Predicting response to neoadjuvant chemotherapy with liquid biopsies and multiparametric MRI in patients with breast cancer.

Accurate prediction of response to neoadjuvant chemotherapy (NAC) can help tailor treatment to individual patients' needs. Little is known about the combination of liquid biopsies and computer extracted features from multiparametric magnetic resonance imaging (MRI) for the prediction of NAC response in breast cancer. Here, we report on a prospective study with the aim to explore the predictive potential of this combination in adjunct to standard clinical and pathological information before, during and after NAC. The study was performed in four Dutch hospitals. Patients without metastases treated with NAC underwent 3 T multiparametric MRI scans before, during and after NAC. Liquid biopsies were obtained before every chemotherapy cycle and before surgery. Prediction models were developed using penalized linear regression to forecast residual cancer burden after NAC and evaluated for pathologic complete response (pCR) using leave-one-out-cross-validation (LOOCV). Sixty-one patients were included. Twenty-three patients (38%) achieved pCR. Most prediction models yielded the highest estimated LOOCV area under the curve (AUC) at the post-treatment timepoint. A clinical-only model including tumor grade, nodal status and receptor subtype yielded an estimated LOOCV AUC for pCR of 0.76, which increased to 0.82 by incorporating post-treatment radiological MRI assessment (i.e., the "clinical-radiological" model). The estimated LOOCV AUC was 0.84 after incorporation of computer-extracted MRI features, and 0.85 when liquid biopsy information was added instead of the radiological MRI assessment. Adding liquid biopsy information to the clinical-radiological resulted in an estimated LOOCV AUC of 0.86. In conclusion, inclusion of liquid biopsy-derived markers in clinical-radiological prediction models may have potential to improve prediction of pCR after NAC in breast cancer.

Nationwide analysis of open groin hernia repairs in Italy from 2015 to 2020.

INTRODUCTION: Inguinal hernia repair is one of the most commonly performed operations in general surgery. A total of 130.000 inguinal hernia repairs are performed yearly in Italy, and approximately 20 million inguinal hernias are treated worldwide annually. This report represents the trend analysis in inguinal hernia repair in Italy from a nationwide dataset for the 6-year period from 2015 to 2020. MATERIALS AND METHODS: Based on regional hospital discharge records, all the inguinal hernia repairs performed in public and private hospitals in Italy between 2015 and 2020 were reviewed based on diagnosis and procedure codes. For the aim of this study, data from the AgeNas (The National Agency for Regional Health Services) data source were analyzed. RESULTS: Elective inguinal hernia repairs outnumbered urgent operations over the 6-year study period, ranging from 122,737 operations in 2015 to 65,780 in 2020 as absolute numbers, and from 87.96 to 83.3% of total procedures in 2019 and 2020 respectively, with an annual change ranging from - 66.58%, between 2020 and 2019, to - 2.49%, between 2019 and 2018 (mean = - 18.74%; CI =- 46.7%-9.22%; p < 0.0001). CONCLUSIONS: This large-scale review of groin hernia data from a nationwide Italian dataset provides a unique opportunity to obtain a snapshot of open groin hernia repair activity. More specifically, there is a trend to perform more elective than urgent procedures and there is a steady decrease in the amount of open hernia repairs in favor to laparoscopy.

Hypoglycemic effect of Coffea arabica leaf extracts and major bioactive constituents.

The present study focused on investigating the antioxidant, antiglycation activity, digestive enzymes inhibition, bioaccessibility and hypoglycemic effect of C. arabica leaves extracts. The extracts deactivated the O2•-, ROO•, H2O2, HOCl reactive oxygen species. Coffee leaves showed strong inhibition of α-glucosidase (IC50 = 40.30 µg mL-1) greater than the isolated metabolites and acarbose. There was also inhibition of pancreatic lipase (IC50 = 56.43 µg mL-1) in addition to a hypoglycemic effect in zebrafish similar to acarbose and metformin. With the exception of rutin, all biocompounds were detected at all stages of in vitro digestion. Finally, these results suggest that C. arabica leaf extracts possess antidiabetic and anti-obesity properties that can be attributed to the main metabolites and the synergistic action between them.Communicated by Ramaswamy H. Sarma.

Bile detection of squamous cell carcinoma antigen (SCCA) in extrahepatic cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a rare biliary tract tumor with poor prognosis that often is challenging to diagnose and the majority of patients present with advanced stage. Squamous cell carcinoma antigen 1 (SCCA1) overexpression has been found in different tumors associated with poor prognosis and chemoresistance. AIMS: To assess the presence and possible prognostic role of SCCA1/2 isoforms in bile and serum of patients with CCA. METHODS: Forty seven surgical patients (36 with CCA and 11 with benign diseases) were prospectively included in the study. Serum and bile specimens were collected at the time of surgery and free and IgM-complexed SCCA was quantified by ELISA (Xeptagen, srl). RESULTS: Free or IgM linked SCCA was rarely found in serum, while SCCA was detectable in bile samples of patients with CCA, especially in those with extrahepatic form (43% vs 17%, p = 0.008), but not in controls. Despite similar tumor stage, these positive patients presented a trend toward a higher percentage of portal invasion (27% vs 15%) and of tumor recurrence than negative cases (62% vs 40%), although the difference was not statistically significant. CONCLUSION: These preliminary results indicate that bile testing for SCCA is a specific marker of extrahepatic CCA, with potential prognostic value.

Laparoscopic approach in emergency for the treatment of acute incarcerated groin hernia: a systematic review and meta-analysis.

PURPOSE: Minimally invasive approach for acute incarcerated groin hernia repair is still debated. To clarify this debate, a literature review was performed. METHODS: Search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane databases, founding 28,183 articles. RESULTS: Fifteen articles, and 433 patients were included (16 bilateral hernia, range 3-8). Three hundred and eighty-eight (75.3%) and 103 patients (22.9%) underwent transabdominal preperitoneal and totally extraperitoneal repair, respectively, and in 5 patients, the defect was buttressed with broad ligament (1.1%) (not specified in 3 patients). Herniated structures were resected in 48 cases (range 1-9). Intraoperative complications and conversion occurred in 4 (range 0-1) and 10 (range 0-3) patients, respectively. Mean operative time and hospital stay ranged between 50 and 147 min, and 2 and 7 days, respectively. Postoperative complications ranged between 1 and 19. Five studies compared laparoscopic and open approaches (163 and 235 patients). Herniated structures were resected in 19 (11.7%) and 42 cases (17.9%) for laparoscopic and open approach, respectively (p = 0.1191). Intraoperative complications and conversion occurred in one (0.6%) and 5 (2.1%) patients (p = 0.4077), and in two (1.2%) and 19 (8.1%) patients (p = 0.0023), in case of laparoscopic or open approach, respectively. Mean operative time and hospital stay were 94.4 ± 40.2 and 102.8 ± 43.7 min, and 4.8 ± 2.2 and 11 ± 3.1 days, in laparoscopic or open approach, respectively. Sixteen (9.8%) and 57 (24.3%) postoperative complications occurred. CONCLUSION: Laparoscopy seems to be a safe and feasible approach for the treatment of acute incarcerated groin hernia. Further studies are required for definitive conclusions.

Validation of a documentary on Chagas disease by a population living in an endemic area / Validação de um documentário sobre a doença de Chagas por uma população de área endêmica

Abstract Educational interventions may trigger actions that contribute to prevent parasitic diseases, such as Chagas disease (CD). This study aimed at investigating the impact of an instructional video named "Documentary on Chagas Disease" on knowledge about CD and its vectors displayed by a population that lives in an endemic area in Brazil, so as to validate it as an educational tool. The video was shown to 226 subjects, divided into two groups. Group 1 was composed of users of Basic Health Units (BHU) in Pelotas and Pinheiro Machado, cities located in Rio Grande do Sul (RS) state, Brazil, where CD is endemic. Group 2 consisted of students who attend three public schools located in the rural area in Pinheiro Machado, RS. Two questionnaires with questions about their knowledge about triatomines and CD were applied, before and after the documentary was shown. After the video was shown, there was significant increase in individuals' knowledge (in both groups) about "kissing bugs", their notification, the disease and its prevention. Besides, watchers considered that the quality of the material was satisfactory. Since the "Documentary on CD" can be easily accessed on the internet and was effective in teaching the population that lives in endemic areas, its use should be encouraged in places and meetings connected to health that aim at fighting against triatominae and at exposing an updated view of CD.

Resumo Intervenções educacionais podem desencadear ações que contribuam para a prevenção de doenças parasitárias, como a doença de Chagas (DC). Este estudo teve como objetivo investigar o impacto de um vídeo instrucional denominado "Documentário Doença de Chagas" no conhecimento sobre DC e seus vetores exibidos a uma população que vive em área endêmica no Brasil, para validá-lo como uma ferramenta educacional. O vídeo foi exibido para 226 indivíduos, divididos em dois grupos. O grupo 1 foi composto por usuários das Unidades Básicas de Saúde (UBS) de Pelotas e Pinheiro Machado, cidades do estado do Rio Grande do Sul (RS), Brasil, onde a DC é endêmica. O grupo 2 foi formado por estudantes que frequentam três escolas públicas localizadas na zona rural de Pinheiro Machado, RS. Dois questionários com perguntas sobre conhecimentos sobre triatomíneos e DC foram aplicados, antes e depois da exibição do documentário. Após a exibição do vídeo, houve um aumento significativo no conhecimento dos indivíduos (em ambos os grupos) sobre "triatomíneos", sua notificação, a doença e sua prevenção. Além disso, os observadores consideraram que a qualidade do material era satisfatória. Como o "Documentário DC" pode ser facilmente acessado na Internet e ser eficaz no ensino à população que vive em áreas endêmicas, seu uso deve ser incentivado em locais e reuniões relacionadas à saúde, que visam combater os triatomíneos e exibir uma informação atualizada sobre a DC.

Genomic profiling of late-onset basal cell carcinomas from two brothers with nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disorder. It is commonly caused by mutations in PTCH1 and chiefly characterized by multiple basal cell carcinomas (BCCs) developing prior to the age of 30 years. In rare cases, NBCCS presents with a late onset of BCC development. OBJECTIVE: To investigate BCC tumorigenesis in two brothers, who showed characteristic features of NBCCS but developed their first BCCs only after the age of 40 years. Two other siblings did not show signs of NBCCS. RESULTS: We obtained blood samples from four siblings and nine BCCs from the two brothers with NBCCS. Whole exome sequencing and RNA sequencing revealed loss of heterozygosity (LOH) of PTCH1 in eight out of nine tumours that consistently involved the same haplotype on chromosome 9. This haplotype contained a germinal splice site mutation in PTCH1 (NM_001083605:exon9:c.763-6C>A). Analysis of germline DNA confirmed segregation of this mutation with the disease. All BCCs harboured additional somatic loss-of-function (LoF) mutations in the remaining PTCH1 allele which are not typically seen in other cases of NBCCS. This suggests a hypomorphic nature of the germinal PTCH1 mutation in this family. Furthermore, all BCCs had a similar tumour mutational burden compared to BCCs of unrelated NBCCS patients while harbouring a higher number of damaging PTCH1 mutations. CONCLUSIONS: Our data suggest that a sequence of three genetic hits leads to the late development of BCCs in two brothers with NBCCS: a hypomorphic germline mutation, followed by somatic LOH and additional mutations that complete PTCH1 inactivation. These genetic events are in line with the late occurrence of the first BCC and with the higher number of damaging PTCH1 mutations compared to usual cases of NBCCS.

Should enhanced recovery after surgery (ERAS) pathways be preferred over standard practice for patients undergoing abdominal wall reconstruction? A systematic review and meta-analysis.

PURPOSE: Although many studies assessing enhanced recovery after surgery (ERAS) pathways in abdominal wall reconstruction (AWR) have recently demonstrated lower rates of postoperative morbidity and a decrease in postoperative length of stay compared to standard practice, the utility of ERAS in AWR remains largely unknown. METHODS: A systematic literature search for randomized and non-randomized studies comparing ERAS (ERAS +) pathways and standard protocols (Control) as an adopted practice for patients undergoing AWR was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and EMBASE databases. A predefined search strategy was implemented. The included studies were reviewed for primary outcomes: overall postoperative morbidity, abdominal wall morbidity, surgical site infection (SSI), and length of hospital stay; and for secondary outcome: operative time, estimated blood loss, time to discontinuation of narcotics, time to urinary catheter removal, time to return to bowel function, time to return to regular diet, and readmission rate. Standardized mean difference (SMD) was calculated for continuous variables and Odds Ratio for dichotomous variables. RESULTS: Five non-randomized studies were included for qualitative and quantitative synthesis. 840 patients were allocated to either ERAS + (382) or Control (458). ERAS + and Control groups showed equivalent results with regard to the incidence of postoperative morbidity (OR 0.73, 95% CI 0.32-1.63; I2= 76%), SSI (OR 1.17, 95% CI 0.43-3.22; I2= 54%), time to return to bowel function (SMD - 2.57, 95% CI - 5.32 to 0.17; I2= 99%), time to discontinuation of narcotics (SMD - 0.61, 95% CI - 1.81 to 0.59; I2= 97%), time to urinary catheter removal (SMD - 2.77, 95% CI - 6.05 to 0.51; I2= 99%), time to return to regular diet (SMD - 0.77, 95% CI - 2.29 to 0.74; I2= 98%), and readmission rate (OR 0.82, 95% CI 0.52-1.27; I2= 49%). Length of hospital stay was significantly shorter in the ERAS + compared to the Control group (SMD - 0.93, 95% CI - 1.84 to - 0.02; I2= 97%). CONCLUSIONS: The introduction of an ERAS pathway into the clinical practice for patients undergoing AWR may cause a decreased length of hospitalization. These results should be interpreted with caution, due to the low level of evidence and the high heterogeneity.

Avaliação da toxicidade pré-natal: estudo de teratogenicidade do inseticida piriproxifeno em ratos Wistar / Prenatal toxicity assessment: teratogenicity study of the insecticide pyriproxyfen in Wistar rats

Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)

This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)

Pre-vaccination screening strategies for the use of the CYD-TDV dengue vaccine: A meeting report.

The first licensed dengue vaccine, CYD-TDV (Dengvaxia) is efficacious in seropositive individuals, but increases the risk for severe dengue in seronegative persons about two years after administration of the first dose. For countries considering the introduction of Dengvaxia, WHO recommends a pre-vaccination screening strategy whereby only persons with evidence of a past dengue infection would be vaccinated. Policy-makers need to consider the risk-benefit of vaccination strategies based on such screening tests, the optimal age to introduce the vaccine, communication and implementation strategies. To address these questions, the Global Dengue and Aedes-transmitted diseases Consortium (GDAC) organized a 3-day workshop in January 2019 with country representatives from Asia and Latin America. The meeting discussions highlighted many challenges in introducing Dengvaxia, in terms of screening test characteristics, costs of such tests combined with a 3-dose schedule, logistics, achieving high coverage rates, vaccine confidence and communication; more challenges than for any other vaccine introduction programme. A screening test would require a high specificity to minimize individual risk, and at the same time high sensitivity to maximize individual and population benefit. The underlying seroprevalence dependent positive predictive value is the best indicator for an acceptable safety profile of a pre-vaccination screening strategy. The working groups discussed many possible implementation strategies. Addressing the bottlenecks in school-based vaccine introduction for Dengvaxia will also benefit other vaccines such as HPV and booster doses for tetanus and pertussis. Levels of public trust are highly variable and context specific, and understanding of population perceptions and concerns is essential to tailor interventions, monitor and mitigate risks.

Is human fibrin sealant a possible choice for the fixation of laparoscopic inguinal hernia repair? A single center experience and the analysis of the results after 326 TAPP in two years.

BACKGROUND: Groin hernioplasty is most intervention performed in the worldwide. The present study aimed to evaluate a combination between ultralight mesh and fibrin human sealant in the laparoscopic treatment of inguinal hernia. PATIENTS AND METHODS: This retrospective study included consecutive patients who underwent laparoscopic transabdominal preperitoneal hernioplasty (TAPP) from 1st of January 2015 to 31st of December 2016. Demographics, surgical data and postoperative outcomes were entered in an anonymized prospective database. Prospective longterm follow-up carried out in all patients. RESULTS: One hundred eighty-four patients with a median age 57.5 (range 19-84) and median BMI (Body Mass Index) of 28.5 (range 18.5-31.5) were included. A median follow-up of 25 months (median 13-35) was carried out. Five recurrences (1.5%) and two cases of missed lipoma were observed and operated. Chronic pain (CP) was observed in eleven (9%) patients but in 9 patients it decreased spontaneously. CONCLUSIONS: Combination of ultralight mesh and Evicel® in TAPP operation is a safe solution for the treatment of groin hernia. Recurrences and chronic pain are similar to other combination of fibrin sealant and meshes. Moreover action of Evicel® may provide to improve the hemostasis and consequently hematoma of the cord.

Plant antiherbivore defenses in Fabaceae species of the Chaco / Defesas das plantas anti-herbivoria em espécies de Fabaceae do Chaco

Abstract The establishment and maintenance of plant species in the Chaco, one of the widest continuous areas of forests in the South American with sharp climatic variations, are possibly related to biological features favoring plants with particular defenses. This study assesses the physical and chemical defenses mechanisms against herbivores of vegetative and reproductive organs. Its analyses of 12 species of Fabaceae (Leguminosae) collected in remnants of Brazilian Chaco shows that 75% present structural defense characters and 50% have chemical defense - defense proteins in their seeds, like protease inhibitors and lectins. Physical defenses occur mainly on branches (78% of the species), leaves (67%), and reproductive organs (56%). The most common physical characters are trichomes and thorns, whose color represents a cryptic character since it does not contrast with the other plant structures. Defense proteins occur in different concentrations and molecular weight classes in the seeds of most species. Protease inhibitors are reported for the first time in seeds of: Albizia niopoides, Anadenanthera colubrina, Mimosa glutinosa, Prosopis rubriflora, and Poincianella pluviosa. The occurrence of physical and chemical defenses in members of Fabaceae indicate no associations between defense characters in these plant species of the Chaco.

Resumo O estabelecimento e a manutenção de espécies no Chaco, uma planície semi-árida da América do Sul com variações climáticas importantes, possivelmente estão relacionados a características biológicas que favorecem as plantas detentoras de defesas particulares. Este estudo teve como objetivos avaliar os mecanismos de defesa física e química anti-herbivoria em órgãos vegetativos e reprodutivos. Analisamos 12 espécies da família Fabaceae (Leguminosae) obtidas em remanescentes de Chaco brasileiro. Observamos que 75% das espécies estudadas apresentam atributo de defesa física e 50% possuem defesa química - proteínas de defesa nas sementes, como inibidores de protease e lectinas. As defesas físicas ocorrem principalmente nos ramos (78% das espécies), nos órgãos reprodutivos (56% das espécies) e nas folhas (67%). Os atributos físicos mais frequentes são tricomas e espinhos, cuja coloração não contrastante com as demais estruturas das plantas representa um caráter críptico. Proteínas de defesa ocorrem nas sementes da maioria das espécies, com diferentes concentrações e classes de pesos moleculares. Inibidores de protease nas sementes estão sendo relatados pela primeira vez em: Albizia niopoides, Anadenanthera colubrina, Mimosa glutinosa, Prosopis rubriflora e Poincianella pluviosa. A ocorrência de defesas física e química entre os membros de Fabaceae indica que não há associações entre as características de defesa das espécies de plantas avaliadas no Chaco.

Validation of a documentary on Chagas disease by a population living in an endemic area

Abstract Educational interventions may trigger actions that contribute to prevent parasitic diseases, such as Chagas disease (CD). This study aimed at investigating the impact of an instructional video named Documentary on Chagas Disease on knowledge about CD and its vectors displayed by a population that lives in an endemic area in Brazil, so as to validate it as an educational tool. The video was shown to 226 subjects, divided into two groups. Group 1 was composed of users of Basic Health Units (BHU) in Pelotas and Pinheiro Machado, cities located in Rio Grande do Sul (RS) state, Brazil, where CD is endemic. Group 2 consisted of students who attend three public schools located in the rural area in Pinheiro Machado, RS. Two questionnaires with questions about their knowledge about triatomines and CD were applied, before and after the documentary was shown. After the video was shown, there was significant increase in individuals knowledge (in both groups) about kissing bugs, their notification, the disease and its prevention. Besides, watchers considered that the quality of the material was satisfactory. Since the Documentary on CD can be easily accessed on the internet and was effective in teaching the population that lives in endemic areas, its use should be encouraged in places and meetings connected to health that aim at fighting against triatominae and at exposing an updated view of CD.

Resumo Intervenções educacionais podem desencadear ações que contribuam para a prevenção de doenças parasitárias, como a doença de Chagas (DC). Este estudo teve como objetivo investigar o impacto de um vídeo instrucional denominado Documentário Doença de Chagas no conhecimento sobre DC e seus vetores exibidos a uma população que vive em área endêmica no Brasil, para validá-lo como uma ferramenta educacional. O vídeo foi exibido para 226 indivíduos, divididos em dois grupos. O grupo 1 foi composto por usuários das Unidades Básicas de Saúde (UBS) de Pelotas e Pinheiro Machado, cidades do estado do Rio Grande do Sul (RS), Brasil, onde a DC é endêmica. O grupo 2 foi formado por estudantes que frequentam três escolas públicas localizadas na zona rural de Pinheiro Machado, RS. Dois questionários com perguntas sobre conhecimentos sobre triatomíneos e DC foram aplicados, antes e depois da exibição do documentário. Após a exibição do vídeo, houve um aumento significativo no conhecimento dos indivíduos (em ambos os grupos) sobre triatomíneos, sua notificação, a doença e sua prevenção. Além disso, os observadores consideraram que a qualidade do material era satisfatória. Como o Documentário DC pode ser facilmente acessado na Internet e ser eficaz no ensino à população que vive em áreas endêmicas, seu uso deve ser incentivado em locais e reuniões relacionadas à saúde, que visam combater os triatomíneos e exibir uma informação atualizada sobre a DC.

Preoperative staging of colorectal cancer using virtual colonoscopy: correlation with surgical results.

OBJECTIVE: The aim of this study was to evaluate the clinical usefulness of computed tomography colonography (CTC) in the preoperative staging in patients with abdominal pain for occlusive colorectal cancer (CRC) and to compare the results of CTC with the surgical ones. PATIENTS AND METHODS: 127 patients with abdominal pain, iron deficiency anemia and occlusive CRC underwent a CTC examination in prone position without intravenous contrast agent and in prone position after administration of intravenous contrast medium. All the patients underwent surgery after CTC. Two radiologists with different experience analyzed the images first independently and then by consensus. They evaluated the location of the lesion, the depth of the invasion of the colon-rectal wall (T stage), lymph node involvement (N stage) and the presence or absence of distant metastasis (M stage). CTC findings were correlated with surgical outcomes. RESULTS: The overall accuracy values for tumour localization according to consensus reading of CTC examinations in comparison to surgical results were 100% (K = 1, p = 0.0001). The overall accuracy values of agreement for T staging of reader 1, reader 2 and consensus reading of CTC examinations in comparison to surgical results were respectively 95.5% (K = 0.876, p = 0.0035), 93.3% (K = 0.858, p = 0.0037) and 97.7% (K = 0.926, p = 0.0014) for ≤ T2; 91.3% (K = 0.839, p = 0.0027), 88.3% (K = 0.817, p = 0.0031), and 92.9% (K = 0.894, p = 0.0025) for T3; 89.6% (K = 0.825, p = 0.0037), 86.2% (K = 0.837, p = 0.0032) and 89.6% (K = 0.821, p = 0.0023) for T4. The overall accuracy values for N staging for reader 1, reader 2 and consensus reading was 90.2% (K = 0.865, p = 0.0029). The overall accuracy values for M staging of reader 1, reader 2 and consensus reading was 92% (K = 0.875, p = 0.0019). CONCLUSIONS: CTC with is a very useful tool for accurate pre-treatment staging and localization of occlusive CRC.

miR-19, a component of the oncogenic miR-17∼92 cluster, targets the DNA-end resection factor CtIP.

MicroRNA-19 (miR-19) was recently identified as the key oncogenic component of the polycistronic miR-17∼92 cluster, also known as oncomiR-1, which is frequently upregulated or amplified in multiple tumor types. However, the gene targets and the pathways underlying the tumor-promoting activity of miR-19 still remain largely elusive. CtIP/RBBP8 promotes DNA-end resection, a critical step in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), and is considered to function as a tumor suppressor. In this study, we show that miR-19 downregulates CtIP expression by binding to two highly conserved sequences located in the 3'-untranslated region of CtIP mRNA. We further demonstrate that CtIP expression is repressed by miR-19 during continuous genotoxic stress in a p53-dependent manner. Finally, we report that miR-19 impairs CtIP-mediated DNA-end resection, which results in reduced HR levels and DNA damage hypersensitivity. By downregulating CtIP, miR-19 overexpression suppresses the faithful repair of DSBs that is crucial for genome maintenance. Our findings thus provide new mechanistic insight into the oncogenic role of the miR-17∼92 cluster.

Incidental discovery of testicular microlithiasis: what is the importance of ultrasound surveillance? Two case reports.

Many studies have demonstrated an association between diffuse bilateral testicular microlithiasis (TM) and gonadal and extragonadal germ cell tumors. Nevertheless, it is still uncertain whether ultrasound surveillance is really necessary in patients with TM in the absence of other risk factors such as previous testicular cancer, a history of cryptorchidism or testicular atrophy. We report the cases of a 33- and a 39-year-old man presenting with a retroperitoneal extragonadal tumor. The first patient underwent an MRI examination in order to rule out a lumbosacral hernia: MRI images showed no slipped disks but a voluminous retroperitoneal solid mass. The histological analysis revealed an immature teratoma. The second patient came to the emergency department complaining of abdominal pain, vomiting, weight loss and mild jaundice: ultrasound examination showed a large, ill-defined heterogeneous abdominal mass, confirmed by CT and MRI examination. The histology diagnosed a yolk sac tumor. In both patients, the testicular sonography was performed to rule out a focal lesion, but it displayed bilateral TM without a focal testicular mass. Based on our direct experience, we highlight the importance of annual ultrasonographic surveillance of the testis and the retroperitoneal space in patients with occasionally detected TM.

[Cryptorchidism: medium- and long-term follow-up].

AIM: Cryptorchidism represents the most frequent male genital anomaly in paediatric population and may potentially interfere with fertility and determine neoplastic testicular diseases. We wanted to evaluate the correlation between age at orchiopexy and follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels in adulthood, determining the long-term complications of surgical treatment. METHODS: Fifty-seven patients (mean age 19 years, range 18-27) surgically treated for cryptorchidism in pediatric age were included in a medium and long-term follow-up (10-19 years). We divided this population into four groups: A) monolateral cryptorchidism operated on before 36 months of age (15); B) monolateral cryptorchidism operated on over 36 months (32); C) bilateral cryptorchidism operated on before 36 months (5); and D) bilateral cryptorchidism operated on over 36 months (5). All patients underwent andrological examination, testosterone, FSH and LH dosage, measurement of testicular volume and spermiogram. RESULTS: Significant different FSH levels were found between group A and C and between A and D (P<0.01), while groups A and D presented also different mean testicular volume (P<0.01). In addition group D showed an abnormal morphology of spermiogram. The main complications found in follow-up were hydrocele (17,5%), varicocele (8,7%) and epididymal cysts (3.6%). CONCLUSION: Monolateral cryptorchidism is associated with normal fertility when treated early (group A). Subjects in Group D, on the contrary, have a rise of FSH, a reduction of testicular volume and semen abnormalities. The long-term follow-up of these patients can also detect associated.

SILS cholecystectomy, early experience of a single institution: pilot study of 21 cases.

Many surgeons have attempted to reduce the number and the size of ports in laparoscopic cholecystectomy to decrease parietal trauma and pain, and to improve cosmetic results. We report a series of laparoscopic cholecystectomies using a single-port technique (SILS) through an umbilical incision in a pilot group of 21 cases. Our goal was to validate and develop the single-port access as a viable option. All the operations were performed using an umbilical SILS port (Ethicon). Most reported techniques utilize special purpose-made instruments. This article provides a stepwise description of the procedure using all straight instruments. No special reticulating instruments or flexible telescopes were used. We report our early difficulties and concerns about the procedure and propose solutions to the problems. Patients' request for improved cosmesis impels surgeons toward the application of SILS, but the true advantage of the technique should be assessed by more evidences. For this reason, we are planning a single-institution, prospective randomized controlled trial to compare postoperative pain, operating time and cosmetic result between one port and standard laparoscopic surgery.

Laparoscopic total mesorectal excision for rectal cancer: experience of a single center with a series of 174 patients.

BACKGROUND: Laparoscopic total mesorectal excision for low rectal cancer is not considered a gold standard treatment due to the high conversion rate and the long operation time. METHODS: A retrospective review examined a surgical series of 174 laparoscopic low rectal resections involving total mesorectal excision (1995-2006), with particular reference to technical points as well as surgical and oncologic outcomes. Miles operations and partial mesorectal excisions were excluded. RESULTS: The cancer affected the low rectum in 110 cases and the medium rectum in 64 cases. A total of 68 patients were subjected to neoadjuvant radiochemotherapy. The anastomosis was mechanical for 83.3% of the cases and intersphinteric through the perineum for 16.6% of the cases. Protective ileostomy was performed in 112 cases. The conversion rate was 4.6%. The mesorectum remained intact in 91.6% of the cases and was partially interrupted in 15 of the cases. In no case was it totally discontinued. The postoperative morbidity rate was 16.7%, and the mortality rate was 0.57%. The incidence of anastomotic fistulas was 14.4%. The percentage was higher for males (18.6 vs 8.3%) and correlated with the low distance of the tumor from the anal verge (18.2 vs 7.8%) and the absence of a protection ileostomy (20.9 vs 10.7%). After an average follow-up period of 48.6 months (range, 24-149 months), six patients (3.44%) experienced a pelvic recurrence. The 5-year overall survival rate was 75.4%, and the disease-free survival rate was 61.9%. CONCLUSION: Laparoscopic total mesorectal excision for low rectal cancer is safe and effective, allowing surgical and oncologic outcomes similar to those reported for open surgery.