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Purpose: This study aimed to compare local regrowth rates after total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy (SNCRT) in locally advanced rectal cancer (LARC) patients that were strictly selected and assessed with a multimodal approach. Secondary outcomes were 4-year disease-free (DFS) and overall survival (OS) rates., Methods: Locally advanced rectal cancer patients without distant metastases treated at Koç Healthcare Group between January 2014 and January 2021 were included. Patients were assessed for complete response with a combination of digital rectal exam, endoscopy, and magnetic resonance imaging with a dedicated rectum protocol. The systemic evaluation was performed with an upper abdomen MRI using intravenous hepatobiliary contrast agent and a thorax CT., Results: Of the 270 patients with LARC, 182 fulfilled the inclusion criteria. Ninety-seven (53.3%) underwent TNT, while 85 (46.7%) underwent SNCRT. A cumulative combination of pathological and sustained clinical complete response was significantly higher in the TNT group than in the SNCRT (45.4% vs. 20.0%, p < 0.0001). After a median follow-up of 48 months, seven patients in the W&W group had regrowth [TNT: 4 (10.8%) vs. SNCRT: 3 (23.1%), p = 0.357]. Based on pathological examination, complete/near complete mesorectum rates (p = 1.000) and circumferential resection margin positivity rates (p = 1.000) were similar between the groups. The 4-year DFS and OS rates were comparable. The patients with clinical or pathological complete response had significantly longer overall survival (p = 0.017) regardless of the type of neoadjuvant treatment., Conclusions: Multimodal assessment after TNT effectively detects complete responders, resulting in low local recurrence and increased cumulative complete response rates. However, these outcomes did not translate into a survival advantage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients’ families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors’ own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia. The coexistence of CLL and papillary thyroid carcinoma (PTC) is extremely rare. PTC sometimes shows microscopic vascular invasion but rarely cause a tumor thrombus in the internal jugular vein (IJV). It is also rare to find both differentiated and poorly differentiated types of thyroid cancer in the same metastatic location. We report a case of 63-year-old Turkish man with history of CLL who had CLL/SLL involvement and PTC metastasis in the same lymph node. Additionally, there was macroscopic metastasis to the IJV with poorly differentiated areas in the removed tumor thrombus. Patient was treated with total thyroidectomy, left radical neck dissection, resection of the left IJV segment that contained the tumor thrombus and radioactive iodine (RAI) therapy. Furthermore, metastatic lesions were found in the brain, lung and bone. Radiotherapy and chemotherapy were performed. However, our patient died approximately 12 months after thyroidectomy. To our knowledge, our present report is the first description with its current features.

Objective: Lymph node metastasis occurs in a subset of papillary microcarcinoma patients. We aimed to analyze the differences between metastatic and non-metastatic papillary microcarcinomas in order to identify a high-risk subgroup that is likely to require more aggressive treatment., Materials and Methods: 126 thyroidectomies with lymph node dissections (central ± lateral), diagnosed as papillary microcarcinoma, were reviewed., Results: Mean age of 126 patients (F/M = 3.3) was 42 years. Mean size of the largest tumor was 7 mm. Classical was the most frequently (89%) encountered subtype. Multiple histologic subtypes co-occurred in 19%. Lymphovascular invasion was present in 16% (n = 20). 55 (44%) and 71 (56%) cases were unifocal and multifocal, respectively. 90 cases (71%) were non-encapsulated with overall infiltrative tumor borders, whereas in 36 cases (29%), the tumor had a well-defined capsule. Among those, 23 (64%) had tumor capsule invasion. 47 (37%) cases had metastasis in lymph nodes. In univariate analysis, metastasis was associated with tumor size of >5 mm (p = 0.02), tumor burden of >5 mm (p = 0.03), lymphovascular invasion (p = 0.02) and non-encapsulation (p = 0.01). No associations were found regarding sex, age, histologic subtype, lymphocytic thyroiditis, tumor capsule invasion (in capsulated tumors), laterality and multifocality (p > 0.05). In multivariate analysis, lymphovascular invasion (p = 0.01, OR = 3.97, 95% CI 1.35-11.67), tumor size >0.5 cm (p = 0.031, OR = 2.92, 95% CI 1.10-7.71) and non-encapsulation (p = 0.033, OR = 2.85, 95% CI 1.08-7.51) were independent risk factors., Conclusion: Size (largest tumor or sum of all foci) of >5 mm, non-encapsulation and lymphovascular invasion were independent predictors of LNM in PMs. Unifocal tumors metastasize the same as multifocal tumors, suggestive of the contribution of other factors. Patients with sporadically resected microcarcinomas should be carefully followed-up, especially those that harbor risk factors in histology., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background. Endoscopic submucosal dissections (ESDs) allow removal of large gastrointestinal tumors and help patients avoid major oncologic surgery. In this study, the challenges and development of approaches toward successfully handling ESDs were analyzed in 279 colorectal specimens (114 rectal, 47 left, 118 right colonic; 90% adenoma with/without carcinoma). Methods. Each specimen was processed according to an established protocol including gross photography, mapping, and total submission for histopathologic examination. Results. Mean lesion size was 4.2 cm (range: 0.5-22 cm; 28% ≥5 cm; 6% ≥10 cm). Invasive carcinoma was present in 38 cases (14%), which had a mean overall tumor size of 3.8 cm (range: 1.1-17.5 cm), and mean largest size of the invasive component was 0.93 cm (range: 0.04-3 cm). Fifteen cases were staged as pT1a (submucosal invasion of <1000 µm) and 13 cases as pT1b (submucosal invasion of ≥1000 µm). En-bloc and R0 resection rates were 99.3% and 90.6%, respectively. Conclusion. Various histopathologic challenges were encountered, which were carefully evaluated by dedicated pathologists with familiarity to the subtleties in handling and reporting these specimens. We recommend these specimens to be prepared in the endoscopy suite, submitted to the Pathology Department oriented, pinned, and placed into copious amount of fixative. Total sampling, gross photography, mapping, and proper fixation are crucial components in the histopathologic evaluation. Micromeasurement of invasion depth and substaging per European/Japanese guidelines as well as accurate measurement of the distance from the resection margins are highly recommended. In conclusion, ESD is an adequate method that can be successfully implemented in a tertiary care center to perform en-bloc and margin-free resections of clinically selected large colorectal superficial lesions.

Objective: To analyze clinicopathologic characteristics of upper gastrointestinal leiomyomas and to determine the distribution and immunohistochemical features of interstitial cells of Cajal, in order to designate whether they can cause diagnostic challenges., Materials and Methods: Twenty-four upper gastrointestinal leiomyomas (14 esophagus, 10 stomach) were retrieved. CD117, DOG-1 and muscle markers were performed. The staining was analyzed based on the distribution and percentage. Interstitial cells of Cajal were distinguished based on their positivity for both CD117 and DOG-1 immunohistochemistry, along with their morphological features., Results: Mean age of patients was 49 years, M/F ratio was 2.4. Patients with gastric leiomyomas were significantly younger than those with esophageal leiomyomas (41.5 vs. 54.3, p = 0.012). Histologically, leiomyomas were similar to their endometrial counterpart. Immunohistochemically, all tumors had strong/diffuse positivity for muscle markers. CD117 highlighted mast cells in all cases. Three cases had prominently increased mast cells. Both CD117 and DOG-1 also highlighted interstitial cells of Cajal in 24/24 (100%) of cases. Interstitial cells of Cajal were distributed in variable proportions, from focal to homogenous. In one case, they constituted 50% of tumor cells. In 16 cases, the distribution was homogenous. Superficial leiomyomas (n = 3) had only focal CD117 and DOG-1 positivity., Conclusion: Upper gastrointestinal leiomyomas harbor expression of CD117 and DOG-1 in entrapped/colonized interstitial cells of Cajal, which can cause a potential pitfall in the differential diagnosis, especially in cases that show prominent immunohistochemical positivity. Evaluation of the immunohistochemistry can be exceptionally challenging in small biopsy/cytology specimens. Careful histologic evaluation of the tumor as well as the recognition of interstitial cells of Cajal will help the pathologist render the accurate diagnosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)