Epidemiology of Adenosquamous Carcinomas.

Background: Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs). Methods: In this study, we summarize these outcomes in eight primary sites, comprising 92.7% of all ASC cases diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Lung ASCs comprise 51.5% of all ASC cases, accounting for 1.1% of all lung cancer cases, followed by uterine/cervical cancers at 29.7% of all ASC cases, translating into 1.8% of all cancers in this site. In descending order, the remaining 20% of ASCs arise in pancreatic, oral cavity, biliary, esophageal, colorectal, and gastric sites, comprising between 0.1% and 0.7% of all cancers in these sites. Apart from pancreatic and oral cavity cancers, ASC tumors tended to favor higher rates of regional or distant disease at presentation with poor tumor differentiation compared to either AC or SCC histologies. After multivariable analysis, adjusting for age, sex, detection stage, grade differentiation, surgery, chemotherapy, and radiotherapy, except for oral cavity cancers, ASCs tended to have worse overall survivals compared to ACs (hazard ratios: 1.1 - 1.6) and SCC (1.0 - 1.3), with colorectal ASCs having the worse overall survival compared to colorectal ACs, with a hazard ratio of 1.4 (95% confidence interval: 1.3 - 1.6). Conclusions: Overall, these results suggest that ASC outcomes are site specific, and in general, tend to have worse outcomes than nonvariant ACs and SCCs even after correction for common clinical and epidemiological factors. These cancers have a poorly understood but unique tumor biology that warrants further characterization.

High Ki67 Gene Expression Is Associated With Aggressive Phenotype in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) with high Ki67 protein expression, the most commonly used cell proliferation marker, is associated with an aggressive biologic phenotype; however, conventional immunostaining is hampered by variability in institutional protocol, specific antibody probe, and by assessor subjectivity. To this end, we hypothesized that Ki67 gene (MKi67) expression would identify highly proliferative HCC, and clarify its association with oncologic outcome, tumor progression, and immune cell population in the tumor microenvironment (TME). Furthermore, we sought to identify the cell-cycle gene expression profile that confers this aggressive phenotype. Methods: A total of 473 HCC patients with clinicopathological data associated with transcriptome were selected for this study: 358 patients from The Cancer Genome Atlas (TCGA) as the testing cohort, and 115 from GSE76427 as the validation cohort. Each cohort was divided into a highly proliferative group (MKi67-high) and the low MKi67 group (MKi67-low) by the median of Ki67 gene (MKi67) expression levels. Results: MKi67-high HCC patients had worse disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) independent of histological grade in the TCGA cohort. MKi67 expression correlated with histological grade and tumor size. MKi67 expression increased throughout the HCC carcinomatous sequence from normal liver, cirrhotic liver, early HCC, and advanced HCC. MKi67-high HCC was associated with higher intratumor heterogeneity, homologous recombination deficiency, and altered fraction as well as intratumoral infiltration of T helper type 1 (Th1) and Th2 cells, but lower interferon-gamma response and M2 macrophage infiltration. Cell proliferation-related gene sets in the Hallmark collection (E2F targets, G2M checkpoint, Myc target v1 and mitotic spindle), MTORC1 signaling, DNA repair, PI3K MTOR signaling, and unfolded protein response were all enriched in the MKi67-high HCC (false discovery rate (FDR) < 0.25). Conclusions: High MKi67 gene expression identified highly proliferative HCC with aggressive biology involving classical pathways in cell cycle regulation and DNA repair, as well as poor overall oncologic outcomes. This suggests potential for personalized treatment strategies, but validation and refinement of these observations require further research to elucidate the underlying mechanisms and validate therapeutic targeting of these pathways in MKi67-high HCC tumors.

Potentially Avoidable Admissions and Prolonged Hospitalization in Patients with Suspected Colon Cancer.

BACKGROUND: Suspicion of cancer in the Emergency Department (ED) may lead to potentially avoidable and prolonged admissions. We aimed to examine the reasons for potentially avoidable and prolonged hospitalizations after admissions from the ED for new colon cancer diagnoses (ED-dx). METHODS: A retrospective, single-institution analysis was conducted of patients with ED-dx between 2017 and 2018. Defined criteria were used to identify potentially avoidable admissions. Patients without avoidable admissions were examined for ideal length of stay (iLOS), using separate defined criteria. Prolonged length of stay (pLOS) was defined as actual length of stay (aLOS) being greater than 1 day longer than iLOS. RESULTS: Of 97 patients with ED-dx, 12% had potentially avoidable admissions, most often (58%) for cancer workup. Very little difference in demographic, tumor characteristics, or symptoms were found, except patients with potentially avoidable admissions were more functional (Eastern Cooperative Oncology Group [ECOG] score 0-1: 83% vs. 46%; p = 0.049) and had longer symptom duration prior to ED presentation {24 days (interquartile range [IQR] 7-75) vs. 7 days (IQR 2-21)}. Among the 60 patients who had necessary admissions but did not require urgent intervention, 78% had pLOS, most often for non-urgent surgery (60%) and further oncologic workup. The median difference between iLOS and aLOS was 12 days (IQR 8-16) for pLOS. CONCLUSIONS: Potentially avoidable admissions following Ed-dx were uncommon but were mostly for oncologic workup. Once admitted, the majority of patients had pLOS, most often for definitive surgery and further oncologic workup. This suggests a lack of systems to safely transition to outpatient cancer management.

High Risk, High Reward: Frailty in Colorectal Cancer Surgery is Associated with Worse Postoperative Outcomes but Equivalent Long-Term Oncologic Outcomes.

BACKGROUND: Frailty is a physiologic state that affects perioperative outcomes. Studies evaluating the impact of frailty on long-term oncologic outcomes are limited. This study evaluated perioperative and long-term oncologic outcomes for elderly patients undergoing colorectal surgery. METHODS: Patients older than 65 years at the time of colorectal resection between July 2011 and September 2020 at Roswell Park Comprehensive Cancer Center were identified. Variables from the National Surgical Quality Improvement Program (NSQIP), the tumor registry, and electronic medical records (EMRs) were used to identify frail patients using the revised Risk Analysis Index (RAI-A) score. A score of 38 or higher defined a patient as "frail." Perioperative outcomes were evaluated using logistic regression and chi-square, and oncologic outcomes were evaluated using Kaplan-Meier analysis. RESULTS: The study analyzed 411 patients. The mean age at surgery was 75.1 years. The median RAI-A score was 37, and 29.9 % of the patients were frail. The frail patients had significantly higher rates of overall complications (30.1 % vs 14.6 %; p < 0.001). They also had significantly higher rates of postoperative hospitalization longer than 30 days, postoperative delirium, and discharge to rehabilitation. No mortality differences were observed. The 318 patients with colorectal adenocarcinoma undergoing curative-intent resection were evaluated for oncologic outcomes. No differences with frailty in terms of overall survival, disease-specific survival, or progression-free survival were observed except for frail patients with stage 0 or 1 adenocarcinoma, who had worse overall survival than non-frail patients but equivalent other outcomes. CONCLUSIONS: For elderly patients undergoing colorectal surgery, frailty is associated with higher postoperative complications, discharge to rehabitation, and prolonged hospitalization rates. Frailty does not affect long-term oncologic outcomes, so frail elderly patients gain the same oncologic benefit with surgery as non-frail patients.

The order of surgery and chemotherapy matters: Multimodality therapy and stage-specific differences in survival in gastric cancer.

BACKGROUND AND OBJECTIVES: Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj). METHODS: Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS). RESULTS: We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90). CONCLUSIONS: In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Safety and efficacy of roux-en-y gastric bypass in older aged patients.

INTRODUCTION: laparoscopic Roux-en-Y Gastric Bypass (LRYGB) has been a revolutionary intervention for weight loss with reduction of up to 60-70% of excess body weight. However, these outcomes are not as well validated at the extremes of age, where the safety of the intervention still has some caveats. The aim of this study is to assess the efficacy and safety of primary LRYGB among different age groups. METHODS: the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried for patients who underwent primary LRYGB from January 2014 to December 2017 at a single institution. Four groups were created and compared by dividing our sample by age quartiles. The primary outcome was percent excess weight loss (%EWL) at 1 year. Additional operative outcomes and complications were also compared across groups. RESULTS: a total of 1013 patients underwent non-revisional LRYGB during the study period. Mean %EWL at one year was 55%. When compared between quartiles, there was a statistically significant difference in %EWL: 1st 62%, 2nd 57%, 3rd 54% and 4th 47% (p=0.010). The differences in the secondary outcomes between age groups did not demonstrate statistical significance. CONCLUSIONS: though patients in the fourth age quartile (range) did not demonstrate a statistically significant increase in adverse outcomes, they did lose less weight compared to other cohorts. The %EWL at one year after RYGB varied by age in our cohort. Goals after bariatric surgery should be individualized as weight loss is less robust with aging.

Robotic abdominal wall repair: adoption and early outcomes in a large academic medical center.

Robotic-assisted abdominal wall repair (RAWR) has seen an exponential adoption over the last 5 years. Skepticism surrounding the safety, efficacy, and cost continues to limit a more widespread adoption of the platform. We describe our initial experience of 312 patients undergoing RAWR at a large academic center. A retrospective review of all patients undergoing any RAWR from July 1, 2016 to March 18, 2020 was completed. Patient specific, operation specific, and 30-day outcomes specific data were collected. Univariate analysis and multivariate logistic regression were used to assess factors associated with 30-day complications. There was a steady adoption of RAWR over the study period. A total of 312 patient were included, 138 (44%) were abdominal wall repairs and 174 (56%) were inguinal repairs. The mean age of the cohort was 54.2 years (SD 16), 69% were males, and the mean BMI was 29 kg/m2 (SD 4.8). There were two reported intraoperative events and nine operative conversions. 60 patients had at least one complication at 30-days. These include: 52 seromas, 4 hematomas, 2 surgical-site infections, 1 deep venous thrombus, and 1 recurrence at 30-days. BMI, type of hernia, and sex were not associated with complications at 30-days. The use of absorbable mesh, longer hospital stay, operative conversion, previous repair, and expert hernia surgeon were significant predictors of 30-day complications. Age, operative conversion, and previous repair were the only predictors of 30-day complications on multivariate regression. Our initial experience of 312 patients demonstrates the adoption and comparable short-term outcomes for a wide variety of robotic-assisted hernia repairs.

Safety and efficacy of roux-en-y gastric bypass in older aged patients / Segurança e eficácia do bypas gástrico em Y de Roux em pacientes idosos

ABSTRACT Introduction: laparoscopic Roux-en-Y Gastric Bypass (LRYGB) has been a revolutionary intervention for weight loss with reduction of up to 60-70% of excess body weight. However, these outcomes are not as well validated at the extremes of age, where the safety of the intervention still has some caveats. The aim of this study is to assess the efficacy and safety of primary LRYGB among different age groups. Methods: the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried for patients who underwent primary LRYGB from January 2014 to December 2017 at a single institution. Four groups were created and compared by dividing our sample by age quartiles. The primary outcome was percent excess weight loss (%EWL) at 1 year. Additional operative outcomes and complications were also compared across groups. Results: a total of 1013 patients underwent non-revisional LRYGB during the study period. Mean %EWL at one year was 55%. When compared between quartiles, there was a statistically significant difference in %EWL: 1st 62%, 2nd 57%, 3rd 54% and 4th 47% (p=0.010). The differences in the secondary outcomes between age groups did not demonstrate statistical significance. Conclusions: though patients in the fourth age quartile (range) did not demonstrate a statistically significant increase in adverse outcomes, they did lose less weight compared to other cohorts. The %EWL at one year after RYGB varied by age in our cohort. Goals after bariatric surgery should be individualized as weight loss is less robust with aging.

RESUMO Introdução: o Bypass Gástrico Laparoscópico em Y de Roux (LRYGB) tem sido uma intervenção revolucionária para perda de peso com redução de até 60-70% do excesso de peso corporal. No entanto, esses resultados não são tão bem validados nos extremos de idade, onde a segurança da intervenção ainda possui algumas ressalvas. O objetivo deste estudo é avaliar a eficácia e segurança do LRYGB entre diferentes faixas etárias. Métodos: O banco de dados do Programa de Acreditação e Melhoria da Qualidade da Cirurgia Metabólica e Bariátrica (MBSAQIP) foi consultado para pacientes submetidos a LRYGB de janeiro de 2014 a dezembro de 2017 em uma única instituição. Quatro grupos foram criados e comparados dividindo a amostra por quartis de idade. O desfecho primário foi perda percentual de excesso de peso (%EWL) em 1 ano. Resultados: 1013 pacientes foram submetidos a LRYGB durante o período do estudo. A média de %EWL em um ano foi de 55%. Quando comparados entre os quartis, houve diferença significante no %EWL: 1º 62%, 2º 57%, 3º 54%, e 4º 47% (p=0,010). As diferenças nos desfechos secundários entre as faixas etárias não demonstraram significância estatística. Conclusões: embora os pacientes no quarto quartil de idade não tenham demonstrado um aumento estatisticamente significativo nos resultados adversos, eles perderam menos peso em comparação com outras coortes. O %EWL um ano após RYGB variou de acordo com a idade em nossa coorte. Os objetivos após a cirurgia bariátrica devem ser individualizados, pois a perda de peso é menos robusta com o envelhecimento.

Adhesion, proliferation, and apoptosis in different molecular portraits of breast cancer treated with silver nanoparticles and its pathway-network analysis.

BACKGROUND: Silver nanoparticles (AgNPs) have attracted considerable attention due to the variety of their applications in medicine and other sciences. AgNPs have been used in vitro for treatment of various diseases, such as hepatitis B and herpes simplex infections as well as colon, cervical, and lung cancers. In this study, we assessed the effect on proliferation, adhesion, and apoptosis in breast cancer cell lines of different molecular profiles (MCF7, HCC1954, and HCC70) exposed to AgNPs (2-9 nm). METHODS: Breast cancer cell lines were incubated in vitro; MTT assay was used to assess proliferation. Adhesion was determined by real-time analysis with the xCELLingence system. Propidium iodide and fluorescein isothiocyanate-Annexin V assay were used to measure apoptosis. The transcriptome was assessed by gene expression microarray and Probabilistic Graphical Model (PGM) analyses. RESULTS: The results showed a decreased adhesion in breast cancer cell lines and the control exposed to AgNPs was noted in 24 hours (p≤0.05). We observed a significant reduction in the proliferation of MCF7 and HCC70, but not in HCC1954. Apoptotic activity was seen in all cell lines exposed to AgNPs, with an apoptosis percentage of more than 60% in cancer cell lines and less than 60% in the control. PGM analysis confirmed, to some extent, the effects of AgNPs primarily on adhesion by changes in the extracellular matrix. CONCLUSION: Exposure to AgNPs causes an antiproliferative, apoptotic, and anti-adhesive effect in breast cancer cell lines cultured in vitro. More research is needed to evaluate the potential use of AgNPs to treat different molecular profiles of breast cancer in humans.