patients were obtained from medical records, including clinical histories, brain magnetic resonance imaging (MRI), and electroencephalography (EEG). A brain autopsy was performed on one of the participants. RESULTS: We enrolled 24 patients from 19 family lines, including 12 males. The mean age at symptom onset was 60.6 years (range, 41-77 years). The incidence rate of the Ariake PRNP P102L variant was 3.32/1,000,000 people per year in Saga city. The initial symptoms were ataxia (ataxic gait or dysarthria) in 19 patients (79.2%), cognitive impairment in 3 (12.5%), and leg paresthesia in 2 (8.3%). The median survival time from symptom onset among the 18 fatal cases was 63 months (range, 23-105 months). Brain MRI revealed no localized cerebellar atrophy, but sparse diffusion-weighted imaging abnormalities were detected in 16.7% of the patients. No periodic sharp-wave complexes were identified in EEG. Neuropathological investigations revealed uni- and multicentric prion protein (PrP) plaques in the cerebral cortex, putamen, thalamus, and cerebellum of one patient. Western blot analysis revealed 8-kDa proteinase-K-resistant PrP. CONCLUSIONS: This is the first report of the accumulation area of a PRNP P102L variant on the coast of Ariake Sea. The Ariake PRNP P102L variant can be characterized by a relatively long disease duration with sparse abnormalities in brain MRI and EEG relative to previous reports. Detailed interviews to obtain information on the birthplace and the family history of related symptoms are important to diagnosing a PRNP P102L variant.

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 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.

Collision tumor of a papillary and follicular thyroid carcinoma: a case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are common differentiated thyroid cancers, but the detection of a collision tumor is an extremely rare event. CASE PRESENTATION: The patient was a 69-year-old Japanese female with multiple cervical lymph node swellings and a thyroid tumor. Preoperative fine needle aspiration cytology of the enlarged lymph node revealed a cytological diagnosis of papillary thyroid carcinoma (PTC). A total thyroidectomy, right cervical dissection and paratracheal dissection were performed. Histopathological and immunohistochemical analyses of resected specimens revealed a collision tumor of PTC and FTC. Multiple metastases of papillary carcinoma were found in the dissected lymph nodes. In the PTC lesion, IHC for BRAF (V600E) was positive but negative for the FTC lesion. Genetic analyses further revealed a TERT promoter C228T mutation in PTC and a NRAS codon 61 mutation in FTC. The patient died of recurrent cancer 8 months after surgery. CONCLUSIONS: A case of a collision tumor of PTC and FTC is very rare, and even fewer cases have been subjected to genetic scrutiny. The present case was successfully diagnosed by pathological examination using immunohistochemical and genetic analyses. The TERT promoter mutation in the PTC lesion was consistent with the aggressive behavior of the cancer.

Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers.

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

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.

Risk Factors for Postoperative Paralytic Ileus in Advanced-age Patients after Laparoscopic Colorectal Surgery: A Retrospective Study of 124 Consecutive Patients.

Objectives: Postoperative paralytic ileus (POI) is one of the most common and troublesome complications following colorectal surgery. However, to date, the risk factors for POI remain unclear. This study aimed to identify the risk factors for POI following laparoscopic colorectal surgery in advanced-age patients. Methods: The clinical data of 124 patients aged ≥75 years who underwent curative colorectal surgery from January 2018 to December 2020 were retrospectively reviewed. The relationship between POI and clinicopathological data including sarcopenia and visceral fat obesity was then assessed. Sarcopenia was defined as a low skeletal muscle mass index; visceral obesity, visceral fat with an area ≥100 cm2 on computed tomography at the level of the third lumbar vertebra; and sarcobesity, sarcopenia with visceral obesity. Results: The rate of POI was 9% (12/124 patients), and all the affected patients improved with conservative treatment. In the univariate and multivariate analyses, sarcopenia and sarcobesity were significant predictive factors for POI. Conclusions: Sarcopenia and sarcobesity may be risk factors for POI in patients aged ≥75 years after laparoscopic colorectal surgery.

Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer.

BACKGROUND: Precision medicine with gene panel testing based on next-generation sequencing for patients with cancer is being used increasingly in clinical practice. HER2, which encodes the human epidermal growth factor receptor 2 (HER2), is a potentially important driver gene. However, therapeutic strategies aimed at mutations in the HER2 extracellular domain have not been clarified. We therefore investigated the effect of EGFR co-targeted therapy with HER2 on patient-derived cancer models with the HER2 extracellular domain mutation E401G, based on our previous findings that this mutation has an epidermal growth factor receptor (EGFR)-mediated activation mechanism. METHODS: We generated a xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) from a patient's cancer containing an amplified HER2 E401G mutation. With these platforms, we compared the efficacy of afatinib, a tyrosine kinase inhibitor having anti-HER2 and anti-EGFR activity, with two other therapeutic options: lapatinib, which has similar properties but weaker EGFR inhibition, and trastuzumab plus pertuzumab, for which evidence exists of treatment efficacy against cancers with wild-type HER2 amplification. Similar experiments were also performed with H2170, a cell line with wild-type HER2 amplification, to contrast the characteristics of these drug's efficacies against HER2 E401G. RESULTS: We confirmed that PDX and CTOS retained morphological and immunohistochemical characteristics and HER2 gene profiles of the original tumor. In both PDX and CTOS, afatinib reduced tumor size more than lapatinib or trastuzumab plus pertuzumab. In addition, afatinib treatment resulted in a statistically significant reduction in HER2 copy number at the end of treatment. On the other hand, in H2170 xenografts with wild-type HER2 amplification, trastuzumab plus pertuzumab was most effective. CONCLUSIONS: Afatinib, a dual inhibitor of HER2 and EGFR, showed a promising effect on cancers with amplified HER2 E401G, which have an EGFR-mediated activation mechanism. Analysis of the activation mechanisms of mutations and development of therapeutic strategies based on those mechanisms are critical in precision medicine for cancer patients.

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.

Diffuse Large B-cell Lymphoma Involving an Abundant Infiltration of T Follicular Helper Cells.

A 76-year-old man presented with skin plaque and splenic nodules, and diffuse large B-cell lymphoma (DLBCL) with infiltration of T-cells was suspected based on the skin lesions. The disease showed indolent clinical behavior for three months, when systemic lymphadenopathy rapidly evolved. An inguinal lymph node biopsy revealed DLBCL with abundant infiltration of T follicular helper (TFH) cells. A polymerase chain reaction-based analysis of immunoglobulin variable heavy chain showed that the skin, splenic nodules, and inguinal lymph node shared the same clone. This case indicates that the dysregulated infiltration of TFH cells in the tumor microenvironment accelerates the lymphomagenesis and progression of DLBCL.

Silence of resident microglia in GPI anchorless prion disease and activation of microglia in Gerstmann-Sträussler-Scheinker disease and sporadic Creutzfeldt-Jakob disease.

GPI anchorless prion diseases (GPIALPs) show numerous coarse prion protein (PrP) deposits in the CNS but neuropil spongiform changes are mild and the incidence of dementia is low. Here, we examined differences in resident microglial phenotypes between GPIALP (D178fs25) and the other prion diseases Gerstmann-Sträussler-Scheinker (GSS) disease and sporadic Creutzfeldt-Jakob disease (sCJD) with respect to homeostasis and activation. Immunohistochemistry was performed on 2 GPIALP (D178fs25), 4 GSS (P102L), and 4 sCJD cases. Homeostatic microglia expressing TMEM119 and P2RY12 were preserved in GPIALP compared to GSS and sCJD. Microglia/macrophage activation in GSS and sCJD was associated with the extent of spongiform change. Immunoelectron microscopy revealed TMEM119 and P2RY12 in PrP plaque cores. Activated microglia/macrophages expressing HLA-DR and CD68 were predominant in GSS and sCJD whereas in GPIALP, homeostatic microglia were retained and activated microglia/macrophages were rarely observed. These data suggest that PrP deposition in GPIALP is less toxic and that microglia may be immune-tolerant to PrP deposition. This may be associated with milder tissue damage and a low incidence of dementia. Whereas microglia/macrophage activation is considered to be a reaction to tissue injury, this study shows that the degree of microglia/macrophage activity might influence the extent of tissue damage.

ALK rearrangement-associated renal cell carcinoma morphologically mimicking mucinous tubular and spindle cell carcinoma: a case report.

BACKGROUND: Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is an extremely rare tumor and ALK-RCC that mimics mucinous tubular and spindle cell carcinoma (MTSCC) has been very reported only in one instance. CASE PRESENTATION: A 42-year-old Japanese woman was admitted to our hospital for the treatment of a left renal tumor measuring 5 cm in maximum dimension. She underwent a laparoscopic left nephrectomy. Histologically, the tumor formed tubular or focally papillary structures with a small amount of spindle-shaped tumor cells against the background of prominent extracellular mucin. Although the tumor cells were negative for immunohistochemistry (IHC) of alpha-methylacyl-CoA racemase (AMACR) and lymph node metastasis was presented (these are atypical findings for MTSCC), we initially diagnosed the tumor as MTSCC based on its morphological characteristics with mucin deposition. However, an additional IHC analysis revealed that the tumor cells were diffusely positive for ALK-IHC. In addition, TPM3 exon 8 - ALK exon 20 fusion gene was detected by RNA sequencing. The tumor was thus correctly diagnosed as ALK rearrangement-associated renal cell carcinoma (ALK-RCC). CONCLUSIONS: Since the use of molecular targeted therapy with an ALK inhibitor for ALK-RCC is promising, the correct pathological diagnosis of ALK-RCC is quite important. We strongly recommend that ALK-IHC be routinely performed for renal tumors with negative AMACR staining that mimic MTSCC.

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.

A case of congenital capillary proliferation of the kidney (CCPK).

We report a case of congenital capillary proliferation of the kidney (CCPK) along with the multimodality imaging findings. Four-day-old boy who had managed due to his mother's gestational diabetes underwent abdominal ultrasound and a mass was detected in the right kidney. On gray scale ultrasound, the mass exhibited a hyperechoic, slight lobulated shape and a circumscribed margin. On Doppler mode, the mass showed hypervascularity in its peripheral to central zones. On MRI, the mass was hyperintense on the T2-weighted image, and no diffusion restriction was noted on DWI/ADC. On computed tomography, strong enhancement was shown at center of the mass at the post-contrast early phase; homogeneous enhancement at the entirety of the mass was observed at the delayed phase. We suspected hemangioma but did not rule out the possibility of malignancy. Surgery was performed. Pathologically, the specimen showed a proliferation of capillaries which were positive for vascular endothelial markers and negative for GLUT1 in immunohistochemistry. A small number of entrapped tubules and glomeruli were also observed. After an intensive pathological examination, the diagnosis of CCPK was finally considered. CCPK was recently described as an extremely rare childhood renal vascular lesion, and to our knowledge, only five other cases have been reported. Our patient's multimodality imaging findings well reflected the characteristics of a vascular lesion.

Fatal fat embolism syndrome during posterior spinal fusion surgery: A case report and literature review.

RATIONALE: Fat embolism syndrome (FES) is a rare but potentially lethal complication. Although serious FES is associated with long bone fractures and major joint surgery, the number of patients who develop fatal FES intraoperatively is probably higher than the described number. We herein report an extremely rare autopsy-confirmed case of fatal FES during posterior spinal fusion to enhance pedicle screw (PS) fixation with allograft bone augmentation. PATIENT CONCERNS: A 74-year-old woman came to the hospital complaining of back pain, lower extremity pain and numbness, and intermittent claudication. DIAGNOSIS: She was diagnosed with lumbar degenerative scoliosis and lumbar spinal canal stenosis based on imaging findings. INTERVENTIONS: During posterior spinal fusion to enhance pedicle screw fixation with allograft bone augmentation, her blood pressure and oxygen saturation dropped significantly, so the operation was stopped, and cardiopulmonary resuscitation was performed. Chest computed tomography demonstrated bilateral diffuse alveolar infiltrates. OUTCOMES: The patient died three days later due to fat embolism. The autopsy revealed diffuse myocardial ischemia and diffuse alveolar damage. Numerous fat emboli were observed at lung, kidney and spleen and small necrotic bone fragments, possibly derived from allograft bone debris, were found in the peripheral pulmonary artery. LESSONS: Fatal FES associated to seemingly harmless isolated osteoporotic vertebral fractures-vertebroplasty and posterior spinal fusion has been reported. The mechanism was hypothesized to be that both vertebral fractures and spine surgery have the potential to involve bone marrow, thereby increasing intraosseous pressure, and this pressure dislodges fat and bone marrow and pushes them out into the venous circulation, causing systemic inflammation.This is the first report to show histological evidence that the allografted bone embolized to the lungs. Although several reports have indicated that inserting reinforcing materials into the tapped screw holes can enhance the pedicle screw fixation, this procedure may cause severe FES due to fat and debris of material augmentation (i.e. cement, hydroxyapatite, allograft bone). It is important for physicians, especially spinal surgeons, and anesthetists, to be aware of the potential for FES to occur during spinal surgery, which can cause serious complications in a small minority of patients.

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.

Intracranial Mönckeberg's Atherosclerosis Is Frequently Found in Autopsy Cases of Advanced Stage Malignancy with Cerebral Infarction.

Cerebral infarction (CI) severely affects the prognosis of patients with malignancy. The aim of the study was to compare the pathology of CI between cases with and without malignancy focusing on intracranial Mönckeberg's atherosclerosis. Among 778 autopsy cases of craniotomy, 53 cases of "cerebral infarction without malignancy group" (CI group), 50 cases of "malignant tumor without CI group" (MT group), and 39 cases of "cerebral infarction with malignancy group" (CM group) were identified. Mönckeberg's atherosclerosis was mainly found in the basal ganglia and its prevalence in the CM group (38.5%) was significantly higher than in the MT group (12.0%, p = 0.005), and apparently higher than in the CI group (18.9%, p = 0.057). The CI group was significantly older, had higher BMIs, and a greater prevalence of hypertension and atrial fibrillation compared to the CM group. In addition, the prevalence of chronic renal disease was significantly lower in the CM group (2.6%, p = 0.012) than in the CI group (20.8%). Our results indicated that Mönckeberg's atherosclerosis was often found in the basal ganglia of CM cases and that intracranial Mönckeberg's atherosclerosis is a potential risk factor for CI in patients with advanced stage malignancy.