Tumour deposits are independently associated with recurrence in colon cancer.

AIM: Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. METHOD: Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. RESULTS: Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. CONCLUSION: Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.

Validation of a Clinical Calculator Predicting Freedom From Colon Cancer Recurrence After Surgery on the Basis of Molecular and Clinical Variables.

BACKGROUND: The Memorial Sloan Kettering clinical calculator for estimating the likelihood of freedom from colon cancer recurrence on the basis of clinical and molecular variables was developed at a time when testing for microsatellite instability was performed selectively, based on patient age, family history, and histologic features. Microsatellite stability was assumed if no testing was done. OBJECTIVE: This study aimed to validate the calculator in a cohort of patients who had all been tested for microsatellite instability. DESIGN: Retrospective cohort analysis. SETTINGS: Comprehensive cancer center. PATIENTS: This study included consecutive patients who underwent curative resection for stage I, II, or III colon cancer between 2017 and 2019. INTERVENTION: Universal testing of mircrosatellite phenotype in all cases. MAIN OUTCOME MEASURES: The calculator's predictive accuracy was assessed using the concordance index and a calibration plot of predicted versus actual freedom from recurrence at 3 years after surgery. For a secondary sensitivity analysis, the presence of a tumor deposit(s) (disease category N1c) was considered equivalent to one positive lymph node (category N1a). RESULTS: With a median follow-up of 32 months among survivors, the concordance index for the 745 patients in the cohort was 0.748 (95% CI, 0.693-0.801), and a plot of predicted versus observed recurrences approached the 45° diagonal, indicating good discrimination and calibration. In the secondary sensitivity analysis for tumor deposits, the concordance index was 0.755 (95% CI, 0.700-0.806). LIMITATIONS: This study was limited by its retrospective, single-institution design. CONCLUSIONS: These results, based on inclusion of actual rather than imputed microsatellite stability status and presence of tumor deposits, confirm the predictive accuracy and reliability of the calculator. See Video Abstract . VALIDACIN DE UNA CALCULADORA CLNICA QUE PREDICE LA AUSENCIA DE RECURRENCIA POSTQUIRURGICA DEL CNCER DE COLON SOBRE LA BASE DE VARIABLES MOLECULARES Y CLNICAS: ANTECEDENTES:La calculadora clínica del Memorial Sloan Kettering para la estimación de la probabilidad de ausencia de recurrencia del cáncer de colon sobre la base de variables clínicas y moleculares, se desarrolló en un momento en que las pruebas para la inestabilidad de microsatélites se realizaban de forma selectiva, basadas en la edad del paciente, los antecedentes familiares y las características histológicas. Se asumía la estabilidad micro satelital si no se realizaba ninguna prueba.OBJETIVO:El objetivo de este estudio fue validar la calculadora en una cohorte de pacientes a los que se les había realizado la prueba de inestabilidad de microsatélites.DISEÑO:Análisis de cohorte retrospectivo.AJUSTE:Centro integral de cáncer.PACIENTES:Pacientes consecutivos con cáncer de colon que fueron sometidos a resección curativa por cáncer de colon en estadios I, II o III entre los años 2017 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:La precisión predictiva de la calculadora fue evaluada mediante el índice de concordancia y un gráfico de calibración de la ausencia de recurrencia predecida versus la real a los 3 años tras la cirugía. A los efectos de un análisis secundario de sensibilidad, la presencia de depósito(s) tumoral(es) (categoría de enfermedad N1c) se consideró equivalente a un ganglio linfático positivo (categoría N1a).RESULTADOS:Con una mediana de seguimiento de 32 meses entre los supervivientes, el índice de concordancia para los 745 pacientes de la cohorte fue de 0,748 (intervalo de confianza del 95 %, 0,693 a 0,801), y una gráfica de recurrencias previstas versus observadas se acercó a la diagonal de 45°, indicando una buena discriminación y calibración. En el análisis secundario de sensibilidad para depósitos tumorales, el índice de concordancia fue de 0,755 (intervalo de confianza del 95 %, 0,700 a 0,806).LIMITACIONES:Diseño retrospectivo, institución única.CONCLUSIONES:Estos resultados, basados en la inclusión real del estado de estabilidad de microsatélites en lugar de imputado y la presencia de depósitos tumorales, confirman la precisión predictiva y la confiabilidad de la calculadora. (Traducción-Dr Osvaldo Gauto ).

An update on the global trends in the burden of primary liver cancers.

Liver cancer (LC) remains one of the major causes of cancer-related mortality worldwide. The Incidence, mortality, and prevalence associated with primary LCs were analyzed over the past decade, using GLOBOCAN 2012 and 2020, to understand the trends related to geographic and socioeconomic factors. While total cases of primary LCs continue to rise, global rates of LC incidence and mortality are slowing, mostly driven by changes seen in historically endemic regions.

Lymph Node Metastases and Associated Recurrence-Free Survival in Microsatellite Stable and Unstable Colon Cancer.

BACKGROUND: In contrast to microsatellite stable (MSS) colon cancer, predictors of lymph node metastases and their association with recurrence are not well-defined in microsatellite instability (MSI) colon cancer. METHODS: A cohort of nonmetastatic colon cancer patients undergoing surgery between 2015 and 2021 were evaluated for predictors of lymph node metastases (LNMs) and their association with recurrence-free survival (RFS). RESULTS: Of 1466 patients included in the analyses, 361 (25 %) had MSI. Compared with MSS, MSI was associated with earlier stage, fewer LNMs in the patients with N1 or N2 disease, and fewer high-risk features. Compared with the T3-T4 MSS patients, the odds ratios for LNM were 0.52 (95% confidence interval [CI], 0.38-0.71) for the T3-T4 MSI patients, 0.27 (95% CI, 0.38-0.71) for the T1-T2 MSS patients, and 0.15 (95 % CI, 0.08-0.26) for the T1-T2 MSI patients. In both groups, LNMs were associated with T category, patient age, and venous, lymphatic, or perineural invasion. In the MSS patients, LNMs were additionally associated with patient sex and histologic grade. Compared with the MSS patients, the MSI patients with N0 and N1 disease had a better 3-year RFS. However, the MSI patients with N2 disease had a lower rate of 3-year RFS than the MSS patients (hazard ratio, 19.75 vs 4.49). CONCLUSIONS: In MSI colon cancer, LNMs are 50 % less prevalent, but the factors associated with LNM are like those in MSS colon cancer. The improved prognosis traditionally associated with early-stage MSI colon cancers dissipates with four or more LNMs. These findings should be taken into consideration by clinicians selecting the most appropriate course of treatment for MSI colon cancer.

Younger Patients with Colon Cancer are More Likely to Experience Financial Toxicity Than Older Patients.

BACKGROUND: The incidence of young-onset colon cancer is increasing. This study investigated the extent to which financial hardships associated with colon cancer care are associated with patient age. METHODS: A consecutive sample of patients with non-metastatic colon cancer who underwent resection at a comprehensive cancer center between 2017 and 2019 were retrospectively enrolled from a clinical database. Patients with one or more of the following events associated with their colon cancer care were categorized as having experienced financial toxicity: two or more bills sent to collections, application for a payment plan, settlement, bankruptcy, or enrollment in a financial assistance program. RESULTS: Of 764 patients identified, 157 (21 %) experienced financial toxicity. In a univariable analysis, financial toxicity was significantly associated with younger age, female sex, nonpartnered marital status, and median income by ZIP code area (p < 0.05). A multivariable analysis showed that with each 10-year decrease in patient age, the odds of financial toxicity increased by 30 % (odds ratio [OR], 1.30; 95 % confidence interval [CI], 1.14-1.48). With each $50,000 decrease in median income by ZIP code area, the odds of financial toxicity increased by 35 % (OR, 1.35; 95 % CI, 1.05-1.74). CONCLUSIONS: Younger patients with colon cancer are at greater risk for financial toxicity than older patients. As this population continues to grow, so will the need for timely and effective financial support mechanisms.

Role of dual anti-HER2 therapy before liver resection for rectal metastases.

This case presents a patient with a diagnosis of metastatic colon cancer on second-line chemotherapy. He demonstrated increased HER2 expression and was placed on dual HER2 antagonists. The patient had excellent repose and was ultimately able to undergo definitive liver resection for cure. We highlight the evolving use targeted therapy in metastatic colorectal cancer to not only extend progression-free survival, but act as a bridge to surgery.

Intratumoral T-cell repertoires in DNA mismatch repair-proficient and -deficient colon tumors containing high or low numbers of tumor-infiltrating lymphocytes.

Colon tumors with deficient DNA mismatch repair (dMMR) are generally infiltrated by T cells more densely than tumors with proficient mismatch repair (pMMR). However, high numbers of tumor-infiltrating lymphocytes (TILs) are found in select pMMR tumors, and low numbers of TILs are seen in select dMMR tumors. In this study, we compared T-cell repertoires in 20 pMMR and 27 dMMR colon tumors with high and low TIL counts. We found that T cells in dMMR tumors are more clonal and their repertoire is less rich compared with T cells in pMMR tumors. In the dMMR group, T cells in TIL-high tumors were more clonal and their repertoire was less rich compared with T cells in TIL-low tumors, but in the pMMR group, T-cell diversity in TIL-high tumors was comparable to T-cell diversity in TIL-low tumors. These findings suggest that T cells clonally expand in dMMR tumors, possibly in response to MMR deficiency-induced tumor neoantigens.

Liver resection after Y-90 radioembolization: a systematic review and meta-analysis of perioperative morbidity and mortality.

BACKGROUND: Data on morbidity and mortality following liver resection after radioembolization (Y90) are limited and controversial. Therefore, the perioperative morbidity and mortality of liver resections after Y90 treatment were investigated with systematic review and meta-analysis. METHODS: A PubMed search was conducted to identify studies of liver resection after previous Y90 treatment. Systematic review and meta-analysis for perioperative morbidity and mortality were perfomed using the 2009 PRISMA guidelines and STATA 16.1 software. RESULTS: A total of 16 studies reporting on 276 patients who underwent liver resection after Y90 met the inclusion criteria and were included in the meta-analysis. Meta-analysis of 30-day mortality rates yielded pooled mortality of 0.5% (95% CI 0.0-3.2%). Six studies (155 patients) reported a pooled 90-day mortality of 3.0% (95% CI 0.3-7.4%). The median time to resection after Y90 ranged from 2 to 12.5 months in various studies. In all studies where the median resection was undertaken eight or more months after Y90, zero 30-day mortality was reported. A meta-analysis of overall grade 3 or higher morbidity noted a rate of 26% (95% CI 16-37%). CONCLUSIONS: Liver resection after Y90 may be safe in very well selected patients. Delaying resection after Y90 may further decrease mortality.

Safety of High-Flow Nasal Cannula Outside the ICU for Previously Healthy Children With Bronchiolitis.

BACKGROUND: High-flow nasal cannula (HFNC), a form of noninvasive respiratory support, is effective for the treatment of respiratory distress in ICUs. Although HFNC has been used outside of the ICU, there is little research that examines its safety in this less-monitored setting. METHODS: Children ≤ 24 months old admitted with bronchiolitis to a pediatric floor at a tertiary care center from April 1 2013, to March 31 2015, were identified by using standard diagnostic codes. Exclusion criteria were concomitant pneumonia or complex comorbidities. Demographic and clinical characteristics were abstracted. Outcomes included transfer to the ICU, higher levels of respiratory support, intubation, pneumothorax, or aspiration events. RESULTS: Eighty children admitted with bronchiolitis who were treated with HFNC while on the pediatric floor were examined. The median age was 4.6 months, 45% were girls, and the majority were either Hispanic (41%) or black (36%). Flow ranged from 3 to 10 L/min. Thirty-three subjects (41% of the sample) required subsequent transfer to the ICU. No children were intubated or developed a pneumothorax. Eighty-three percent were fed while on HFNC. No children had an aspiration event. CONCLUSIONS: HFNC may be a safe modality of respiratory support outside of the ICU for children ages ≤ 24 months with bronchiolitis and without comorbidities up to a maximum flow of 10 L/min. There were no adverse events among the subjects who were fed while on HFNC.

Risk Factors for Respiratory Decompensation Among Healthy Infants With Bronchiolitis.

BACKGROUND: Although most children with bronchiolitis only require supportive care, some decompensate and require ventilatory support. We examined predictors of respiratory decompensation among hospitalized children to identify which patients may benefit from expectant monitoring. METHODS: We examined children ≤24 months old with bronchiolitis admitted to the general infant and toddler floor. Children with pneumonia or comorbidities were excluded. Demographic and clinical characteristics were abstracted from a clinical database and medical records. Respiratory decompensation was defined as the need for initiating high-flow nasal cannula oxygen, continuous positive airway pressure, nasal intermittent mandatory ventilation, bilevel positive airway pressure, or intubation. A multivariable logistic regression model was constructed to identify independent predictors of respiratory decompensation. RESULTS: A total of 1217 children were included. The median age was 6.9 months, 41% were girls, 49% were Hispanic, 21% were black, and 18% were premature. Significant independent predictors of respiratory decompensation were age ≤3 months (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.09-5.07), age 3 to 6 months (OR: 1.76; 95% CI: 1.04-3.0), black race (OR: 1.94; 95% CI: 1.27-2.95), emergency department hypoxemia (OR: 2.34; 95% CI: 1.30-4.21), and retractions or accessory muscle use (OR: 2.26; 95% CI: 1.48-3.46). Children with 0 of 4 predictors were found to have a low risk of decompensation (3%). CONCLUSIONS: Young age, black race, emergency department hypoxemia, and retractions or accessory muscle use were associated with respiratory decompensation in children with bronchiolitis. These factors should be considered at presentation, as they identify children who require a higher level of respiratory monitoring and support and others who may not benefit.