Hepatic failure in a patient with rheumatoid arthritis treated with methotrexate: A case report.

INTRODUCTION: Chronic liver damage from methotrexate (MTX) is not uncommon, and fatal outcome is rare. We experienced a case of hepatic failure leading to death. We considered the cause of death through this case and proposed a method to prevent the progression of this liver injury. PATIENT CONCERNS: We report the case of a patient with rheumatoid arthritis treated with MTX for 15 years. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: A liver biopsy revealed histological changes similar to those of advanced nonalcoholic steatohepatitis (NASH), most likely induced by MTX. MTX was discontinued after 4 years. Two years after the discontinuation, the patient died of irreversible hepatic failure. Her obesity, complicated by type 2 diabetes mellitus, might have aggravated MTX-induced NASH-like liver injury. CONCLUSION: Early diagnosis and immediate MTX discontinuation following NASH diagnosis and strict type 2 diabetes mellitus control might have prevented the irreversible progression of liver injury.

[A Case of Ileal Perforated Peritonitis 50 Years after Radiotherapy for Uterine Cancer].

Here we report a rare case of peritonitis caused by radiation enteritis. The 82-year-old woman who underwent surgery and radiotherapy for uterine cancer in her 30s. Emergency operation was performed for the perforation of the ileum. The small intestine showed changes of radiation enteritis extensively on macroscopy. The first surgery was performed to resect the perforated ileum and make intestinal anastomosis at the change of radiation enteritis. However, suture failure was occurred, reoperation was performed after conservative therapy. Reoperation was performed extensively resection of the intestinal tract and made anastomosis where was mild change of radiation enteritis. Pathological findings of the intestinal stump revealed that the arterial vessels of the submucosal layer were highly thicken and the lumen of artery was stenosis and occlusion with severe changes of radiation enteritis at the first operation. Blood flow disorders by irradiation were presumed to be the cause of suture failure. On the other hand, the intestinal stump did not indicate thickened of vascular wall and lumen stenosis of the vessels, only edematous changes in the submucosal layer were observed at the reoperation. It was important to determine the surgical procedure with the change of radiation enteritis for gastrointestinal operation with abdominal irradiation.

Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1.

BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.

Validation of the fibrosis-4 (FIB-4) index in the diagnosis of liver disease of rheumatoid arthritis patients treated with methotrexate.

Objectives: To validate the usefulness of a hepatic fibrosis scoring system fibrosis-4 (FIB-4) index to diagnose liver diseases in rheumatoid arthritis (RA) patients treated with methotrexate (MTX).Methods: The FIB-4 index (age(years) × AST(U/L)/platelet (PLT) (109/L) × âˆšALT(U/L)), proposed as a predictor for liver fibrosis in HIV/HCV coinfection, was evaluated in this study. RA patients on MTX treatment were screened by FIB-4 index values to detect fibrotic change in the liver. Liver biopsy specimens were examined histologically in patients with high values.Results: Thirteen of 14 patients showed histology closely resembling non-alcoholic steatohepatitis. In three of them, two biopsies were performed: 1st, during MTX treatment; and 2nd, after discontinuation of MTX. All of them showed improvement in histology along with decreased FIB-4 values. Age, AST/√ALT, and 1/PLT, as well as creatinine levels and cumulative MTX doses were significantly higher in the high FIB-4 group compared with the low FIB-4 group. In the high FIB-4 group, 1/PLT and AST/√ALT were significantly correlated with FIB-4 values, but age was not.Conclusions: The FIB-4 index is simple to calculate and a valuable marker to diagnose liver disease in RA patients treated with long-term MTX administration.

[Airway obstruction due to localized tracheal lesion of extranodal NK/T-cell lymphoma, nasal type].

A 76-year-old man presented with a tracheal tumor associated with severe respiratory obstruction. A tracheotomy was performed due to respiratory failure. F-fluorodeoxyglucose (FDG) -positron emission tomography/computed tomography revealed an abnormal accumulation of FDG (maximum standardized uptake value: 16) in the trachea. A histopathological examination of the tracheal biopsy revealed extranodal NK/T-cell lymphoma, nasal type (ENKL). He was treated with concurrent radiotherapy (50 Gy) for the tracheal tumor and three courses of two-thirds dose ofdexamethasone, etoposide, ifosfamide, and carboplatin. Although the tumor responded remarkably well to this therapy, the patient died of an ENKL recurrence in the lungs and liver 11 months post therapy.

Behçet disease associated with gastrointestinal amyloidosis manifested as hematochezia: A case report.

RATIONALE: Behçet disease (BD) is an inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, ocular lesions, and skin lesions. Complication of amyloidosis in patients with BD is rare. Here, we report a case of BD with immunoglobulin light chain (AL)-amyloidosis manifested as hematochezia. PATIENT CONCERNS: A 61-year-old man developed sudden hematochezia due to bleeding from multiple small colonic ulcers; AL-amyloid deposition was found on immunohistochemical examination of biopsy specimen of colonic ulcer. Systemic investigation revealed cardiac disfunction with cardiomegaly and progressive renal dysfunction, which indicated the presence of systemic AL-amyloidosis. DIAGNOSES: Based on the findings of colonic ulcers with cardiac and renal involvement, a diagnosis of systemic AL-amyloidosis complicated by incomplete BD was established. INTERVENTIONS: He was treated with increased dose of oral prednisolone (20 mg/day), colchicine and mesalazine, because he was reluctant to receive aggressive chemotherapy (melphalan and dexamethasone) or autologous stem cell transplantation. OUTCOMES: Colonic ulcers completely diminished after treatment, however, he died because of severe urinary tract infection and progressive renal failure after one year of gastrointestinal (GI) manifestations. LESSONS: Our case shows that patients with BD may have GI manifestations due not only to entero-BD but also due to GI amyloidosis.

Usefulness of fluorodeoxyglucose positron emission tomography/computed tomography for detection of a neuroblastic nodule in a ganglioneuroblastoma: a case report.

BACKGROUND: Ganglioneuroblastoma, nodular is defined as a composite tumor of biologically distinct clones. The peripheral neuroblastic tumors in this category are characterized by the presence of grossly visible neuroblastoma nodules coexisting with ganglioneuroblastoma, intermixed, or with ganglioneuroma. Making a correct diagnosis of ganglioneuroblastoma, nodular is often difficult by biopsy or partial tumor resection, because the neuroblastic nodule could be hidden and not sampled for pathological examination. CASE PRESENTATION: We report a case of a Japanese boy aged 3 years, 8 months, with an unresectable abdominal tumor and elevated vanillylmandelic acid and homovanillic acid levels. The initial biopsy was ganglioneuroma. However, after the second biopsy from a hidden neuroblastoma nodule that was clearly highlighted by fluorodeoxyglucose positron emission tomography/computed tomography, we reached the diagnosis of ganglioneuroblastoma, nodular. Because the nodule demonstrated neuroblastoma, differentiating subtype, with a low mitosis-karyorrhexis index (favorable histology) and nonamplified MYCN, the boy was treated according to the intermediate-risk protocol and is now alive and well 4 years after the diagnosis. CONCLUSIONS: This case illustrates the critical role of fluorodeoxyglucose positron emission tomography/computed tomography for detecting a neuroblastoma nodule in a ganglioneuroblastoma.

A novel gene expression scoring system for accurate diagnosis of basaloid squamous cell carcinoma of the esophagus.

Basaloid squamous cell carcinoma of the esophagus (BSCE) is a rare variant of squamous cell carcinoma that is difficult to distinguish from other carcinomas by preoperative endoscopic biopsy because of its histological varieties. Accurate diagnosis is essential for adequate treatment, and the methods proposed so far (e.g., immunohistochemical staining) have limitations. In this study, we tried to identify the characteristic bundles of gene expression in BSCE using comprehensive gene expression analysis (CGEA). Subsequently, we constructed a gene expression scoring system for the proper diagnosis of BSCE. Fifty-seven surgical specimens, including seven BSCEs, obtained from 30 patients who underwent esophagectomy were used for constructing the scoring system. Three hundred and twelve biopsy specimens, including eight BSCEs, obtained from 80 patients and 20 commercially available formalin-fixed paraffin-embedded (FFPE) specimens diagnosed as esophageal cancer, including 13 BSCEs, were used for validation. After our original mathematical extraction algorithm, 75 genes were extracted to distinguish BSCE from non-BSCE. The cumulative converted values (gene expression score) of the respective 75 genes from each specimen were obtained and lined up in ascending order to assess the optimal gene expression cut-off score for a definitive diagnosis of BSCE. The validation of this scoring system showed high prediction of the biopsy specimens [area under the curve (AUC)=0.981; 95% confidence interval (CI): 0.952­1.000] and the commercially available FFPE specimens (AUC=0.901; 95% CI: 0.750-1.000). In conclusion, using CGEA in a gene expression scoring system helps in differentiating BSCE from non-BSCE with high accuracy and may contribute in improving BSCE treatment.

Placental recess accompanied by a T2 dark band: a new finding for diagnosing placental invasion.

PURPOSE: Our aim was to assess the usefulness of a new magnetic resonance imaging (MRI) finding, the placental recess, for diagnosing placental invasion. METHODS: This retrospective study included 51 patients (mean age 34.1 years, range 26-43 years) with suspected placental invasion who underwent cesarean section. Preoperative MRI was performed using a 1.5-T unit and included axial, sagittal, and coronal T2-weighted imaging (T2WI) with half-Fourier fast spin-echo sequences. Overall, 9 patients showed placental invasion, and 42 did not. Placental recess was defined as a placental deformity with contraction of the placental surface and outer rim of the uterus accompanied by a T2 dark band. Two radiologists independently assessed the presence of the placental recess and conventional findings including uterine bulging, abnormal placental vascularity, placental heterogeneous intensity on T2-weighted imaging (T2WI), and the T2 dark band. Fisher's two-sided exact test was used to compare findings between patients with and without placental invasion. Interobserver reliability was assessed using the kappa statistic. RESULTS: MRI features had interobserver reliability of >0.40. Placental recess yielded the highest kappa value (0.898). Significant differences were identified between patients with and without placental invasion regarding abnormal placental vascularity, placental heterogeneous intensity, a T2 dark band, and the placental recess on T2WI (p = 0.0282, 0.0003, 0.0003, <0.0001, respectively). The placental recess had sensitivity, specificity, positive and negative predictive values, and accuracy of 56, 100, 100, 91, and 92%, respectively. CONCLUSION: The placental recess was useful for diagnosing placental invasion, with high interobserver variability and accuracy.

M1 macrophage infiltrations and histological changes in the liver after portal vein embolization using fibrinogen and OK432 in the rat.

The mechanism of anti-tumor effect of transarterial Immuno-Embolization (TIE) using OK-432 has not been well elucidated. In this study, we aimed to investigate the tissue injury and immune response after portal venous embolization (PVE) with/without OK-432. Embolic materials (L group: lipiodol, LF group: lipiodol+fibrinogen, LO group: lipiodol+OK-432, LFO group: lipiodol+fibrinogen+OK-432) were administered via the right portal vein in Wistar rats. The histological findings in LFO group demonstrated liver damage with severe architectural changes. The concentrations of CD68(+) cells were observed in a time-dependent manner; it was significantly increased in the LO group on day 1 and in the LFO group on day 3. CD68(+)CD163(-) macrophages significantly increased in the LFO group on day 7 (P<0.05). In conclusion, PVE with fibrinogen and OK-432 markedly increased the CD68(+)CD163(-) infiltrating macrophages around the peri-portal area in the liver. This novel technique could be applied as immune-enhanced chemo-embolization of liver tumors.

[A Case of Primary Poorly Differentiated/Small Cell Carcinoma of the Breast in a Patient with Von Recklinghausen's Disease].

We report a case of neuroendocrine carcinoma and poorly differentiated/small cell carcinoma ofthe breast in a patient with von Recklinghausen's disease. The patient was a 46-year-old woman who was diagnosed with von Recklinghausen's disease when she was 22 years old. She presented with left breast pain, and physical examination revealed a firm mass in the left breast. A core needle biopsy of the tumor revealed triple negative breast cancer with neuroendocrine features. We performed a simple mastectomy with lymph node dissection. We did not plan neoadjuvant chemotherapy because the tumor would be possibly inoperative if neoadjuvant chemotherapy was not effective for this neuroendocrine cancer. The tumor was diagnosed as a neuroendocrine carcinoma and poorly differentiated/small cell carcinoma. The patient was treated with CDDP and CPT- 11, which is a regimen often used to treat small cell lung cancer.

[Surgical Resection for a Metachronous Liver Metastasis of an Esophagogastric Junction Adenocarcinoma].

The patient was a 56-year-old man with advanced esophagogastric junction cancer. He received neoadjuvant chemotherapy with 5-FU plus CDDP followed by lower esophagectomy and total gastrectomy via the left thoracoabdominal approach in October 2011. Pathological examination revealed EGJ adenocarcinoma (ypT4aN1M0, Stage ⅢA, Japanese Classification of Gastric Carcinoma ver.14), and histological analysis indicated Grade 0 (no change). Adjuvant chemotherapy with S-1 was administered. Nevertheless, 6 months after the operation, a solitary hepatic metastasis (f: 32 mm) was detected in S7 of the liver. The patient underwent proton beam irradiation of the liver metastasis, resulting in a complete response, and he was followed up without any chemotherapy. However, 21 months after the irradiation, regrowth of the previous lesion with FDG re-accumulation was noted. Given the absence of any neoplasms other than the liver metastasis, right hepatic lobectomy was performed. Pathological examination revealed a small cluster of viable tumor cells surrounded by extensive fibrotic tissue (Grade 2). At 45 months after the initial operation (10 months after the liver lobectomy), the patient is living without any signs of recurrence. Surgical resection for liver metastasis of EGJ cancer may be feasible after careful selection.

Pleural solitary fibrous tumor complicated with autoimmune hemolytic anemia.

We herein report a 74-year-old woman who presented with autoimmune hemolytic anemia (AIHA) associated with pleural solitary fibrous tumor (SFT). Her AIHA was initially treated with 1 mg/kg daily of oral prednisolone (PSL) for 2 months, which had a limited effect. However, after surgical tumor resection, the patient showed remarkable improvement of AIHA with normalizations of serum lactate dehydrogenase and bilirubin levels, and we were able to rapidly reduce the PSL dosage. This is the first description of a case of AIHA caused by SFT.

Radiological and pathological characteristics of giant cell tumor of bone treated with denosumab.

We describe a case of giant cell tumor of the proximal tibia with skip bone metastases of the ipsilateral femur in a 20-year-old man. After the neoadjuvant treatment with denosumab, plain radiographs and computed tomography showed marked osteosclerosis and sclerotic rim formation, and 18F-FDG PET/CT showed a decreased standardized uptake value, whereas magnetic resonance imaging showed diffuse enhancement of the tumor, nearly the same findings as those at pretreatment. Pathological findings of the surgical specimen after the denosumab treatment showed benign fibrous histiocytoma-like features with complete disappearance of both mononuclear stromal cells and multinuclear osteoclast-like giant cells. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1090602085125068.

An automated spring-loaded needle for endoscopic ultrasound-guided abdominal paracentesis in cancer patients.

AIM: To evaluate the feasibility of using an automated spring-loaded needle device for endoscopic ultrasound (EUS)-guided abdominal paracentesis (EUS-P) to see if this would make it easier to puncture the mobile and lax gastric wall for EUS-P. METHODS: The EUS database and electronic medical records at Fukushima Medical University Hospital were searched from January 2001 to April 2011. Patients with a history of cancer and who underwent EUS-P using an automated spring-loaded needle device with a 22-gauge puncture needle were included. The needle was passed through the instrument channel and advanced through the gastrointestinal wall under EUS guidance into the echo-free space in the abdominal cavity and ascitic fluid was collected. The confirmed diagnosis of malignant ascites included positive cytology and results from careful clinical observation for at least 6 mo in patients with negative cytology. The technical success rate, cytology results and complications were evaluated. RESULTS: We found 11 patients who underwent EUS-P with an automated spring-loaded needle device. In 4 cases, ascites was revealed only with EUS but not in other imaging modalities. EUS-P was done in 7 other cases because there was minimal ascitic fluid and no safe window for percutaneous abdominal aspiration. Ascitic fluid was obtained in all cases by EUS-P. The average amount aspirated was 14.1 mL (range 0.5-38 mL) and that was sent for cytological exam. The etiology of ascitic fluid was benign in 5 patients and malignant in 6. In all cases, ascitic fluid was obtained with the first needle pass. No procedure-related adverse effects occurred. CONCLUSION: EUS-P with an automated spring-loaded needle device is a feasible and safe method for ascites evaluation.

MCP-1 promotes invasion and adhesion of human ovarian cancer cells.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) can accelerate tumor progression by attracting tumor-associated macrophages. We studied the effects of MCP-1 on SKOV-3 cells in order to investigate MCP-1 biological activity ovarian cancer. MATERIALS AND METHODS: A SKOV-3 cell invasion assay (Transwell assay) and cell adhesion assay (96-well assay) were performed. Immunohistochemical staining for C-C motif chemokine receptor-2 (CCR2), a receptor for MCP-1, was also performed on cultured SKOV-3 cells. RESULTS: Migration and adhesion of MCP-1-treated SKOV-3 cells were significantly increased compared to untreated cells (p<0.01). A CCR2 antagonist attenuated the invasion and adhesion of MCP-1-treated cells. CCR2 was expressed in the cytoplasm of SKOV-3 cells. CONCLUSION: MCP-1 promoted invasion and adhesion of ovarian cancer cells, and a CCR2 antagonist attenuated the effects of MCP-1 in vitro. These data suggest that MCP-1 is a potential therapeutic target for ovarian cancer therapy.

A Japanese case of chronic lymphocytic leukemia with t (1;6).

Chronic lymphocytic leukemia (CLL) rarely exhibits an aggressive clinical course and its patients often have chromosomal deletions or additions. Furthermore, reciprocal translocations are barely observed in CLL. There have only been a few reports of CLL with t(1;6), and here we report the first Asian case of CLL with reciprocal translocation t(1;6). Since our case and previously reported CLL patients with t(1;6) consistently showed aggressive clinical course, t(1;6) may define a distinct type of CLL.

Prospective evaluation of the optimal number of 25-gauge needle passes for endoscopic ultrasound-guided fine-needle aspiration biopsy of solid pancreatic lesions in the absence of an onsite cytopathologist.

INTRODUCTION: A prior study with 22-gauge needles recommended more than seven needle passes for endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) of solid pancreatic lesions (SPL) without onsite cytopathology for optimal acquisition of cytopathological diagnosis. The feasibility of this recommendation should be re-evaluated considering the later development and popularity of 25-gauge EUS-FNA needles. We aimed to determine the optimal number of needle passes for cytopathological specimen acquisition with 25-gauge needles for EUS-FNA of SPL. METHODS: A preliminary prospective study of 22 patients with an onsite cytopathology technician showed a sensitivity of 93.3% and a specificity of 100% with four needle passes that was not statistically different from five needle passes. Based on our preliminary study, we fixed the number of needle passes to four (Group A). As a control group, we carried out sampling in consecutive patients using 25-gauge needles with an onsite cytopathologist (Group B). Sampling rate, diagnostic value and complications were evaluated. RESULTS: We enrolled 20 patients in each group. Sampling rate was higher in Group B (20/20, 100%) than in Group A (19/20, 95%), but there was no statistical difference between them (P-value = 0.31). In Group A, sensitivity, specificity and accuracy were 100% among 19. In Group B, sensitivity was 94.1%, specificity 100%, accuracy 95%. There were also no statistical differences between the groups. No complications were seen. CONCLUSION: Our study suggests that four needle passes using a 25-gauge needle may be sufficient for EUS-FNA of SPL where onsite cytology is not available.

Case of scrub typhus complicated by severe disseminated intravascular coagulation and death.

Scrub typhus is an infectious disease that is caused by Orientia tsutsugamushi. The authors describe an autopsied case of scrub typhus complicated with severe disseminated intravascular coagulation (DIC). An 82-year-old man complained of fever 4 days after climbing a mountain. The patient was admitted to an urban hospital, and meropenem and ceftriaxone were administered. The patient's condition deteriorated and he was transferred to a second hospital. On physical examination, a black scab was found and scrub typhus was suspected. Despite intensive treatment, the patient died on the fifth day. High levels of O. tsutsugamushi IgM antibody were confirmed. An autopsy revealed systemic vasculitis and perivasculitis. The endothelial tissue of the white pulp of the spleen was markedly infiltrated by plasma cells. The authors speculated that a severe immune reaction against O. tsutsugamushi enhanced an inflammatory response, leading to DIC. This case is a warning to doctors who are not familiar with scrub typhus.