Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH).

AIM: Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. MATERIALS AND METHODS: Hematoxylin-eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. RESULTS: In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). CONCLUSION: In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

Comparison of Fibroscan, Shear Wave Elastography, and Shear Wave Dispersion Measurements in Evaluating Fibrosis and Necroinflammation in Patients Who Underwent Liver Biopsy.

OBJECTIVE: Our aim was to predict these stages of hepatic fibrosis and necroinflammation using measurements from two-dimensional shear wave elastography (2D-SWE), transient elastography (Fibroscan, TE), and shear wave dispersion (SWD). MATERIALS AND METHODS: In this prospectively designed study, chronic liver patients with nonspecific etiology whose biopsy was performed for up to 1 week were included. Two-dimensional SWE, SWD, and TE measurements were performed. The METAVIR and F-ISHAK classification was used for histopathological evaluation. RESULTS: Two-dimensional SWE and TE were considered significant for detecting hepatic fibrosis. In distinguishing ≥F2, for 2D-SWE, area under the receiver operating characteristics (AUROC) was 0.86 (confidence interval [CI], 0.75-0.96) for the cutoff value of 8.05 kPa ( P = 0.003); for TE, AUROC was 0.79 (CI, 0.65-0.94) for the cutoff value of 10.4 kPa ( P < 0.001). No significance was found for TE in distinguishing ≥F3 ( P = 0.132). However, for 2D-SWE, a cutoff value of 10.45 kPa ( P < 0.001), with AUROC = 0.87 (CI, 0.78-0.97) was determined for ≥F3. Shear wave dispersion was able to determine the presence of necroinflammation ( P = 0.016) and a cutoff value of 15.25 (meter/second)/kiloHertz ([m/s]/kHz) ( P = 0.006) and AUROC of 0.71 (CI, 0.57-0.85) were calculated for distinguishing ≥A2. In addition, a cutoff value of 17.25 (m/s)/kHz ( P = 0.023) and AUROC = 0.72 (CI, 0.51-0.93) were found to detect severe necroinflammation. The cutoff value for SWD was 15.25 (m/s)/kHz ( P = 0.013) for detecting ≥A2 in the reversible stage of fibrosis (F0, F1, and F2), and AUROC = 0.72 (CI, 0.56-0.88). CONCLUSIONS: Two-dimensional SWE and TE measurements were significant in detecting the irreversible stage and the stage that should be treated in hepatic fibrosis noninvasively. Shear wave dispersion measurements were significant in detecting necroinflammation noninvasively.

Evaluation of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Using MR Images and Deep Learning Neural Networks.

INTRODUCTION: The aim of the study was to develop deep-learning neural networks to guide treatment decisions and for the accurate evaluation of tumor response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer using magnetic resonance (MR) images. METHODS: Fifty-nine tumors with stage 2 or 3 rectal cancer that received nCRT were retrospectively evaluated. Pathological tumor regression grading was carried out using the Dworak (Dw-TRG) guidelines and served as the ground truth for response predictions. Imaging-based tumor regression grading was performed according to the MERCURY group guidelines from pre-treatment and post-treatment para-axial T2-weighted MR images (MR-TRG). Tumor signal intensity signatures were extracted by segmenting the tumors volumetrically on the images. Normalized histograms of the signatures were used as input to a deep neural network (DNN) housing long short-term memory (LSTM) units. The output of the network was the tumor regression grading prediction, DNN-TRG. RESULTS: In predicting complete or good response, DNN-TRG demonstrated modest agreement with Dw-TRG (Cohen's kappa= 0.79) and achieved 84.6% sensitivity, 93.9% specificity, and 89.8% accuracy. MR-TRG revealed 46.2% sensitivity, 100% specificity, and 76.3% accuracy. In predicting a complete response, DNN-TRG showed slight agreement with Dw-TRG (Cohen's kappa= 0.75) with 71.4% sensitivity, 97.8% specificity, and 91.5% accuracy. MR-TRG provided 42.9% sensitivity, 100% specificity, and 86.4% accuracy. DNN-TRG benefited from higher sensitivity but lower specificity, leading to higher accuracy than MR-TRG in predicting tumor response. CONCLUSION: The use of deep LSTM neural networks is a promising approach for evaluating the tumor response to nCRT in rectal cancer.

Evaluating complete response prediction rates in locally advanced rectal cancer with different radiomics segmentation approaches.

Purpose: Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV. Methods and materials: Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machine-learning models. Results: CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively. Conclusion: Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.

Value of GCET1, HGAL (GCET2), and LMO2 in the Determination of Germinal Center Phenotype in Diffuse Large B-cell Lymphoma

Objective: Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous disease that is classified into germinal center B-cell (GCB) and non-GCB subtypes, which are prognostically different. The Hans algorithm is the most widely used tool based on CD10, BCL6, and MUM1 expression, but some cases with the non-GCB phenotype are still known to be misclassified. In this study, we investigate the extent to which GCET1, HGAL, and LMO2 protein expressions reflect GCB phenotype together with their roles in determining the GCB phenotype of DLBCL and their contributions to the performance of the Hans algorithm. Materials and Methods: Sixty-five cases of DLBCL-not otherwise specified, 40 cases of follicular lymphoma (FL), and 19 non-GC-derived lymphoma cases were included in this study. The DLBCL cases were grouped as CD10+ (Group A) or only MUM1+ (Group B), and the remaining cases constituted the intermediate group (Group C). GCET1, HGAL, and LMO2 expressions were evaluated. Results: In the FL group, GCET1, HGAL, and LMO2 were positive in 85%, 77.5%, and 100% of the cases, respectively. Among the non-GC-derived lymphoma cases, all three markers were negative in cases of small lymphocytic lymphoma, plasmablastic lymphoma, peripheral T-cell lymphoma, and anaplastic large cell lymphoma. GCET1 and HGAL were negative in cases of marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). Two of the 3 MZL and 2 of the 4 MCL cases were positive for LMO2. In the DLBCL group, the number of cases with GCET1, HGAL, and LMO2 positivity was 18 (90%), 17 (85%), and 20 (100%), respectively, in Group A and 0 (0%), 2 (13.3%), and 2 (13.3%), respectively, in Group B. Considering these rates, when the cases in the intermediate group were evaluated, it was concluded that 13 cases typed as non-GCB according to the Hans algorithm may have the GCB phenotype. Conclusion: GCET1, HGAL, and LMO2 are highly sensitive markers for determining the germinal center cell phenotype and can increase the accuracy of the subclassification of DLBCL cases, especially for cases that are negative for CD10.

An Evaluation of the Efficacy of Systemic Immune-Inflammation Index in Predicting Enterobius-Associated Appendicitis Preoperatively.

Objective Our study aimed to retrospectively evaluate Enterobius-associated appendicitis cases and compare them with acute appendicitis cases in terms of parameters such as the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP)-to-lymphocyte ratio (CLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). We primarily aimed to evaluate the utility of SII in the differential diagnosis of Enterobius-associated appendicitis. Methods The appendectomy specimens of pediatric patients who were operated on for acute appendicitis between June 2016 and August 2022 were retrospectively evaluated. Enterobius-associated appendicitis cases were included for analysis. All patients were evaluated regarding age, gender, blood count, surgery, and pathology reports. Pathology reports were evaluated for the presence of histological signs of acute appendicitis. The patients were classified into an Enterobius-associated appendicitis group and a regular acute appendicitis group. CRP, white blood cell (WBC), red cell distribution width (RDW), neutrophils, lymphocytes, NLR, monocytes, eosinophils, platelet (PLT), PLR, CLR, and SII values were compared between the two groups. Results Eleven cases of Enterobius-associated appendicitis were identified out of 430 total cases (2.55%) examined. The mean age of the group with acute appendicitis was 12.83 ±3.16 years, while the mean age of the group with Enterobius-associated appendicitis was 8.55 ±2.54 years. There was no statistically significant difference in terms of CRP, WBC, RDW, lymphocytes, neutrophils, NLR, monocytes, eosinophils, PLT, PLR, and CLR values between the two groups (p>0.05). However, when the SII values of the participants were analyzed, it was observed that the SII values of the participants in the regular appendicitis group were significantly higher than those of the participants in the Enterobius group (p<0.05). Among the 11 Enterobius-associated appendicitis patients, seven appendectomy specimens revealed no inflammation and were regarded as negative appendectomy (63.63%). Conclusion This is the first study to demonstrate the utility of preoperative SII evaluation in Enterobius-associated appendicitis. SII is a simple, easy-to-calculate indicator of Enterobius-associated appendicitis and aids in the preoperative differential diagnosis of acute appendicitis.

Malignant Colorectal Polyps: Are Pathology Reports Sufficient for Decision Making?

AIM: This study aims to assess the completeness of pathology reports of T1 colorectal cancers from different healthcare centers and the change of treatment decision after reevaluation of the polyps. MATERIALS AND METHODS: In this single-center retrospective cohort study, several pathology reports of endoscopically excised malignant colorectal polyps at diverse healthcare centers in Turkey were reassessed at a comprehensive cancer center in Istanbul. Reassessment was mainly focused on core elements such as the size of invasive carcinoma, histologic type and grade, tumor extension, surgical margin (deep and mucosal), and lymphovascular invasion. RESULTS: Sixty-seven endoscopically resected malignant polyps were analyzed. The mean age of patients was 62.2 years and 38 (58%) patients were males. Tumor size, histologic type and grade, surgical margin (deep and mucosal), and lymphovascular invasion were reported in 11%, 100%, 31%, 9%, and 19%, respectively. All 5 prognostic factors were reported only in 1 (1.5%) pathology report. Because of the missing (incomplete) data, the pathologic examination of 59 (88%) patients was determined to be inadequate to make an accurate treatment decision. CONCLUSION: Several variables are not considered and frequently missing for decision-making, suggesting the reassessment of the specimen by a second pathologist at a high-volume comprehensive cancer center.

A rare cause of intestinal obstruction in children: signet-ring cell adenocarcinoma of the colon.

BACKGROUND: Signet-ring cell adenocarcinoma of the colon is well-recognized in adult patients who are extremely rare and not well-documented in children. Our study aims to raise awareness about this rare disease and its long-term outcomes. METHODS: We retrospectively evaluated patients with signet-ring cell colon adenocarcinoma. RESULTS: Six patients, three boys and three girls, with a mean age of 14.83 (range, 13-17 years), presented with signs of intesti-nal obstruction and were diagnosed with signet-ring cell colon adenocarcinoma. All patients had air-fluid levels on abdominal X-ray. Abdominal ultrasonography of all patients revealed subileus. Abdominal computed tomography was performed in five patients, and pre-operative colonoscopy was conducted in two patients before the emergency intervention. All of the patients underwent emergent exploratory laparotomy with the preliminary diagnosis of acute abdomen. In two patients, debulking surgery followed by a stoma was performed. The remaining four patients were treated with anastomosis following intestinal resection. All girls had metastases on the ovary. One of the patients died due to the burden of multiple metastases in the early period, and three died in the sixth post-operative year. We have been following the remaining two patients since then. CONCLUSION: Although signet-ring cell carcinomas (SRCCs) are rare, they should be considered in the differential diagnosis of acute abdomen and intestinal obstruction in pediatric patients. Despite early diagnosis and treatment, SRCC has a poor prognosis in the pediatric population.

Is the increased ozone dosage key factor for its anti-inflammatory effect in an experimental model of mesenteric ischemia?

BACKGROUND: Ischemia/reperfusion injury of the intestines is a severe surgical condition. This study aimed to reveal ozone therapy effects with relatively increased ozone dosage in a created ischemia/reperfusion injury model. METHODS: In this study, 24 albino Wistar rats were examined in three groups. Rats in the control group (CG, n=8) underwent only a laparotomy. In the sham group (SG, n=8) and ozone group (OG, n=8), the superior mesenteric artery (SMA) of the rats was occluded for 1 h. After deoccluding the SMA, the abdomen was closed, physiological saline was infused intraperitoneally in the SG, and an increased ozone/oxygen mixture dose (from 0.7 mg/kg to 1 mg/kg) was infused intraperitoneally in the OG. Small intestine samples were obtained at the 24th h for histopathological examination of intestinal mucosal injury and evaluated according to the Chiu score. In addition, Malondialdehyde and Myeloperoxidase levels were evaluated for oxidant levels, whereas, Glutathione (GSH) enzyme activity was measured to evaluate the tissue antioxidant system. RESULTS: Histopathologically, the Chiu score was the lowest in the CG. It was lower in the OG compared to the SG showing the ameliorating effect of ozone on the intestinal mucosa. Chiu score in the OG was higher compared to that in the CG, but not statistically significant. A significantly higher GSH level was observed in the OG compared to the SG, proving antioxidant activity. CONCLUSION: In this experimental model of ischemia/reperfusion in rats, treatment with an increased ozone level decreased the inflammatory process through antioxidant mechanisms and reduced intestinal mucosal damage. However, the effectiveness of ozone therapy depends on its dosages.

Acinar Cystic Transformation of the Pancreas: Report of Three Cases.

Acinar cystic transformation (ACT) of the pancreas is a rare non-neoplastic cystic lesion. It is most frequently observed in the head of the pancreas. Despite advances in radiologic imaging methods, preoperative diagnosis of acinar cystic transformation is difficult, it is often confused with other cystic lesions. Here, we report three cases of acinar cystic transformation, one of which showed diffuse involvement of the pancreas, and the remaining two were multilocular localized cystic lesions. We analyzed their histomorphologic and immunohistochemical features. The patients' ages ranged between 15 and 43 years and the ratio of females to males was 2:1. On microscopic examination, the cysts were lined by a single layer of flattened-cuboidal or columnar epithelial cells. The epithelial cells were diffusely positive with trypsin and keratin 7, but patchy with keratin 19. Due to its rarity and lack of radiologic and clinical awareness compared with other pancreatic cystic lesions, preoperative diagnosis of acinar cystic transformation is difficult and not definitive. All cases reported to date have been clinically benign and there is no evidence of recurrence or malignant transformation. The optimal treatment and whether to perform surgery remain controversial.

Comparison of Renal Anastomosing Hemangiomas in End-Stage and Non-End-Stage Kidneys: A Meta-Analysis With a Report of 2 Cases.

BACKGROUND: Renal anastomosing hemangioma (RAH) is a very rare distinct entity composed of anastomosing sinusoidal (spleen-like) capillary-sized vessels lined by flat or hobnail endothelial cells. Most of the published cases of RAH occurred in the setting of end-stage renal disease (ESRD). METHODS: We present 2 cases of RAH in ESRD along with a literature review. We compared clinicopathologic features of RAHs in end-stage and non-end-stage kidneys. A meta-analysis was conducted with PubMed and a manual search through references of relevant publications. Individual patient data gathered from the literature were used in the analysis. RESULTS: Our systematic review revealed 49 RAHs, including our 2 cases. Thirty-two (65.3%) cases were in ESRD, only 17 (34.7%) were in patients with non-ESRD. RAHs in ESRD were in younger patients, smaller in size, multifocal, and seen more with renal epithelial neoplasms when compared with RAHs in non-ESRD ( P < .05). Extramedullary hematopoiesis was seen mostly in RAHs in ESRD kidneys (85% vs 41.7%) ( P = .018). Follow-up data were available for 25 cases with a mean follow-up of 24.58 ± 38.54 months. Recurrence, metastasis, or death have never been described related to RAH in any patients. CONCLUSIONS: In conclusion, RAHs are rare and mostly arise in kidneys with end-stage damage. RAHs in ESRD and non-ESRD differ in terms of clinicopathologic features.

Renal carcinoma associated with a novel succinate dehydrogenase A mutation: a case report and review of literature of a rare subtype of renal carcinoma.

Renal cell carcinoma (RCC) linked to germline mutation of succinate dehydrogenase subunits A, B, C, and D (SDHA, SDHB, SDHC, and SDHD, respectively) has been recently included as a provisional entity in the 2013 International Society of Urological Pathology Vancouver classification. Most SDH-deficient tumors show SDHB mutation, with only a small number of RCC with SDHC or SDHD having been reported to date. Only one case of SDH-deficient renal carcinoma known to be SDHA mutated has been previously reported. Here we report an additional RCC harboring an SDHA mutation occurring in a 62-year-old man with right flank pain and nodal metastasis. The tumor was characterized by an infiltrative pattern with solid, acinar, and papillary components. Loss of SDHA and SDHB protein by immunohistochemistry confirmed the diagnosis. Hybrid capture-based comprehensive genomic profiling identified 3 genomic alterations in tumor tissue: (i) a novel single-nucleotide splice site deletion in SDHA gene, (ii) single-nucleotide deletion in NF2 gene, and (iii) EGFR gene amplification of 19 copies. This is the second report of SDHA-mutated RCC. With increased awareness, this rare tumor can be recognized on the basis of distinctive morphology and confirmation by immunohistochemistry and genomic profiling.