Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

Parieto-Occipital Interhemispheric Transfalcine, Trans-Bitentorial Approach for Radical Resection of Falcotentorial Meningiomas.

OBJECTIVE: Falcotentorial meningioma occurs close to the falcotentorial edges and the confluence of the vein of Galen. The posterosuperior approach conventionally used to reach this site does not allow direct visualization of the tumor matrix, making detachment difficult. Meningiomas at this location are therefore among those that are not well amenable to radical resection. We devised an alternative anterolateral approach that, when used in addition to the posterosuperior approach, provides an operating field which allows to overview large, bilaterally extending tumors. We report this parieto-occipital interhemispheric transfalcine, trans-bitentorial approach, together with associated procedural modifications. METHODS: We used the approach in four patients with falcotentorial meningioma between February 2008 and July 2017. We began by extending a parieto-occipital craniotomy slightly beyond the midline, to pass across the most caudal bridging vein on the rostral side. We then created a fan-shaped fenestration as large as possible in the falx, between the superior sagittal sinus and the inferior sagittal and straight sinuses (window 1). We further performed wedge-shaped resections of both tentorial edges to the left and right of window 1 (windows 2 and 3). Tumor debulking was then carried out via these three windows (the triple-window method). Finally, we detached the tumor in the area of the falcotentorial edges and the confluence of the vein of Galen. To obtain a superorostral operating field as wide as possible from laterally, thereby exposing the potential blind spots, the operating surgeon used both hands while retracting the precuneus, and the assistant surgeon used both hands to turn over the falcotentorial edges (twosome four-hand retractorless microsurgery). RESULTS: The wide operating field provided by this parieto-occipital interhemispheric transfalcine, trans-bitentorial approach and twosome four-hand retractorless microsurgery provides a direct view of delicate structures at the falcotentorial edges and the confluence of the vein of Galen, a site that is most likely to be a blind spot in conventional approaches. Retraction of the precuneus on the nondominant side enabled radical resection with no neurologic deficit in any of the patients. CONCLUSIONS: The parieto-occipital interhemispheric transfalcine, trans-bitentorial approach with the triple-window method opens an anterolateral operating field in addition to a posterosuperior operating field in large tumors located in the falcotentorial and pineal region, extending anteroposteriorly and bilaterally. The twosome four-hand retractorless technique via this approach enables visualization of the tumor matrix at sites, which are barely visible with the conventional approach. Thus, the tumor can be removed more radically and safely.

Treatment of hepatocellular carcinoma with hepatic vein tumor thrombosis protruding into the inferior vena cava by conversion surgery following chemotherapy with regorafenib: a case report.

Regorafenib is an oral multikinase inhibitor affecting angiogenesis, oncogenesis, metastasis, and tumor immunity. As a systemic treatment, it has been shown to provide survival benefits in hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment. We report herein a case of HCC with hepatic vein tumor thrombosis protruding into the inferior vena cava (IVC-HVTT) which was successfully treated by surgery following second-line chemotherapy with regorafenib. A 79-year-old man with chronic hepatitis was diagnosed with HCC. Computed tomography revealed a solitary tumor in segments 7 and 8 and an IVC-HVTT from the right hepatic vein. Since IVC-HVTT removal is a difficult procedure, the tumor was diagnosed as unresectable, and administration of sorafenib was started. Five weeks later, the lesion had increased in size by 15.3%; subsequently, regorafenib was given as second-line therapy for 12 months. After shrinkage of the IVC-HVTT, the patient was referred to our hospital for surgery. One month after the cessation of regorafenib, an extended resection of segment 8 and total removal of the IVC-HVTT was successfully performed without using total hepatic vascular exclusion. There were no serious postoperative complications. Additionally, there has been no recurrence for about 2 years since the initial therapy.

[A case of resected synchronous hepatocellular and cholangiolocellular carcinoma in the background of resolved hepatitis B virus infection].

An 85-year-old male patient was referred to our hospital for further examination of a liver tumor. Imaging examination revealed a 90-mm tumor in segment 4/8 and 30-mm tumor in segment 6 of the liver. Histopathological examination revealed that the tumor in segment 4/8 was cholangiolocellular carcinoma (CLC) and the tumor in segment 6 was hepatocellular carcinoma (HCC). This case shows that although the frequency of CLC is very low, recent studies have indicated the novel knowledge of CLC. Herein, we report a surgical case of CLC and HCC in the background of resolved hepatitis B virus infection.

RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review.

AIMS: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia-associated transcription factor family on chromosome Xp11.2. Dual-colour break-apart fluorescence in-situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA-binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10-TFE3 fusion results from paracentric inversion. RBM10-TFE3 RCC may yield a false-negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10-TFE3 RCC. METHODS AND RESULTS: Ten patients with RBM10-TFE3 RCC aged 31-71 years were investigated. Histological analysis, immunostaining, dual-colour break-apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. CONCLUSIONS: The present study suggests that the carcinogenesis of RBM10-TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10-TFE3 RCC should be considered, as five patients experienced metastases.

Esophageal Carcinosarcoma that Was Diagnosed as a Granulocyte-colony Stimulating Factor and Interleukin-6-producing Tumor with a Tumor Fever.

A 51-year-old man visited our hospital with a main complaint of precordial pain, difficulty swallowing, and pyrexia. The patient was diagnosed with esophageal carcinosarcoma, based on the characteristic morphology noted on upper gastrointestinal endoscopy and histology tests, and he underwent surgical treatment. His preoperative blood granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6) levels were high, and the surgical specimens were positive in both immunohistochemical tests; therefore, he was diagnosed with a G-CSF- and IL-6-producing tumor. When pyrexia is seen as a paraneoplastic symptom, it is important to consider and investigate the possibility of a cytokine-producing tumor.

Isolated breast metastasis from gastric cancer in a male patient.

A 72-year-old man underwent total gastrectomy for gastric cancer (por2, T3, N2, Stage IIIA). Eleven courses of postoperative chemotherapy with TS-1 (tegafur/gimeracil/oteracil) were administered. Five months after surgery, the serum carcinoembryonic antigen value was slightly elevated. However, computed tomography did not reveal any metastatic lesions in other organs. Two years after surgery, the patient felt a mass in the left mammary. A 2-cm tumor was palpable in the central portion of the breast. Ultrasonography revealed a hypoechoic tumor, which was Class 3 on aspiration biopsy cytological examination. No mass was detected on positron emission tomography-computed tomography. The mammary gland tumor increased in size to 3 cm, and a core needle biopsy procedure was performed. Histological examination findings revealed breast metastasis of gastric cancer. No other recurrence was found, and radical mastectomy was performed 2 years and 5 months after gastrectomy. Immunohistological analysis of the resected material confirmed breast metastasis of the gastric cancer. Two courses of TS-1 + cisplatin were administered, but this treatment was subsequently terminated because the patient experienced Grade 3 diarrhea and neutropenia. Three years and 1 month after the gastrectomy, the tumor recurred in the pelvic area. Chemotherapy and radiation therapy were performed, but the patient's overall condition became progressively worse, and he died 3 years and 9 months after gastrectomy.

Unicystic Ameloblastomatoid Cystic Craniopharyngioma: Pathological Discussion and Clinical Significance of Cyst Formation in Adamantinomatous Craniopharyngioma.

An 8-year-old boy presented complaining principally of headache and vomiting. A single large cystic lesion extending from the suprasellar region to the ventral brainstem was identified, and total extirpation was performed via a right orbitozygomatic, transtemporal transchoroidal fissure approach. The cyst contents resembled motor oil, and no strong adhesions were identified between the tumor and the surrounding tissue except at the site of origin of the tumor, allowing easy dissection. The tumor originated at the junction of the adenohypophysis and the pituitary stalk. Although the histopathological diagnosis was adamantinomatous craniopharyngioma, the cyst walls comprising the majority of the tumor were not thin, fragile tissues formed by squamous metaplasia, but were thick and robust, bearing a close resemblance to unicystic ameloblastoma mixed with solid tissue. The existence of this type of cyst wall represents corroborating evidence that craniopharyngiomas are derived from the oral primordium. The existence of such tumors that can be totally extirpated in a single procedure while preserving hypothalamo-pituitary function may be taken as a warning not to rush at random to perform treatments that might encourage recurrence or regrowth by carrying out cyst fenestration and drug injection with the addition of stereotactic radiotherapy.

Colonic low-grade endometrial stromal sarcoma and orthotopic endometrial stromal tumor with limited infiltration sharing the JAZF1-SUZ12 gene fusion.

Endometrial stromal tumors (ESTs) are composed of cells resembling endometrial stroma, and are divided into benign and malignant types based on morphology. Endometrial stromal nodule (ESN) is a benign localized tumor, and endometrial stromal sarcoma (ESS) is an infiltrative and potentially metastatic neoplasm. A series of genetic aberrations contribute to pathological diagnosis of ESTs. At present, subsets of ESN and ESS-low grade (ESS-LG) are characterized as JAZF1-SUZ12/JJAZ1 gene fusion. The ESTs that show higher grade atypia but lack nuclear pleomorphism include YWHAE-FAM22 ESS. Here we report an unusual case of ESTs. Sudden colonic perforation occurred to the patient, and emergency surgery was performed. Pathological findings suggested metastatic ESS. Thorough medical examination of the genital organs detected a 1 cm-sized well-demarcated uterine tumor. Microscopically, the tumor lacked infiltrative features, conforming to the definition of ESN. Both lesions demonstrated identical cytology and shared JAZF1-SUZ12 gene fusion. Endometriosis was not found in any areas of the resected organs, strongly suggesting that the uterine orthotopic tumor metastasized. The current case uncovered the problems of differential diagnosis between ESN and ESS-LG. We demonstrate detailed pathological features of the two lesions, and discuss the possibility of orthotopic EST with limited infiltration to develop into ESS-LG.

A strongly CD34-positive meningioma that was difficult to distinguish from a solitary fibrous tumor.

Fibrous or transitional meningioma and solitary fibrous tumor (SFT) are frequently difficult to differentiate from each other on the basis of histopathology. It is extremely unusual for a meningioma to exhibit diffuse, strongly positive immunoreactivity for cluster of differentiation 34 (CD34), and this has never been previously reported from a histopathological specimen. A patient with transitional meningioma that exhibited strongly positive for CD34, which has been regarded as characteristic of SFT and is considered to be useful for distinguishing the latter from meningioma, is reported.

Histopathologic profiles of coronary atherosclerosis by myocardial bridge underlying myocardial infarction.

OBJECTIVE: Anatomic properties of myocardial bridge (MB) are sometimes responsible for myocardial infarction (MI) through the changes in the atherosclerosis distribution in the left ascending coronary artery (LAD). The purpose of this study was to investigate histopathologic profiles of atherosclerotic lesions resulting from the MB presence in the LAD in the MI cases. METHODS: In 150 consecutive autopsied MI hearts either with MBs [MI(+)MB(+); n = 67] or without MBs [MI(+)MB(-); n = 83] and 100 normal hearts with MBs [MI(-)MB(+)], LADs were consecutively cross-sectioned at 5-mm intervals. The most advanced intimal lesion and unstable plaque-related lesion characteristics (UPLCs) in each section were histopathologically evaluated in conjunction with the anatomic properties of the MB, such as its thickness, length, location, and MB muscle volume burden (MMV: the total volume of MB thickness multiplied by MB length). RESULTS: The MB showed a significantly greater thickness (P = 0.0090), length (P = 0.0300), and MMV (P = 0.0019) in MI(+)MB(+) than in MI(-)MB(+). Mean age of acute MI cases was significantly younger (P = 0.0227) in MI(+)MB(+) than in MI(+)MB(-). Frequency of plaque fissure/rupture in the proximal LAD was significantly higher in acute MI cases of MI(+)MB(+) than in MI(+)MB(-). UPLCs tended to be located proximally in MI(+)MB(+) and frequent 2.0 cm or more proximal to the MB entrance in MI(+)MB(+). CONCLUSION: In MI(+)MB(+), UPLCs tend to be located more proximally, and a plaque in the LAD proximal to the MB is prone to rupture, resulting in MI at younger age.

Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: case report and discussion of etiology and pathology.

Craniopharyngiomas are histopathologically classified as adamantinomatous type (AD) and squamous-papillary type (SP). However coexistence of a mixed type seen on histopathologic specimens has not been reported. In this report, a patient diagnosed with mixed type craniopharyngioma is presented and the etiology and pathologic features are discussed.

Histopathological predictors of regional lymph node metastasis at the invasive front in early colorectal cancer.

AIMS: In early colorectal cancer (ECC), prediction of lymph node (LN) metastasis is vital for the decision of additional surgical treatment after endoscopic mucosal/submucosal resection. The aim of this study was to determine the relationship between LN metastasis and comprehensive histopathological findings including the cancer microenvironment in ECC. METHODS AND RESULTS: Using 111 ECC cases, including 36 cases with LN metastasis, histopathological observations and immunohistochemistry for lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, matrix metalloproteinase-7 (MMP-7), CXC chemokine ligand-12 (CXCL12) and angiopoietin-like-4 (ANGPTL4) were conducted. Relationships between LN metastasis and growth pattern, status of muscularis mucosae, depth of cancer invasion, overall histopathological type, histopathological type at the invasive front, tumour budding, neutrophil infiltration in cancer cells (NIC), fibrotic cancer-stroma type, Crohn's-like lymphoid reaction, microscopic abscess formation and lymphatic invasion were determined. In addition, the expression of MMP-7, CXCL12 and ANGPTL4 in cancer cells at the invasive front were also considered in the context of LN metastasis. By multivariate analysis, lymphatic invasion, NIC and MMP-7 expression at the invasive front were independent predictors of LN metastasis. CONCLUSIONS: LN metastasis is regulated not only by the characteristics of cancer cells but also by microenvironmental factors of lymphatics and neutrophils, especially at the invasive front.

[Deep sylvian meningioma without dural attachment: a case report].

A 34-year-old female presented with an 8-year history of temporal lobe epilepsy. Magnetic resonance imaging showed a multilobular, well-demarcated and homogeneous tumorous lesion of 5 cm in diameter deep in the left sylvian fissure. Intraoperative findings revealed that the tumor was mainly in the left insular region without dural attachment and strongly adhered to the left middle cerebral artery and its perforators. The histopathological diagnosis was transitional meningioma without malignancy. There are few reported cases of deep sylvian meningioma without dural attachment. We review the literature and summarize the clinicopathological characteristics of this condition.

Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial.

BACKGROUND: Experimental studies have revealed that green tea catechins and theanine prevent influenza infection, while the clinical evidence has been inconclusive. This study was conducted to determine whether taking green tea catechins and theanine can clinically prevent influenza infection. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial of 200 healthcare workers conducted for 5 months from November 9, 2009 to April 8, 2010 in three healthcare facilities for the elderly in Higashimurayama, Japan. INTERVENTIONS: The catechin/theanine group received capsules including green tea catechins (378 mg/day) and theanine (210 mg/day). The control group received placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of clinically defined influenza infection. Secondary outcomes were (1) laboratory-confirmed influenza with viral antigen measured by immunochromatographic assay and (2) the time for which the patient was free from clinically defined influenza infection, i.e., the period between the start of intervention and the first diagnosis of influenza infection, based on clinically defined influenza infection. RESULTS: Eligible healthcare workers (n = 197) were enrolled and randomly assigned to an intervention; 98 were allocated to receive catechin/theanine capsules and 99 to placebo. The incidence of clinically defined influenza infection was significantly lower in the catechin/theanine group (4 participants; 4.1%) compared with the placebo group (13 participants; 13.1%) (adjusted OR, 0.25; 95% CI, 0.07 to 0.76, P = 0.022). The incidence of laboratory-confirmed influenza infection was also lower in the catechin/theanine group (1 participant; 1.0%) than in the placebo group (5 participants; 5.1%), but this difference was not significant (adjusted OR, 0.17; 95% CI, 0.01 to 1.10; P = 0.112). The time for which the patient was free from clinically defined influenza infection was significantly different between the two groups (adjusted HR, 0.27; 95% CI, 0.09 to 0.84; P = 0.023). CONCLUSIONS: Among healthcare workers for the elderly, taking green tea catechins and theanine may be effective prophylaxis for influenza infection. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT01008020.

Chronic encapsulated intracerebral hematoma associated with cavernous angioma--case report.

An 80-year-old male presented with a chronic encapsulated intracerebral hematoma (CEIH) with surrounding edema under the right frontal lobe manifesting as slow exacerbation of disturbance of orientation and gait. He had a history of cerebral infarction with an asymptomatic cavernous angioma in the right frontal lobe. The CEIH was diagnosed as bleeding from the cavernous angioma, and surgical removal was performed. The hematoma was chronic and covered by a thick capsule. In addition, mass tissue covered with the organized hematoma was found near the capsule, which was excised and found to be a cavernous angioma. CEIH is a special type of intracerebral hemorrhage, and bleeding from a cavernous angioma is occasionally seen. CEIH should be considered in the case of a hemorrhagic intracranial lesion with a chronic, progressive course with capsule formation and edema around the lesion. The source of bleeding is unknown in about half of the reported cases, and occult vascular malformation may be involved, necessitating care in diagnosis.

Ciliated craniopharyngioma--case report and pathological study.

BACKGROUND: Craniopharyngioma has two subtypes: adamantinomatous and squamous-papillary. Squamous-papillary craniopharyngioma may develop from remnants of the craniopharyngeal duct, anterior pituitary cells with squamous metaplasia, suprasellar epidermoid cyst, or Rathke cleft cyst. AIM: While ciliated craniopharyngioma is considered to represent a transitional stage between Rathke cleft cyst and squamous-papillary craniopharyngioma, ciliated craniopharyngioma following Rathke cleft cyst at the same site has not previously been described. RESULTS: We report a case of ciliated craniopharyngioma developing from Rathke cleft cyst. CONCLUSION: The clinical course for this case is discussed together with a review of the pathological literature for ciliated craniopharyngioma.

Effects of co-administration of tea epigallocatechin-3-gallate (EGCG) and caffeine on absorption and metabolism of EGCG in humans.

Based on the ratios of (-)-epigallocatechin-3-gallate (EGCG) and caffeine (CAF) levels found in commercial tea drinks, EGCG and CAF were co-administered to human volunteers at various EGCG/CAF ratios, and plasma EGCG was determined by high performance liquid chromatography with chemiluminescence detection. As for the results, in plasma taken after ingestion of a beverage containing 95 mg of EGCG alone, the area under the plasma EGCG concentration-time curve (AUC) was 857 ngxh/ml. A higher AUC (1,370 ngxh/ml) was observed when subjects ingested a beverage containing EGCG (95 mg) and a low amount of CAF (40 mg). In the case of ingestion of a beverage containing EGCG (95 mg) and a high amount of CAF (180 mg), the AUC tended to be somewhat higher (1,165 ngxh/ml), but not significantly so, compared with the beverage with EGCG alone. These findings (modulation of plasma EGCG level by CAF) provide ideas for modulating the bioavailability of tea catechins, which can be applied to tea-related drinks and foods.