Utility of the revised FIGO2023 staging with molecular classification in endometrial cancer.

OBJECTIVES: Molecular classification was introduced in endometrial cancer staging following the transition of the International Federation of Gynecology and Obstetrics (FIGO) 2008 to FIGO2023. In the early stages, p53 abnormal endometrial carcinoma with myometrial involvement was upstaged to stage IICm, in addition to the downstaging of POLE mutation endometrial cancer to stage IAm. This study compared the goodness of fit and discriminatory ability of FIGO2008, FIGO2023 without molecular classification (FIGO2023), and FIGO2023 with molecular classification (FIGO2023m); no study has been externally validated to date. METHODS: The study included 265 patients who underwent initial surgery at the National Cancer Center Hospital between 1997 and 2019 and were pathologically diagnosed with endometrial cancer. The three classification systems were compared using Harrell's concordance index (C-index), Akaike information criterion (AIC), and time-dependent receiver operating characteristic (ROC) curves. A higher C-index score and a lower AIC value indicated a more accurate model. RESULTS: Among the three classification systems, FIGO2023m had the lowest AIC value (FIGO2023m: 455.925; FIGO2023: 459.162; FIGO2008: 457.901), highest C-index (FIGO2023m: 0.768; FIGO2023: 0.743; FIGO2008: 0.740), and superior time-dependent ROC curves within 1 year after surgical resection. In the stage IIIC, patients with p53 abnormalities had considerably lower 5-year overall survival than those with a p53 wild-type pattern (24.3% vs. 83.7%, p = 0.0005). CONCLUSIONS: FIGO2023m had the best discriminatory ability compared with FIGO2008 and FIGO2023. Even in advanced stages, p53 status was a poor prognostic factor. When feasible, molecular subtypes can be added to the staging criteria to allow better prognostic prediction in all stages.

Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex.

Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target.

Risk of non-colorectal cancer-related death in elderly patients with the disease: A comparison of five preoperative risk assessment indices.

BACKGROUND: A considerable number of elderly patients with colorectal cancer (CRC) die of non-CRC-related causes. The Controlling Nutritional Status (CONUT) score, American Society of Anesthesiologists Physical Status classification, Charlson Comorbidity Index, National Institute on Aging, and National Cancer Institute Comorbidity Index, and Adult Comorbidity Evaluation-27 score are all known predictors of survival in patients with CRC. However, the utility of these indices for predicting non-CRC-related death in elderly CRC patients is not known. METHODS: The study population comprised 364 patients aged 80 years or more who received curative resection for stage I-III CRC between 2000 and 2016. The association of each index with non-CRC-related death was compared by competing-risks analysis such as the cumulative incidence function and proportional subdistribution hazards regression analysis as well as time-dependent receiver-operating characteristic (ROC) analysis. RESULTS: There were 85 deaths (40 CRC-related and 45 non-CRC-related) during a median observation period of 53.2 months. Cumulative incidence function analysis identified CONUT score as the most suitable for risk stratification for non-CRC-related death. In proportional subdistribution hazards regression, risk of non-CRC-related death increased significantly as CONUT score worsened (2/3/4 vs. 0/1, hazard ratio 1.73, 95% confidence interval [CI] 0.91-3.15; ≥5 vs. 2/3/4, hazard ratio 2.71, 95% CI 1.08-6.81). Time-dependent ROC curve analysis showed that CONUT score were consistently superior to other indices during the 5-year observation period. CONCLUSIONS: The majority of deaths in elderly patients with CRC were not CRC-related. CONUT score was the most useful predictor of non-CRC-related death in these patients.

Motile sperm domain containing 1 is upregulated by the Wnt/ß-catenin signaling pathway in colorectal cancer.

Aberrant activation of the Wnt/ß-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and the present study focused on motile sperm domain containing 1 (MOSPD1). Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumor cells from colorectal cancer tissues compared with in non-tumor cells. Using ChIP-seq data and the JASPAR database, the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/ß-catenin signaling pathway were searched, and a region containing three putative TCF-binding motifs in the 3'-flanking region was identified. Additional analyses using reporter assay and ChIP-quantitative PCR suggested that this region harbors enhancer activity through an interaction with transcription factor 7 like 2 (TCF7L2) and ß-catenin. In addition, chromatin conformation capture assay revealed that the 3'-flanking region interacts with the MOSPD1 promoter. These data suggested that MOSPD1 was regulated by the ß-catenin/TCF7L2 complex through the enhancer element located in the 3'-flanking region. These findings may be helpful for future studies regarding the precise regulatory mechanisms of MOSPD1.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

Evaluation of Recurrence Risk After Curative Resection for Patients With Stage I to III Colorectal Cancer Using the Hazard Function: Retrospective Analysis of a Single-institution Large Cohort.

OBJECTIVE: This study aimed to investigate transitions of recurrence hazard and peak recurrence time in patients with nonmetastatic CRC using the hazard function. SUMMARY OF BACKGROUND DATA: A postoperative surveillance period of 5 years is consistent across major guidelines for patients with nonmetastatic CRC, but surveillance intervals differ. Estimates of instantaneous conditional recurrence rate can help set appropriate intervals. METHODS: The study population consisted of 4330 patients with stage I to III CRC who underwent curative resection at the National Cancer Center Hospital between January 2000 and December 2013. Hazard rates of recurrence were calculated using the hazard function. RESULTS: Recurrence rates in patients with stage I, II, and III CRC were 4% (50/1432), 11% (136/1231), and 25% (424/1667), respectively. The hazard curve for stage I was relatively flat and hazard rates were consistently low (<0.0015) for 5 years after surgery. The hazard curve for stage II had a peak hazard rate of 0.0046 at 13.7 months, after which the curve had a long hem to the right. The hazard curve for stage III had an earlier and higher peak than that of stage II (0.0105 at 11.6 months), with a long hem to the right. CONCLUSIONS: Changes in recurrence hazard for CRC patients varied considerably by stage. Our findings suggest that short-interval surveillance might be unnecessary for stage I patients for the first 3 years after surgery, whereas short-interval surveillance for the first 3 years should be considered for stage III patients.

Severe thrombocytopenia induced by chemotherapy after total gastrectomy: A report of three cases.

Pancytopenia associated with vitamin B12 and folic acid deficiency has been reported in patients who have undergone total gastrectomy. Therefore, myelosuppression due to chemotherapy following total gastrectomy is considered to be more serious. We encountered three cases of severe thrombocytopenia in patients who received chemotherapy after total gastrectomy. The lowest platelet levels in these patients were 1.7 × 104/mm3, 2.3 × 104/mm3, and 0.9 × 104/mm3, respectively. None of the patients presented with vitamin B12 deficiency, and one patient presented with folic acid deficiency. The association between serum vitamin levels and chemotherapy-related adverse events is controversial. Since folic acid has a shorter half-life (6 hours) and cannot accumulate in the body, unlike vitamin B12 that is stored for a long time in the liver, folic acid deficiency is suspected to be associated with thrombocytopenia induced by post-total gastrectomy chemotherapy. However, serum folic acid levels fluctuate depending on the timing of evaluation and require a few days to evaluate. In conclusion, patients who undergo chemotherapy after total gastrectomy should be monitored for severe thrombocytopenia but serum vitamin B12 levels are not necessarily clinically important. By measuring serum folic acid levels at appropriate times, folic acid deficiency may prove to be a reference for predicting severe thrombocytopenia.

Chemotherapy-related dysphonia: Similar and differentiating features of six cases.

Dysphonia has been reported with anti-angiogenic chemotherapy agents. Dysphonia in patients with cancer receiving chemotherapy tends to be overlooked in clinical practice since it is non-life-threatening. However, it reduces quality of life. Although inhibition of vascular endothelial growth factor receptor is the reported mechanism of dysphonia, it has not been elucidated. We report 6 cases of patients with dysphonia suspected to be due to panitumumab and nivolumab that have not been reported previously. Peripheral edema, a factor in dysphonia, can be seen with aflibercept, bevacizumab, panitumumab, and nivolumab. Therefore, chemotherapy drugs with peripheral edema may be related to dysphonia.

Association between thiamine decrease and neuropsychiatric symptoms in gastrointestinal and hematological cancer patients receiving chemotherapy.

BACKGROUND: Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy. METHOD: We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy. RESULTS: Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p < 0.001, odds ratio = 0.040, 95% confidence interval [CI]: 0.010-0.163). The Mann-Whitney U test showed that patients with neuropsychiatric symptoms had significantly lower serum thiamine levels (19.5 ± 5.4 ng/mL, n = 39) than patients without neuropsychiatric symptoms (31.9 ± 14.2 ng/mL, n = 48) (p = 0.001). In hematological cancer patients, serum thiamine levels gradually declined after chemotherapy, with the lowest levels at 5-8 weeks (23.5 ± 7.6 ng/mL, P = 0.035 vs. 0 weeks, Wilcoxon rank sum test). CONCLUSION: Our study showed that a decrease in serum thiamine levels can be a risk factor for neuropsychiatric symptoms, and chemotherapy can lead to a decrease in serum thiamine levels.

Comparison of model fit and discriminatory ability of the 8th edition of the tumor-node-metastasis classification and the 9th edition of the Japanese classification to identify stage III colorectal cancer.

BACKGROUND: The most widely accepted staging system for colorectal cancer (CRC) is the tumor-node-metastasis (TNM) classification. In Japan, the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC) system is used. The two systems differ mainly in relation to tumor deposits (TD) and metastasis in the regional lymph nodes along the main feeding arteries and lateral pelvic lymph nodes (N3). Here, we investigated the prognostic ability of the two systems for stage III CRC. METHODS: We reviewed 696 consecutive patients who underwent curative resection of stage III CRC at the National Cancer Center Hospital between May 2007 and April 2014. We examined the clinicopathological features of CRC and predicted overall survival (OS) and relapse-free survival (RFS) according to the 8th TNM and 9th JCCRC systems. The systems were compared using Akaike's information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver-operating characteristic (ROC) curves. RESULTS: The 9th JCCRC system was more clinically effective according to AIC (OS, 1199 vs. 1206; RFS, 2047 vs. 2057), showed better discriminatory ability according to the C-index (OS, 0.65 vs. 0.62; RFS, 0.62 vs. 0.58), and its time-dependent ROC curve was superior compared with the 8th TNM system. CONCLUSION: These results suggest that the 9th JCCRC system has superior discriminative ability to the 8th TNM system, because the 9th JCCRC accounts for the presence of TD and N3 disease, which were both significant predictors of poor prognosis. Reconsidering the clinical value of these two factors in the TNM system could improve its clinical significance.

Preoperative Nutritional Scores as Host-Related Prognostic Factors for Both Overall Survival and Postoperative Complications in Patients With Stage II to III Colorectal Cancer.

BACKGROUND: In the TNM eighth edition, nutritional status and inflammatory scores are newly described as host-related prognostic factors for esophageal cancer, hepatocellular carcinoma, and pancreatic cancer. However, only age and race are listed as host-related prognostic factors for colorectal cancer. OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of nutritional and inflammatory scores for postoperative outcomes in patients with colorectal cancer. DESIGN: This was a retrospective study using a database that prospectively collects data. SETTINGS: The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: Study participants were 1880 consecutive patients with stage II to III colorectal cancer who underwent curative resection at the National Cancer Center Hospital between 2004 and 2012. Two nutritional scores (prognostic nutritional index and controlling nutritional status score) and 4 inflammatory scores (modified Glasgow prognostic score, neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and C-reactive protein:albumin ratio) were calculated. MAIN OUTCOME MEASURES: Correlations of nutritional scores and inflammatory scores with overall survival and postoperative complications were measured. RESULTS: After adjusting for key clinical and pathologic factors by multivariable analysis, 2 nutritional scores (prognostic nutritional index and controlling nutritional status score) and 2 inflammatory scores (neutrophil:lymphocyte ratio and C-reactive protein:albumin ratio) were independent prognostic factors for overall survival. With respect to discriminative ability, time-dependent receiver operating characteristic curves and Harrell concordance index revealed that prognostic nutritional index and controlling nutritional status score were superior to the 4 inflammatory scores for predicting overall survival. Multivariable logistic regression analyses also revealed that prognostic nutritional index, controlling nutritional status score, and C-reactive protein:albumin ratio were independent predictors for postoperative complications. LIMITATIONS: The retrospective design of the study was a limitation. CONCLUSIONS: Preoperative nutritional scores are promising host-related prognostic factors for overall survival and postoperative complications in patients with stage II and III colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B587. EVALUACIN DE SCORE NUTRICIONALES PREOPERATORIOS COMO FACTORES PRONSTICOS PARA SOBREVIDA Y COMPLICACIONES POSTOPERATORIAS EN PACIENTES CON CANCER COLORECTAL ETAPA II Y III: ANTECEDENTES:En las últimas etapificaciones T-N-M, tanto el estado nutricional como inflamatorio han sido descritos como factores pronósticos en cáncer de esófago, hepático y pancreático. Sin embargo en cáncer colorectal solo la edad y la raza son enumerados como factores pronósticos.OBJETIVO:Evaluar la importancia pronóstica de los scores nutricionales e inflamatorias para los resultados posoperatorios en pacientes con cáncer colorrectal.DISEÑO:Estudio retrospectivo utilizando una base de datos.AJUSTE:Centro oncológico teciario en Japón.PACIENTES:Fueron incluidos en el estudio 1880 pacientes, consecutivos, con cancer colorectal etapa II y III sometidos a reseeción curativa en el National Cancer Center Hospital entre 2004 y 2012. Se aplicaron dos scores: nutricional (índice nutricional pronóstico y puntuación del estado nutricional) e inflamatorias (Glasgow modificada, proporción de neutrófilos a linfocitos, de plaquetas a linfocitos y de proteína C reactiva a albúmina).PRINCIPALES MEDIDAS DE RESULTADO:Evaluar scores nutricional e inflamatorio con sobrevida y complicaciones postoperatoria.RESULTADOS:Después de ajustar los factores clínicos y patológicos clave mediante análisis multivariable, dos scores nutricionales (índice nutricional pronóstico y puntuación del estado nutricional de control) y dos inflamatorias (proporción de neutrófilos a linfocitos y proporción de proteína C reactiva a albúmina) fueron pronósticos independientes factores para la sobrevida. Con respecto a la capacidad discriminativa, las curvas de características operativas del receptor, dependientes del tiempo y el índice de concordancia de Harrell, revelaron que el índice nutricional pronóstico y del estado nutricional de control eran superiores a las cuatro inflamatorias para predecir la sobrevida general. Los análisis de regresión logística multivariable también revelaron que el índice nutricional pronóstico, el estado nutricional de control y la relación proteína C reactiva / albúmina fueron predictores independientes de complicaciones postoperatorias.LIMITACIONES:Estudio de tipo retrospectivo.CONCLUSIONES:Los scores nutricionales preoperatorias son factores pronósticos prometedores relacionados con la sobrevida y las complicaciones postoperatorias en pacientes con cáncer colorrectal en estadio II y III. Consulte Video Resumen en http://links.lww.com/DCR/B587.

Recurrence hazard of rectal cancer compared with colon cancer by adjuvant chemotherapy status: a nationwide study in Japan.

BACKGROUND: Previous studies of stage III colon cancer using the hazard function demonstrated that the risk of recurrence in patients with adjuvant chemotherapy never exceeded that of patients without adjuvant chemotherapy. However, it is unclear whether the same can be said for rectal cancer patients and whether adjuvant chemotherapy reduces recurrence. This study aimed to compare the recurrence hazard of stage III rectal cancer with that of colon cancer by adjuvant chemotherapy status using the hazard function, a method that allows for the assessment of instantaneous risk of recurrence over time. METHODS: This retrospective nationwide study consisted of 10,356 patients with stage III colorectal cancer who underwent curative resection between January 1997 and December 2012 in Japan. Recurrence hazards of rectal and colon cancers were compared between patients treated with adjuvant chemotherapy and those who were not. Analyses in which recurrence was divided into local and distant recurrence were also performed. RESULTS: The hazard rate of recurrence in rectal cancer patients with adjuvant chemotherapy was consistently lower throughout the follow-up period, and the peak time of recurrence later, compared to patients without adjuvant chemotherapy (peaked at 15.7 vs. 7.1 months). Adjuvant chemotherapy also strongly suppressed distant recurrence but not local recurrence in rectal cancer patients. Similar results were observed in colon cancer patients. CONCLUSIONS: Our results using nationwide real-world data in Japan suggest that, similar to what is observed in colon cancer patients, adjuvant chemotherapy delays the peak of recurrence and suppresses distant recurrence in stage III rectal cancer patients.

Laparoscopic versus Open Colectomy for Elderly Patients with Colon Cancer: A Propensity Score Analysis with the Controlling Nutritional Status (CONUT) Score.

The feasibility of laparoscopic surgery for elderly patients remains unclear, as these patients usually present with comorbidities. Recently, the controlling nutritional status (CONUT) score has drawn attention as an evaluation score of patients' general status as well as a predictor of survival. We retrospectively analyzed overall survival in 424 patients aged ≥75 years with colon cancer, who underwent curative surgery (laparoscopic (n = 167) or open surgery (n = 257)) between January 2004 and December 2013. To adjust for heterogeneity in both groups, a propensity score-matched analysis was performed, with the CONUT score as a confounding covariate. 5-year overall survival rates of patients with normal (0-1), mildly abnormal (2-4), or abnormal (≥5) CONUT score were 88.6%, 79.4%, and 41.4%, respectively (p < 0.001). T3 or less, N negative, late period (2009-2013), and normal CONUT score were associated with the tendency to undergo laparoscopic surgery (p < 0.001). The analysis of the propensity score-matched cohort (124 pairs) revealed that patients in the laparoscopic surgery group had a similar prognosis to those in the open surgery group, with a 5-year overall survival of 91.9% vs. 82.0%, respectively (p = 0.102). Laparoscopic surgery for colon cancer is an acceptable surgical approach in elderly patients.

Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients.

BACKGROUND: Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial. METHODS: The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors. RESULTS: For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS. CONCLUSIONS: Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.

Nutritional and inflammatory measures predict survival of patients with stage IV colorectal cancer.

BACKGROUND: This study aimed to evaluate the prognostic impact of nutritional and inflammatory measures (controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS)) on overall survival (OS) in patients with stage IV colorectal cancer (CRC). METHODS: Subjects were 996 patients with stage IV CRC who were referred to the National Cancer Center Hospital between 2001 and 2015. We retrospectively investigated correlations between OS and CONUT score, PNI, and mGPS. Multivariate analyses were performed using Cox proportional hazards regression models. RESULTS: After adjusting for known factors (age, gender, BMI, ECOG performance status, location of primary tumor, CEA levels, histological type, M category, and prior surgical treatment), all three measures were found to be independent prognostic factors for OS in patients with stage (CONUT score, p < 0.001; PNI, p < 0.001; mGPS, p < 0.001). Significant differences in OS were found between low CONUT score (0/1) (n = 614; 61%) and intermediate CONUT score (2/3) (n = 276; 28%) (hazard ratio (HR) = 1.20, 95% confidence interval (CI): 1.02-1.42, p = 0.032), and intermediate CONUT score and high CONUT score (≥4) (n = 106; 11%) (HR = 1.30, 95% CI: 1.01-1.67, p = 0.045). Significant differences in OS were found between mGPS = 0 (n = 633; 64%) and mGPS = 1 (n = 234; 23%) (HR = 1.84, 95% CI: 1.54-2.19, p < 0.001), but not between mGPS = 1 and mGPS = 2 (n = 129; 13%) (HR = 1.12, 95% CI: 0.88-1.41, p = 0.349). Patients with low PNI (< 48.0) (n = 443; 44%) showed a significantly lower OS rate than those with high PNI (≥48.0) (n = 553; 56%) (HR = 1.39, 95% CI: 1.19-1.62, p < 0.001). CONCLUSIONS: CONUT score, PNI, and mGPS were found to be independent prognostic factors for OS in patients with stage IV CRC, suggesting that nutritional and inflammatory status is a useful host-related prognostic indicator in stage IV CRC.

Prognostic impact of preoperatively elevated and postoperatively normalized carcinoembryonic antigen levels following curative resection of stage I-III rectal cancer.

BACKGROUND: Preoperative and early postoperative serum carcinoembryonic antigen (CEA) levels are known prognostic factors in rectal cancer. Recently, a large-scale study on colon cancer revealed that "preoperatively elevated and postoperatively normalized CEA levels" is not an indicator of poor prognosis. However, whether this hold true in rectal cancer patients is unknown. This study aimed to investigate the prognostic significance of preoperatively elevated and postoperatively normalized CEA levels in rectal cancer patients undergoing curative resection. METHODS: Subjects were consecutive stage I-III rectal cancer patients who underwent curative resection without preoperative treatment at National Cancer Center Hospital between 2000 and 2015. Overall survival (OS) and the hazard function of recurrence or death were analyzed according to the CEA levels, as follows: normal preoperative CEA (normal group), preoperatively elevated but postoperatively normalized CEA (normalized group), and preoperatively and postoperatively elevated CEA (elevated group). RESULTS: The normalized group (n =235) had worse OS (HR 1.49, 95% CI 1.08-2.04; P = .0142) compared to the normal group (n = 1208), and better OS compared to the elevated group (n = 47) (HR 0.53, 95% CI 0.31-0.91; P = .0208). The elevated group had the highest and earliest peak in hazard function, followed by the normalized group and the normal group, with median times to recurrence of 8.8, 15.5, and 18.5 months, respectively (P = .0223). CONCLUSIONS: Prognosis after resection of rectal cancer was worse in patients with preoperatively elevated and postoperatively normalized CEA compared to those with normal preoperative CEA. Patients with elevated preoperative CEA might require intensive follow-up even if levels normalize after resection, especially in earlier periods, for early detection of recurrence.

Controlling nutritional status (CONUT) score as a preoperative risk assessment index for older patients with colorectal cancer.

BACKGROUND: Assessment of preoperative general condition to predict postoperative outcomes is important, particularly in older patients who typically suffer from various comorbidities and exhibit impaired functional status. In addition to various indices such as Charlson Comorbidity Index (CCI), National Institute on Aging and National Cancer Institute Comorbidity Index (NIA/NCI), Adult Comorbidity Evaluation-27 (ACE-27), and American Society of Anesthesiologists Physical Status classification (ASA-PS), controlling nutritional status (CONUT) score is recently gaining attention as a tool to evaluate the general condition of patients from a nutritional perspective. However, the utility of these indices in older patients with colorectal cancer has not been compared. METHODS: The study population comprised 830 patients with Stage I - IV colorectal cancer aged 75 years or older who underwent surgery at the National Cancer Center Hospital from January 2000 to December 2014. Associations of each index with overall survival (OS) (long-term outcome) and postoperative complications (short-term outcome) were examined. RESULTS: For the three indices with the highest Akaike information criterion values (i.e., CONUT score, CCI and ACE-27), but not the remaining indices (NIA/NCI and ASA-PS), OS significantly worsened as general condition scores decreased, after adjusting for known prognostic factors. In contrast, for postoperative complications, only CONUT score was identified as a predictive factor (≥4 versus 0-3; odds ratio: 1.90; 95% CI: 1.13-3.13; P = 0.016). CONCLUSION: For older patients with colorectal cancer, only CONUT score was a predictive factor of both long-term and short-term outcomes after surgery, suggesting that CONUT score is a useful preoperative risk assessment index.

Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan.

BACKGROUND: The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear. METHODS: This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance. RESULTS: Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033). CONCLUSIONS: Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.