Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

Deep learning to predict lymph node status on pre-operative staging CT in patients with colon cancer.

INTRODUCTION: Lymph node (LN) metastases are an important determinant of survival in patients with colon cancer, but remain difficult to accurately diagnose on preoperative imaging. This study aimed to develop and evaluate a deep learning model to predict LN status on preoperative staging CT. METHODS: In this ambispective diagnostic study, a deep learning model using a ResNet-50 framework was developed to predict LN status based on preoperative staging CT. Patients with a preoperative staging abdominopelvic CT who underwent surgical resection for colon cancer were enrolled. Data were retrospectively collected from February 2007 to October 2019 and randomly separated into training, validation, and testing cohort 1. To prospectively test the deep learning model, data for testing cohort 2 was collected from October 2019 to July 2021. Diagnostic performance measures were assessed by the AUROC. RESULTS: A total of 1,201 patients (median [range] age, 72 [28-98 years]; 653 [54.4%] male) fulfilled the eligibility criteria and were included in the training (n = 401), validation (n = 100), testing cohort 1 (n = 500) and testing cohort 2 (n = 200). The deep learning model achieved an AUROC of 0.619 (95% CI 0.507-0.731) in the validation cohort. In testing cohort 1 and testing cohort 2, the AUROC was 0.542 (95% CI 0.489-0.595) and 0.486 (95% CI 0.403-0.568), respectively. CONCLUSION: A deep learning model based on a ResNet-50 framework does not predict LN status on preoperative staging CT in patients with colon cancer.

Association Between RAS/BRAF Mutations and Complete Response Following Total Neoadjuvant Therapy in Patients with Rectal Cancer: A Prospective Multicentered Study.

BACKGROUND: The impact of RAS/BRAF mutation on primary response rates after total neoadjuvant therapy (TNT) in patients with advanced rectal cancer is unclear. The aim of this study was to assess complete response rates after TNT according to RAS/BRAF mutation status. METHODS: A prospective observational study was performed in patients with rectal cancer who underwent TNT with curative intent at three South Australian hospitals between 2019 and 2023. Patients were classified according to their mutation status: mutant RAS/BRAF (mutRAS) or wild-type RAS/BRAF (wtRAS). The primary endpoint was overall complete response (oCR) rate, defined as the proportion of patients who achieved clinical complete response (cCR) and/or pathological complete response (pCR). RESULTS: Of the 150 patients eligible for inclusion, 80 patients with RAS/BRAF status available were identified. Of these, 43 (53.8%) patients were classified as mutRAS and 37 (46.3%) patients as wtRAS. Patients with mutRAS had significantly lower cCR and oCR rates after TNT than patients with wtRAS (14% vs. 37.8%, p = 0.014; 11.6% vs. 43.2%, p = 0.001, respectively). There was no significant difference in pCR rate between the groups. Of the 80 rectal cancer patients tested, 35 (43.8%) had metastatic disease (M1). There was no significant difference in complete M1 response rates between the groups (17.6% vs. 38.9%, p = 0.254). CONCLUSION: RAS/BRAF mutations negatively impact primary tumor response rates after TNT in patients with advanced rectal cancer. Large-scale national studies are needed to determine whether RAS/BRAF status could be used to select optimal oncologic therapy in rectal cancer patients.

Use of acetylcholinesterase inhibitors in reducing time to gastrointestinal function recovery following abdominal surgery: A systematic review.

INTRODUCTION: Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is one of the major pathways involved in developing POI, but current recommendations to prevent POI do not target this. This review aims to summarise evidence for the use of acetylcholinesterase inhibitors, neostigmine and pyridostigmine, to reduce the time to return of gastrointestinal function (GI) following abdominal surgery. METHODS: A systematic search of various databases was performed from 1946 to May 2023. Randomised controlled trials (RCT) on acetylcholinesterase inhibitors in intra-abdominal surgery were included. Data on time to flatus and/or stool and side effects were extracted. RESULTS: Among 776 screened manuscripts, 8 RCTs (703 patients) investigating acetylcholinesterase inhibitors, in intra-abdominal surgery were analysed. Five studies showed a significant reduction in time to flatus and/or stool by 17-47.6 hours. Methodological variations, differing procedure types, and potential bias were observed. Limited studies reported side effects or length of stay. CONCLUSION: Acetylcholinesterase inhibitors may reduce the time for gastrointestinal function to return. However, current evidence is limited and biased. Further studies incorporating acetylcholinesterase inhibitors in an enhanced recovery protocol are required to address this question, especially for patients undergoing colorectal surgery.

Clinical predictors of rectal cancer response after neo-adjuvant (Chemo)Radiotherapy in Australia and New Zealand: Analysis of the Bi-National Colorectal Cancer Audit (BCCA).

Pathological complete response (pCR) is observed in 11-26% of locally advanced rectal cancers undergoing neoadjuvant chemoradiotherapy (nCRT). This study aims to determine pCR rates and clinicopathological predictors in the Australian and New Zealand (ANZ) cohort. The Bi-National Colorectal Cancer Audit (BCCA) was interrogated for all rectal cancer patients who underwent nCRT prior to surgical resection between 2007 and 2020. Patients were divided in two groups: pCR (AJCC tumour regression grade 0) and partial/no response (pPR, regression grade 1,2 or 3). In total, 3230 patients were included. Rates of pCR and pPR were 704 (21.8%) and 2526 (78.2%), respectively. Long-course nCRT (p < 0.0001), lower clinical tumour stage (cT; p < 0.0001), and nodal stage (cN; p = 0.003) were associated with pCR on univariate analysis. On multivariable analysis, cN0 stage and long-course nCRT remained independent factors for a pCR. Awareness of these predictors provides valuable information when counseling patients regarding prognosis and treatment options.

Incidence and associated morbidity of sarcopenia in non-malignant small and large bowel anastomosis: propensity score-matched analysis.

PURPOSE: Sarcopenia is a prognostic factor for poor outcomes in colorectal cancer, but data are scarce in colorectal surgery for benign conditions where patients could benefit from a deferral of surgery to enter a prehabilitation programme. We assessed the incidence of sarcopenia and complications in patients with benign colorectal disease. METHODS: Patients who underwent elective non-malignant colorectal surgery during 2018-2022 were retrospectively identified. The cross-sectional psoas area was calculated using computed tomography (CT) imaging mid-3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome was complications measured by the comprehensive complication index (CCI). RESULTS: Of 188 patients identified, 39 (20.7%) were sarcopenic. Patients diagnosed with sarcopenia were older (63 vs. 58 years, p = 0.047) and had a reduced BMI (24.7 vs. 27.38 kg/m2, p = 0.001). Sarcopenic patients had more complications (82.1 vs. 64.4%, p = 0.036), and CCI was statistically but not clinically higher (20.9 vs. 20.9, p = 0.047). On univariate linear regression analysis, age ≥ 65 years old, ASA grade ≥ 3, active smokers, sarcopenia, and preoperative anaemia were predictive of CCI. Propensity score-matched analysis was performed, matching 78 cases to remove selection bias, which demonstrated sarcopenia had no impact on postoperative complications. On multivariate analysis, age (p = 0.022), smoking (p = 0.005), and preoperative anaemia (p = 0.008) remained predictive of CCI. CONCLUSION: Sarcopenia is prevalent in one-fifth of patients undergoing benign colorectal surgery. Taking advantage of the longer preoperative waiting periods, sarcopenia could be explored as a target for prehabilitation programmes to improve outcomes.

Management of rectal cancer in the era of total neoadjuvant therapy and watch and wait: A multidisciplinary team discussion at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting 2022.

Rectal cancer is a common malignancy. The management of rectal cancer has recently evolved and has undergone a paradigm shift with the advent of treatment approaches such as total neoadjuvant therapy and the watch-and-wait approach. However, despite the recently available evidence, there is no consensus on the optimal management approach in the setting of locally advanced rectal cancer. To address some of the controversies, a joint multidisciplinary panel discussion was conducted at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in November 2022. Members from different subspecialties formed two panels and discussed three clinical cases in a debate format. Each case represented some of the complex issues faced by clinicians in this setting. The discussion is now presented in this manuscript, which depicts the different available management approaches and reiterates the importance of a multidisciplinary approach.

Global cost of postoperative ileus following abdominal surgery: meta-analysis.

BACKGROUND: Following abdominal surgery, postoperative ileus is a common complication significantly increasing patient morbidity and cost of hospital admission. This is the first systematic review aimed at determining the average global hospital cost per patient associated with postoperative ileus. METHODS: A systematic search of electronic databases was performed from January 2000 to March 2023. Studies included compared patients undergoing abdominal surgery who developed postoperative ileus to those who did not, focusing on costing data. The primary outcome was the total cost of inpatient stay. Risk of bias was assessed using the Newcastle-Ottawa assessment tool. Summary meta-analysis was performed. RESULTS: Of the 2071 studies identified, 88 papers were assessed for full eligibility. The systematic review included nine studies (2005-2022), investigating 1 860 889 patients undergoing general, colorectal, gynaecological and urological surgery. These studies showed significant variations in the definition of postoperative ileus. Six studies were eligible for meta-analysis showing an increase of €8233 (95 per cent c.i. (5176 to 11 290), P < 0.0001, I2 = 95.5 per cent) per patient with postoperative ileus resulting in a 66.3 per cent increase in total hospital costs (95 per cent c.i. (34.8 to 97.9), P < 0.0001, I2 = 98.4 per cent). However, there was significant bias between studies. Five colorectal-surgery-specific studies showed an increase of €7242 (95 per cent c.i. (4502 to 9983), P < 0.0001, I2 = 86.0 per cent) per patient with postoperative ileus resulting in a 57.3 per cent increase in total hospital costs (95 per cent c.i. (36.3 to 78.3), P < 0.0001, I2 = 85.7 per cent). CONCLUSION: The global financial burden of postoperative ileus following abdominal surgery is significant. While further multicentre data using a uniform postoperative ileus definition would be useful, reducing the incidence and impact of postoperative ileus are a priority to mitigate healthcare-related costs, and improve patient outcomes.

Double barrelled uro-colostomy versus Ileal conduit for urinary diversion following pelvic exenteration: a single centre experience.

INTRODUCTION: The ideal method for urinary diversion following total pelvic exenteration (TPE) remains unclear. This study compares the outcomes of double-barrelled uro-colostomy (DBUC) and ileal conduit (IC) in a single Australian centre. METHODS: All consecutive patients who underwent pelvic exenteration with the formation of either a DBUC or an IC between 2008 and November 2022 were identified from the prospective database from the Royal Adelaide Hospital and St. Andrews Hospital. Demographic, operative characteristics, general perioperative, long-term urological and other relevant surgical complications were compared via univariate analyses. RESULTS: Of 135 patients undergoing exenteration, 39 patients were eligible for inclusion: 16 patients with a DBUC, and 23 patients with an IC. More patients in the DBUC group had previous radiotherapy (93.8% vs. 65.2%, P = 0.056) and flap pelvic reconstruction (93.7% vs. 45.5%, P = 0.002). The rate of ureteric stricture trended higher in the DBUC group (25.0% vs. 8.7%, P = 0.21), but in contrast, urine leak (6.3% vs. 8.7%, P>0.999), urosepsis (43.8% vs. 60.9%, P = 0.29), anastomotic leak (0.0% vs. 4.3%, P>0.999), and stomal complications requiring repair (6.3% vs. 13.0%, P = 0.63) trended lower. These differences were not statistically significant. Rates of grade III or greater complications were similar; however, no patients in the DBUC group died within 30-days or had grade IV complications requiring ICU admission compared with two deaths and one grade IV complication in the IC group. CONCLUSION: DBUC is a safe alternative to IC for urinary diversion following TPE, with potentially fewer complications. Quality of life and patient-reported outcomes are required.

Is preoperative sarcopenia associated with postoperative complications after pelvic exenteration surgery?

PURPOSE: Pelvic exenteration (PE) involves radical surgical resection of pelvic organs and is associated with considerable morbidity. Sarcopenia is recognised as a predictor of poor surgical outcomes. This study aimed to determine if preoperative sarcopenia is associated with postoperative complications after PE surgery. METHODS: This retrospective study included patients who underwent PE with an available preoperative CT scan between May 2008 and November 2022 at the Royal Adelaide Hospital and St. Andrews Hospital in South Australia. Total Psoas Area Index (TPAI) was estimated by measuring the cross-sectional area of the psoas muscles at the level of the third lumbar vertebra on abdominal CT, normalised for patient height. Sarcopenia was diagnosed based on gender-specific TPAI cut-off values. Logistic regression analyses were performed to identify risk factors for major postoperative complications with a Clavien-Dindo (CD) grade ≥ 3. RESULTS: In total, 128 patients who underwent PE were included, 90 of whom formed the non-sarcopenic group (NSG) and 38 the sarcopenic group (SG). Major postoperative complications (CD grade ≥ 3) occurred in 26 (20.3%) patients. There was no detectable association with sarcopenia and an increased risk of major postoperative complications. Preoperative hypoalbuminemia (P = 0.01) and a prolonged operative time (P = 0.002) were significantly associated with a major postoperative complication on multivariate analysis. CONCLUSION: Sarcopenia is not a predictor of major postoperative complications in patients undergoing PE surgery. Further efforts aimed specifically at optimising preoperative nutrition may be warranted.

Colorectal cancer detection and treatment with engineered probiotics.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool. We also demonstrate specific colonization of EcN to solitary neoplastic lesions in an orthotopic murine model of CRC. We then exploit this neoplasia-homing property of EcN to develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate, and demonstrate that oral delivery of this strain results in significantly increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. We also assess EcN engineered to locally release immunotherapeutics at the neoplastic site. Oral delivery to mice bearing adenomas, reduced adenoma burden by ∻50%, with notable differences in the spatial distribution of T cell populations within diseased and healthy intestinal tissue, suggesting local induction of robust anti-tumor immunity. Together, these results support the use of EcN as an orally-delivered platform to detect disease and treat CRC through its production of screening and therapeutic molecules.

Can sarcopenia predict complete response after total neoadjuvant therapy in advanced rectal cancer? A multicentre observational cohort study.

BACKGROUND: The association between sarcopenia and response to neoadjuvant treatment remains unclear. This study investigates sarcopenia as a predictor of overall complete response (oCR) after Total Neoadjuvant Therapy (TNT) for advanced rectal cancer. METHOD: A prospective observational study was performed of patients with rectal cancer undergoing TNT at three South Australian hospitals between 2019 and 2022. Sarcopenia was diagnosed by pretreatment computed tomography measurement of psoas muscle cross-sectional area at the third lumbar vertebra level, normalised for patient height. The primary endpoint was oCR rate defined as the proportion of patients who achieved either clinical complete response (cCR) or pathological complete response. RESULTS: This study included 118 rectal cancer patients with an average age of 59.5 years, 83 (70.3%) of whom formed the non-sarcopenic group (NSG) and 35 (29.7%) the sarcopenic group (SG). The oCR rate was significantly higher in NSG compared with the SG (p < 0.001). cCR rate was significantly greater in NSG compared with the SG (p = 0.001). Multivariate analysis revealed sarcopenia (p = 0.029) and hypoalbuminemia (p = 0.040) were risk factors for cCR and sarcopenia was an independent risk factor for oCR (p = 0.020). CONCLUSION: Sarcopenia and hypoalbuminemia were negatively associated with tumour response following TNT in advanced rectal cancer patients.

A prospective study of diagnostic accuracy of multidisciplinary team and radiology reporting of preoperative colorectal cancer local staging.

INTRODUCTION: The aim of this study was to correlate and assess diagnostic accuracy of preoperative staging at multidisciplinary team meeting (MDT) against the original radiology reports and pathological staging in colorectal cancer patients. METHODS: A prospective observational study was conducted at two institutions. Patients with histologically proven colorectal cancer and available preoperative imaging were included. Preoperative tumor and nodal staging (cT and cN) as determined by the MDT and the radiology report (computed tomography [CT] and/or magnetic resonance imaging [MRI]) were recorded. Kappa statistics were used to assess agreement between MDT and the radiology report for cN staging in colon cancer, cT and cN in rectal cancer, and tumor regression grade (TRG) in patients with rectal cancer who received neoadjuvant therapy. Pathological report after surgery served as the reference standard for local staging, and AUROC curves were constructed to compare diagnostic accuracy of the MDT and radiology report. RESULTS: A total of 481 patients were included. Agreement between MDT and radiology report for cN stage was good in colon cancer (k = .756, Confidence Interval (CI) 95% .686-.826). Agreement for cT and cN and in rectal cancer was very good (kw = .825, CI 95% .758-.892) and good (kw = .792, CI 95% .709-.875), respectively. In the rectal cancer group that received neoadjuvant therapy, agreement on TRG was very good (kw = .919, CI 95% .846-.993). AUROC curves using pathological staging indicated no difference in diagnostic accuracy between MDT and radiology reports for either colon or rectal cancer. CONCLUSION: Preoperative colorectal cancer local staging was consistent between specialist MDT review and original radiology reports, with no significant differences in diagnostic accuracy identified.

Clinical and biochemical predictors of tumor response after neoadjuvant therapy in rectal cancer.

BACKGROUND: Patients who have a good clinical and/or pathologic response to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have better long-term outcomes and can potentially be spared morbid surgery. This study aimed to identify pretreatment clinical and biochemical predictors of response to neoadjuvant treatment for rectal cancer. METHODS: Patients undergoing neoadjuvant therapy for rectal cancer between 2007 and 2022 were retrospectively included. Those patients who achieved a complete clinical response were offered a nonoperative management strategy and the remaining patients underwent surgical resection. The primary endpoint was tumor regression grade (TRG) based on radiological imaging (mrTRG) or pathology (pTRG). Patient response was classified as good (mrTRG 1-2 or pTRG 0-1) versus poor (mrTRG 3-4 or pTRG 2-3). Logistic regression was performed to determine predictors of TRG. RESULTS: A total of 984 patients with rectal cancer were identified of which 274 met the inclusion criteria. Of 274 patients, 228 (83%) underwent surgical resection. A good TRG response was observed in 119 (41%) patients, and a complete response was achieved in 53 (17%) patients. On univariable and multivariable logistic regression, clinical T2 stage and body mass index of ≥25 kg/m2 were significant predictors of a good TRG. Clinical T2 stage and a personalised total neoadjuvant therapy regimen were significant predictors of complete response. CONCLUSION: Clinical T2 stage and a BMI≥25 kg/m2 were predictors of good response to neoadjuvant therapy for rectal cancer. Future prospective studies are required to confirm these findings and evaluate their potential use in better targeting of nCRT.

Personalized total neoadjuvant therapy (pTNT) for advanced rectal cancer with tailored treatment sequencing based on clinical stage at presentation.

BACKGROUND: This study aimed to assess short-term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. METHODS: A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two-schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non-operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. RESULTS: Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty-three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non-operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy-related toxicity, with no treatment related mortality. CONCLUSION: Early results with a defined two-schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity.

Does Sarcopenia Predict Local Response Rates After Chemoradiotherapy for Locally Advanced Rectal Cancer?

BACKGROUND: The predictive value of sarcopenia for tumor response to neoadjuvant chemoradiotherapy is unclear. OBJECTIVE: This study aimed to investigate the association between sarcopenia and pathological tumor regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. DESIGN: Retrospective cohort study from a prospectively collected database. Univariate logistic regression was performed to assess the association between sarcopenia and tumor response. SETTINGS: This study was conducted at 2 tertiary care centers. PATIENTS: Participants were patients undergoing neoadjuvant chemoradiotherapy for locally advanced rectal cancer (T3/4, N0/+) between 2007 and 2018. INTERVENTION: Sarcopenia was diagnosed using sex-specific cutoffs of lean muscle mass. Using the initial staging CT, lean muscle mass was estimated using the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra, normalized for patient height. MAIN OUTCOME MEASURES: The primary end point was pathological tumor regression grade, defined as good (tumor regression grade 0/1) vs poor (tumor regression grade 2/3). RESULTS: The study included 167 patients with locally advanced rectal cancer with a median age of 60 (20-91) years, with 132 in the nonsarcopenia group and 35 in the sarcopenia group. Eighty-nine percent of patients had stage 3 cancer. Nine patients (5.4%) had a complete clinical response, 1 patient did not respond to treatment and opted for nonoperative management, and the remaining 157 patients (94.0%) proceeded to surgery. Pathological data revealed no significant difference between good tumor regression grade patients in the sarcopenia group compared with the nonsarcopenia group. Univariate analysis revealed BMI ≥25 kg/m 2 to be a risk factor for good tumor regression grade ( p = 0.002). LIMITATIONS: This study was limited by its retrospective design and small sample size. CONCLUSIONS: Sarcopenia is not a predictor of poor neoadjuvant chemoradiotherapy response in patients with locally advanced rectal cancer. Increasing BMI was associated with good tumor regression grade. Future multicentered studies are warranted to validate this finding. See Video Abstract at http://links.lww.com/DCR/C78 . LA SARCOPENIA PREDICE LAS TASAS DE RESPUESTA LOCAL DESPUS DE LA QUIMIORRADIOTERAPIA PARA EL CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El valor predictivo de la sarcopenia para la respuesta tumoral a la quimiorradioterapia neoadyuvante no está claro.OBJETIVO:Este estudio investiga la asociación entre la sarcopenia y el grado de regresión tumoral patológica después de la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo a partir de una base de datos recolectada prospectivamente. Se realizó una regresión logística univariante para evaluar la asociación entre la sarcopenia y la respuesta tumoral.ENTORNO CLINICO:Este estudio se realizó en dos centros de atención terciaria.PACIENTES:Pacientes sometidos a quimiorradioterapia neoadyuvante por cáncer de recto localmente avanzado (T3/4, N0/+) entre 2007-2018.INTERVENCIÓNES:La sarcopenia se diagnosticó utilizando puntos de corte de masa muscular magra específicos por género. Utilizando la tomografía computarizada de estadificación inicial, se estimó la masa muscular magra utilizando el área transversal del músculo psoas a nivel de la tercera vértebra lumbar, normalizada para la altura del paciente.PRINCIPALES MEDIDAS DE VALORACIÓN:El criterio principal de valoración fue el grado de regresión tumoral patológica, definido como bueno (grado de regresión tumoral 0/1) frente a malo (grado de regresión tumoral 2/3).RESULTADOS:El estudio incluyó a 167 pacientes con cáncer de recto localmente avanzado con una mediana de edad de 60 años (20-91), 132 en el grupo sin sarcopenia y 35 en el grupo con sarcopenia. Ochenta y nueve por ciento estaban en etapa III. Seis pacientes (5,4%) tuvieron respuesta clínica completa sostenida, un paciente no respondió al tratamiento y optó por manejo conservador, los 157 restantes (94,0%) procedieron a cirugía. Los datos patológicos no revelaron diferencias significativas entre los pacientes con buen grado de regresión tumoral en el grupo de sarcopenia en comparación con el grupo sin sarcopenia. El análisis univariado reveló que un IMC ≥25 kg/m2 era un factor de riesgo para un buen grado de regresión tumoral (p = 0,002).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo y tamaño de muestra pequeño.CONCLUSIÓNES:La sarcopenia no es un predictor de mala respuesta a la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado. El aumento del IMC se asoció con un buen grado de regresión tumoral. Se justifican futuros estudios multicéntricos para validar este hallazgo. Consulte Video Resumen en http://links.lww.com/DCR/C78 . (Traducción-Dr. Ingrid Melo ).

Establishing a state-wide pelvic exenteration multidisciplinary team meeting in South Australia.

BACKGROUND: Pelvic exenteration surgery is complex, necessitating co-ordinated multidisciplinary input and improved referral pathways. A state-wide pelvic exenteration multidisciplinary team (MDT) meeting was established in SA and the outcomes of this were audited and compared with historical data. METHODS: All patients referred for discussion between August 2021 and July 2022 to the SA State-wide Pelvic Exenteration MDT were included in this study. MDT discussion centred around disease resectability, risk versus benefit of surgery, and need for local or interstate referral. Prospective data collection included patient demographics and MDT recommendations of surgery, palliation, or referral. Patients referred for surgery locally or interstate were compared with a retrospective patient cohort treated previously between January and December 2020. RESULTS: Over 12 months, 91 patients were discussed (including nine multiple times), by a mean of 18 meeting participants each month. Forty-eight patients (58.5%) had primary malignancy, 25 (30.5%) recurrent malignancy, and 9 (11.0%) had non-malignant disease. Colorectal cancer was the most common presentation (56.1%), followed by gynaecological (30.5%) and urological (6.1%) malignancy. Pelvic exenteration surgery was recommended to be performed locally in 53.7% of patients and the remainder for non-surgical treatment, palliation, or re-discussion. During this time, 44 patients underwent surgery locally (versus 34 in 2020) and only 4 referred interstate (versus 8 in 2020). CONCLUSION: The establishment of a dedicated state-wide pelvic exenteration MDT has resulted in better coordination of care for patients with locally advanced pelvic malignancy in SA, and significantly reduced the need for interstate referral.