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.

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.

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.

Evaluation of MUC1, MUC2, MUC5AC, and MUC6 Expression Differences in Lung Adenocarcinoma Subtypes by Using a Final Immunoreactivity Score (FIRS).

OBJECTIVE: Lung adenocarcinomas are divided into acinar, lepidic, papillary, micropapillary, and solid predominant subtypes according to the current World Health Organization (WHO) classification. We designed this retrospective study to demonstrate profiles of MUC expression (MUC1, MUC2, MUC5AC, and MUC6) of different histologic patterns within the same tumor among pulmonary adenocarcinomas and investigate correlations of MUC expression with clinicopathologic features. MATERIAL AND METHOD: We analyzed the expression of mucins (MUC1, MUC2, MUC5AC, and MUC6) in a series of 99 resected lung adenocarcinomas, which included a total of 193 patterns (71 acinar, 30 lepidic, 25 papillary, 20 micropapillary, 34 solid and 13 mucinous) and calculated a final immune reactivity score (FIRS) per tumor. RESULTS: MUC1 IRS scores were significantly higher in lepidic and solid patterns compared with mucinous patterns (p=0.013). MUC2 expression was seen only in three cases (1 acinar, 2 mucinous). MUC5AC and MUC2 expression was more common in mucinous patterns (p < 0.001 and p=0.028, respectively). MUC6 expression was only detected in seven patterns and the expression was weak. No significant difference was seen among histologic patterns for the staining scores of MUC6. Mucinous adenocarcinoma differed from other histologic subtypes regarding MUC1 and MUC5AC expression. Mucinous adenocarcinoma showed less MUC1 expression with lower IRS scores and higher MUC5AC expression. Tumor size (p=0.006), lymphatic invasion (p=0.018), vascular invasion (p=0.025), perineural invasion (p=0.019), MUC1 IRS scores (p=0.018), and MUC1 IRS scores > 8.5 (p=0.018) were significant predictors for lymph node metastasis. CONCLUSION: An alternative scoring for MUC1 can be used as a predictor for lymph node metastasis regardless of the histologic subtype.

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.

Diagnostic accuracy of core biopsies of renal masses: Experience in a real-life setting from a tertiary center.

OBJECTIVE: To document and analyze diagnostic accuracy of renal core biopsy (RCB), its diagnostic correlation with resection specimens, and to question the need for immunohistochemistry (IHC) in the preoperative diagnosis of renal masses. MATERIAL AND METHOD: RCBs performed at a reference center between 2007 and 2017 were included. Pathological, clinical, and radiological data were obtained from medical records. RESULTS: Among 302 biopsies included in this study, 274 (90.7%) were diagnostic. Two hundred sixty-six were neoplastic and 179 were of primary renal origin. The most common secondary neoplasms were hematolymphoid (n = 35) and metastatic (n = 17). Sixty-nine tumors were classified as small renal masses (SRMs) (≤4 cm in diameter) and 53 of them were malignant. Nephrectomy was performed in 58 patients. Overall diagnostic accuracy between resections and RCBs was 88.7%. IHC was performed in 160 (53%) cases. In 15 of those, a definite diagnosis could not be rendered. Renal cell origin and subtype were determined by histomorphology alone in 81 and 75 cases, respectively. Sixty primary neoplasms of renal cell origin required IHC for diagnosis. CONCLUSION: RCB is a safe and highly accurate method for the diagnosis of both primary and secondary renal neoplasms. IHC is mostly required for the diagnosis of secondary tumors. Histomorphology is still the primary diagnostic tool, highly dependent on the experience of the surgical pathologist.

Metastases to the Stomach: Clinicopathologic Features of Metastases Mimicking Gastric Primaries.

OBJECTIVE: Metastatic involvement of the stomach is a rare event. Our aim in this study was to document the clinicopathological findings in patients with gastric metastases and find out if there are any potentially significant features to be used in the differential diagnosis. MATERIAL AND METHOD: Our cohort consisted of 17 histologically verified gastric metastasis cases. Clinical, endoscopic and microscopic features were retrospectively analyzed. RESULTS: The primary sites were the breast, skin, lungs, ovaries, colon, and gluteal soft tissue. Three patients were symptomatic because of the metastatic involvement of the stomach and 9 patients had concomitant metastasis in other sites. Invasive lobular breast carcinoma and malignant melanoma were the most common metastatic malignancies. The most common macroscopic appearance was the diffuse infiltrative type (Borrmann Type 4). Most of the metastatic lesions endoscopically mimicked primary gastric cancer. Furthermore, some of the metastatic lesions, particularly invasive lobular carcinoma of the breast and malignant melanoma, displayed histopathologic features similar to the primary gastric malignancies to a certain extent. CONCLUSION: The possibility of metastatic involvement of stomach must be kept in mind while dealing with a gastric mass lesion in a cancer patient, even though the clinical and endoscopic features suggest primary gastric cancer. Our study points out the importance of conveying the information about medical history and clinical findings of the patients for correct pathologic differential diagnosis.

What are the predictors for recurrence of Crohn's disease after surgery?

ABSTRACT: Surgical resection is an unavoidable part of the current treatment options for Crohn's disease (CD), and more than half of patients develop recurrence. The aim of this study was to investigate the predictors for recurrence in the long-term follow-up of CD patients after surgery.Medical records of consecutive CD patients who were operated on between January 2003 and January 2015 were retrospectively analyzed. Data including demographic and clinical characteristics of the patients were recorded. Recurrence was evaluated based on the Crohn's Disease Activity Index or endoscopic findings.The majority of 112 patients were males (n = 64, 57.1%), and 61 (54.4%) of them were active smokers. The median follow-up was 113 (range: 61-197) months. Disease recurrence occurred in 16 (14.3%) patients at a median of 13.5 months. The endoscopic recurrence rate was 8% (n = 9) at 1 year, 12.5% (n = 14) at 5 years, and 13.4% (n = 15) at 10 years. One (0.9%) patient underwent colonoscopic balloon dilatation at 1 year, and 7 (6.3%) patients needed re-resection at a median of 36 months. The age of the patient at the time of diagnosis (P = .033), penetrating disease behavior (P = .011), intra-abdominal abscess (P = 0.040) and, concomitant fistula and intra-abdominal abscess (P = .017) were associated with disease recurrence.Our study results suggest that the patients' age at the time of diagnosis, penetrating disease, intra-abdominal abscess, and concomitant fistula and abscess are the risk factors for CD recurrence after surgery.

Diagnostic significance of cytomegalovirus DNA quantitation in gastrointestinal biopsies: comparison with histopathological data and blood cytomegalovirus DNA.

OBJECTIVES: This study aims to improve the diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease. It presents the results of a novel study in which CMV blood viral load (BVL), tissue viral load (TVL) determined by PCR and hematoxylin-eosin (HE)/immunohistochemistry (IHC) results of GI biopsies are examined comparatively. METHODS: CMV DNA was investigated by quantitative real-time PCR in blood and GI biopsy specimens of 76 patients suspected of CMV disease. Biopsies were also performed HE/IHC stainings in the pathology laboratory. RESULTS: This study included 76 patients whose median age was 34.5 years and 58% (44) were male. Tissue CMV PCR positivity was detected in the highest colon (40/53;75.5%) samples. HE, IHC, blood and tissue CMV PCR positivity rates of all samples were 15.8, 25, 50 and 71.1%, respectively. When IHC was used as the gold standard test for ROC analysis, the optimal cutoff values for the maximum sensitivity and specificity for BVL and TVL were 1.91 log10 copies/ml and 3.82 log10 copies/mg, respectively. Sensitivity and specificity for the cutoff value of tissue CMV DNA were 78.9 and 74.3%, respectively (P < 0.001). CONCLUSION: In this study, CMV DNA was detected in 71.1% of the tissue samples of the cases by PCR. Since the sensitivity of the histopathological examinations accepted as the gold standard is low, simultaneous with the histopathological examinations, determination of BVL, TVL and the identification of optimal cutoff values have been shown to support the diagnosis of GI CMV disease.

Determining the number and distribution of intraparotid lymph nodes according to parotidectomy classification of European Salivary Gland Society: Cadaveric study.

BACKGROUND: To investigate the distribution of the parotid gland's intraglandular lymph nodes using the parotidectomy zones determined by the parotidectomy classification of the European Salivary Gland Society (ESGS). MATERIALS AND METHODS: A total of 128 parotid glands were dissected from 64 fresh cadavers, by bilateral parotidectomy without additional incision within the standard autopsy procedure, and categorized. RESULTS: Eighty-six percent of the IGLNs were located in the superficial lobe and 14% in the deep lobe. An average of 7.09 ± 3.55 IGLNs were found for each of the gland; there were 6.11 ± 3.28 in the superficial lobe and 0.98 ± 1.46 in the deep lobe. While the most common lymph nodes were found in level 2 with 47.7%, only 5% of IGLNs were at level 4. According to the proposed modification, the most common lymph nodes (35.24%) were located at level 2B. CONCLUSION: Level 2B was found to contain significantly more lymph nodes than other levels, which has not been evaluated before in literature.

The effect of neoadjuvant therapy on the size, number, and distribution of mesorectal lymph nodes.

The current therapeutic approach to patients with locally advanced rectal cancer is neoadjuvant radiotherapy or chemoradiotherapy followed by total mesorectal excision. We aimed to investigate the number, size, and distribution of metastatic and nonmetastatic lymph nodes within the mesorectum; whether neoadjuvant therapy has any impact on the number and size of the lymph nodes; and the impact of metastatic lymph node localization on overall and disease-free survival. Specimens from 50 consecutive patients with stage II/III rectal cancer receiving either neoadjuvant radiotherapy or chemoradiotherapy were investigated. Lymph node dissection was carried out by careful visual inspection and palpation. The localization of the each lymph node within the mesorectum and the relation with the tumor site were noted. The size and the number of lymph nodes retrieved decreased significantly with neoadjuvant therapy. Majority of the metastatic and nonmetastatic lymph nodes were located at or proximally to the tumor level and posterior side of the mesorectum. No relation was observed between the overall and disease-free survival, and the localization of the metastatic lymph nodes. Presence of lymph node metastases proximal to the tumor level has no impact on survival compared with the presence of lymph node metastasis only in the peritumoral region of the mesorectum. Although neoadjuvant therapy decreases the size and the number of lymph nodes, reaching an ideal number of lymph nodes for accurate staging is still possible with careful naked eye examination and dissection of perirectal fat. As the majority of metastatic and nonmetastatic lymph nodes are located in peritumoral and proximal compartment, and posterior side of the mesorectum, these regions should be the major interest of dissection.