Percutaneous core needle biopsy of neuroblastoma in the pediatric population: what have we learned in the last decade.

INTRODUCTION: Historically, neuroblastoma has been diagnosed by surgical open biopsy (SB). In recent decades, core needle biopsy (CNB) has replaced surgical biopsy due to its safe and adequate method of obtaining tissue diagnosis. AIM: Our study aimed to assess the effectiveness of CNB in obtaining tissue diagnosis for neuroblastoma and evaluate its safety profile in terms of post-operative complications, in comparison to SB. METHODS: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with neuroblastoma from 2012 until 2022 in a single tertiary medical center. Patients' demographics, tumor size and location, pathological results, and clinical outcomes were collected. RESULTS: 79 patients were included in our study: 35 biopsies were obtained using image-guided CNB and 44 using SB. Patients' and tumor characteristics including age, gender, tumor volume, and stage were similar in both groups. The biopsy adequacy rate in the CNB group was 91% and 3 patients in this group underwent repeated biopsy. The safety profile in the CNB group was similar to the SB group. CONCLUSIONS: CNB is a safe method and should be considered the first choice for obtaining tissue diagnosis when feasible due to its high adequacy in terms of tumor histopathological features.

Cutting balloon septotomy for repair of right common iliac artery aneurysm in the setting of type B aortic dissection.

We report a case of using cutting balloon septotomy for a 5-cm right common iliac artery aneurysm repair in a patient with a chronic type B aortic dissection after open repair 10 years before. This technique uses intravenous ultrasound to facilitate deployment of a cutting balloon to shear through the dissection flap, allowing for optimization of the landing zone for endovascular repair of a right common iliac artery aneurysm. Various methods are available for performing septotomy, and the use of a cutting balloon is one that helps with stent placement and position.

Inferior vena cava reconstruction to alleviate back pain.

We present the case of a 38-year-old man with end-stage renal disease receiving hemodialysis via a left femoral loop graft who developed debilitating back pain. During a maintenance fistulogram, we found a completely occluded inferior vena cava and engorged lumbar veins. The patient underwent inferior vena cava reconstruction with stenting, which resulted in complete resolution of the engorged lumbar veins on venography and a significant reduction in his back pain. Engorgement of the lumbar veins can cause significant pain, and treatment of the underlying pathology can alleviate these symptoms.

Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data.

BACKGROUND: Hepatitis B virus (HBV) is a cause of hepatocellular carcinoma (HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment. AIM: To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets. METHODS: We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information's Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent non-tumor samples and analyzed results with ingenuity pathway analysis. RESULTS: Our analysis revealed liver X receptors/retinoid X receptor (RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6 (RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10 (HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms. CONCLUSION: This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.

Transcriptome changes in stages of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a 'multiple hit' hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury. AIM: To examine the genetic expression of NAFLD and non-alcoholic steatohepatitis (NASH) tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis. METHODS: We employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology. For NAFLD, we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies; for NASH, we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies. RESULTS: Our results from the NAFLD analysis reinforce the role of altered metabolism, inflammation, and cell survival in pathogenesis and support recently described contributors to disease activity, such as altered androgen and long non-coding RNA activity. The top upstream regulator was found to be sterol regulatory element binding transcription factor 1 (SREBF1), a transcription factor involved in lipid homeostasis. Downstream of SREBF1, we observed upregulation in CXCL10, HMGCR, HMGCS1, fatty acid binding protein 5, paternally expressed imprinted gene 10, and downregulation of sex hormone-binding globulin and insulin-like growth factor 1. These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver. Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis. Top canonical pathways, disease networks, and disease functions were related to cholesterol synthesis, lipid metabolism, adipogenesis, and metabolic disease. Top upstream regulators included pro-inflammatory cytokines tumor necrosis factor and IL1B, PDGF BB, and beta-estradiol. Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism, extracellular matrix deposition, and tumor suppression. Lastly, we found riciribine (an AKT inhibitor) and ZSTK-474 (a PI3K inhibitor) as potential drugs that targeted the differential gene expression in our dataset. CONCLUSION: In this study we describe several molecular processes that may correlate with NAFLD disease and progression. We also identified ricirbine and ZSTK-474 as potential therapy.

Case Report: Modified Laparoscopic Subtotal Cholecystectomy: An Alternative Approach to the "Difficult Gallbladder".

BACKGROUND Laparoscopic cholecystectomy is a commonly performed surgical procedure. In certain situations visualization of the Callot triangle can become difficult due to inflammation, adhesions, and sclerosing of the anatomy. Without being able to obtain the "critical view of safety" (CVS), there is increased risk of damage to vital structures. An alternative approach to the conventional conversion to an open cholecystectomy (OC) would be a laparoscopic subtotal cholecystectomy (LSC). CASE REPORT We present a case of a 56-year-old male patient with acute cholecystitis with a "difficult gallbladder" managed with LSC. Due to poor visualization of the Callot triangle due to adhesions, safe dissection was not feasible. In an effort to avoid injury to the common bile duct (CBD), dissection began at the dome of the gallbladder allowing an alternative view while ensuring safety of critical structures. CONCLUSIONS We discuss the potential benefits and risks of LSC versus conversion to OC. Our discussion incorporates the pathophysiology that allows LSC in this particular circumstance to be successful, and the considerations a surgeon faces in making a decision in management.

Meta-analysis of open and endovascular repair of popliteal artery aneurysms.

OBJECTIVE: Endovascular popliteal artery aneurysm repair (EPAR) is increasingly used over open surgical repair (OPAR). The purpose of this study was to analyze the available literature on their comparative outcomes. METHODS: The PubMed and Embase databases were searched to identify studies comparing OPAR and EPAR. Studies with only one treatment and fewer than five patients were excluded. Demographics and outcomes were collected. Bias risk was assessed using a modified version of the Newcastle-Ottawa Scale. Results were computed from random-effects meta-analyses using the DerSimonian-Laird algorithm. RESULTS: A total of 14 studies were identified encompassing 4880 popliteal artery aneurysm repairs (OPAR, 3915; EPAR, 1210) during the last decade. OPAR patients were younger (standard mean difference, -0.798 [-0.798 to -1.108]; P < .001) and more likely to have worse tibial runoff (odds ratio [OR], 1.949 (1.15-3.31); P = .013) than EPAR patients. OPAR had higher odds of wound complications (OR, 5.182 [2.191-12.256]; P < .001) and lower odds of thrombotic complications (OR, 0.362 [0.155-0.848]; P < .001). OPAR had longer length of stay (standardized mean difference, 2.158 [1.225-3.090]; P < .001) and fewer reinterventions (OR, 0.275 [0.166-0.454]; P < .001). Primary patency was better for OPAR at 1 year and 3 years (relative risk, 0.607 [P = .01] and 0.580 [P = .006], respectively). There was no difference in secondary patency at 1 year and 3 years (0.770 [P = .458] and 0.642 [P = .073], respectively). CONCLUSIONS: EPAR has a lower wound complication rate and shorter length of hospital stay compared with OPAR. This comes at the cost of inferior primary patency but not secondary patency out to 3 years. Studies reporting long-term outcomes are lacking and necessary.

Is the diagnostic yield of prostate needle biopsies affected by prostate volume?

OBJECTIVES: To determine the effect of prostate volume on the diagnostic yield of prostate biopsies. MATERIALS AND METHODS: 155 consecutive patients underwent 12-core transrectal ultrasound guided needle biopsies. Data were collected prospectively on age, serum PSA, digital rectal examination (DRE), previous prostate biopsies, prostate volume and pathologic result. Univariate and multivariate logistic regressions were undertaken to determine the effect of prostate volume on the risk for a positive biopsy. RESULTS: 45 patients (29%) were diagnosed with cancer. The median patient age was 63 (range 48-82) years, the median PSA level was 6.7 ng/ml (0.5-156 ng/ml), and the median prostate volume was 57 ml (16-273 ml). 42 patients (27%) had an abnormal DRE and 51 (33%) had undergone previous prostate biopsies. Positive biopsy rates were 39%, 33%, and 14% for prostate volume below 46 ml, between 45 and 73 ml, and above 72 ml, respectively. Univariate analysis showed that age, serum PSA, DRE and prostate volume were all associated with a positive biopsy. Multivariate analysis adjusted for age, PSA and DRE showed a significant risk increase for a positive biopsy in smaller prostates. (OR = 5.6 95% CI 1.75-17.89; and 8.86 95% CI 2.72-28.82, for prostate volume between 45 and 72 ml and below 45 ml, respectively). CONCLUSION: The diagnostic yield of prostate biopsies is significantly lower in large prostates. As the result the standard 12-core biopsy may be insufficient for the diagnosis of cancer in large prostates.

Testicular sparing surgery for small masses.

OBJECTIVES: To determine the proportion of benign testicular lesions among candidates for testicular sparing surgery (TSS) and to assess the safety and efficacy of this procedure. METHODS AND MATERIALS: Sixteen patients underwent surgical exploration for testicular tumors with TSS intent in our center. Surgery was performed via an inguinal approach with temporary cord occlusion and frozen section (FS) analysis of the lesions. Benign findings allowed for TSS, whereas cancer prompted total orchiectomy. RESULTS: The lesions measured 8-25 mm in the largest diameter. Eleven of the 16 lesions were benign (69%) and TSS was accomplished in these cases. Complete concordance was observed between the results of FS and permanent sections. Of the 5 patients with cancer, 3 had pure seminoma, and embryonal carcinoma and teratoma were found in 1 patient, each. Surveillance was applied in 4 of these patients, and chemotherapy was used in the patient with embryonal carcinoma. With an average follow-up duration of 48 months, all are alive and free of disease. All 11 patients in whom TSS was accomplished had an uneventful postoperative course, and with an average follow-up duration of 28 months, 9 have normal scrotal physical examination and ultrasound, whereas 2 patients were lost to follow-up. CONCLUSIONS: Sixty-nine percent of testicular lesions under 25 mm are benign. TSS is safe and effective in patients with small benign lesions. Cancer is reliably detected by FS, and testicular exploration is not associated with local or distant recurrence in any of our patients.

The predominance of benign histology in small testicular masses.

OBJECTIVES: To evaluate the concordance between testicular tumor size and benign histology in order to identify a cut-off size, below which the rate of benign lesions would be highest. METHODS AND MATERIALS: During the years 1995-2008, we performed 131 consecutive testicular operations for testicular tumors. Ten of these were testicular preserving surgery, whereas the other 121 patients had radical orchiectomy. We searched for the rate of benign lesions in the following 3 groups of tumor diameter: 10 mm or less, 11-20 mm, and greater than 20 mm. ROC analysis was used to find the optimal size cut-off below which the rate of benign lesions would be highest. RESULTS: Benign lesions were found in 11 patients (8%), including epidermoid cyst (n = 4), Leydig cell tumor (n = 3), fibrosis (n = 1), adenomatoid tumor (n = 2), and 1 patient with a simple cyst. Small tumor size strongly correlated with benign histology. The mean diameter of benign vs. malignant lesions was 15 mm and 41 mm, respectively (P < 0.05). The rate of benign lesions in tumors with a diameter of 10 mm or less, 11-20 mm and greater than 20 mm was 50%, 17%, and 2%, respectively. Receiver Operating characteristic (ROC) analysis with 87% sensitivity and 83% specificity revealed a cut-off value of 18.5 mm tumor diameter below which the proportion of benign lesions was 38.5% compared with 2% above it (P < 0.05). CONCLUSIONS: While benign lesions comprise only 8% of all testicular tumors, their proportion among small lesions is much higher. With a size cut-off of 18.5 mm, 38.5% of smaller lesions are benign. These findings support consideration of testicular exploration for small testicular lesions aiming at preservation rather than predetermined radical orchiectomy.

Prolactin and estradiol serum levels in unmedicated male paranoid schizophrenia patients.

There is evidence for the involvement of the endocrine system in schizophrenia. This involment was widely investigated in female patients. In the current study, we examined prolactin and estradiol serum levels in hospitalized unmedicated men with first-episode and recurrent schizophrenia and then tested possible correlation with various subtypes of the disease. In addition, the estradiol and prolactin levels were compared with a healthy control group. The serum samples were assessed the morning following admission in fifty-seven schizophrenia male patients. There was a significant difference in prolactin serum levels between the paranoid and "nonparanoid" schizophrenia subgroups. However, no significant differences were found in estradiol serum levels between schizophrenia subtypes or between the patients and their healthy counterparts. Finally, a significant and positive correlation was found between the prolactin and estradiol levels in the paranoid subgroup alone. Thus, it appears that low estradiol levels are associated with low prolactin levels, alleged hyperdopaminergic tone and psychotic breakdown in paranoid schizophrenia. The results of the present study further support our previous report of the association between prolactin serum levels and the schizophrenia cluster subtypes, indicating a different dopaminergic activity for the various forms of the disease.

Can hamartoma of the breast be distinguished from fibroadenoma using fine-needle aspiration cytology?

In an attempt to determine if it is possible to distinguish hamartoma of the breast from fibroadenoma using fine-needle aspiration cytology, we reviewed the cytological slides of 13 histopathologically confirmed cases of hamartoma of the breast and compared them with the cytological features of 13 histologically confirmed fibroadenomas. In each case, we studied the epithelial and stromal features. Cytologic characteristics were retrospectively evaluated in a semiquantitative manner. In conclusion, the finding of intact lobular units and a relative paucity of stroma may suggest the diagnosis of hamartoma.

Giant cell tumor of bone. The role of fibroblast growth factor 3 positive mesenchymal stem cells in its pathogenesis.

OBJECTIVES: Giant cell tumor of bone is typified by massive infiltration of a bland neoplastic stroma by osteoclasts and monocyte progenitors. The current study aimed at evaluating the nature of the neoplastic cells and the mechanisms underlying the massive giant cell recruitment. METHODS: Five different giant cell tumors were evaluated by immunohistochemistry, and explant cell cultures were established from the same tumors. Antigen expression profiles of both the tumors and the derived cultures were assessed. In order to determine if the mesenchymal cells are capable of differentiating into mature osteoblasts, retinoic acid was added to cell cultures and osteocalcin and alkaline phosphatase levels were measured. The proliferative effects of the mesenchymal cells on histiocyte-like cells were evaluated using the U-937 cell line. RESULTS: A large stromal subpopulation expresses fibroblast growth factor receptor 3 (FGF-R3), indicating a mesenchymal origin of these cells. Few cells express bone- or cartilage-specific markers. Cell cultures are predominated by mesenchymal cells, as indicated by a strong staining by FGF R3. Retinoic acid induces osteoblastic differentiation, i.e. osteocalcin expression and alkaline phosphatase production. Conditioned medium of giant-cell-tumor-derived stromal cell cultures induces proliferation of U-937 cells, derived from histiocytic lymphoma. Papain digestion and dialysis of the conditioned media indicates the effector molecule to be a protein over 40 kD in size. The giant cell tumors as well as stromal cell cultures derived from giant cell tumors express osteoprotegerin ligand, the osteoclast activator. CONCLUSIONS: The neoplastic stromal spindle-shaped subpopulation of cells in giant cell tumors are mesenchymal stem cells capable of inducing histiocyte proliferation. Retinoid acid is capable of inducing differentiation of the cells into mature osteoblasts. This should be further investigated in an in vivo model to ascertain whether induction of differentiation will prevent bone loss and retard tumor progression.

Neuroleptic malignant syndrome: Possible induction by olanzapine in a case with relapsing catatonia.

Neuroleptic malignant syndrome is a serious medical condition with a significant mortality risk. Although it is less common with the atypical than the typical agents, it is described in association with clozapine and olanzapine. This report documents a case of possible induction of NMS in a patient with relapsing catatonia.