Short stump and high anastomosis pull-through (SHiP) procedure for delayed coloanal anastomosis with no protective stoma for low rectal cancer

Despite advances in coloanal anastomosis techniques, satisfactory procedures completed without complications remain lacking. We investigated the effectiveness of our recently developed 'Short stump and High anastomosis Pull-through' (SHiP) procedure for delayed coloanal anastomosis without a stoma. In this retrospective study, we analysed functional outcomes, morbidity, and mortality rates and local recurrence of 37 patients treated using SHiP procedure, out of the 282 patients affected by rectal cancer treated in our institution between 2012 and 2020. The inclusion criterion was that the rectal cancer be located within 4 cm from the anal margin. One patient died of local and pulmonary recurrence after 6 years, one developed lung and liver metastases after 2 years, and one experienced local recurrence 2.5 years after surgery. No major leak, retraction, or ischaemia of the colonic stump occurred; the perioperative mortality rate was zero. Five patients (13.51%) had early complications. Stenosis of the anastomosis, which occurred in nine patients (24.3%), was the only long-term complication; only three (8.1%) were symptomatic and were treated with endoscopic dilation. The mean Wexner scores at 24 and 36 months were 8.3 and 8.1 points, respectively. At the 36-month check-up, six patients (24%) had major LARS, ten (40%) had minor LARS, and nine (36%) had no LARS. The functional results in terms of LARS were similar to those previously reported after immediate coloanal anastomosis with protective stoma. The SHiP procedure resulted in a drastic reduction in major complications, and none of the patients had a stom

Expanded carrier screening: A current perspective

Prenatal carrier screening has expanded to include a large number of genes offered to all couples considering pregnancy or with an ongoing pregnancy. Expanded carrier screening refers to identification of carriers of single-gene disorders outside of traditional screening guidelines. Expanded carrier screening panels include numerous autosomal recessive and X-linked genetic conditions, including those with a very low carrier frequency, as well as those with mild or incompletely penetrant phenotype. Therefore, the clinical utility of these panels is still subject of debate. Priority should be given to carrier screening panels that include a comprehensive set of severe childhood-onset disorders. Psychosocial support and genetic couseling should be available prior to screening and for the return of positive results. Systems are needed to reduce the risk of misinterpreting results. Finally, attention should be paid on the impact of expanded carrier screening on health care organizations and burden of cost

Predictive role of node-rads score in patients with prostate cancer candidates for radical prostatectomy with extended lymph node dissection: comparative analysis with validated nomograms

Background and objectives: The Reporting and Data System (RADS) have been used in the attempts to standardize the results of oncological scans in different scenarios, such as lymph nodes, adding configuration criteria to size determination. We analyze the predictive value of preoperative Node-RADS determination at imaging for pelvic lymph node (PLN) involvement in cases of prostate cancer (PC) considered for radical prostatectomy (RP) with extended lymph node dissection (eLND) and we compare it with validate predictive nomograms (MSKCC, Briganti and Gandaglia). Methods: 150 patients with a histological diagnosis of PC (high risk or intermediate with an estimated risk for pN+ higher than 5% using the Briganti or 7% using the Gandaglia nomogram) submitted for RP with an ePLND from 2018 and 2021 were retrospectively examined. Node-RADS determination was performed in all cases using the preoperative magnetic resonance (MR), performed by a radiologist blinded for pathologic results and compared with the MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms. Results: PLN involvement at final pathology (pN+) was found in 36/150 (24.0%) of cases and the mean percentage of positive LNs in pN+ cases was 15.90 ± 13.40. The mean number of PLNs removed at RP was similar (p = 0.188) between pN0 (23.9 ± 8.0) and pN+ (25.3 ± 8.0) cases. Considering a Node RADS 4-5 positive and a Node RADS 1-2 negative, the PPV was 100% and the NPV was 79.6%. A Node RADS score 4-5 showed a lower sensitivity (0.167 versus 0.972, 1.000, 0.971, 0.960 respectively), a higher specificity (1.000 versus 0.079, 0.096, 0.138, 0.186 respectively) and a similar AUC (0.583 versus 0.591, 0.581, 0.574, 0.597 respectively) when compared to MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms. Conclusions: Our evaluation suggests that Node RADS score, combining configuration criteria to size determination could improve specificity in terms of pathologic PLN prediction but a very low sensitivity has been also described

Elicitation of Preferences under Ambiguity

This paper is about behaviour under ambiguity ‒ that is, a situation in which probabilities either do not exist or are not known. Our objective is to find the most empirically valid of the increasingly large number of theories attempting to explain such behaviour. We use experimentally-generated data to compare and contrast the theories. The incentivised experimental task we employed was that of allocation: in a series of problems we gave the subjects an amount of money and asked them to allocate the money over three accounts, the payoffs to them being contingent on a ‘state of the world’ with the occurrence of the states being ambiguous. We reproduced ambiguity in the laboratory using a Bingo Blower. We fitted the most popular and apparently empirically valid preference functionals [Subjective Expected Utility (SEU), MaxMin Expected Utility (MEU) and α­-MEU], as well as Mean-Variance (MV) and a heuristic rule, Safety First (SF). We found that SEU fits better than MV and SF and only slightly worse than MEU and α­-MEU

A Geological Itinerary Through the Southern Apennine Thrust-Belt (Basilicata—Southern Italy)

Open access via Springer Compact AgreementPeer reviewedPublisher PD

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis

Introduction: The aim of this article was to analyze whether operative time and blood loss during radical prostatectomy (RP) can significantly influence surgical margins (SM) status and post-operative functional outcomes. Material and methods: We prospectively analyzed prostate cancer (PC) patients undergoing RP, using robot-assisted (RARP) or laparoscopic (LRP) procedures. Blood loss was defined using the variation in hemoglobin (Hb, g/dl) values from the day before surgery and no later than 4 hours after surgery. Results: From a whole population of 413 cases considered for RP, 67% underwent LRP and 33.0% RARP. Positive SM (SM+) were found in 33.9% of cases. Mean surgical operative time was 172.3 ±76 min (range 49-485), whereas blood loss was 2.3 ±1.2 g/dl (range 0.3-7.6). Operative time and blood loss at RP were not significantly correlated (r = -0.028275; p = 0.684). SM+ rates significantly (p = 0.002) varied by operative time; a higher SM+ rate was found in cases with an operative time <120 min (41.2%) and >240 min (53.4%). The risk of SM+ significantly increased 1.70 and 1.94 times in cases with an operative time <120 min and >240 min, respectively, independently to the surgical approach. The rate of erectile disfunction (ED) varied from 22.4% to 60.3% between <120 min and >240 min procedures (p = 0.001). According to blood loss, SM+ rates slightly but significantly (p = 0.032) varied; a higher rate of SM+ was found in cases with a Hb variation between 2-4 g/dl (35.9%). Conclusions: Independently to the surgical approach, operative time, more than blood loss at RP, represents a significant variable able to influence SM status and post-operative ED

Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1

ETS Transcription Factors Control Transcription of EZH2 and Epigenetic Silencing of the Tumor Suppressor Gene Nkx3.1 in Prostate Cancer

ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and have emerged as important players in prostate cancer. However, the biological impact of ETS factors in prostate tumorigenesis is still debated.We performed an analysis of the ETS gene family using microarray data and real-time PCR in normal and tumor tissues along with functional studies in normal and cancer cell lines to understand the impact in prostate tumorigenesis and identify key targets of these transcription factors. We found frequent dysregulation of ETS genes with oncogenic (i.e., ERG and ESE1) and tumor suppressor (i.e., ESE3) properties in prostate tumors compared to normal prostate. Tumor subgroups (i.e., ERG(high), ESE1(high), ESE3(low) and NoETS tumors) were identified on the basis of their ETS expression status and showed distinct transcriptional and biological features. ERG(high) and ESE3(low) tumors had the most robust gene signatures with both distinct and overlapping features. Integrating genomic data with functional studies in multiple cell lines, we demonstrated that ERG and ESE3 controlled in opposite direction transcription of the Polycomb Group protein EZH2, a key gene in development, differentiation, stem cell biology and tumorigenesis. We further demonstrated that the prostate-specific tumor suppressor gene Nkx3.1 was controlled by ERG and ESE3 both directly and through induction of EZH2.These findings provide new insights into the role of the ETS transcriptional network in prostate tumorigenesis and uncover previously unrecognized links between aberrant expression of ETS factors, deregulation of epigenetic effectors and silencing of tumor suppressor genes. The link between aberrant ETS activity and epigenetic gene silencing may be relevant for the clinical management of prostate cancer and design of new therapeutic strategies

Unicentric mixed variant castleman disease associated with intrabronchial plasmacytoma.

Castleman disease (CD), described as a heterogeneous lymphoproliferative disorder, can be divided into different subtypes according to clinical appearance (unicentric and multicentric form) and histopathological features (hyaline vascular, plasma cell, mixed type, human herpesvirus 8-associated and multicentric not otherwise specified). Unicentric CD is known to be usually of the hyaline vascular variant, plasma cell and mixed type of this form are quite uncommon. Malignancies are mainly associated with the multicentric form. We report a rare case of unicentric mixed variant CD evolving into intrabronchial, extramedullary plasmacytoma.Intrabronchial mass with consequential obstruction of the left main bronchus, left lung atelectasis and mediastinal lymphadenomegaly was detected by chest CT in our patient suffering from cough and hemoptysis. Pulmonectomy was performed, histopathological and immunhistochemical analysis of lymph nodes revealed mixed type of CD with interfollicular monotypic plasma cell proliferation. The intrabronchial mass consisted of monotypic plasma cells confirming plasmacytoma. Systemic involvement was not confirmed by further tests.Although malignancies more often present in multicentric CD that usually belongs to the plasma cell subtype, this case confirms the neoplastic potential of the rarest, unicentric mixed variant of CD.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2872096831190851

Perspective taking and theory of mind in hide and seek

Does theory of mind play a significant role in where people choose to hide an item or where they search for an item that has been hidden? Adapting the "Hide-Find Paradigm" of Anderson et al. (2014), participants viewed homogenous or popout visual arrays on a touchscreen table. Their task was to indicate where in the array they would hide an item, or to search for an item that had been hidden, by either a friend or a foe. Critically, participants believed that their sitting location at the touchtable was the same as - or opposite to - their partner's location. Replicating Anderson et al. participants tended to (1) select items nearer to themselves on homogenous displays, and this bias was stronger for a friend than foe; and (2) select popout items, and again, more for a friend than foe. These biases were observed only when participants believed that they shared the same physical perspective as their partner. Collectively the data indicate that theory of mind plays a significant role in hiding and finding, and demonstrate that the hide-find paradigm is a powerful tool for investigating theory of mind in adults