Multiple High-Risk Features for Stage II Colon Carcinoma Portends Worse Survival Than Stage III Disease.

BACKGROUND: High-risk features in stage II colon cancer worsen survival and serve as an impetus for adjuvant chemotherapy. Limited data exist on the effect of multiple high-risk features on survival. OBJECTIVE: The study aimed to compare the survival of 0, 1, or multiple high-risk features in stage II to stage III colon cancer. DESIGN: Patients with stage II and III colon cancer diagnosed between 2010 and 2016 were identified using the Survival, Epidemiology, and End Results database. Patients with stage II colon cancer were then classified according to the presence of 0, 1, or 2 or more of the following high-risk features: pathologic T4, perineural invasion, fewer than 12 lymph nodes assessed, or poor histologic differentiation. Overall survival and cause-specific survival were calculated. Each group was then stratified on the basis of whether chemotherapy was given. SETTINGS: This study used the Survival, Epidemiology, and End Results database (2010-2016). PATIENTS: Patients who had stage II or III colon cancer were included. MAIN OUTCOME MEASURES: The primary outcome measures were 5-year overall survival and cause-specific survival. RESULTS: A total of 65,831 patients were studied. Of these, 18,056 patients with stage II cancer had 0 high-risk features, 9426 had 1 high-risk feature, and 3503 had 2 or more high-risk features. There were 34,842 patients diagnosed with stage III disease. The 5-year overall survival and cause-specific survival for patients with stage II cancer with 2 or more high-risk features (49.2%, 59.5%) were lower than those without high-risk features (74.9%, 90.7%), with 1 high-risk feature (67.1%, 82.4%), or stage III disease (59.1%, 68.1%; p < 0.05). Although chemotherapy is associated with improved cause-specific survival in stage III disease, it is associated with worse cause-specific survival in patients with stage II disease. LIMITATIONS: This study being a retrospective database analysis is the main limitation. Also, lymphovascular invasion, margin status, and clinical obstruction or perforation were absent from the dataset. CONCLUSIONS: Multiple high-risk features in stage II colon cancer predict worse survival than lymph node metastasis. Chemotherapy is associated with adverse cause-specific survival in patients with stage II disease. Further study into this group should focus on the type and duration of adjuvant therapy and biological features of these tumors. See Video Abstract at http://links.lww.com/DCR/B929 . MLTIPLES CARACTERSTICAS DE ALTO RIESGO PARA EL CARCINOMA DE COLON EN ESTADIO II PRESAGIAN PEOR SUPERVIVENCIA QUE LA ENFERMEDAD EN ESTADIO III: ANTECEDENTES:Las características de alto riesgo en el cáncer de colon en estadio II empeoran la supervivencia y sirven como impulso para la quimioterapia adyuvante. Existen datos limitados sobre el efecto de múltiples características de alto riesgo en la supervivencia.OBJETIVO:Comparar la supervivencia de cero, una o múltiples características de alto riesgo en el cáncer de colon en estadio II con la enfermedad en estadio III.DISEÑO:Los pacientes con cáncer de colon en estadio II y III diagnosticados entre 2010 y 2016 se identificaron mediante la base de datos de supervivencia, epidemiología y resultados finales. Luego, los pacientes en etapa II se clasificaron según la presencia de cero, 1 o 2+ de las siguientes características de alto riesgo: T4 patológico, invasión perineural, menos de 12 ganglios linfáticos evaluados (< 12 ganglios linfáticos) o mala diferenciación histológica. Se calculó la supervivencia observada y específica de la causa. Luego, cada grupo se estratificó en función de si se administró quimioterapia.ESCENARIO:Este estudio utilizó la base de datos de supervivencia, epidemiología y resultados finales, 2010-2016.PACIENTES:Los pacientes tenían cáncer de colon en estadio II o III.PRINCIPALES MEDIDAS DE RESULTADO:La medida principal fue la supervivencia observada a 5 años y la supervivencia por causa específica.RESULTADOS:Se estudiaron un total de 65,831 pacientes. 18,056 pacientes estaban en estadio II sin características de alto riesgo, 9.426 con 1 característica de alto riesgo y 3.503 con 2+ características de alto riesgo. Hubo 34.842 pacientes a los que se les diagnosticó enfermedad en estadio III. La supervivencia observada a los 5 años y la supervivencia específica de la causa para los pacientes con cáncer en estadio II con 2+ características de alto riesgo (49.2 %, 59.5 %) fueron más bajas, en comparación con aquellos sin características de alto riesgo (74.9 %, 90.7 %), con 1 característica de alto riesgo (67.1 %, 82.4 %) o enfermedad en estadio III (59.1 %, 68.1 %) (p < 0.05). Si bien la quimioterapia se asocia con una mejor supervivencia por causa específica en la enfermedad en estadio III, se asocia con una peor supervivencia por causa específica en pacientes con enfermedad en estadio II.LIMITACIONES:Este es un análisis de base de datos retrospectivo. La invasión linfovascular, el estado de los márgenes y la obstrucción o perforación clínicas estaban ausentes en la base de datos.CONCLUSIONES:Múltiples características de alto riesgo en el cáncer de colon en estadio II predicen una peor supervivencia que la metástasis en los ganglios linfáticos. La quimioterapia se asocia con una supervivencia específica de causa adversa en pacientes con enfermedad en estadio II. El estudio adicional de este grupo deberá centrarse en el tipo y la duración de la terapia adyuvante y las características biológicas de estos tumores. Consulte Video Resumen en http://links.lww.com/DCR/B929 . (Traducción-Dr. Jorge Silva Velazco ).

Liposomal Bupivacaine Transversus Abdominis Plane Blocks in Laparoscopic Colorectal Resections: A Single-Institution Randomized Controlled Trial.

BACKGROUND: Transversus abdominis plane blocks improve postoperative pain after colon and rectal resections, but the benefits of liposomal bupivacaine use for these blocks have not been clearly demonstrated. OBJECTIVE: This study aimed to determine whether using liposomal bupivacaine in transversus abdominis plane blocks improves postoperative pain and reduces opioid use after colorectal surgery compared to standard bupivacaine. DESIGN: This study was a single-blinded, single-institution, prospective randomized controlled trial comparing liposomal bupivacaine to standard bupivacaine in transversus abdominis plane blocks in patients undergoing elective colon and rectal resections. SETTINGS: This study was conducted at a single-institution academic medical center with 6 staff colorectal surgeons and 2 colorectal surgery fellows. PATIENTS: Ninety-six patients aged 18 to 85 years were assessed for eligibility; 76 were included and randomly assigned to 2 groups of 38 patients. INTERVENTIONS: Patients in the experimental group received liposomal bupivacaine transversus abdominis plane blocks, whereas the control group received standard bupivacaine blocks. MAIN OUTCOME MEASURES: The primary outcome was maximum pain score on postoperative day 2. Secondary outcomes included daily maximum and average pain scores in the 3 days after surgery, as well as daily morphine milligram equivalent use and length of hospital stay. RESULTS: Patients receiving liposomal bupivacaine blocks had lower maximum pain scores on the day of surgery (mean, 6.5 vs 7.7; p = 0.008). No other difference was found between groups with respect to maximum or average pain scores at any time point postoperatively, nor was there any difference in morphine milligram equivalents used or length of stay (median, 3.1 d). LIMITATIONS: This was a single-institution study with only patients blinded to group assignment. CONCLUSIONS: Liposomal bupivacaine use in transversus abdominis plane blocks for patients undergoing laparoscopic colorectal resections does not seem to improve postoperative pain, nor does it reduce narcotic use or decrease length of stay. Given its cost, use of liposomal bupivacaine in transversus abdominis plane blocks is not justified for colon and rectal resections. See Video Abstract at http://links.lww.com/DCR/B979 . CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Identifier: NCT04781075. BLOQUEOS TAP DE BUPIVACANA LIPOSOMAL EN RESECCIONES COLORRECTALES LAPAROSCPICAS UN ENSAYO CONTROLADO ALEATORIO DE UNA SOLA INSTITUCIN: ANTECEDENTES:Los bloqueos del plano transverso del abdomen, mejoran el dolor posoperatorio después de las resecciones de colon y recto, pero los beneficios del uso de bupivacaína liposomal para estos bloqueos, no se han demostrado claramente.OBJETIVO:Investigar la eficacia de la inyección con tejido adiposo autólogo recién recolectado en fístulas anales criptoglandulares complejas.DISEÑO:Ensayo controlado, aleatorio, prospectivo, simple ciego, de una sola institución, que compara la bupivacaína liposomal con la bupivacaína estándar en bloqueos del plano transverso del abdomen, en pacientes sometidos a resecciones electivas de colon y recto. Identificador de ClinicalTrials.gov : NCT04781075.ENTORNO CLINICO:Centro médico académico de una sola institución con seis cirujanos de plantilla y becarios de cirugía colorrectal.PACIENTES:Se evaluó la elegibilidad de 96 pacientes de 18 a 85 años; 76 fueron incluidos y aleatorizados en dos grupos de 38 pacientes.INTERVENCIONES:Los pacientes del grupo experimental recibieron bloqueos del plano transverso del abdomen con bupivacaína liposomal, mientras que el grupo de control recibió bloqueos de bupivacaína estándar.PRINCIPALES MEDIDAS DE VALORACION:El resultado primario fue la puntuación máxima de dolor en el segundo día posoperatorio. Los resultados secundarios incluyeron las puntuaciones máximas y medias diarias de dolor en los 3 días posteriores a la cirugía, así como el uso diario equivalente en miligramos de morfina y la duración de la estancia hospitalaria.RESULTADOS:Los pacientes que recibieron bloqueos de bupivacaína liposomal, tuvieron puntuaciones máximas de dolor más bajas, el día de la cirugía (media 6,5 frente a 7,7, p = 0,008). No hubo ninguna otra diferencia entre los grupos con respecto a las puntuaciones de dolor máximas o promedio en cualquier momento después de la operación, ni hubo ninguna diferencia en los equivalentes de miligramos de morfina utilizados o la duración de la estancia (mediana de 3,1 días).LIMITACIONES:Estudio de una sola institución con cegamiento de un solo paciente.CONCLUSIONES:El uso de bupivacaína liposomal en bloqueos del plano transverso del abdomen, para pacientes sometidos a resecciones colorrectales laparoscópicas, no parece mejorar el dolor posoperatorio, ni reduce el uso de narcóticos ni la duración de la estancia hospitalaria. Dado su costo, el uso de bupivacaína liposomal en bloqueos TAP no está justificado para resecciones de colon y recto. Consulte Video Resumen en http://links.lww.com/DCR/B797 . Traducción Dr. Fidel Ruiz Healy.

Minimally Invasive Surgery is Associated with Improved Outcomes Following Urgent Inpatient Colectomy.

Objectives: The use of minimally invasive techniques for urgent colectomies remains understudied. This study compares short-term outcomes following urgent minimally invasive colectomies to those following open colectomies. Methods & Procedures: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) colectomy database was queried between January 1, 2013 and December 31, 2018. Patients who underwent elective and emergency colectomies, based on the respective NSQIP variables, were excluded. The remaining patients were divided into two groups, minimally invasive surgery (MIS) and open. MIS colectomies with unplanned conversion to open were included in the MIS group. Baseline characteristics and 30-day outcomes were compared using univariable and multivariable regression analyses. Results: A total of 29,345 patients were included in the study; 12,721 (43.3%) underwent MIS colectomy, while 16,624 (56.7%) underwent open colectomy. Patients undergoing MIS colectomy were younger (60.6 vs 63.8 years) and had a lower prevalence of either American Society of Anesthesiology (ASA) IV (9.9 vs 15.5%) or ASA V (0.08% vs 2%). After multivariable analysis, MIS colectomy was associated with lower odds of mortality (odds ratio = 0.75, 95% confidence interval: 0.61, 0.91 95% confidence interval), and most short-term complications recorded in the ACS NSQIP. While MIS colectomies took longer to perform (161 vs 140 min), the length of stay was shorter (12.2 vs 14.1 days). Conclusions: MIS colectomy affords better short-term complication rates and a reduced length of stay compared to open colectomy for patients requiring urgent surgery. If feasible, minimally invasive colectomy should be offered to patients necessitating urgent colon resection.

Laparoscopic Colectomy for Acute Diverticulitis in the Urgent Setting is Associated with Similar Outcomes to Open.

PURPOSE/BACKGROUND: The role of minimally invasive surgery (MIS) for the surgical treatment of diverticular disease is evolving. The aim of this study is to compare the outcomes of MIS colectomy to those of open surgery for patients with acute diverticulitis requiring urgent surgery. METHODS: The American college of Surgeons National Surgical Quality Improvement Project database was queried for all patients undergoing an urgent colectomy for acute diverticulitis between 2013 and 2018. The patients were then divided into 2 groups: MIS and open. Baseline characteristics and short-term outcomes were compared using univariable and multivariable regression analyses. RESULTS/OUTCOMES: 3487 patients were included in the analysis. Of these, 1272 (36.5%) underwent MIS colectomy and 2215 (63.5%) underwent open colectomy. Patients undergoing MIS colectomy were younger (58.7 vs 61.9 years) and less likely to be American Society of Anesthesiologists Classification (ASA) III (52.5 vs 57.9%) or IV (6.3 vs 10.5%). After adjusting for baseline differences, the odds of mortality for MIS and open groups were similar. While there was no difference in short-term complications between groups, the odds of developing an ileus were lower following MIS colectomy (OR .61, 95% CI: .49, .76). Both total length of stay (LOS) (12.3 vs 13.9 days) and post-operative LOS (7.6 days vs 9.5 days) were shorter for MIS colectomy. Minimally invasive surgery colectomy added an additional 40 minutes of operative time (202.2 vs 160.1 min). CONCLUSION/DISCUSSION: Minimally invasive surgery colectomy appears to be safe for patients requiring urgent surgical management for acute diverticulitis. Decreased incidence of ileus and shorter LOS may justify any additional operative time for MIS colectomy in suitable candidates.

Endoscopy in Inflammatory Bowel Disease.

The roles of flexible endoscopy in the setting of inflammatory bowel disease include diagnosis, surveillance, and determining response to treatment and monitoring for the development of recurrence, dysplasia, or malignancy. Advanced techniques, such as chromoendoscopy and narrow band imaging, can be useful adjuncts when performing endoscopy in patients with inflammatory bowel disease. There are several roles for therapeutic endoscopy in the setting of inflammatory bowel disease, including endoscopic balloon dilation and endoscopic stricturotomy.

Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis.

Cancer patients have poor prognoses when lymph node (LN) involvement is present in both high-grade urothelial cell carcinoma (HG-UCC) of the bladder and colorectal cancer (CRC). More than 50% of patients with muscle-invasive UCC, despite curative therapy for clinically-localized disease, will develop metastases and die within 5 years, and metastatic CRC is a leading cause of cancer-related deaths in the US. Xenograft models that consistently mimic UCC and CRC metastasis seen in patients are needed. This study aims to generate patient-derived orthotopic xenograft (PDOX) models of UCC and CRC for primary tumor growth and spontaneous metastases under the influence of LN stromal cells mimicking the progression of human metastatic diseases for drug screening. Fresh UCC and CRC tumors were obtained from consented patients undergoing resection for HG-UCC and colorectal adenocarcinoma, respectively. Co-inoculated with LN stromal cell (LNSC) analog HK cells, luciferase-tagged UCC cells were intra-vesically (IB) instilled into female non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and CRC cells were intra-rectally (IR) injected into male NOD/SCID mice. Tumor growth and metastasis were monitored weekly using bioluminescence imaging (BLI). Upon sacrifice, primary tumors and mouse organs were harvested, weighed, and formalin-fixed for Hematoxylin and Eosin and immunohistochemistry staining. In our unique PDOX models, xenograft tumors resemble patient pre-implantation tumors. In the presence of HK cells, both models have high tumor implantation rates measured by BLI and tumor weights, 83.3% for UCC and 96.9% for CRC, and high distant organ metastasis rates (33.3% detected liver or lung metastasis for UCC and 53.1% for CRC). In addition, both models have zero mortality from the procedure. We have established unique, reproducible PDOX models for human HG-UCC and CRC, which allow for tumor formation, growth, and metastasis studies. With these models, testing of novel therapeutic drugs can be performed efficiently and in a clinically-mimetic manner.

The Role of Bowel Preparation in Colorectal Surgery: Results of the 2012-2015 ACS-NSQIP Data.

OBJECTIVE: To analyze potential benefits with regards to infectious complications with combined use of mechanical bowel preparation (MBP) and ABP in elective colorectal resections. BACKGROUND: Despite recent literature suggesting that MBP does not reduce infection rate, it still is commonly used. The use of oral antibiotic bowel preparation (ABP) has been practiced for decades but its use is also controversial. METHODS: Patients undergoing elective colorectal resection in the 2012 to 2015 American College of Surgeons National Surgical Quality Improvement Program cohorts were selected. Doubly robust propensity score-adjusted multivariable regression was conducted for infectious and other postoperative complications. RESULTS: A total of 27,804 subjects were analyzed; 5471 (23.46%) received no preparation, 7617 (32.67%) received MBP only, 1374 (5.89%) received ABP only, and 8855 (37.98%) received both preparations. Compared to patients receiving no preparation, those receiving dual preparation had less surgical site infection (SSI) [odds ratio (OR) = 0.39, P < 0.001], organ space infection (OR = 0.56, P ≤ 0.001), wound dehiscence (OR = 0.43, P = 0.001), and anastomotic leak (OR = 0.53, P < 0.001). ABP alone compared to no prep resulted in significantly lower rates of surgical site infection (OR = 0.63, P = 0.001), organ space infection (OR = 0.59, P = 0.005), anastomotic leak (OR = 0.53, P = 0.002). MBP showed no significant benefit to infectious complications when used as monotherapy. CONCLUSIONS: Combined MBP/ABP results in significantly lower rates of SSI, organ space infection, wound dehiscence, and anastomotic leak than no preparation and a lower rate of SSI than ABP alone. Combined bowel preparation significantly reduces the rates of infectious complications in colon and rectal procedures without increased risk of Clostridium difficile infection. For patients undergoing elective colon or rectal resection we recommend bowel preparation with both mechanical agents and oral antibiotics whenever feasible.

Clopidogrel bisulfate (Plavix) does not increase bleeding complications in patients undergoing rubber band ligation for symptomatic hemorrhoids.

BACKGROUND: The incidence of postprocedural bleeding in patients undergoing rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk of RBL for patients taking clopidogrel compared with age- and sex-matched controls. MATERIALS AND METHODS: This is a retrospective case-controlled cohort study analyzing data from 2005 to 2013 conducted at a single tertiary care academic center. The study included a total of 80 rubber bands placed on 41 patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients not taking clopidogrel matched for age and sex. The 30-d rates of significant and insignificant bleeding events after RBL were recorded. A bleeding event was considered significant if the patient required admission to the hospital, transfusion of blood products, or additional procedures to stop the bleeding. Insignificant bleeding was defined as passage of blood or clots per rectum with spontaneous cessation and no need for additional intervention. RESULTS: There was no significant difference in the number of bleeding events per band placed in the clopidogrel group when compared with the control group (3.75% versus 2.78%, P = 0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar between the two groups. Two significant bleeding events occurred in the clopidogrel group requiring intervention: cauterization in one patient and colonoscopy and transfusion in the other. CONCLUSIONS: The risk of a bleeding complication after RBL for hemorrhoids does not appear to be increased in patients taking clopidogrel. Our results support the practice of continuing clopidogrel bisulfate in the periprocedural period as the associated risk of thrombosis is greater than the risk of bleeding.

An Optimal Orthotopic Mouse Model for Human Colorectal Cancer Primary Tumor Growth and Spontaneous Metastasis.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Small animal models allow for the study of different metastatic patterns, but an optimal model for metastatic colorectal cancer has not been established. OBJECTIVE: The purpose of this study was to determine which orthotopic model most accurately emulates the patterns of primary tumor growth and spontaneous liver and lung metastases seen in patients with colorectal cancer. DESIGN: Using luciferase-tagged HT-29 cells coinoculated with lymph node stromal analog HK cells, 3 tumor cell delivery models were compared: intrarectal injection, intracecal injection, and acid enema followed by cancer cell instillation. Tumor growth was monitored weekly by bioluminescent imaging, and mice were sacrificed based on primary tumor size or signs of systemic decline. Liver and lungs were evaluated for metastases via bioluminescent imaging and histology. SETTINGS: The study was conducted at a single university center. MAIN OUTCOME MEASURES: Primary tumor and metastasis bioluminescent imaging were measured. RESULTS: Intrarectal injection had the lowest mortality at 4.0% (1/25) compared with the intracecal group at 17.4% (4/23) and the acid enema followed by cancer cell instillation group at 15.0% (3/20).The primary tumors in intrarectal mice had the highest average bioluminescence (3.78 × 10 ± 4.94 × 10 photons) compared with the mice in the intracecal (9.52 × 10 ± 1.92 × 10 photons; p = 0.012) and acid enema followed by cancer cell instillation groups (6.23 × 10 ± 1.23 × 10 photons; p = 0.0016). A total of 100% of intrarectal and intracecal mice but only 35% of mice in the acid enema followed by cancer cell instillation group had positive bioluminescent imaging before necropsy. Sixty percent of intrarectal mice had liver metastases, and 56% had lung metastases. In the intracecal group, 39% of mice had liver metastases, and 35% had lung metastases. Only 2 acid enema followed by cancer cell instillation mice developed metastases. LIMITATIONS: Tumor injections were performed by multiple investigators. Distant metastases were confirmed, but local lymph node status was not evaluated. CONCLUSIONS: Intrarectal injection is the safest, most reproducible, and successful orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis.

In vitro effects of tamoxifen on adipose-derived stem cells.

In breast reconstructive procedures, adipose-derived stem cells (ASCs) that are present in clinical fat grafting isolates are considered to play the main role in improving wound healing. In patients following chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. However, it is unclear if tamoxifen (TAM) as the most widely used hormonal therapeutic agent for breast cancer treatment, affects the ASCs and ultimately wound healing. This study evaluated whether TAM exposure to in vitro human ASCs modulate cellular functions. Human ASCs were isolated and treated with TAM at various concentrations. The effects of TAM on cell cycle, cell viability and proliferation rates of ASCs were examined by growth curves, MTT assay and BrdU incorporation, respectively. Annexin V and JC-1 Mitochondrial Membrane Potential assays were used to analyze ASC apoptosis rates. ASCs were cultured in derivative-specific differentiation media with or without TAM (5 uM) for 3 weeks. Adipogenic and osteogenic differentiation levels were measured by quantitative RT-PCR and histological staining. TAM has cytotoxic effects on human ASCs through apoptosis and inhibition of proliferation in dose- and time-dependent manners. TAM treatment significantly down-regulates the capacity of ASCs for adipogenic and osteogenic differentiation (p<0.05 vs. control), and inhibit the ability of the ASCs to subsequently formed cords in Matrigel. This study is the first findings to our knowledge that demonstrated that TAM inhibited ASC proliferation and multi-lineage ASC differentiation rates. These results may provide insight into the role of TAM with associated poor soft tissue wound healing and decreased fat graft survival in cancer patients receiving TAM.