Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 106/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 106/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.

Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Biliary Rhabdomyosarcoma in an Infant Male With Neurofibromatosis Type 1.

Different types of malignancies can be seen in patients with neurofibromatosis type 1 (NF-1). Herein we present a rare combination of NF-1 and biliary rhabdomyosarcoma in a male infant. An 11-month-old boy, who was recently diagnosed with NF-1, presented to the outpatient clinic with a 3-month history of prolonged jaundice, and failure to thrive. Clinical examination showed >20 café au let spots distributed mainly over the abdominal trunk. Hepatomegaly (4 cm below the costal margin) was additionally observed. His father was diagnosed with NF-1. Radiologic imaging studies showed a 6×5×5 cm in diameter cystic mass with multiple septations in the segment 4A of the liver. Surgical excision of the left hepatic lobe followed by hepatojejunostomy was further performed. Histopathology examination showed embryonal type rhabdomyosarcoma originating from the biliary duct. Chemotherapy regimen consisting of cyclophosphamide, actinomycin D, and vincristine, and radiotherapy were then initiated. This treatment led to a significant improvement in the patient's clinical status, and radiologic finding portrayed attainment of complete resolution. He is still in complete remission without any sequelae for 8 years.

The effect of FoxP3 on tumour stage, treatment response, recurrence and survivalability in nasopharynx cancer patients.

OBJECTIVES: To investigate the relationship between the cell percentage of T regulator (Treg) cells of patients' specimens and disease severity, survivability, recurrence and metastasis in patients who were diagnosed with nasopharyngeal carcinoma (NPC). DESIGN, SETTING AND PARTICIPANTS: Sixty patients who were diagnosed as NPC and treated by the same protocol were enrolled to the study. Patient files were reviewed retrospectively and their clinical and pathological results were recorded. Deparaffinized samples of nasopharyngeal carcinoma patients were stained immunohistochemically with anti-FoxP3 monoclonal antibody. All patients's Anti-FoxP3 stained slides were evaluated by the same pathologist. Stained Treg lymphocytes around the tumoral foci were investigated. Patients were divided into two groups according to the total anti-FoxP3-stained Treg cell counts of the specimens; that is, less than 20% of the total or more than 20% of the total. These groups were compared statistically. MAIN OUTCOME MEASURES: Intensity of FoxP3 which is related to negative tumor response was the main outcome measure. It was evaluated in terms of stage, survival, recurrence and metastasis. RESULTS: The study group consisted of 42 male patients (70%) and 18 female patients (30%). The mean age was 47 ± 14.9. NPC subtypes among the patients were undifferentiated non-keratinized type in 54 patients (90%), differentiated non-keratinized type in 4 patients (6.66%) and keratinized type squamous cell carcinoma (SCC) in 2 patients (3.33%). When the two groups were compared in terms of pathological subtype, there was no significant variation between the two groups. There was also no significant variation between the two groups when compared on the basis of tumor stage (P = 0.36 for T phase, P = 0.122 for N phase), early stage, late phase (P = 0.15), survival rate (P = 0.69 for general survival), recurrence (P = 0.2 for local recurrence, P = 0.37 for regional recurrence) and distant metastasis (P = 0.3). CONCLUSION: There was no significant relationship between the concentration of these cells in the stained specimens and the disease stage, survival rate, recurrence and distant metastasis discovered.

Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS-ERG and common pitfalls in detecting EWSR1-ERG fusions by FISH.

The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1-ERG being identified in 5-10% of cases, while only a handful of reports document a FUS-ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS-ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS-positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG-rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1-ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3-color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break-apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT-PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG-rearranged SBRCTs.

Serum Visfatin Levels in Ulcerative Colitis.

BACKGROUND: Previous studies have suggested that adipokines play a role in inflammatory bowel disease by inducing proinflammatory cytokines, but it is uncertain whether visfatin is causally involved in ulcerative colitis (UC). We evaluated visfatin levels in patients who presented with UC flares before and after treatment. METHODS: In this cohort study, we assessed 31 patients with UC in the activation period and remission in the same patients after treatment, and a healthy control group, consisting of 29 persons, at a single academic medical centre between 2010 and 2013. Disease severity was evaluated clinically using Trulove and Witt's criteria. RESULTS: Serum visfatin levels did not vary according to the extent of disease and were significantly higher in patients in the activation period (7.77 ± 2.41 ng/ml) than in remission (6.18 ± 2.04 ng/ml) and the healthy controls (6.54 ± 2.20 ng/ml; P < 0.01 and < 0.05, respectively). In a comparison of patients in the inactive period with the control group, there was no statistically significant difference (P > 0.05). To assess activation of the disease, a visfatin cut-off point for active UC was determined as 6.40, with sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) of 72%, 52%, 66.7% (43.0-85.4) and 50.0% (29.1-70.9), respectively. CONCLUSIONS: The visfatin level was higher in the active group than in post-treatment remission and the healthy control group. Sensitivity and specificity were similar to other inflammatory markers for assessing clinical activity, which did not improve clinical outcomes in patients with acute respiratory distress syndrome (ARDS). These findings did not provide a rationale for assessment of UC activation.

Percutaneous ultrasound-guided core needle biopsy of solid pancreatic masses: Results in 250 patients.

BACKGROUND: To determine the diagnostic accuracy and complications of percutaneous sonographic (US)-guided core needle-needle biopsy in the diagnosis of solid pancreatic masses. METHODS: Cases of US-guided percutaneous core needle biopsy of solid pancreatic masses performed in our department between July 2009 and June 2015 were analyzed retrospectively. The demographic data, lesions' size and location, pathology results, accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and complications of the biopsies were determined. RESULTS: A total of 250 patients (150 males, 100 females; age range, 16-88 years; mean age, 64.3 ± 12.1 years) were included in the study. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of all 250 biopsies were 94.8%, 94.3%, 97.2%, 99.5%, and 75%, respectively, and changed to 98.4%, 99%, 94.7%, 99%, and 94.7%, respectively, after the biopsy was repeated in 12 patients. Four (1.6%) major complications, including a pseudoaneurysm of the gastroduodenal artery, and three cases of acute pancreatitis, and one (0.4%) minor complication (a vaso-vagal syncope), were observed. There was no biopsy-related death. CONCLUSIONS: US-guided percutaneous core needle biopsy is a safe and highly effective method with acceptable complication rates in the diagnosis of solid pancreatic masses. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:470-473, 2016.

Regression of steatohepatitis-related cirrhosis.

The authors document regression of cirrhosis in an obese 56-year-old man after significant weight loss by sequential liver biopsies. The patient had a known history of steatohepatitis. His initial laboratory workup 6 years earlier revealed elevated liver enzyme activities and blood triglyceride levels, and negative viral hepatitis serology screen. A liver biopsy at that time showed histological features consistent with precirrhotic stage of active steatohepatitis. A liver biopsy performed 4 years later revealed progression of the disease to cirrhosis. Following this diagnosis he went on a special strict diet and lost 49 kg. His body mass index decreased from 46 to 28 during a 2-year period and his liver enzyme activities returned to normal. A liver biopsy at this time demonstrated significant regression of the liver fibrosis and disappearance of the steatosis and necroinflammation. In conclusion, massive weight loss resulted in resolution of liver fibrosis in this obese patient with steatohepatitis-related cirrhosis.

Red blood cell distribution width as a non-invasive marker for the assessment of inflammation in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The aim of this study was to assess the association between red cell distribution width and inflammation in biopsy proven non-alcoholic steatohepatitis. METHODOLOGY: Fifty four subjects with non-alcoholic steatohepatitis and thirty nine controls were enrolled for the study. Liver biopsy specimens were scored by using non-alcoholic fatty liver disease activity score by a single experienced liver pathologist. RESULTS: Red cell distribution width was higher in the severe inflammation group in non-alcoholic steatohepatitis (p < 0.05). The areas under the receiver operating characteristic curves for the predictive performance of aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and red cell distribution width in identifying inflammation in non-alcoholic steatohepatitis were 0.55 (0.41-0.68), 0.51 (0.37-0.64), 0.53 (0.39-0.67) and 0.73 (0.59-0.84) respectively and the differences of these values between red cell distribution width and other parameters were found to be statistically significant (p < 0.05). To determine the grading of inflammation, the specificity for using the red cell distribution width as an indicator in non-alcoholic steatohepatitis patients was calculated to be 73.3%, with 79.5% sen- sitivity. CONCLUSION: Red cell distribution width was a sensitive and specific method for the assessment of the inflammation in patients with non-alcoholic steatohepatitis.

Pericardial, pleural and peritoneal involvement in a patient with primary gastric mantle cell lymphoma.

Primary gastric mantle cell lymphoma is a rare form of gastointestinal tumour. Although peritoneal carcinomatosis accompanied by malignant ascites is relatively common, mantle cell lymphoma presenting with ascites is rare. Also, effusions involving pericardial and pleural cavities are uncommon during the course of lymphomas. We report the first case in which pericardial, pleural and peritoneal effusion of a primary gastric mantle cell lymphoma.

Odontogenic tumors: a collaborative study of 218 cases diagnosed over 12 years and comprehensive review of the literature.

OBJECTIVES: The objective of this study was to analyze the frequency and distribution of odontogenic tumors (OTs) in the Cappadocia region of Turkey, and to compare the findings with those reported in the literature. STUDY DESIGN: The records of the Oral and Maxillofacial Surgery and Pathology Departments at Erciyes University, with histologic diagnosis of odontogenic tumors (based on the World Health Organization classification, 2005), over a 12-year period, were analyzed. The relative frequency of different types of tumors was also analyzed and compared with the literature. RESULTS: OTs in the present study constituted 2.74% of all the 7,942 registered biopsies. A total of 218 cases of OTs were collected and reviewed. Of these, (94.04%) were benign and (5.96%) were malignant. The mandible was the most commonly affected anatomic location, with 170 cases (77.9%). Ameloblastoma with a predilection for the posterior mandible was the most frequent odontogenic tumor (30.28%), followed by keratocystic odontogenic tumor (19.5%), odontoma (13.4%), and odontogenic myxoma (8.5%). CONCLUSIONS: OTs are rare neoplasms and appear to show geographic variations in the world. In Cappadocia, Turkey, they are more common in the mandible, with ameloblastoma followed by keratocystic odontogenic tumors with the incidences observed in the present study being similar to those of previous studies from Asia and Africa, and in contrast to those reported from American countries.

Cranial metastatic alveolar rhabdomyosarcoma mimicking hematological malignancy in an adolescent boy.

BACKGROUND: Widespread alveolar rhabdomyosarcoma (ARMS) with bone marrow involvement and with an unknown primary tumor, especially presenting with acute tumor lysis syndrome can be easily misdiagnosed as a hematological malignancy. Furthermore, brain metastasis of ARMS is rare seen in children. CASE REPORT: Herein, we report a 14-year-old boy presenting with acute tumor lysis syndrome due to bone marrow invasion of ARMS, who was diagnosed after abdominal paraaortic lymph node biopsy. Despite radiological and nuclear medicine imaging, the primary tumor site could not be found. He was treated with vincristine, topotecan, and cyclophosphamide for 42 weeks. Six months after the completion of treatment, he suffered from severe headache, blurred vision, right hemiplegia, and severe bone pain. Cranial magnetic resonance imaging showed multiple hemorrhagic infarctions. Brain biopsy showed brain metastasis with PAX3-FKHR fusion transcript. CONCLUSION: The clinicians must be vigilant about solely brain metastasis in ARMS without additional metastasis.

The Depth of Invasion and Level IV Cervical Node Metastasis in Patients with Clinically N0 Tongue Cancer.

BACKGROUND: The accurate indication for level IV dissection is crucial for preventing complications such as phrenic nerve damage and chylous fistulas in clinically N0 tongue cancer. Although the depth of invasion is an established independent risk factor for occult lymph node metastasis in tongue cancer, its relationship with level IV metastasis has not been evaluated. This study investigated the relationship between the depth of invasion and level IV nodal metastasis in clinically N0 tongue cancer. METHODS: We retrospectively investigated clinical N0 patients who underwent glossectomy and level I-IV neck dissection. We examined lymph node metastasis, risk factors, and the relationship between depth of invasion and metastasis. RESULTS: Our study included 58 patients, and no patient had isolated level IV metastasis. Additionally, there was no level IV metastasis in well-differentiated tumors. Tumor size, depth of invasion, differentiation, and perineural invasion were significantly associated with level IV neck metastasis. We found a critical tumor size of 2.5 cm and depth of invasion of 8 mm for level IV neck metastasis. CONCLUSION: Based on our findings, we recommend that level IV dissection should be considered for poorly differentiated tumors, tumors greater than 2.5 cm in size, and those deeper than 8 mm. This study highlights the importance of depth of invasion as a prognostic factor for predicting level IV metastasis and suggests that our findings can be used to prevent unnecessary level IV dissections that may lead to complications in tongue cancer surgery.

Alantolactone ameliorates graft versus host disease in mice.

The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in pro-inflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.

Gastric signet ring carcinoma in a patient with ataxia-telangiectasia: a case report and review of the literature.

Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency disease characterized by progressive cerebellar ataxia, telangiectasia, sinopulmoner recurrent infections, and cancer susceptibility. Individuals with A-T are known to be at increased risk of certain malignancies including leukemia, lymphoma, and breast and gastric cancer. We present an 18-year-old case of A-T with Hashimoto thyroiditis who admitted with complaints of nausea, vomiting, anorexia, and weight loss. An upper endoscopic biopsy revealed gastric signet ring cell carcinoma. To the best of our knowledge, we report the first case of signet ring cell carcinoma in the patient with A-T. Our experience with occurrence of Hashimoto thyroiditis and gastric signet ring cell carcinoma in the same case of A-T underlines that the clinicians handling A-T must be vigilant about both malignancy and autoimmune disorders.

Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD has a strong association with metabolic syndrome and its component like insulin resistance (IR). Cardiovascular disease has a relation with NAFLD. Platelet volume is an indicator of platelet function and activation. Mean platelet volume (MPV) has been reported as a risk factor for atherothrombosis. In our study, we aimed to investigate the relation of MPV with NAFLD and IR in the NAFLD patients. A total of 54 patients with histologically proven NAFLD and 41 healthy age-matched control subject were enrolled in this study. The NAFLD subjects were divided into two subgroups: 42 patients in the insulin resistant group (median age 39.5, females 22 [52%]) and 12 patients in the insulin sensitive group (median age 38, females 5 [41.7%]). MPV were significantly higher in the NAFLD group in univariate analysis (p < 0.05). In the NAFLD patients, we did not find any relation between steatosis grade, lobular inflammation, hepatocellular ballooning, NAFLD activity score and fibrosis with MPV value. Among the insulin resistant and sensitive groups in the NAFLD patients MPV values were similar. The results of this study showed that MPV, an indicator of platelet activation, increased in biopsy proven NAFLD patients but MPV is not correlated with the increase of IR in NAFLD patients. MPV is not related with inflammation and steatosis degree, hepatocellular ballooning and fibrosis in NAFLD patients.

Carpal tunnel release surgery and venous hypertension in early hemodialysis patients without amyloid deposits.

AIM: Carpal tunnel syndrome (CTS) is one of the frequent problems of the patients who underwent hemodialysis (HD). The role of venous hypertension due to arteriovenous fistula (AVF) has not been clarified completely; therefore, we aimed to investigate the role of venous hypertension due to AVF in hemodialysis patients who had CTS. PATIENTS AND METHODS: We included 12 patients who had been receiving HD treatment for less than 8 years and the newly diagnosed CTS patients with the same arm of AVF. All patients were diagnosed clinically and the results were confirmed by both nerve conduction studies and electromyography. Open carpal tunnel release surgery was performed on all of them. Venous pressure was measured in all patients before and after two weeks of surgery. RESULTS: There were significant differences before and after the surgery with regard to pressures (P > 0.05). After the surgery, all carpal ligament specimens of the patients were not stained with Congo red for the presence of amyloid deposition. CONCLUSION: Increased venous pressure on the same arm with AVF could be responsible for CTS in hemodialysis patients. Carpal tunnel release surgery is the main treatment of this disease by reducing the compression on the nerve.

Is There an Association Between Synovial CD30+ T Lymphocyte Count and Chondral Lesion Depth?

BACKGROUND: Exact role of the inflammation in osteoarthritis is still unclear, but it is thought to originate from synovitis due to micro-crystals or breakdown products of the cartilage. OBJECTIVE: To determine the effect of CD30+ T lymphocytes on the development of osteoarthritis by comparing the lesion depth and synovial CD30+ count in patients with chondral lesions undergoing knee joint arthroscopy. DESIGN: A total of 79 patients with chondral lesions detected during arthroscopy were categorized in 4 different groups based on chondral lesion classification. CD30+ lymphocyte counts were calculated using flow cytometry on synovial fluid samples obtained at the time of initial entrance into the joint and compared between the groups. In addition, biopsy samples obtained from the suprapatellar bursa were stained for histologic examination to identify existence of CD30+ lymphocytes in the synovium. RESULTS: Although there were no significant differences between the first 3 groups in terms of synovial fluid CD30+ lymphocyte counts, patients in Group IV had significantly higher counts (6.2 8 [2.48] vs 2.51 [1.84], 2.97 [2.40], and 3.80 [2.07], respectively; P < 0.05). Except for a single patient with a Grade III chondral lesion, there were no cases of CD30 positivity in synovial tissue. Also there was a correlation between CD30 levels and chondral lesion depth when controlled for age. CONCLUSIONS: Our results indicate higher CD30+ lymphocyte counts in patients with modified Outerbridge Grade IV chondral lesions than in other groups. The origin of the CD30+ lymphocytes may not be the synovial tissue per se. Thus, it was hypothesized that the injured chondral tissues and the associated subchondral structures might have been the source of CD30+ lymphocytes with a possible influence on the development of osteoarthritis.

Traditional Serrated Adenoma of the Urinary Bladder: The First Report.

A 71-year-old woman was hospitalized with hematuria and underwent cystourethroscopy. Cystourethroscopy revealed a polypoid bladder tumor. Histopathologic examination showed complex villiform growth pattern, slit-like serrations, and ectopic crypts lined by epithelium with eosinophilic cytoplasm, pseudostratified elongated nuclei, consistent with traditional serrated adenoma. Nephrogenic and intestinal metaplasia with severe inflammation were present in adjacent bladder mucosa. Molecular study of the polyp revealed mutation (p.G12V) in codon 12 of exon 2 of the KRAS gene. Traditional serrated adenoma is a rare type of colonic serrated polyp, making up less than 1% of the colonic polyps with a predilection to distal colon. In the literature, there is no traditional serrated adenoma reported outside the gastrointestinal tract. Here in we report the first extra-gastrointestinal traditional serrated adenoma within the bladder and bladder diverticulum, arising from intestinal metaplasia. The present study reports an additional information on molecular background of this unusual bladder polyp.