[A Case of Diffuse Large B-Cell Lymphoma Which Was Diagnosed during the Best Supportive Care of Recurrent Ascending Colon Cancer].

A 70s male, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N3M0, Stage Ⅲc(without adjuvant chemotherapy), had enhanced-computed tomography(CT)for 3-month follow-up and a hepatic low-density area, an newly emergent nodule behind inferior vena cava and distal ileal tumor were found. Three months later, enhanced CT showed that the distal ileal tumor got exponentially larger and the diagnosis of"malignant lymphoma"was suspected. The patient became sepsis, so we planned and safely performed partial resection of the tumor. The pathological diagnosis was diffuse large B-cell lymphoma. Postoperative course was smooth except for the Clostridium difficile colitis and he was discharged on postoperative day 19. Although the regrowth of the remnant tumor was observed soon after surgery, partial response was confirmed after introduction of systemic chemotherapy. When we cope with malignant lymphoma of small intestine, we need to keep it in mind that surgery is an option for the prevention of perforation and bacterial translocation.

[A Case of Fibromatosis-Like Tumor Which Was Difficult to Differentiate from Local Recurrence of Ascending Colon Cancer].

A 60s female, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N1bM0, Stage Ⅲb, followed by adjuvant therapy with 8 courses CAPOX 2 years ago, had enhanced- computed tomography(CT)for follow-up and a 15-mm nodule near anastomotic site was found. 18F-fluorodeoxyglucose (FDG)-positron emission tomography(PET)CT revealed abnormal accumulation of 18F-FDG only to the lesion and diagnosis of"anastomotic recurrence"was made. We planned and safely performed resection of the anastomotic site and the nodule. The pathological diagnosis was fibromatosis-like tumor without evidence of recurrence, and margin was negative. Postoperative course was smooth and she was discharged on postoperative day 9. When we diagnose local recurrence, we need to keep it in mind that fibromatosis is one of the differential diagnoses, although its incidence rate is low.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

KDM2B-Rearranged Soft Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma.

Sarcomas with BCOR genetic alterations (BCOR-associated sarcomas) represent a recently recognized family of soft tissue and bone tumors characterized by BCOR fusion, BCOR internal tandem duplication, or YWHAE::NUTM2B fusion. Histologically, the tumors demonstrate oval to spindle cell proliferation in a variably vascular stroma and overexpression of BCOR and SATB2. Herein, we describe 3 soft tissue sarcomas with KDM2B fusions that phenotypically and epigenetically match BCOR-associated sarcomas. The cases included 1 infant, 1 adolescent, and 1 older patient. All tumors showed histologic findings indistinguishable from those of BCOR-associated sarcomas and were originally diagnosed as such based on the phenotype. However, none of the tumors had BCOR or YWHAE genetic alterations. Instead, targeted RNA sequencing identified in-frame KDM2B::NUTM2B, KDM2B::CREBBP, and KDM2B::DUX4 fusions. KDM2B fusions were validated using reverse-transcription PCR, Sanger sequencing, and in situ hybridization assays. Genome-wide DNA methylation analysis matched all 3 tumors with BCOR-associated sarcomas using the Deutsches Krebsforschungszentrum (DKFZ) classifier and t-distributed stochastic neighbor embedding analysis. One localized tumor showed a flat genome-wide copy number profile, and the patient remained disease-free after treatment. The other tumors showed multiple copy number alterations, including MDM2/CDK4 amplification and/or CDKN2A/B loss, and both tumors metastasized, leading to the patient's death in one of the cases. When tested using KDM2B immunohistochemistry, all 3 KDM2B-rearranged sarcomas showed diffuse strong staining, and all 13 sarcomas with BCOR genetic alterations also demonstrated diffuse, strong, or weak staining. By contrast, among 72 mimicking tumors, only a subset of synovial sarcomas showed focal or diffuse weak KDM2B expression. In conclusion, our study suggests that KDM2B-rearranged soft tissue sarcomas belong to the BCOR-associated sarcoma family and expand its molecular spectrum. This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.

The effect of specimen processing time on HER2 expression in gastric cancer and esophagogastric junction cancer: a single-center retrospective observational study.

BACKGROUND: Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation. METHODS: The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing. RESULTS: Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44-8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51-10.55, p = 0.005), and time to specimen processing of < 120 min (OR: 2.65, 95% CI: 1.01-6.98, p = 0.049) were independent factors that affected HER2-positivity. CONCLUSIONS: The outcomes of the present study indicated that intestinal type, pM, and time to specimen processing are important factors affecting HER2-positive rates in GC and EGJC. Therefore, the risk of false-negative HER2 results may be reduced by decreasing the time required to process the resected specimen. Additionally, accurate diagnosis of HER2 expression may increase the opportunity to administer molecular-targeted drugs that can expect therapeutic effects to patients appropriately. TRAIL REGISTRATION: Retrospectively registered.

Mortality, Recurrent Thromboembolism and Major Bleeding in Cancer-Associated and Non-Cancer Pulmonary Embolism Patients Treated With Direct Oral Anticoagulants.

BACKGROUND: Pulmonary embolism (PE) is a potentially fatal form of venous thromboembolism (VTE). This study compares the mortality, incidence of recurrent VTE, and incidence of major bleeding between non-cancer and cancer-associated PE patients treated with direct oral anticoagulants (DOACs).Methods and Results:This was a retrospective, observational, single-center study involving 130 consecutive patients (87 with active cancer; 43 without cancer) who received DOAC treatment for PE between January 2016 and December 2019. Kaplan-Meier analysis showed significantly higher mortality in cancer-associated PE patients than in non-cancer patients (35/87 [40%] vs. 1/43 [2%], P<0.001, log-rank test, HR 18.6 [95% CI: 2.5-136.0]). In contrast, the cumulative incidences of recurrent VTE and major bleeding were comparable between the 2 groups. Among the cancer-associated PE patients, the incidence for the composite outcome of recurrent VTE or major bleeding was significantly higher in patients undergoing chemotherapy than in those not undergoing chemotherapy (9/37 [24%] vs. 2/50 [4%], P=0.004, log-rank test, HR 6.9 [95% CI: 1.5-32.0]). CONCLUSIONS: Although cancer-associated PE patients treated with DOACs showed higher mortality compared with non-cancer patients, presumably because of the presence of cancer, the risk of recurrent VTE or major bleeding was comparable between the 2 groups. Thus, DOAC is an important treatment option for cancer-associated PE, although underlying cancer-related risks (e.g., chemotherapy) remain.

Lymphangioleiomyoma of the Uterus and Pelvic Lymph Nodes: A Report of 3 Cases, Including the Potentially Earliest Manifestation of Extrapulmonary Lymphangioleiomyomatosis.

We present 3 cases of extrapulmonary lymphangioleiomyomatosis (LAM) identified incidentally in the uterine corpus and pelvic nodes resected for other reasons. One patient, a 47-yr-old female with corpus cancer, underwent a total hysterectomy and nodal dissection; the other 2 patients, aged 44 and 49 yr, underwent simple hysterectomy for corpus leiomyomas. None of the patients had evidence of tuberous sclerosis complex or any significant lesions in other organs. An area of spindle cell proliferation, intimately associated with dilated and tortuous lymphatic vessels, was found in the myometrium of all 3 patients, and nodal involvement with spindle cell proliferation was observed in the patient with corpus cancer. The spindle cells had faintly eosinophilic cytoplasm and a bland appearance. They were immunoreactive for α-SMA, gp100 (HMB45), and Melan-A. Tumor cell clusters lined with a single layer of lymphatic endothelium were floating in the lymphatic vessel lumen. These lesions were diagnosed as lymphangioleiomyoma in the uterine corpus and associated lymph nodes. Two of the cases seemed to be the earliest manifestations of extrapulmonary LAM, and the other case represents early-phase metastasis of LAM from the uterus. The present cases support the speculation that the uterus is the primary source of LAM cells.

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry.

Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein-Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed-Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing 'confluent' sheets in the diagnostic workup for SV-CHL.

Assessment of Severity in Chronic Thromboembolic Pulmonary Hypertension by Quantitative Parameters of Dual-Energy Computed Tomography.

OBJECTIVE: The objective of this study was to assess the correlation between dual-energy computed tomography quantitative parameters and hemodynamics in patients with chronic thromboembolic pulmonary hypertension. METHODS: Dual-energy computed tomography of 52 chronic thromboembolic pulmonary hypertension patients were evaluated retrospectively. The mean lung perfused blood volume (lung PBV) and the mean pulmonary artery (PA) enhancement measured at pulmonary parenchymal phase were compared with the hemodynamics by Spearman rank correlation coefficient (rs) and receiver operating characteristic analysis. RESULTS: Lung PBV was correlated with mean pulmonary arterial pressure (rs = 0.47, P < 0.001). Pulmonary artery enhancement was correlated with cardiac index (rs = -0.49, P < 0.001) and pulmonary vascular resistance (rs = 0.48, P < 0.001). The areas under the curves were 0.86 for lung PBV to predict mean pulmonary arterial pressure of >50 mm Hg and 0.86 for PA enhancement to predict pulmonary vascular resistance of >1000 dyne·s/cm. CONCLUSIONS: Lung PBV and PA enhancement could be indicators of hemodynamics.

Single-center prognostic validation of the risk assessment of the 2015 ESC/ERS guidelines in patients with pulmonary arterial hypertension in Japan.

The 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension include a multidimensional risk assessment for patients with pulmonary arterial hypertension (PAH). However, prognostic validations of this risk assessment are limited, especially outside Europe. Here, we validated the risk assessment strategy in PAH patients in our institution in Japan. Eighty consecutive PAH patients who underwent right heart catheterization between November 2006 and December 2018 were analyzed. Patients were classified as low, intermediate, or high risk by using a simplified version of the risk assessment that included seven variables: World Health Organization functional class, 6-min walking distance, peak oxygen consumption, brain natriuretic peptide, right atrial pressure, mixed venous oxygen saturation, and cardiac index. The high-risk group showed significantly higher mortality than the low- or intermediate-risk group at baseline (P < 0.001 for both comparisons), and the mortalities in the intermediate- and low-risk groups were both low (P = 0.989). At follow-up, patients who improved to or maintained a low-risk status showed better survival than those who did not (P = 0.041). Our data suggest that this risk assessment can predict higher mortality risk and long-term survival in PAH patients in Japan.

Automatic Remasking of Digital Subtraction Angiography Images in Pulmonary Angiography.

In pulmonary angiography, the heartbeat creates artifacts that hinder extraction of blood vessel images in digital subtraction angiography. Remasking according to the cardiac phase of the angiogram may be effective but has yet to be automated. Here, automatic remasking was developed and assessed according to the cardiac phase from electrocardiographic information collected simultaneously with imaging. Manual remasking, fixed remasking, and our proposed automatic remasking were applied to 14 pulmonary angiography series from five participants with either chronic thromboembolic pulmonary hypertension or pulmonary arteriovenous malformation. The processing time and extent of artifacts from the heartbeat were compared. In addition, the peak signal-to-noise ratio (PSNR) was measured from differential images between mask image groups before the injection of the contrast medium to investigate optimal mask images. The mean time required for automatic remasking was 4.7 s/series, a significant reduction in processing time compared with the mean of 266 s/series for conventional manual processing. A visual comparison of the different approaches showed virtually no misregistration artifacts from the heartbeat in manual or automatic remasking according to cardiac phase. The results from measuring the PSNR for differential images between mask image groups also showed that smaller cardiac phase difference and time difference between two images ensure higher PSNR (p < 0.01). Automatic remasking according to the cardiac phase was fast and easy to implement and reduced misregistration artifacts from heartbeat.

Effects of Tobacco Smoking on Cardiovascular Disease.

Tobacco smoking continues to be a major risk factor for cardiovascular disease (CVD) and the leading avoidable cause of death worldwide. Tobacco smoking has declined in high-income countries, but the average smoking rate in Japan remains high: 29.4% for men and 7.2% for women in 2017. Of note, the average smoking rate among middle-aged men remains approximately 40%, indicating that a high incidence of smoking-related CVD will continue for a couple of decades in Japan. The adverse effects of tobacco smoking on CVD are more extensive than previously thought. Physicians should be particularly alert to the development and progression of heart failure, atrial fibrillation, and venous thromboembolism, as well as ischemic CVD among tobacco smokers. Increasing use of heat-not-burn tobacco as cigarette alternatives is an emerging issue. Harmful effects do not disappear just by changing the delivery system of tobacco.

Follicular cholangitis mimicking cholangiocarcinoma treated with right hepatectomy: A case report and review of published works.

Follicular cholangitis is a new, rare disease that causes severe biliary stricture. We herein describe the findings from a resected case of follicular cholangitis, suggesting a distinct disease entity that causes benign biliary stricture. A 60-year-old man who was referred to our hospital due to elevated γ-glutamyl transpeptidase levels and dilatation of the B8 bile duct. Although bile juice cytology and bile duct brushing cytology showed no malignancy, the dilatation was progressive. Therefore, right hepatectomy combined with caudate lobectomy was carried out on suspicion of intrahepatic cholangiocarcinoma. The wall of the resected bile duct was markedly thickened due to severe fibrosis under the mucosal layer. Histology of the mucosal epithelium indicated no malignancy. Infiltration of plasma cells characterized by remarkable formation of lymphoid follicles with germinal centers was observed around the bile ducts. The patient was diagnosed with follicular cholangitis based on histological findings. We thus observed a rare case of follicular cholangitis. This case and review of published reports suggest that, despite its rarity, follicular cholangitis should be considered at the differential diagnosis of biliary stricture. This case report could contribute to a better understanding of how to address this disease.

Medium-term health-related quality of life in patients with pulmonary arterial hypertension treated with goal-oriented sequential combination therapy based on exercise capacity.

BACKGROUND: Pulmonary arterial hypertension (PAH) remains a life-threatening condition, despite modern therapies. We prospectively investigated the therapeutic health-related quality of life (HRQOL) effects of goal-oriented sequential combination therapy based on exercise capacity in patients newly diagnosed with PAH. METHODS: To examine the changes in HRQOL in PAH patients, we treated 30 patients newly diagnosed with PAH with goal-oriented sequential combination therapy based on exercise capacity. We monitored exercise capacity by cardiopulmonary exercise testing and observed the benefit of using a peak VO2 cut-off of 15 mL/kg/min to guide combination therapy. First-line treatment was an endothelin receptor antagonist (ERA); second-line treatment was the addition of a phosphodiesterase-5 inhibitor (PDE-5I). At baseline and at 3, 6, and 12 months, HRQOL was evaluated by using the eight-item Medical Outcomes Survey Short Form Health Survey. RESULTS: At 12 months, 100% of PAH patients were receiving an ERA, and 82% an ERA + PDE-5I. The mean physical component summary (PCS) score was 33.5 at baseline, 41.2 at 3 months, 40.8 at 6 months, and 42.0 at 12 months, and the mean mental component summary (MCS) scores were 45.6, 47.0, 50.0, and 50.1, respectively. PCS score was significantly greater at 3 months than at baseline (P = 0.035). MCS score was comparable at 3 months and at baseline, but was significantly greater at 6 and 12 months than at baseline (P = 0.033, P = 0.028, respectively). Thus, PCS score improved soon after initiation of therapy, and MCS score improved later. CONCLUSIONS: Together, these results suggest that goal-oriented sequential combination therapy based on exercise capacity improves HRQOL in patients with PAH.

[A Resected Case of Reactive Lymphoid Hyperplasia of the Liver Preoperatively Diagnosed as Hepatocellular Carcinoma].

A60s woman was followed-up regularly for primary biliary cholangitis and a solitary enlarging hepatic mass in the S6 segment of her liver was discovered by ultrasonography. We diagnosed the mass as hepatocellular carcinoma by contrast ultrasonography, contrast computed tomography, and ethoxbenzyl magnetic resonance imaging and laparoscopic partial hepatectomy of S6 segment was performed. The resected specimen was histopathologicaly diagnosed as liver-reactive lymphoid hyperplasia(RLH). The patient is alive without recurrence 17 months after the surgery. Although liver RLH is a rare disease, it should be considered in the differential diagnosis of small liver tumors.

[Pulmonary Metastases of Hepatocellular Carcinoma Treated with Repeated Pulmonary Resection-A Case Report].

A 65-year-old man visited our hospital for hepatocellular carcinoma(HCC)and underwent extended posterior sectionectomy. Eight months after the hepatic resection, follow-up computed tomography(CT)revealed a solitary, recurrent tumor in S4 of the liver, and transcatheter arterial chemoembolization and radiofrequency ablation were performed for the intrahepatic recurrence. After 12 postoperative months, follow-up CT demonstrated pulmonary metastases in S5 of the right lung and S10 of the left lung. Since there were no other metastases, the 2 metastatic lesions were resected using video-assisted thoracoscopic surgery(VATS). The resected tumors were histologically diagnosed as pulmonary metastases of HCC. Three years after the pulmonary resection, 3 additional pulmonary metastases were detected on CT in S3 and S10 of the right lung and S4 of the left lung. No other metastases were found. Bilateral VATSmetastasectomy was performed for the metastases. The tumors were diagnosed as pulmonary metastases of HCC on histological examination. One year and 8 months after the surgery, he was alive in a good condition, with no recurrences. The present case suggested that some patients with pulmonary metastasis of HCC can have long-term survival with surgical resection of the metastasis. Therefore, while systemic chemotherapy is generally considered the standard treatment for extrahepatic metastasis of HCC, surgical resection might be an option.

[Long-Term Survival after Surgical Treatment of Neuroendocrine Carcinoma of the Ampulla of Vater-A Case Report].

A 60s man underwent upper gastrointestinal endoscopy at a regular medical check-up without symptoms, which showed an ulcerative region in the duodenal ampulla, measuring 3 cm in diameter. He was diagnosed with poorly differentiated adenocarcinoma on biopsy and referred to our hospital. Abdominal contrast-enhanced CT scan revealed an enhanced-ulcerative tumor, measuring 3 cm, at the duodenal ampulla. After the preoperative diagnosis of adenocarcinoma of the duodenal ampulla, subtotal stomach-preserving pancreatoduodenectomy with regional lymph node dissection was performed. The final diagnosis was neuroendocrine carcinoma(NEC)of the duodenal ampulla. He has been alive for 9 years with no recurrences. NEC of the duodenal ampulla is rare, and its prognosis is poor. We report a case of long-term survival after resection of NEC of the duodenal ampulla.

[A Case of Resected Primary Hepatic Neuroendocrine Tumor].

A 70s man presented with a solitary liver tumor measuring 4.5 cm on CT. On contrast-enhanced CT, the tumor appeared partly well-enhanced in the late phase, and the remaining part was enhanced in the early phase and washed out in the late phase. Contrast-enhanced MRIshowed fused multiple nodules, and the enhancement/washout pattern was clearer than that of the contrast-enhanced CT. The tumor showed a defective image in the hepatobiliary phase and a high signal on diffusionweighted imaging. Then, the tumor was diagnosed as hepatocellular carcinoma, and thus, left liver lobectomy was performed. On histological examination of the resected specimen, the tumor was found to be composed of uniform and small tumor cells with solid or trabecular growth fashion. On immunohistochemical staining, synaptophysin and chromogranin A positivity was noted, and the Ki-67 index was 14%. Finally, the tumor was diagnosed as a NET G2. Postoperatively, somatostatin receptor scintigraphy was performed to identify the primary site; however, no obvious primary site could not be identified, and thus a diagnosis of primary hepatic NET was made. Eighteen months postoperatively, the patient is alive without relapse. Preoperative diagnosis of primary hepatic NETs is difficult because NETs present various imaging findings and are rare. Moreover, no accurate preoperative diagnosis was reached in our case, suggesting the difficulty in the preoperative diagnosis of NETs.