Artificial intelligence measured 3D body composition to predict pathological response in rectal cancer patients.

BACKGROUND: The treatment of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Of particular interest are predictors of pathological complete response (pCR) that can guide personalized treatment. There are currently no clinical biomarkers which can accurately predict neoadjuvant therapy (NAT) response but body composition (BC) measures present as an emerging contender. The primary aim of the study was to determine if artificial intelligence (AI) derived body composition variables can predict pCR in patients with LARC. METHODS: LARC patients who underwent NAT followed by surgery from 2012 to 2023 were identified from the Australian Comprehensive Cancer Outcomes and Research Database registry (ACCORD). A validated in-house pre-trained 3D AI model was used to measure body composition via computed tomography images of the entire Lumbar-3 vertebral level to produce a volumetric measurement of visceral fat (VF), subcutaneous fat (SCF) and skeletal muscle (SM). Multivariate analysis between patient body composition and histological outcomes was performed. RESULTS: Of 214 LARC patients treated with NAT, 22.4% of patients achieved pCR. SM volume (P = 0.015) and age (P = 0.03) were positively associated with pCR in both male and female patients. SCF volume was associated with decreased likelihood of pCR (P = 0.059). CONCLUSION: This is the first study in the literature utilizing AI-measured 3D Body composition in LARC patients to assess their impact on pathological response. SM volume and age were positive predictors of pCR disease in both male and female patients following NAT for LARC. Future studies investigating the impact of body composition on clinical outcomes and patients on other neoadjuvant regimens such as TNT are potential avenues for further research.

Postoperative chemoradiotherapy in patients with locally advanced gastric cancer with poor pathologic response to neoadjuvant chemotherapy.

PURPOSE: To evaluate the effect of postoperative chemoradiotherapy (CRT) in patients with locally advanced gastric cancer (LAGC) who respond poorly to neoadjuvant chemotherapy (ChT). MATERIALS AND METHODS: The database of a tertiary medical center (2009-2020) was retrospectively reviewed for patients with LAGC in whom the initial treatment strategy consisted of perioperative ChT and surgery. Those who were subsequently referred for postoperative CRT because of a poor pathologic primary-tumor response (ypT3-4, ypN2-3, R1 resection) were selected for the study. CRT consisted of 45 Gy in 25 fractions of 1.8 Gy combined with capecitabine 825 mg/m2 twice daily on radiotherapy days or continuous infusion of 5-fluorouracil 180 mg/m2/day. RESULTS: The cohort included 26 patients of median age 61 years with LAGC (clinical stage IIA-III) after surgery with D1-D2 lymphadenectomy. R0 resection was achieved in 15 (58%). The pathological stage was III in 69% (IIA-IVA). Treatment was well tolerated. During a median follow-up time of 39 months, recurrences were documented in 14 patients (54%): 11 distant and 3 locoregional. Median progression-free survival was 23 months, and median overall survival was 65 months. Estimated 5-year survival rates were 42 and 54%, respectively. CONCLUSIONS: This small retrospective study suggests that in patients with LAGC who show a poor pathologic response to neoadjuvant ChT, a good outcome relative to reference arms in randomized trials can still be achieved with the addition of postoperative CRT. Further studies of the benefit of a tailored adaptive treatment approach to LAGC based on the response to neoadjuvant ChT are warranted.

Exploring the impact of stage and tumor site on colorectal cancer survival: Bayesian survival modeling.

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis.

BACKGROUND: Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. METHODS: Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot. RESULTS: Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21-1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13-1.70) for patients with lower VD levels, as indicated by fixed-effects models. CONCLUSIONS: Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.

Chitinase-3 like-protein-1 (YKL-40) Promotes Anorectal Mucosal Melanoma Progression via the PI3K-AKT Signaling Pathway.

Objective: Anorectal mucosal melanoma is a rare and aggressive cancer with limited treatment options. Investigating specific molecular pathways may provide insight into the development and progression of this cancer. This study aims to investigate the role of chitinase-3-like protein-1 (YKL-40) in promoting the development of anorectal mucosal melanoma through the PI3K-AKT signaling pathway. Methods: Perianal cells from healthy volunteers and melanoma cells from patients with early, middle and advanced anorectal melanoma were obtained. Western blotting was performed to detect the protein expression of PI3K, AKT, and the downstream proteins mTOR, p-mTOR, ERK, and p-ERK, respectively. Subsequently, we constructed knockout and overexpression of YKL-40 melanoma cell lines, then used western blot assay to test for YKL-40, PI3K and AKT protein expression. Results: A significant increase in the expression of PI3K, AKT, and the downstream proteins mTOR, pmTOR, ERK, and pERK was observed in melanoma cells, and the expression of these proteins increased with the development of melanoma. After YKL-40 was knocked out, PI3K and AKT expression decreased in melanoma cells in patients with advanced melanoma. On the contrary, PI3K and AKT protein expression increased significantly after YKL-40 overexpression. Conclusion: There is a positive correlation between the expression levels of PI3K, AKT, mTOR, p-mTOR, ERK, and p-ERK and the stage of tumor development. The PI3K-AKT signaling pathway promotes the progress of anorectal mucosal melanoma. Chitinase-3-like protein-1 (YKL-40) regulates the progression of anorectal mucosal melanoma through the PI3K-AKT signaling pathway. Investigating specific molecular pathways may provide a better understanding of anorectal mucosal melanoma. The findings from this study could contribute to the development of new diagnosis and treatment strategies for this rare and aggressive cancer. Future research directions may include investigating other possible pathways involved in melanoma progression.

Is proctoscopy sufficient for the evaluation of colorectal anastomosis prior to ileostomy reversal? A nationwide retrospective analysis of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative group (SICO-CCN).

AIM: Several methods for assessing anastomotic integrity have been proposed, but the best is yet to be defined. The aim of this study was to compare the different methods to assess the integrity of colorectal anastomosis prior to ileostomy reversal. METHOD: A retrospective cohort analysis on patients between 1 January 2010 and 31 December 2020 with a defunctioning stoma for middle and low rectal anterior resection was performed. A propensity score matching comparison between patients who underwent proctoscopy alone and patients who underwent proctoscopy plus any other preoperative method to assess the integrity of colorectal anastomosis prior to ileostomy reversal (transanal water-soluble contrast enema via conventional radiology, transanal water-soluble contrast enema via CT, and magnetic resonance) was performed. RESULTS: The analysis involved 1045 patients from 26 Italian referral colorectal centres. The comparison between proctoscopy alone versus proctoscopy plus any other preoperative tool showed no significant differences in terms of stenoses (p = 0.217) or leakages (p = 0.103) prior to ileostomy reversal, as well as no differences in terms of misdiagnosed stenoses (p = 0.302) or leakages (p = 0.509). Interestingly, in the group that underwent proctoscopy and transanal water-soluble contrast enema the comparison between the two procedures demonstrated no significant differences in detecting stenoses (2 vs. 0, p = 0.98), while there was a significant difference in detecting leakages in favour of transanal water-soluble contrast enema via CT (3 vs. 12, p = 0.03). CONCLUSIONS: We can confirm that proctoscopy alone should be considered sufficient prior to ileostomy reversal. However, in cases in which the results of proctoscopy are not completely clear or the surgeon remains suspicious of an anastomotic leakage, transanal water-soluble contrast enema via CT could guarantee its detection.

Metastatic Colorectal Cancer Treated with Combined Liver Resection, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Predictive Factors for Early Recurrence.

BACKGROUND: Selection of colorectal cancer patients with concomitant peritoneal (PM) and liver metastases (LM) for radical treatment with cytoreductive surgery (CRS), including liver resection and hyperthermic intraperitoneal chemotherapy (HIPEC), needs improvement. This retrospective, monocentric study was designed to evaluate the predictive factors for early recurrence, disease-free survival (DFS), and overall survival (OS) in such patients treated in a referral center. METHODS: Consecutive colorectal cancer patients with concomitant LM and PM treated with curative intent with perioperative systemic chemotherapy, simultaneous complete CRS, liver resection, and HIPEC in 2011-2022 were included. Clinical, radiological (before and after preoperative chemotherapy), surgical, and pathological data were investigated, along with long-term oncologic outcomes. A multivariate analysis was performed to identify predictive factors associated with early recurrence (diagnosed <6 months after surgery), DFS, and OS. RESULTS: Of more than 61 patients included, 31 (47.1%) had pT4 and 27 (40.9%) had pN2 primary tumors. Before preoperative chemotherapy, the median number of LM was 2 (1-4). The median surgical PCI (peritoneal carcinomatosis index) was 3 (5-8.5). The median DFS and OS were 8.15 (95% confidence interval [CI] 5.5-10.1) and 34.1 months (95% CI 28.1-53.5), respectively. In multivariate analysis, pT4 (odds ratio [OR] = 4.14 [1.2-16.78], p = 0.032]) and pN2 (OR = 3.7 [1.08-13.86], p = 0.042) status were independently associated with an early recurrence, whereas retroperitoneal lymph node metastasis (hazard ratio [HR] = 39 [8.67-175.44], p < 0.001) was independently associated with poor OS. CONCLUSIONS: In colorectal cancer patients with concomitant PM and LM, an advanced primary tumor (pT4 and/or pN2) was associated with a higher risk of early recurrence following a radical multimodal treatment, whereas RLN metastases was strongly detrimental for OS.

Oncological Clearance Following Resection of the Carcinoma Rectum: A Comparison between Laparoscopic and Open Anterior Resection.

Till the day the rectal cancer deaths in the world is in eighth position. For rectal cancer surgery, short-term benefits are expected to be similar for laparoscopic resection of rectum (LRR) and open resection of rectum (ORR). In Bangladesh though the rectal cancer is the sixteenth most common cause of cancer deaths, there is lack of data regarding outcomes of laparoscopic and open surgical approaches for carcinoma rectum. Purpose of study was to compare oncopathological outcomes by quality of surgical resection between LRR and ORR groups. The quasi experimental study was conducted among 46 subjects who attended in the Department of Colorectal Surgery, Bangabandhu Sheikh Mujib Medical University, Bangladesh from July 2020 to June 2021 with rectal adenocarcinoma within 15cm from the anal verge. Equal number of subjects were allocated for LRR and ORR group. Oncopathological end points such as circumferential resection margin (CRM), distal resection margin (DRM), lymph nodes and quality of mesorectal excision were assessed and compared. Here every patients have given their written consent for this study. Mean age of the subjects for LRR and ORR were 45.47±12.66 and 44.47±12.48 years respectively. Majority of the subjects were in age above 40 years (67.0%). The proportion of male (56.5%) were higher than those of female (43.5%). The complete resection was better in LRR (91.3%) than ORR (87.0%) group though statistically not significant. CRM was lower in LRR (0.0%) than ORR (13.0%) group in respect of frequency distribution. DRM was negative for both LRR and ORR group (95.7% each) and it was not statistically significant. ORR met the National Comprehensive Cancer Network (NCCN) criteria of harvesting 12 lymph nodes were as in LRR group 10 lymph nodes were harvested. The mean harvested lymph nodes were 12.2±5.55 and 10.1±5.55 in LRR and ORR group respectively. The study demonstrated that LRR is better (though statistically not significant) in respect of complete resection and CRM while in harvesting lymph nodes, ORR met the NCCN criteria but LRR does not. There is no difference observed regarding DRM in both groups. On oncopathological point of view both the group showed almost equally effective results. Laparoscopic surgery can be opted as the standard operative technique for surgical management of rectal cancer.

NCCN Guideline Concordance Improves Survival in Pediatric and Young Adult Rectal Cancer.

BACKGROUND: Although management guidelines in adult rectal cancer are widely studied, no consensus guidelines exist for the management of pediatric and young adult rectal cancer. METHODS: The National Cancer Database (2004-2018) was queried for pediatric (age 0-21) and young adult (age 22-40) patients with rectal cancer. Patients were analyzed for receipt of National Comprehensive Cancer Network (NCCN) guideline-concordant therapy. Impact on survival was evaluated using Cox regression and Kaplan-Meier analysis. RESULTS: 6655 patients (108 pediatric and 6547 young adult patients) with rectal cancer were included. Similar to previously published NCCN quality measures with overall guideline concordance approaching 90 % in adults, 89.6 % of pediatric and 84.6 % of young adult patients were classified as receiving pre-operative guideline-concordant therapy. However, pediatric patients were significantly less likely to receive post-operative guideline-concordant therapy than young adult patients (65.3 % verse 76.7 %, respectively, p = 0.008). Risk of death was significantly lower for pediatric patients who received post-operative guideline-concordant therapy (HR, 0.313; CI, 0.168-0.581; p < 0.001). In young adult patients, risk of death was significantly lower for those who received pre-operative guideline-concordant therapy (HR, 0.376, CI 0.338-0.417, p < 0.001), and post-operative guideline-concordant therapy (HR, 0.456; CI 0.413-0.505; p < 0.001). DISCUSSION: NCCN-based guidelines may reasonably guide peri-operative management decisions and improve survival in pediatric and young adult rectal cancer. Given the rarity of this cancer in young patients, employment of an experienced surgical and oncologic multidisciplinary team, along with discussion and involvement of the patient and family, are keys for balancing risks and benefits to offering the best therapeutic strategy. TYPE OF STUDY: Retrospective. LEVEL OF EVIDENCE: Level III.

The Therapeutic Effect of Laparoscopic Combined with Plasma Electric Cutting Knife on Patients with Rectal Cancer and its Impact on Serum Inflammatory Factors: A Retrospective Study.

Objective: This study investigated the therapeutic effect of laparoscopic surgery combined with the plasma electric cutting knife on patients diagnosed with rectal cancer and its impact on serum inflammatory factors in the bloodstream. Methods: The researchers examined the clinical data of 85 patients who underwent laparoscopic low anterior resection for rectal cancer in our hospital from April 2020 to December 2021. The patients comprised two groups: an observation group of 40 cases and a control group of 45 cases. The CD3+, CD4+, CD8+, and CD4+/CD8+ levels in both groups were detected using flow cytometry. The levels of relevant inflammatory factors in serum were measured using an automatic biochemical analyzer. The researchers then compared the perioperative outcomes between the two groups. Results: The observation group demonstrated significantly shorter duration for the first time passing gas after surgery (P = .029) and hospital stays (P = .002) than the control group. Both groups experienced decreased levels of CD8+ cells following treatment, with the observation group exhibiting lower levels than the control group (P < .05). After three months of treatment, both groups showed reduced levels of relevant serum inflammatory factors, TNF-α, IL-1, IL-6, and IL-8; however, the observation group was significantly lower than the control group with statistical significance (P < .05). Similarly, after three months of treatment, both groups exhibited lower levels of relevant serum electrolytes K+, Na+, and Cl-, with the observation group having lower levels than the control group (P < .05). Throughout the 12-month follow-up period, the two groups had no significant differences (P > .05) in complications such as urinary tract infection, anastomotic leakage, or anastomotic bleeding. Conclusion: Using a combination of laparoscopic techniques and a plasma electric cutting knife proved a highly effective surgical approach in treating rectal cancer. The method has numerous advantages, such as enhanced safety and few complications. When considering perioperative complications, it was evident that laparoscopic combined with the plasma electric cutting knife surpassed other surgical methods in treating rectal cancer.

Improvement of Diarrhea-Type Defecation Habit Changes and Other Complications After Dixon Surgery for Rectal Cancer With Discriminative Chinese Herbs Combined With Levator Ani Muscle Training.

Objective: To evaluate the clinical efficacy of discriminative Chinese herbs combined with levator ani muscle training in improving diarrhea-type defecation habit changes and other complications after Dixon surgery for rectal cancer. Methods: 200 patients with Dixon surgery for rectal cancer who were hospitalized in the Department of Gastrointestinal Surgery of Suining Central Hospital from June 2021 to December 2022 were selected, and all patients were divided into 100 cases each in the control and experimental groups by the random number table method. The control group was taken Live Combined Bifidobacterium and Lactobacillus Tablets and Montmorillonite Powder orally after surgery, and the experimental group was treated by discriminative Chinese herbs combined with levator ani muscle training after surgery. Both groups adhered to treatment until 3 months postoperatively. The anal rectal pressure was assessed in both groups at 3 months postoperatively, the anal function and European Organization for Research and Treatment of cancer quality of life questionnaire-colorectal cancer 30 (EORTC QLQ-C30) score before and after treatment were compared between the two groups and the incidence of other perianal complications at 3 months postoperatively was counted. Results: After treatment, the anal canal rest pressure (ARP) in the experimental group (50.80±7.80) mmHg was higher than that in the control group (46.64±7.92) mmHg (P < .05), and the anal canal maximum contraction pressure (AMCP) in the experimental group (89.81±19.39) mmHg was higher than that in the control group (72.02±17.27) mmHg (P < .05). Before treatment, there were 0, 14, 34, 34 and 52 persons with excellent, good, general and poor anal function in the control group and 0, 17, 28 and 55 persons in the experimental group, respectively, after treatment, there were 3, 36, 50, and 11 persons with excellent, good, general and poor anal function in the control group and 12, 44, 42 and 2 persons in the experimental group, respectively, after treatment, the anal function grade improved in both groups, and the experimental group was better than the control group (P < .05). After treatment, the functional modules and overall health scores of the EORTC QLQ-C30 scale increased in both groups compared with those before treatment, and the experimental group was higher than the control group (P < .05), after treatment, the frequency of symptom modules in the experimental group was lower than that before treatment and lower than that in the control group after treatment (P < .05). Within 3 months after surgery, the total incidence of other perianal complications in the control group was 16.00% (16/100), which was higher than the total incidence of other perianal complications in the experimental group 7.00% (7/100) (P < .05). Conclusion: The treatment of diarrhea-type defecation habit changes after Dixon surgery for rectal cancer with discriminative Chinese herbs combined with levator ani muscle training is effective in enhancing patients' anal function, relieving diarrhea symptoms, improving survival quality and reducing the risk of other perianal complications.

Clinical, Functional, and Nutritional Efficacy of a Glutamine-Enriched Oligomeric Diet in Patients with Rectal Cancer.

AIMS: This work aims to evaluate the efficacy of nutritional supplementation with a glutamine-enriched oligomeric diet (GEOD) compared to a standard polymeric diet (SPD) in terms of oncology treatment-related diarrhea (OTRD) (frequency and consistency of stools), gastrointestinal toxicity, and functional and nutritional progress. METHODS: This prospective cohort study compared two groups of patients with rectal cancer in treatment with neoadjuvant chemotherapy and radiotherapy who were at risk of malnutrition. Patients were randomized to receive either 400 ml of GEOD or of SPD from the start of radiotherapy to 30 days after its completion. RESULTS: Eighty patients were recruited, 40 per arm. The GEOD arm had improved stool consistency and a greater reduction in the number of stools compared to the SPD arm (p < 0.001). The relative risk (RR) of developing diarrhea in the GEOD arm was 0.059 (95% CI 0.015-0.229). There was a reduced risk of developing intestinal mucositis in the GEOD arm compared to the SPD arm [RR 0.202 (95% CI 0.102 - 0.399)]. The GEOD arm had greater improvements in functional and nutritional status (p < 0.001). CONCLUSIONS: GEOD had a protective effect in terms of the development of gastrointestinal toxicity associated with chemotherapy and radiotherapy treatment in patients with rectal cancer.

Sacral Neuromodulation in Patients With Low Anterior Resection Syndrome: The SANLARS Randomized Clinical Trial.

BACKGROUND: Sacral neuromodulation might be effective to palliate low anterior resection syndrome after rectal cancer surgery, but robust evidence is not available. OBJECTIVE: To assess the impact of sacral neuromodulation on low anterior resection syndrome symptoms as measured by validated scores and bowel diaries. DESIGN: Randomized, double-blind, 2-phased, controlled, multicenter crossover trial (NCT02517853). SETTINGS: Three tertiary hospitals. PATIENTS: Patients with major low anterior resection syndrome 12 months after transit reconstruction after rectal resection who had failed conservative treatment. INTERVENTIONS: Patients underwent an advanced test phase by stimulation for 3 weeks and received the pulse generator implant if a 50% reduction in low anterior resection syndrome score was achieved. These patients entered the randomized phase in which the generator was left active or inactive for 4 weeks. After a 2-week washout, the sequence was changed. After the crossover, all generators were left activated. MAIN OUTCOME MEASURES: The primary outcome was low anterior resection syndrome score reduction. Secondary outcomes included continence and bowel symptoms. RESULTS: After testing, 35 of 46 patients (78%) had a 50% or greater reduction in low anterior resection syndrome score. During the crossover phase, all patients showed a reduction in scores and improved symptoms, with better performance if the generator was active. At 6- and 12-month follow-up, the mean reduction in low anterior resection syndrome score was -6.2 (95% CI -8.97 to -3.43; p < 0.001) and -6.97 (95% CI -9.74 to -4.2; p < 0.001), with St. Mark's continence score -7.57 (95% CI -9.19 to -5.95, p < 0.001) and -8.29 (95% CI -9.91 to -6.66; p < 0.001). Urgency, bowel emptiness sensation, and clustering episodes decreased in association with quality-of-life improvement at 6- and 12-month follow-up. LIMITATIONS: The decrease in low anterior resection syndrome score with neuromodulation was underestimated because of an unspecific measuring instrument. There was a possible carryover effect in sham stimulation sequence. CONCLUSIONS: Neuromodulation provides symptoms and quality-of-life amelioration, supporting its use in low anterior resection syndrome. See Video Abstract . NEUROMODULACIN SACRA EN PACIENTES CON SNDROME DE RESECCIN ANTERIOR BAJA ENSAYO CLNICO ALEATORIZADO SANLARS: ANTECEDENTES:La neuromodulación sacra podría ser eficaz para paliar el síndrome de resección anterior baja después de la cirugía de cáncer de recto, pero no hay pruebas sólidas disponibles.OBJETIVO:Evaluar el impacto de la neuromodulación sacra en los síntomas del síndrome de resección anterior baja, medido mediante puntuaciones validadas y diarios intestinales.DISEÑO:Ensayo cruzado multicéntrico, controlado, aleatorizado, doble ciego, de dos fases (NCT02517853).LUGARES:Tres hospitales terciarios.PACIENTES:Pacientes con puntuación de resección anterior baja importante, 12 meses después de la reconstrucción del tránsito después de la resección rectal en quienes había fracasado el tratamiento conservador.INTERVENCIONES:Los pacientes se sometieron a una fase de prueba avanzada mediante estimulación durante tres semanas y se les implantó el generador de impulsos si se lograba una reducción del 50% en la puntuación del síndrome de resección anterior baja, ingresando a la fase aleatorizada en la que el generador se dejaba activo o inactivo durante cuatro semanas. Después de observar por 2 semanas, se cambió la secuencia. Después del cruce, todos los generadores quedaron activados.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la reducción de la puntuación del síndrome de resección anterior baja. Los resultados secundarios incluyeron continencia y síntomas intestinales.RESULTADOS:Después de las pruebas, 35 de 46 pacientes (78%) tuvieron una reducción ≥50% en la puntuación del síndrome de resección anterior baja. Durante el cruce, todos los pacientes mostraron una reducción en las puntuaciones y una mejora de los síntomas, con un mejor rendimiento si el generador estaba activo. A los 6 y 12 meses de seguimiento, la reducción media en la puntuación del síndrome de resección anterior baja fue -6,2 (-8,97; -3,43; p < 0,001) y -6,97 (-9,74; -4,2; p < 0,001), con Puntuación de continencia de St. Mark's -7,57 (-9,19; -5,95, p < 0,001) y -8,29 (-9,91; -6,66; p < 0,001). La urgencia, la sensación de vacío intestinal y los episodios de agrupamiento disminuyeron en asociación con una mejora en la calidad de vida a los 6 y 12 meses de seguimiento.LIMITACIONES:La disminución en la puntuación del síndrome de resección anterior baja con neuromodulación se subestimó debido a un instrumento de medición no específico. Posible efecto de arrastre en la secuencia de estimulación simulada.CONCLUSIONES:La neuromodulación mejora los síntomas y la calidad de vida, lo que respalda su uso en el síndrome de resección anterior baja. (Traducción-Dr. Mauricio Santamaria ).

Practice Patterns for Organ Preservation in US Patients With Rectal Cancer, 2006-2020.

Importance: In March 2023, the National Comprehensive Cancer Network endorsed watch and wait for those with complete clinical response to total neoadjuvant therapy. Neoadjuvant therapy is highly efficacious, so this recommendation may have broad implications, but the current trends in organ preservation in the US are unknown. Objective: To describe organ preservation trends among patients with rectal cancer in the US from 2006 to 2020. Design, Setting, and Participants: This retrospective, observational case series included adults (aged ≥18 years) with rectal adenocarcinoma managed with curative intent from 2006 to 2020 in the National Cancer Database. Exposure: The year of treatment was the primary exposure. The type of therapy was chemotherapy, radiation, or surgery (proctectomy, transanal local excision, no tumor resection). The timing of therapy was classified as neoadjuvant or adjuvant. Main Outcomes and Measures: The primary outcome was the absolute annual proportion of organ preservation after radical treatment, defined as chemotherapy and/or radiation without tumor resection, proctectomy, or transanal local excision. A secondary analysis examined complete pathologic responses among eligible patients. Results: Of the 175 545 patients included, the mean (SD) age was 63 (13) years, 39.7% were female, 17.4% had clinical stage I disease, 24.7% had stage IIA to IIC disease, 32.1% had stage IIIA to IIIC disease, and 25.7% had unknown stage. The absolute annual proportion of organ preservation increased by 9.8 percentage points (from 18.4% in 2006 to 28.2% in 2020; P < .001). From 2006 to 2020, the absolute rate of organ preservation increased by 13.0 percentage points for patients with stage IIA to IIC disease (19.5% to 32.5%), 12.9 percentage points for patients with stage IIIA to IIC disease (16.2% to 29.1%), and 10.1 percentage points for unknown stages (16.5% to 26.6%; all P < .001). Conversely, patients with stage I disease experienced a 6.1-percentage point absolute decline in organ preservation (from 26.4% in 2006 to 20.3% in 2020; P < .001). The annual rate of transanal local excisions decreased for all stages. In the subgroup of 80 607 eligible patients, the proportion of complete pathologic responses increased from 6.5% in 2006 to 18.8% in 2020 (P < .001). Conclusions and Relevance: This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy. Given the National Comprehensive Cancer Network endorsement of watch and wait, the increasing trends in organ preservation, and the nearly 3-fold increase in complete pathologic responses, international professional societies should urgently develop multidisciplinary core outcome sets and care quality indicators to ensure high-quality rectal cancer research and care delivery accounting for organ preservation.

Rectal cancer - avoiding surgery?

Nonoperative treatment of rectal cancer is gaining popularity. Several trials recently demonstrated advantages in disease-free survival with total neoadjuvant treatment (TNT) with the addition of the watch and wait (WW) strategy for locally advanced rectal cancer. On longer follow-up, an unexpected increased risk in local recurrence in the TNT group at the RAPIDO trial suggested early surgery for nonresponding tumours. The WW option is globally accepted for a complete clinical response; however, a high rate of regrowth was found in a registry with an increased risk of distant metastases, questioning the deleterious effect of deferral of surgery in this group. The short- and long-term toxic effects of neoadjuvant treatment are costs to consider in the National Comprehensive Cancer Network guidelines compared with the European Society for Medical Oncology guidelines, which favour surgery alone if good mesorectal resection is assured with increasing surgical proficiency adjusted to the precise anatomical location.

Anal Adenocarcinoma Treated in the Era of Total Neoadjuvant Therapy and Nonoperative Management.

BACKGROUND: Anal adenocarcinoma bears a treatment strategy unique to other anal cancers. OBJECTIVE: This study aimed to describe oncologic outcomes of total neoadjuvant therapy followed by watch-and-wait approach for anal adenocarcinoma. DESIGN: Retrospective analysis. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: Patients with anal adenocarcinoma treated between 2004 and 2019 were selected. INTERVENTIONS: Fifty-four patients received neoadjuvant therapy and were divided into 2 groups according to their treatment strategy: total neoadjuvant therapy versus single neoadjuvant modality therapy. MAIN OUTCOME MEASURES: Organ preservation, tumor regrowth, local failure, distant metastasis rates, recurrence-free survival, and overall survival. RESULTS: This study included 70 patients with anal adenocarcinoma. Fifty-four patients (77%) received neoadjuvant therapy, of whom 30 (42%) received total neoadjuvant therapy and 24 (34%) received single neoadjuvant modality. Twenty-three (33%) patients achieved complete clinical response and were managed by watch-and-wait approach. The proportion of patients able to continue to watch-and-wait approach was higher after receiving total neoadjuvant therapy (60%) compared with single neoadjuvant modality therapy (20%; p = 0.004). A tumor regrowth rate of 22% was observed in the total neoadjuvant therapy group. The 5-year overall survival rate was 70% (95% CI, 59%-83%), including 61% (95% CI, 42%-88%) for the total neoadjuvant therapy and 65% (95% CI, 48%-88%) for the single neoadjuvant modality groups. Colostomy was avoided in 50% of patients who received total neoadjuvant therapy and 83% of watch-and-wait patients. Five-year recurrence-free survival rates of 55% (95% CI, 39%-79%) and 30% (95% CI, 15%-58%) were observed in the total neoadjuvant therapy and single neoadjuvant modality groups. LIMITATIONS: Retrospective nature. CONCLUSIONS: This is the first report in the literature describing the safety and feasibility of nonoperative management for anal adenocarcinoma. Anal adenocarcinoma treated with total neoadjuvant therapy and nonoperative management achieve regrowth rates comparable to those observed in rectal cancer, with oncologic outcomes similar to those of traditional treatment strategies. See Video Abstract . ADENOCARCINOMA ANAL TRATADO EN LA ERA DE LA TERAPIA NEOADYUVANTE TOTAL Y EL TRATAMIENTO NO QUIRRGICO: ANTECEDENTES:El adenocarcinoma anal conlleva una estrategia de tratamiento único para otros cánceres anales.OBJETIVO:Describir los resultados oncológicos de la terapia neoadyuvante total seguida de observar y esperar en adenocarcinoma anal.DISEÑO:Análisis retrospectivo.AJUSTE:Este estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Se seleccionaron pacientes con adenocarcinoma anal tratados entre 2004-2019.INTERVENCIONES:Cincuenta y cuatro pacientes recibieron terapia neoadyuvante y se dividieron en dos grupos según su estrategia de tratamiento: terapia neoadyuvante total versus terapia de modalidad neoadyuvante única.PRINCIPALES MEDIDAS DE RESULTADO:Preservación de órganos, recurrencia tumoral, falla local, tasas de metástasis a distancia, libre de recurrencia y supervivencia general.RESULTADOS:El estudio incluyó a 70 pacientes con adenocarcinoma anal. Cincuenta y cuatro pacientes (77%) recibieron terapia neoadyuvante, de los cuales 30 (42%) recibieron terapia neoadyuvante total y 24 (34%) recibieron modalidad neoadyuvante única. Veintitrés (33%) pacientes presentaron una respuesta clínica completa y fueron tratados con vigilancia y espera. La proporción de pacientes capaces de continuar en observar y esperar fue mayor después de recibir terapia neoadyuvante total (60%) en comparación con la terapia de modalidad neoadyuvante única (20%) ( p = 0,004). Se observó una tasa de recurrencia tumoral del 22% en el grupo de terapia neoadyuvante total. La tasa de supervivencia general a 5 años fue del 70% (IC95% 59%-83 %), incluido el 61% (IC95% 42%-88%) para la terapia neoadyuvante total y el 65% (IC95% 48%-88%) para grupos de modalidad neoadyuvante única. Se evitó la colostomía en el 50% de los pacientes que recibieron terapia neoadyuvante total y el 83% de los pacientes en observar y esperar. Se observaron tasas de supervivencia libre de recurrencia a cinco años del 55% (IC95% 39%-79%) y del 30% (IC95% 15%-58%) en los grupos de terapia neoadyuvante total y modalidad neoadyuvante única, respectivamente.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:Este es el primer informe en la literatura que describe la seguridad y viabilidad del tratamiento no quirúrgico del adenocarcinoma anal. El adenocarcinoma anal tratado con terapia neoadyuvante total y manejo no quirúrgico logra tasas de recurrencia comparables a las observadas en el cáncer de recto, con resultados oncológicos similares a las estrategias de tratamientos tradicionales. (Traducción-Dr. Fidel Ruiz Healy ).

Tumor Marker Trajectories and Survival Analysis in Patients With Normal Carcinoembryonic Antigen Ranges After Colorectal Cancer Resection.

BACKGROUND: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA. OBJECTIVE: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection. DESIGN: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018. SETTINGS: Retrospective cohort study. PATIENTS: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded. INTERVENTIONS: Standard curative radical resection was performed. MAIN OUTCOME MEASURES: Ten-year overall survival and disease-free survival were analyzed. RESULTS: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups. LIMITATIONS: Retrospective design. CONCLUSIONS: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract. TRAYECTORIAS DE MARCADORES TUMORALES Y ANLISIS DE SUPERVIVENCIA EN PACIENTES CON RANGOS NORMALES DE ANTGENO CARCINOEMBRIONARIO POSTERIOR A RESECCIN DE CNCER COLORRECTAL: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto ).

Concordance of MRI With Pathology for Primary Staging of Rectal Cancer in Routine Clinical Practice: A Single Institution Experience.

PURPOSE: MRI is the preferred imaging modality for primary staging of rectal cancer, used to guide treatment. Patients identified with clinical stage I disease receive upfront surgical resection; those with clinical stage II or greater undergo upfront neoadjuvant therapy. Although clinical under-/over-staging may have consequences for patients and presents opportunities for organ preservation, the correlation between clinical and pathologic staging in routine clinical practice within a single institute has not been fully established. METHODS: This retrospective, Institutional Review Board-approved study, conducted at a National Cancer Institute-Designated Comprehensive Cancer Center with a multi-disciplinary rectal cancer disease center, included patients undergoing rectal MRI for primary staging January 1, 2018-August 30, 2020. Data collection included patient demographics, initial clinical stage via MRI report, pathologic diagnosis, pathologic stage, and treatment. The primary outcome was concordance of overall clinical and pathologic staging. Secondary outcomes included reasons for mismatched staging. RESULTS: A total 105 rectal adenocarcinoma patients (64 males, mean age 57 ± 12.7 years) had staging MRI followed by surgical resection. A total of 28 patients (27%) had mismatched under-/over- staging. Ten patients (10%) were understaged with mismatched T stage group (clinical stage I, pathologic stage II), five (5%) were understaged with mismatched N stage group (clinical stage I, pathologic stage III), and 13 (12%) were overstaged (clinical stage II-III, pathologic stage 0-I). Treatment matched concordance between clinical and pathologic stages was 86%. CONCLUSION: MRI for primary rectal cancer staging has high concordance with pathology. Future studies to assess strategies for reducing clinically relevant understaging would be beneficial.

Transanal minimally invasive surgery for benign and malignant rectal lesions: midterm outcomes from a tertiary center.

BACKGROUND: Although transanal minimally invasive surgery (TAMIS) for rectal neoplasia has gained wide acceptance, the mid-term and long-term outcomes are not widely reported in the literature. OBJECTIVE: Describe the mid-term outcomes of patients who underwent TAMIS for benign and malignant rectal lesions in a single center. DESIGN: Retrospective cohort study. SETTINGS: Tertiary referral center. PATIENTS AND METHODS: Demographic, clinical, and oncological outcomes of patients who underwent TAMIS between January 2015 and December 2022 were prospectively collected. The indication for TAMIS was based on the National Comprehensive Cancer Network guidelines. The follow up for the cancer patients included clinical examination, tumor markers every 6 months and MRI rectum at the end of one year. In addition, colonoscopy and CT scan at years one and three and a final CT scan and colonoscopy at year five. MAIN OUTCOME MEASURES: Mid-term oncological and clinical outcome. RESULTS: Thirty elective TAMIS procedures included adenocarcinoma for 33.3% (n=10) of the patients, 20% (n=6) neuroendocrine tumor and the 40% (n=12) were adenomatous lesions. Negative resection margins were achieved in all malignant lesions. Perioperative complications occurred in 2 patients (6.6%), one patient had breaching into the peritoneal cavity, and postoperative hypotension occurred in another patient. The median follow-up time was 23 months (range: 5-72 months). Two patients with adenoma and positive margins developed recurrent adenoma (6.6%) and one patient with initial polypectomy biopsy of adenocarcinoma, had TAMIS with histopathology of adenoma and distant metastasis had developed. CONCLUSIONS: TAMIS for local excision of rectal neoplasia is a valid option with favorable mid-term outcomes provided there is adherence to careful selection criteria. LIMITATIONS: Retrospective nature and small number of the patients.

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.