Combined Endoscopy-Laparoscopy Surgery: When and How to Utilize This Tool.

Combined endoscopic and laparoscopic surgery (CELS) has been used to resect colon polyps since the 1990s. These colon-sparing techniques, however, have not yet been widely adopted. With the evolution of technology in both diagnosing and treating colon cancer, colorectal surgeons should strive for a diverse and complete armamentarium through which they can best serve their patients. In this article, we hope to provide clarity on CELS by discussing three topics: (1) the history and fruition of CELS; (2) the techniques involved in CELS; and (3) the utility of CELS within different clinical scenarios. Our goal is to educate readers and stimulate consideration of CELS in select patients who might benefit greatly from these techniques.

Pathologic Outcomes of Short-Course and Long-Course Radiotherapy for Locally Advanced Rectal Cancers Treated With Total Neoadjuvant Therapy.

INTRODUCTION: Total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is now the standard of care. Randomized trials suggest the use of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are oncologically equivalent. OBJECTIVE: To describe pathologic outcomes after surgical resections of patients receiving SCRT versus LCRT as part of TNT for LARC. PARTICIPANTS: All patients with LARC treated at a single tertiary hospital who underwent proctectomy after completing TNT were included. Patients were excluded if adequate details of TNT were not available in the electronic medical record. RESULTS: A total of 53 patients with LARC were included. Thirty-nine patients (73.5%) received LCRT and 14 (26.4%) received SCRT. Forty-nine patients (92.5%) were clinical stage III (cN1-2) prior to treatment. The average lymph node yield after proctectomy was 20.9 for SCRT and 17.0 for LCRT (P = .075). Of the 49 patients with clinically positive nodes before treatment, 76.9% of those who received SCRT and 72.2% of those who received LCRT achieved pN0 disease after TNT. Additionally, there were no significant differences in rates of pathologic complete response between patients who received SCRT and LCRT, 7.1% and 12.8%, respectively (P = .565). CONCLUSION: Pathologic outcomes of patients with LARC treated with SCRT or LCRT, as part of TNT, may be similar. Further prospective trials are needed to assess long-term clinical outcomes and to determine best treatment protocols.

Rectal Cancer Survival for Residual Carcinoma In Situ Versus Pathologic Complete Response After Neoadjuvant Therapy.

BACKGROUND: Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. OBJECTIVE: To compare the survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. DESIGN: Retrospective cohort study. SETTING: National public database. PATIENTS: A total of 4594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative ypTis or ypT0 on final pathology were included. Of these, 4321 patients (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. MAIN OUTCOME MEASURE: Overall survival. RESULTS: The median age was 60 years, and 1822 patients (39.7%) were women. On initial staging, 54.5% (n = 2503) had stage II disease and 45.5% (n = 2091) had stage III disease. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42; 95% CI, 1.04-1.95; p = 0.028). Other factors associated with decreased overall survival were older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage II and stage III. LIMITATIONS: Standard therapy versus total neoadjuvant therapy could not be abstracted. Overall survival was defined as the time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. CONCLUSIONS: ypTis is associated with worse overall survival than ypT0 for patients with locally advanced rectal cancer who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract . SUPERVIVENCIA DEL CNCER DE RECTO PARA EL CARCINOMA RESIDUAL IN SITU VS RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE: ANTECEDENTESLa respuesta patológica completa después de la quimiorradioterapia neoadyuvante para el cáncer de recto se asocia con una mayor supervivencia. No está claro si el carcinoma residual in situ presagia un resultado similar.OBJETIVOComparar la supervivencia de pacientes con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante y lograron un carcinoma patológico in situ versus una respuesta patológica completa.DISEÑOEstudio de cohorte retrospectivo.ESCENARIOBase de datos pública nacional.PACIENTESSe incluyeron 4,594 pacientes de la Base de Datos Nacional de Cáncer de 2006 a 2016 con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante, fueron sometidos a cirugía y tuvieron ganglios negativos, ypTis o ypT0 en el reporte patológico final. 4.321 (94,1%) tuvieron ypT0 y 273 (5,9%) tuvieron ypTis en el reporte final.PRINCIPALES MEDIDAS DE RESULTADOSupervivencia general.RESULTADOSLa mediana de edad fue de 60 años. 1.822 pacientes (39,7%) fueron mujeres. El 54,5% (n = 2.503) tuvo la enfermedad en estadio II y el 45,5% (n = 2.091) tuvo la enfermedad en estadio III según la estadificación inicial. El grupo ypTis tuvo una supervivencia general reducida en comparación con el grupo ypT0 (HR 1,42, IC 95 % 1,04-1,95, p = 0,028). Otros factores asociados con una menor supervivencia general fueron una edad más avanzada al momento del diagnóstico, un aumento de la puntuación de Charlson-Deyo y un grado tumoral poco diferenciado. Las variables asociadas con una mejor supervivencia fueron el sexo femenino, el seguro privado y la recepción de quimioterapia neoadyuvante y adyuvante. Para la cohorte total, no hubo diferencias en la supervivencia entre el estadio clínico 2 y el estadio 3.LIMITACIONESNo se pudo resumir el tratamiento estándar versus el tratamiento neoadyuvante total. La supervivencia general se definió como el tiempo transcurrido desde la cirugía hasta la muerte por cualquier causa o último contacto, lo que permite algunas muertes erróneamente clasificadas.CONCLUSIONESypTis se asocia con una peor supervivencia general que ypT0 en pacientes con cáncer de recto localmente avanzado que reciben quimiorradioterapia neoadyuvante seguida de cirugía. Para esta cohorte, el estadio clínico no fue un predictor significativo de supervivencia. Se necesitan ensayos prospectivos que comparen la supervivencia de estos resultados patológicos. ( Traducción-Dr Osvaldo Gauto ).

The global burden of lymphoma: estimates from the Global Burden of Disease 2019 study.

OBJECTIVES: The aim of this study was to describe the global trends in the burden of lymphoma from 1990 to 2019. STUDY DESIGN: The data used in this study were from the Global Burden of Disease 2019 study. METHODS: This study described the age-standardised rates of incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lymphoma (non-Hodgkin and Hodgkin's lymphoma, NHL and HL, respectively) annually from 1990 to 2019, stratified by sociodemographic index (SDI) and 21 world regions. The estimated annual percentage changes in these indexes were calculated. RESULTS: In 2019, the age-standardised rates of HL per 100,000 population were lower than those of NHL in terms of incidence (1.1 vs 6.7 per 100,000 person-years, respectively) and prevalence (0.3 vs 5.7 per 100,000 person-years, respectively) but not mortality (21.6 vs 3.2 per 100,000 person-years, respectively). From 1999 to 2019, the global incidence of HL decreased and the incidence of NHL increased, and the prevalence of both HL and NHL increased, but the mortality rates decreased. When stratified by SDI, the incidence of HL decreased in all but middle-SDI regions, the mortality rate of HL decreased in all regions, and both the incidence and mortality rate of NHL increased in all but high-SDI regions. The prevalence of HL and NHL increased in all SDI regions, especially in middle-SDI regions. YLLs and DALYs of HL in all SDI regions and those of NHL in high-SDI regions decreased. YLDs slightly increased in middle- to high-SDI regions. CONCLUSIONS: Lymphoma remains a major public health issue, and better prevention, precise identification, and promising treatments are vitally important.

[Observation of liver indexes in patients with relapsed/refractory multiple myeloma treated with CAR-T-cells based on BCMA].

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

Glucose Deprivation Induces Cancer Cell Death through Failure of ROS Regulation.

In previous work, we showed that cancer cells do not depend on glycolysis for ATP production, but they do on fatty acid oxidation. However, we found some cancer cells induced cell death after glucose deprivation along with a decrease of ATP production. We investigated the different response of glucose deprivation with two types of cancer cells including glucose insensitive cancer cells (GIC) which do not change ATP levels, and glucose sensitive cancer cells (GSC) which decrease ATP production in 24 h. Glucose deprivation-induced cell death in GSC by more than twofold after 12 h and by up to tenfold after 24 h accompanied by decreased ATP production to compare to the control (cultured in glucose). Glucose deprivation decreased the levels of metabolic intermediates of the pentose phosphate pathway (PPP) and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) in both GSC and GIC. However, glucose deprivation increased reactive oxygen species (ROS) only in GSC, suggesting that GIC have a higher tolerance for decreased NADPH than GSC. The twofold higher ratio of reduced/oxidized glutathione (GSH/GSSG) in GIS than in GSC correlates closely with the twofold lower ROS levels under glucose starvation conditions. Treatment with N-acetylcysteine (NAC) as a precursor to the biologic antioxidant glutathione restored ATP production by 70% and reversed cell death caused by glucose deprivation in GSC. The present findings suggest that glucose deprivation-induced cancer cell death is not caused by decreased ATP levels, but rather triggered by a failure of ROS regulation by the antioxidant system. Conclusion is clear that glucose deprivation-induced cell death is independent from ATP depletion-induced cell death.

Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism.

OBJECTIVE: Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes, and intestinal adaptation is a proposed mechanism for these effects. It was hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. METHODS: This was a prospective, longitudinal, first-in-human study of gene expression (GE) in the "Roux limb" (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across six postoperative months, including at an early postoperative (1 month ± 15 days) time point. RESULTS: RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid use. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibited GE changes characterized by anabolic growth and shift in metabolic substrate use. Paradoxically, anabolic growth in RL appeared to contribute to the catabolic state elicited by RYGB. CONCLUSIONS: These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without type 2 diabetes.

Increased cost burden associated with robot-assisted rectopexy: do patient outcomes justify increased expenditure?

BACKGROUND: Robot-assisted surgical techniques have flourished over the years, with refinement in instrumentation and optics allowing for adaptation and increasing utilization across surgical fields. Transabdominal rectopexy with mesh for rectal prolapse may stand to benefit significantly from the use of a robotic platform. However, increased operative times and immediate associated costs of robotic surgery may provide a counterargument to widespread adoption. METHODS: To determine which approach to the treatment of rectal prolapse, laparoscopic or robotic, is more cost effective and provides better outcomes with fewer complications, a retrospective review was performed at a single tertiary care academic institution from May 2013 to December 2020. Twenty-two patients underwent transabdominal mesh rectopexy through a robot-assisted DaVinci platform (Intuitive Sunnyvale, CA), and thirty through a laparoscopic platform. Main outcome measures included operative, hospital, and total cost as defined by total charges billed. Secondary outcomes included rate of recurrence, intra-operative complications, median operative time, post-operative complications, average hospital length of stay, inpatient pain medication usage, and post-operative functional outcomes. RESULTS: Cost analysis for robot-assisted versus laparoscopic rectopexy demonstrated operating room costs of $46,118 ± $9329 for the robotic group, versus $33,090 ± $15,395 (p = 0.002) for the laparoscopic group. Inpatient hospital costs were $60,723 ± $20,170 vs. $40,798 ± $14,325 (p = 0.001), and total costs were $106,841 ± $25,513 vs. $73,888 ± $28,129 (p ≤ 0.001). When secondary outcomes were compared for the robotic versus laparoscopic groups, there were no differences in any of the aforementioned outcome variables except for operative time, which was 79 min longer in the robotic group (p ≤ 0.001). CONCLUSIONS: Robot-assisted mesh rectopexy demonstrated no clinical benefit over traditional laparoscopic mesh rectopexy, with significantly higher operative and hospital costs. A reduction in the acquisition and maintenance costs for robotic surgery is needed before large-scale adoption and implementation of the robotic platform for this procedure.

Assessing the Association Between Endoscopic Tattooing and Lymph Node Yield in Rectal Cancer.

INTRODUCTION: Preoperative endoscopic tattooing is an effective tool for intraoperative tumor localization in colon cancer. Endoscopic tattooing in rectal cancer may have unidentified benefits on lymph node yield, making it easier for pathologists to identify nodes during histopathologic assessment. There remains concern that tattoo ink may alter anatomical planes, increasing surgical difficulty. METHODS: Retrospective chart reviews from 2016 to 2021 of n = 170 patients presenting with rectal cancer were divided into two groups: with (n = 79) and without (n = 91) endoscopic tattoos. Demographics, operative details, tumor characteristics, prior chemoradiation, and pathologic details were collected. Primary outcome was total lymph node yield. Secondary outcomes were rates of adequate (> 12) nodes, margin status, and operative variables including operative time. RESULTS: No differences between pathologic stage, tumor height, high inferior mesenteric artery ligation, operative times, conversion rate, or surgical approach (open versus minimally invasive) were noted between groups. Receipt of neoadjuvant chemoradiation was less frequent in the endoscopic tattooing group (53.2% versus 76.9%, P ≤ 0.001). Total node number and rate of adequate lymph node yield were higher with endoscopic tattooing (20.5 ± 7.6 versus 16.8 ± 6.6 lymph nodes and 100.0% versus 83.5% adequate lymph node harvest, both P ≤ 0.001). Rates of positive circumferential and distal margins and complete total mesorectal excision were also similar. Regression analysis identified endoscopic tattooing (Incidence Risk Ratio 1.17, 95% confidence interval 1.04-1.31) and operative time more than 300 min (Incidence Risk Ratio 0.88, 95% confidence interval 0.77-0.99) had significant effects on lymph node harvest. Removal of patients with inadequate lymph node yield resulted in similar rates of total and positive lymph nodes. CONCLUSIONS: Endoscopic rectal tattooing is associated with increased lymph node yield (including after neoadjuvant chemoradiotherapy) without sacrificing oncologic or perioperative outcomes, although this effect is inconsistent when only considering patients with an adequate lymph node yield.

Construction of Bimetallic Hybrid Multishell Hollow Spheres via Sequential Template Approach for Less Cytotoxic Antimicrobial Effect.

This work has aimed to synthesize less cytotoxic but antibacterial effective materials. Here we synthesized zinc, titanium nanoparticles based multishell hollow spheres (ZnO@TiO2 MSHS) via sequential template approach (STA) and studied their comparative antimicrobial activity with pure zinc and titanium nanoparticles (NPs). Various techniques have been used to explore the physico-chemical properties of the hybrid shells (ZnO@TiO2 MSHS). FTIR, XRD measurements approved the enhanced crystallinity of synthesized hybrid MSHS via STA technique constructed by ZnO, TiO2 NPs. The optical transmittance was enhanced 67.08% for ZnO@TiO2 MSHS where 50.59 %, and 53.32 % of pure ZnO, TiO2 NPs respectively. TEM images showed MSHS made up of zinc and titanium nanoparticles distributed evenly in the structure. The antibacterial activity has been studied and measured via MIZ confirmed that the ZnO@TiO2 multishell hollow spheres exhibit the antibacterial performance. On the other hand the cytotoxicity studies show the cell toxicity was decreased for ZnO@TiO2 MSHS than pure ZnO and TiO2 NPs. So it is recommended that ZnO@TiO2 multishell hollow spheres may be used as a safe and potential antibacterial agent in the field of food packaging, painting, drug delivery and other antibacterial applications.

Prevalence of and Risk Factors for Incidental Colonic Diverticulosis.

INTRODUCTION: The true prevalence and pathogenesis of diverticulosis is poorly understood. Risk factors for diverticulosis are presently unclear, with most clinicians attributing its development to years of chronic constipation. Previous studies have been limited by their failure to include young, ethnically diverse patient populations. METHODS: Patients who presented to the emergency department of our hospital from January-September 2019 and underwent abdominal computerized tomography (CT) scan for the evaluation of appendicitis were included. CT's were reviewed for the presence of diverticulosis. Risk factors for diverticulosis were determined for two age groups: >40 and ≤ 40. RESULTS: A total of 359 patients were included in the study. The median age was 38.57.1% were male. 81.6% were Hispanic. 43.5% had colonic diverticulosis on CT. 198 patients (55.1%) were ≤ age 40. The rate of diverticulosis in this group was 35.3% (n = 70). Those with diverticulosis were not significantly older (median age 29 versus 27, P = 0.061) but had a higher median body mass index (BMI) (28.4 versus 25.3, P = 0.003) compared to those without diverticulosis. On multivariate analysis, no characteristics were associated with the presence of diverticulosis for this group. Over age 40, 53.4% of patients (n = 86) had diverticulosis. Patients with diverticulosis were more likely to be Hispanic (95.3% versus 73.3%, P ≤ 0.001), less likely to be Asian (2.4% versus 16.0%, P = 0.004), had a higher median BMI (28.7 versus 25.5, P ≤ 0.001), and were more likely to use alcohol (30.2% versus 14.7%, P = 0.024) than those without diverticulosis. On multivariate analysis, characteristics associated with the presence of diverticulosis were BMI >30 (odds ratio OR 2.22, 95% confidence interval CI 1.03-4.80), Hispanic ethnicity (OR 10.05, 95% CI 1.74-58.26), and alcohol use (OR 3.44, 95% CI 1.26-9.39). CONCLUSIONS: There was a higher rate of asymptomatic diverticulosis in the <40 cohort than previously reported in the literature. Obesity, alcohol use, and Hispanic ethnicity were associated with the presence of diverticulosis in patients > age 40, but no risk factors for diverticulosis were identified for patients ≤ age 40, suggesting that diverticular pathogenesis may differ by age. Constipation was not a risk factor for diverticulosis in either age group. The data regarding the prevalence of diverticulosis in Hispanic patients is lacking and should be the focus of future inquiry.

Endoscopy Reports for Rectosigmoid Tumors: Frequently Missing Key Information Needed for Surgical Planning.

INTRODUCTION: Endoscopy reports by gastroenterologists describing rectosigmoid tumors often are missing crucial data for surgical planning, leading to high rates of repeat exams before surgical decision-making. We hypothesize that there will be significant deficiencies in the endoscopic reporting of rectosigmoid lesions leading to high rates of repeat endoscopic examination at our institution. METHODS: Retrospective review from January 2016 to November 2019 included 188 patients with rectosigmoid lesions referred for surgery with an outside endoscopy report. Three criteria were abstracted from these reports or included pictures: (1) distance from the tumor to an anatomical landmark (anal verge, dentate line, sphincter), (2) Tattoo placement (if performed) and location, and (3) tumor relationship to the valves of Houston. Reports were classified exemplary, nearly adequate, or inadequate if 3, 2, and ≤ 1 of these criteria were met, respectively. RESULTS: Distance was reported in 38.8% (n = 73) of reports, with the anal verge being the most commonly reported anatomical landmark (32.4%, n = 61 reports). Tattoo was placed in 34.6% (n = 65), though only 21.8% (n = 41) described the location of the tattoo relative to the tumor. Relationship to the valves of Houston was seen in 29.2% (n = 55) of reports. Only 5.3% (n = 10) of outside endoscopy reports were graded as exemplary, 20.2% (n = 38) nearly adequate, and the remaining 74.5% (n = 140) inadequate. A total of 87.5% (n = 165) of patients required repeat endoscopy with a significantly higher proportion from the inadequate group. CONCLUSIONS: Many referring endoscopy reports contain inadequate information for the surgical planning of rectosigmoid tumor resection. Efforts to improve documentation (particularly about distance and location within the rectum) must be undertaken.

Trimodality therapy for patients with stage III non-small-cell lung cancer: A comprehensive surveillance, epidemiology, and end results analysis.

PURPOSE: Debate exists regarding the optimal management for patients with stage III non-small-cell lung cancer (NSCLC). Recent inclusion of chemotherapeutic data in the Surveillance, Epidemiology, and End Results (SEER) database has made it possible to identify patients with NSCLC who received chemotherapy. We hypothesized that patients with stage III NSCLC experience improved overall survival from trimodality therapy (TMT) versus definitive chemoradiation therapy (CRT) alone. MATERIALS AND METHODS: We analyzed the overall survival of stage III NSCLC patients based on the receipt of TMT versus CRT alone. This included crude and adjusted univariate models as well as crude and doubly robust adjusted multivariable analyses, both utilizing propensity score matching and inverse probability of treatment weighting. Factors included in the multivariable analyses included: age, sex, marital status, income, date of diagnosis, primary site, histology, grade, T stage, N stage, and intended treatment. Planned subset analyses were performed for stage III(N2) patients. RESULTS: Adult patients with stage III NSCLC (N = 9008) from the SEER database were included in our analyses. In our univariate analyses, an overall survival benefit was observed for TMT versus CRT (CrudeHR = 0.58, 95% CI = 0.55-0.61, p < 0.001; AdjHR = 0.58, 95% CI = 0.54-0.61, p < 0.001). This persisted in both crude and doubly robust multivariable analyses (CrudeHR = 0.57, 95% CI = 0.53-0.61, p < 0.001; AdjHR = 0.56, 95% CI = 0.53-0.59, p < 0.001). Patients with stage III(N2) disease also demonstrated a significant benefit to OS with TMT versus CRT alone. CONCLUSION: The significant difference in overall survival seen with TMT suggests this may be an effective treatment approach for select patients.

New Frontiers in Management of Early and Advanced Rectal Cancer.

It is important to understand advances in treatment options for rectal cancer. We attempt to highlight advances in rectal cancer treatment in the form of a systematic review. Early-stage rectal cancer focuses on minimally invasive endoluminal surgery, with importance placed on patient selection as the driving factor for improved outcomes. To achieve a complete pathologic response, various neoadjuvant chemoradiation regimens have been employed. Short-course radiation therapy, total neoadjuvant chemotherapy, and others provide unique advantages with select patient populations best suited for each. With a clinical complete response, a "watch and wait" non-operative surveillance has been introduced with preliminary equivalency to radical resection. Various modalities for total mesorectal excision, such as robotic or transanal, have advantages and can be utilized in select patient populations. Tumors demonstrating solid organ or peritoneal spread, traditionally defined as unresectable lesions conveying a terminal diagnosis, have recently undergone advances in hepatic and pulmonary metastasectomy. Hepatic and pulmonary metastasectomy has demonstrated clear advantages in 5-year survival over standard chemotherapy. With the peritoneal spread of colorectal cancer, HIPEC with cytoreductive therapy has emerged as the preferred treatment. Understanding the various therapeutic interventions will pave the way for improved patient outcomes.

Layer-by-Layer Biomimetic Microgels for 3D Cell Culture and Nonviral Gene Delivery.

Localized release of nucleic acid therapeutics is essential for many biomedical applications, including gene therapy, tissue engineering, and medical implant coatings. We applied the substrate-mediated transfection and layer-by-layer (LbL) technique to achieve an efficient local gene delivery. In the experiments presented herein, we embeded lipoplexes containing plasmid DNA encoding for enhanced green fluorescent protein (pEGFP) within polyelectrolyte alginate-based microgels composed of poly(allylamine hydrochloride) (PAH), chondroitin sulfate (CS), and poly-l-lysine (PLL) with diameters between 70 and 90 µm. Droplet-based microfluidics was used as the main process to produce the alginate (ALG)-based microgels with discrete size, shape, and low coefficient of variation. The physicochemical and morphological properties of the polyelectrolyte microgels were characterized via optical microscopy, scanning electron microscopy (SEM), and zeta potential analysis. We found that polyelectrolyte microgels provide low cytotoxicity and cell-material interactions (adhesion, spreading, and proliferation). In addition, the microsystem showed the ability to load lipoplexes and a loading efficiency equal to 83%, and it enabled in vitro surface-based transfection of MCF-7 cells. This approach provides a new suitable route for cell adhesion and local gene delivery.

Multiple functions of pyruvate kinase M2 in various cell types.

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.