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Background Mutations in micro-RNA (miRNA) regulators DICER1 and DGCR8 have recently been uncovered, revealing a potential novel mechanism driving thyroid tumor development. However, the true frequency of these hotspot mutations in follicular-patterned thyroid tumors (FTs) and their relation to established driver gene events remain elusive. Methods A total of 440 FTs from 2 institutions were interrogated for DICER1, DGCR8, and RAS family hotspot mutations using Sanger sequencing. Whole-exome sequencing was also performed to identify additional driver gene aberrations in DICER1/DGCR8 -mutant cases. Subsets of cases were further analyzed using miRNA expression profiling, and key dysregulated miRNAs were validated as markers of DICER1 mutations using quantitative RT-PCR analysis. The Cancer Genome Atlas (TCGA) database was also probed for DICER1 / DGCR8 mutations and miRNA dysregulation. Results Fourteen (3.2%) and 4 (1%) FTs harbored DICER1 and DGCR8 hotspot mutations, respectively, in the combined cohort, and no cases with normal tissue available were found to exhibit a constitutional variant. Two DGCR8 -mutant cases also harbored oncogenic RAS mutations. Whole-exome sequencing analysis did not identify additional driver gene events in DICER1 / DGCR8- positive cases. Comprehensive miRNA expression profiling revealed a unique pattern of dysregulated miRNAs in DICER1 / DGCR8- mutant cases compared with wild-type lesions. Moreover, DICER1 -mutant cases showed a remarkable reduction of 5′ arm miRNAs, findings corroborated in the TCGA cohort. Conclusion DICER1 and DGCR8 hotspot mutations are rare in unselected cohorts of FTs, and mutated cases exhibit a specific miRNA profile. Although DGCR8 mutations may coexist with established RAS gene alterations, FTs with DICER1 variants were devoid of other driver gene events. [ABSTRACT FROM AUTHOR]

Context: Infection by SARS-CoV-2 may be associated with testicular dysfunction that could affect male fertility. Objective: Testicles of fatal COVID-19 cases were investigated to detect virus in tissue and to evaluate histopathological and transcriptomic changes. Methods: Three groups were compared: (a) uninfected controls (subjects dying of trauma or sudden cardiac death; n= 10); (b) subjects dying of COVID-19 (virus-negative in testes; n= 15); (c) subjects dying of COVID-19 (virus-positive in testes; n= 9). SARS-CoV-2 genome and nucleocapsid antigen were probed using RT-PCR, in situ hybridization, and immunohistochemistry (IHC). Infiltrating leukocytes were typed by IHC. mRNA transcripts of immune-related and testis-specific genes were quantified using the nCounter method. Results: SARS-CoV-2 was detected in testis tissue of 9/24 (37%) COVID-19 cases accompanied by scattered T-cell and macrophage infiltrates. Size of testicles and counts of spermatogenic cells were not significantly different among groups. Analysis of mRNA transcripts showed that in virus-positive testes immune processes were activated (interferon-alpha and -gamma pathways). By contrast, transcription of 12 testis-specific genes was downregulated, independently of virus positivity in tissue. By IHC, expression of the luteinizing hormone/choriogonadotropin receptor was enhanced in virus-positive compared to virus-negative testicles, while expression of receptors for androgens and the follicle-stimulating hormone were not significantly different among groups. Conclusion: In lethal COVID-19 cases, infection of testicular cells is not uncommon. Viral infection associates with activation of interferon pathways and downregulation of testis-specific genes involved in spermatogenesis. Due to the exceedingly high numbers of infected people in the pandemic, the impact of virus on fertility should be further investigated. [ABSTRACT FROM AUTHOR]

Background: The Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) includes six diagnostic categories (TIR 1/1C, TIR 2, TIR 3A, TIR 3B, TIR 4, and TIR 5), each indicating a different risk of malignancy. The objective of this monocentric retrospective study was to evaluate the distribution of the ICCRTC classes at the authors' institution and assess their cytohistologic correlations. Methods: The authors retrospectively collected 37,371 consecutive cytologic reports of thyroid nodules and described the clinical–pathologic features of the different cytologic categories. The cytologic diagnoses also were compared with histologic outcomes in a subset of patients. Results: The cytologic classes were distributed as follows: nondiagnostic, 15.6%; benign, 66.5%; low‐risk indeterminate, 10% (TIR 3A); high‐risk indeterminate, 3.5% (TIR 3B); suspicious, 1.7%; and malignant, 2.6%. According to histology, the risk of malignancy was very high in the nondiagnostic category (29.8%), with young male patients more exposed to malignancy, and it was relatively high among benign (7.8%) and indeterminate nodules (32.5% in TIR 3A; 52.1% in TIR 3B), mainly because of the high prevalence of follicular architecture in malignant tumors. On histology, the malignancy rates were 92.4% and 99.3% for the suspicious and malignant categories, respectively; aggressive variants of papillary thyroid carcinoma were mostly diagnosed in these categories. Conclusions: In this series, nondiagnostic nodules showed high prevalence and, surprisingly, high malignancy rates. Malignant tumors with follicular architecture represented a diagnostic pitfall in benign and indeterminate nodules. The suspicious and malignant categories had high specificity for malignancy. Importantly, the ICCRTC had high reliability for identifying preoperatively aggressive histotypes of thyroid carcinoma. The Italian Consensus for the Classification and Reporting of Thyroid Cytology includes six diagnostic categories, each suggesting a different risk of malignancy. In this monocentric retrospective study, the objective was to evaluate the distribution of the cytologic classes at a single institution and to assess cytohistologic correlations.© 2022 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. [ABSTRACT FROM AUTHOR]

In the present review we discuss the recent developments and future directions in the multimodal treatment of locally advanced rectal cancer, with respect to staging and re-staging modalities, to the current role of neoadjuvant chemo-radiation and to the conservative and more limited surgical approaches based on tumour response after neoadjuvant combined therapy. When initial tumor staging is considered a high accuracy has been reported for T pre-treatment staging, while preoperative lymph node mapping is still suboptimal. With respect to tumour re-staging, all the current available modalities still present a limited accuracy, in particular in defining a complete response. The role of short vs long-course radiotherapy regimens as well as the optimal time of surgery are still unclear and under investigation by means of ongoing randomized trials. Observational management or local excision following tumour complete response are promising alternatives to total mesorectal excision, but need further evaluation, and their use outside of a clinical trial is not recommended. The preoperative selection of patients who will benefit from neoadjuvant radiotherapy or not, as well as the proper identification of a clinical complete tumour response after combined treatment modalities,will influence the future directions in the treatment of locally advanced rectal cancer.

Aim: To investigate the impact of laparoscopic colectomy on short and long-term outcomes in obese patients with colorectal diseases., Methods: A total of 98 obese (body mass index > 30 kg/m(2)) patients who underwent laparoscopic (LPS) right or left colectomy over a 10 year period were identified from a prospective institutionally approved database and manually matched to obese patients who underwent open colectomy. Controls were selected to match for body mass index, site of primary disease, American Society of Anesthesiologists score, and year of surgery (± 3 year). The parameters analyzed included age, gender, comorbid conditions, American Society of Anaesthesiologists class, diagnosis, procedure, and duration of operation, operative blood loss, and amount of homologous blood transfused. Conversion rate, intra and postoperative complications as were as reoperation rate, 30 d and long-term morbidity rate were also analyzed. For continuous variables, the Student's t test was used for normally distributed data the Mann-Whitney U test for non-normally distributed data. The Pearson's χ(2) tests, or the Fisher exact test as appropriate, were used for proportions., Results: Conversion to open surgery was necessary in 13 of 98 patients (13.3%). In the LPS group, operative time was 29 min longer and blood loss was 78 mL lower when compared to open colectomy (P = 0.03, P = 0.0001, respectively). Overall morbidity, anastomotic leak and readmission rate did not significantly differ between the two groups. A trend toward a reduction of wound complications was observed in the LPS when compared to open group (P = 0.09). In the LPS group, an earlier recovery of bowel function (P = 0.001) and a shorter length of stay (P = 0.03) were observed. After a median follow-up of 62 (range 12-132) mo 23 patients in the LPS group and 38 in the open group experienced long-term complications (LPS vs open, P = 0.03). Incisional hernia resulted to be the most frequent long-term complication with a significantly higher occurrence in the open group when compared to the laparoscopic one (P = 0.03)., Conclusion: Laparoscopic colectomy in obese patients is safe, does not jeopardize postoperative complications and resulted in lower incidence of long-term complications when compared with open cases.