This study aimed to establish a clinical nomogram model based on a radiomics signatures derived from 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET/CT) and clinical parameters to predict disease-free survival (DFS) in patients with stage II/III colorectal adenocarcinoma. Understanding and predicting DFS in these patients is key to optimizing treatment strategies.

A retrospective analysis included 332 cases from July 2011 to July 2021 at The Sixth Affiliated Hospital, Sun Yat-sen University, with PET/CT assessing radiomics features and clinicopathological features. Univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox, and multivariable Cox regression identified recurrence-related radiomics features. We used a weighted radiomics score (Rad-score) and independent risk factors to construct a nomogram. Evaluation involved time-dependent receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

The nomogram, incorporating Rad-score, pN, and pT demonstrated robust predictive ability for DFS in stage II/III colorectal adenocarcinoma. Training cohort areas under the curve (AUCs) were 0.78, 0.80, and 0.86 at 1, 2, and 3 years, respectively, and validation cohort AUCs were 0.79, 0.75, and 0.73. DCA and calibration curves affirmed the nomogram's clinical relevance.

The 18F-FDG PET/CT based radiomics nomogram, including Rad-score, pN, and pT, effectively predicted tumor recurrence in stage II/III colorectal adenocarcinoma, significantly enhancing prognostic stratification. Our findings highlight the potential of this nomogram as a guide for clinical decision making to improve patient outcomes.

Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute.

To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor.

Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling.

We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006).

RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.

To identify factors associated with post-recurrence survival (PRS), we examined our institutional recurrence patterns following definitive resection for rectal cancer. We reviewed all patients with rectal cancer diagnosed at three hospitals in the east of Iran from 2011 to 2020. The optimal cut-off value was determined by receiver operating characteristic (ROC) analysis to determine early recurrence. The effect of recurrence time was evaluated on PRS. 326 eligible patients with a mean ± SD age of 56 ± 12.8 years were included in this study. In a median (IQR: Inter-quartile range) follow-up time of 76 (62.2) months, 106 (32.5%) patients experienced at least any recurrence (locoregional or distant metastasis) following primary resection. The median (IQR) time from initial surgery to recurrence was 29.5 (31.2) months. Based on ROC analysis, early recurrence was specified at ≤ 29 months. However, for the patients who experienced only locoregional recurrence, 33 months was the cut-off to define early recurrence. Recurrence time and recurrence management were both significant variables on PRS. Moreover, TNM staging was significantly associated with early recurrence (P = 0.003). In this research, recurrence time, recurrence management and TNM staging were found to be correlated with PRS.

As a disease with high morbidity and high mortality, lung cancer has seriously harmed people's health. Therefore, early diagnosis and treatment are more important. PET/CT is usually used to obtain the early diagnosis, staging, and curative effect evaluation of tumors, especially lung cancer, due to the heterogeneity of tumors and the differences in artificial image interpretation and other reasons, it also fails to entirely reflect the real situation of tumors. Artificial intelligence (AI) has been applied to all aspects of life. Machine learning (ML) is one of the important ways to realize AI. With the help of the ML method used by PET/CT imaging technology, there are many studies in the diagnosis and treatment of lung cancer. This article summarizes the application progress of ML based on PET/CT in lung cancer, in order to better serve the clinical. In this study, we searched PubMed using machine learning, lung cancer, and PET/CT as keywords to find relevant articles in the past 5 years or more. We found that PET/CT-based ML approaches have achieved significant results in the detection, delineation, classification of pathology, molecular subtyping, staging, and response assessment with survival and prognosis of lung cancer, which can provide clinicians a powerful tool to support and assist in critical daily clinical decisions. However, ML has some shortcomings such as slightly poor repeatability and reliability.

The definition of early recurrence (ER) for right-sided colon cancer patients after complete mesocolic excision (CME) with D3 lymphadenectomy remains unclear. This study aimed to define the optimal time for ER and clarify risk factors for ER and post-recurrence survival (PRS). A total of 578 right-sided colon cancer patients who underwent CME with D3 lymphadenectomy were included. The minimum p value method was used to evaluate theme optimal time of recurrence-free survival to discriminate between ER and late recurrence (LR). Risk factors for ER were determined by a logistics regression model. The PRS was compared between ER and LR. The optimal time to define ER was 15 months (P = 1.8697E-7). 93 patients developed tumor recurrence, 46 patients had ER (≤15 months) and 47 patients had LR (>15 months). Preoperative serum CA19-9 > 37 U/mL (OR = 3.185, P = 0.001), pathological N+ stage (OR = 3.042, P = 0.027), and lymphovascular invasion (OR = 2.182, P = 0.027) were identified as independent risk factors associated with ER. Age > 75 years (HR = 1.828, P = 0.040), pathological N2 stage (HR = 1.850, P = 0.009), multiple sites of recurrence (HR = 1.680, P = 0.024), and time to recurrence ≤15 months (HR = 2.018, P = 0.043) were significantly associated with worse PRS in patients with recurrence. 15 months was the optimal time to distinguish ER and LR. ER was associated with a poor PRS. Elevated preoperative serum CA19-9 level, pathological N+ stage, and lymphovascular invasion were significantly predictive of ER.

Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing preoperative and postoperative plasma levels in patients with CRC, with and without recurrence. The association between preoperative plasma miR-4442 levels, clinicopathological features, and recurrence-free survival was analyzed in 108 patients with CRC after curative surgery. Furthermore, cell-function analyses were performed, and the involvement of miR-4442 in regulating epithelial-mesenchymal transition (EMT) was examined. Preoperatively plasma miR-4442 levels were associated with CRC recurrence and exhibited an incremental increase with earlier recurrence dates. Moreover, miR-4442 demonstrated high sensitivity and specificity as a potential biomarker for early CRC recurrence. The expression of miR-4442 in cancer tissues of patients with metastatic liver cancer from CRC was higher than in normal liver, CRC, and normal colorectal tissues. The overexpression of miR-4442 promoted the proliferative, migratory, and invasive activities of CRC cells, decreased levels of RBMS1 and E-cadherin, and increased levels of N-cadherin and Snail1. Plasma miR-4442 is a clinically useful biomarker for predicting the early recurrence of CRC. Furthermore, miR-4442 regulates EMT in CRC by directly targeting the messenger RNA of RBMS1.

Early recurrence (ER) of rectal mucinous adenocarcinoma (MAC) has yet to be defined. We therefore explored risk factors for ER and constructed a predictive nomogram.

A total of 145 rectal MAC patients undergoing radical surgery were included. The minimum P value method was used to determine the optimal cut-off point to discriminate between ER and late recurrence (LR). Risk factors for ER were determined by a logistic regression analysis, and a predictive nomogram was constructed.

A total of 62 (42.8%) patients developed tumor recurrence. The optimal time to define ER was 12 months. A pre-treatment tumor distance from the anal verge ≤ 7 cm, pathological N stage, lymphovascular invasion, tumor deposits, and time to recurrence ≤ 12 months were significantly associated with a poor post-recurrence survival in patients with recurrence. A pre-treatment serum carcinoembryonic antigen (CEA) level > 10 ng/ml, pre-treatment tumor distance from the anal verge ≤ 7 cm, pathological N + stage, perineural invasion, and tumor deposits were identified as independent risk factors associated with ER. A nomogram predicting ER was constructed (C-index 0.870).

The pre-treatment serum CEA level, pre-treatment tumor distance from the anal verge, pathological N + stage, perineural invasion, and tumor deposits were significantly predictive of ER for rectal MAC patients.

Risk factors for disease recurrence following curative resection for locally advanced colon cancer (LACC) remain unclear as conflicting results have been reported in the literature. The aim of this study was to examine these factors in the setting of developing country's health care system affected by limited accessibility to the multimodal cancer treatment. Patients who had undergone curative colon resection for LACC between 2004 and 2018 were included. Data were obtained from a prospectively maintained database. Factors associated with disease recurrence, types of recurrence and recurrence-free survival were studied. A total of 118 patients with LACC were operated within the study period. Median follow-up was 36 (2-147) months. Adjuvant therapy was used in 41 (34.7%) patients and 62 (52.5%) were diagnosed with recurrence. In the multivariable analysis, disease recurrence was associated with tumor and nodal stages, as well as with the lymph node yield. Local recurrence, distant metastases, and peritoneal carcinomatosis were observed in 8 (6.8%), 30 (25.4%), and 24 (20.3%) patients, respectively. Early recurrence was diagnosed in 27 (22.9%) cases with peritoneal carcinomatosis being its most common type. Preoperative serum CA 19-9 levels, tumor, and nodal stages were linked to recurrence-free survival in the univariable analysis. Only tumor stage remained such in the multivariable model. Our findings suggest that lymph node yield, tumor, and nodal stages are associated with recurrence following curative resection for LACC.

The online version contains supplementary material available at 10.1007/s13193-022-01672-x.

To predict the recurrence of non-small cell lung cancer (NSCLC) within 2 years after curative-intent treatment using a machine-learning approach with PET/CT-based radiomics.

A total of 77 NSCLC patients who underwent pretreatment 18 F-fluorodeoxyglucose PET/CT were retrospectively analyzed. Five clinical features (age, sex, tumor stage, tumor histology, and smoking status) and 48 radiomic features extracted from primary tumors on PET were used for binary classifications. These were ranked, and a subset of useful features was selected based on Gini coefficient scores in terms of associations with relapsed status. Areas under the receiver operating characteristics curves (AUC) were yielded by six machine-learning algorithms (support vector machine, random forest, neural network, naive Bayes, logistic regression, and gradient boosting). Model performances were compared and validated via random sampling.

A PET/CT-based radiomic model was developed and validated for predicting the recurrence of NSCLC during the first 2 years after curation. The most important features were SD and variance of standardized uptake value, followed by low-intensity short-zone emphasis and high-intensity zone emphasis. The naive Bayes model with the 15 best-ranked features displayed the best performance (AUC: 0.816). Prediction models using the five best PET-derived features outperformed those using five clinical variables.

The machine learning model using PET-derived radiomic features showed good performance for predicting the recurrence of NSCLC during the first 2 years after a curative intent therapy. PET/CT-based radiomic features may help clinicians improve the risk stratification of relapsed NSCLC.

Oxaliplatin is a key drug for colorectal cancer and causes peripheral neuropathy. Oxaliplatin-induced laryngopharyngeal dysesthesia is an acute peripheral neuropathy similar to a hypersensitivity reaction. Hypersensitivity reactions to oxaliplatin do not require immediate discontinuation, but re-challenge and desensitization therapy can be very burdensome for patients. We encountered 2 cases in which laryngopharyngeal dysesthesia could be differentiated from hypersensitivity reactions to oxaliplatin, and treatment could continue. The first case was that of a 58-year-old woman who developed dyspnea during the first course of combination therapy with capecitabine and oxaliplatin as the primary treatment for advanced rectal cancer. After laryngopharyngeal dysesthesia was differentiated from hypersensitivity reaction based on these typical symptoms, she was considered to have grade 3 (Common Terminology Criteria for Adverse Events [CTCAE] ver. 5) laryngopharyngeal dysesthesia. The second course of oxaliplatin was extended from 2 to 4 h, but symptoms recurred. The third course was performed with a reduced dose of oxaliplatin from 130 mg/m2 to 100 mg/m2, and the patient could complete the treatment without symptom recurrence. The second case involved a 76-year-old woman who developed grade 3 laryngopharyngeal dysesthesia during the first course of combination therapy with capecitabine and oxaliplatin as the primary treatment for localized colon cancer. Based on the experience of the first case, we reduced the oxaliplatin dose from 130 mg/m2 to 100 mg/m2 for the second course, and the patient completed the treatment without symptoms. This dose reduction was effective for grade 3 laryngopharyngeal dysesthesia caused by oxaliplatin without reducing therapeutic efficacy.

Few studies have evaluated the feasibility and safety of intracorporeal anastomosis (IA) for left hemicolectomy. Here, we aimed to investigate the potential advantages and disadvantages of laparoscopic left hemicolectomy with IA and compare the short- and medium-term outcomes between IA and extracorporeal anastomosis (EA).

We retrospectively analyzed 133 consecutive patients who underwent laparoscopic left hemicolectomies from July 2016 to September 2019 and categorized them into the IA and EA groups. Patients with stage 4 disease and conversion to laparotomy or those lost to follow-up were excluded. Postoperative outcomes between IA and EA groups were compared. Short-term outcomes included postoperative pain score, bowel function recovery, complications, duration of hospital stay, and pathological outcome. Medium outcomes included overall survival and disease-free survival for at least 2 years.

After excluding ineligible patients, the remaining 117 underwent IA (n = 40) and EA (n = 77). The IA group had a shorter hospital stay, a shorter time to tolerate liquid or soft diets, and higher serum C-reactive protein level on postoperative day 3. There was no difference between two groups in operative time, postoperative pain, specimen length, or nearest margin. A 2-year overall survival (IA vs. EA: 95.0% vs. 93.5%, p = 0.747) and disease-free survival (IA vs. EA: 97.5% vs. 90.9%, p = 0.182) rates were comparable between two groups.

Laparoscopic left hemicolectomy with IA was technically feasible, with better short-term outcomes, including shorter hospital stays and shorter time to tolerate liquid or soft diets. The IA group had higher postoperative serum C-reactive protein level; however, no complications were observed. Regarding medium-term outcomes, the overall survival and disease-free survival rates were comparable between IA and EA procedures.

Objective In this study, we aimed to explore the potential diagnostic utility of human epidermal growth factor receptor 2 (HER2) expression in colorectal carcinoma. We investigated the association of HER2 expression with the type and grade of the tumor along with the pattern, staining intensity, and the percentage of cells stained. Methods This was an observational study involving 50 cases of colorectal carcinoma that underwent immunohistochemistry to analyze the HER2 expression. Results The positive expression of HER2 was seen in 16 (32%) cases. The majority of the study population was between the fifth-seventh decades of life. The most commonly diagnosed tumor was conventional adenocarcinoma with grade II, cytoplasmic pattern, +2 positivity, and moderate intensity. The maximum positivity for HER2 was seen in tumors of the rectum in eight (16%) cases. Conclusion A substantial rate of HER2 overexpression paves the way for it to become a potential future target in cancer therapeutics.

The definition of early recurrence (ER) in rectal cancer is unclear, and the association of ER with post-recurrence survival (PRS) is poorly described. We therefore sought to identify if time to recurrence (TTR) is associated with PRS.

We reviewed all curative-intent resections of nonmetastatic rectal cancer from 2003 to 2018 in our institutional registry within an NCI-Designated Comprehensive Cancer Center. Clinicopathologic data at diagnosis and first recurrence were collected and analyzed. ER was pre-specified at < 24 months and late recurrence (LR) at ≥ 24 months. PRS was evaluated by the Kaplan-Meier method and Cox proportional hazards modeling.

At a median follow-up of 53 months, 61 out of 548 (11.1%) patients undergoing resection experienced recurrence. Median TTR was 14 months (IQR 10-18) with 45 of 61 patients (74%) classified as ER. There were no significant baseline differences between patients with ER and LR. Most recurrences were isolated to the liver (26%) or lung (31%), and 16% were locoregional. ER was not associated with worse PRS compared to LR (P > 0.99). On multivariable analysis, detection of recurrence via workup for symptoms, CEA > 10 ng/mL at recurrence, and site of recurrence were independently associated with PRS.

ER is not associated with PRS in patients with resected rectal cancer. Symptomatic recurrences and those accompanied by CEA elevations are associated with worse PRS, while metastatic disease confined to the liver or lung is associated with improved PRS. Attention should be directed away from TTR and instead toward determining therapy for patients with treatable oligometastatic disease.

Machine learning algorithms have proven to be effective for predicting survival after surgery, but their use for predicting 10-year survival after breast cancer surgery has not yet been discussed. This study compares the accuracy of predicting 10-year survival after breast cancer surgery in the following five models: a deep neural network (DNN), K nearest neighbor (KNN), support vector machine (SVM), naive Bayes classifier (NBC) and Cox regression (COX), and to optimize the weighting of significant predictors. The subjects recruited for this study were breast cancer patients who had received breast cancer surgery (ICD-9 cm 174-174.9) at one of three southern Taiwan medical centers during the 3-year period from June 2007, to June 2010. The registry data for the patients were randomly allocated to three datasets, one for training (n = 824), one for testing (n = 177), and one for validation (n = 177). Prediction performance comparisons revealed that all performance indices for the DNN model were significantly (p < 0.001) higher than in the other forecasting models. Notably, the best predictor of 10-year survival after breast cancer surgery was the preoperative Physical Component Summary score on the SF-36. The next best predictors were the preoperative Mental Component Summary score on the SF-36, postoperative recurrence, and tumor stage. The deep-learning DNN model is the most clinically useful method to predict and to identify risk factors for 10-year survival after breast cancer surgery. Future research should explore designs for two-level or multi-level models that provide information on the contextual effects of the risk factors on breast cancer survival.

Indications for local excision in patients with rectal cancer remain controversial. We reviewed factors affecting survival rate and treatment effectiveness in cancer recurrence after local excision among patients with rectal cancer.

A total of 831 patients was enrolled. Of these, 391 patients were diagnosed with primary rectal cancer and underwent local excision. A retrospective observational study was performed on patients who underwent full-thickness local excision for rectal cancer.

The median duration of follow-up was 61 months. The overall recurrence rate was 11.5%. The rate of local recurrence was 5.1%. Five-year overall survival rate among recurrent patients was 66.8%; the rate among patients who underwent salvage operation due to recurrence was 84.7%, compared with 44.2% among patients treated with non-operative management (p<0.001). Multivariate analysis of disease-free survival identified distance from the anal verge (p=0.038) and histologic grade (p=0.047) as factors predicting poor prognosis. Multivariate analysis of overall survival showed that age (p<0.001), serum carcinoembryonic antigen (CEA) levels (p=0.001), and histologic grade (p=0.013) also affected poor prognosis. In subgroup analysis of patients with recurrence, 25 patients underwent reoperation, while 20 patients did not. For 5-year overall survival rate, there was a significant difference between 84.7% of the reoperation group and 44.2% of the non-operation group (p<0.001).

The risk factors affecting overall survival rate after local excision were age 65 years or older, preoperative CEA level 5 or higher, and high histologic grade. In cases of recurrence after local excision of rectal cancer, salvage operation might improve overall survival.

The significance of the duration of the recurrence-free survival after curative resection for colorectal cancer remains unclear. The purpose was to reveal the association between time to recurrence after surgery and the survival after recurrence.

Patients with stage II and III colorectal cancer who underwent curative resection between 2007 and 2015 were retrospectively reviewed (n = 645). Patients with recurrence after surgery (n = 133) were divided into 2 groups: early recurrence (within 13 months after surgery, n = 63) and late recurrence (more than 13 months after surgery, n = 70). The overall survival after recurrence and clinicopathological features were compared between early recurrence, late recurrence, and without recurrence groups.

The overall survival after recurrence was significantly shorter in patients with early recurrence occurring at less than 13 months (hazard ratio: 1.70, p = 0.03). A high preoperative CA19-9 level (odds ratio [OR]: 2.38, p = 0.03), venous invasion (OR: 2.26, p = 0.03), and the absence of adjuvant chemotherapy (OR: 2.08, p = 0.04) were independently correlated with early recurrence.

Early recurrence was associated with a poor prognosis after recurrence. Venous invasion correlated with early recurrence. Adjuvant chemotherapy may reduce the risk of early recurrence. These results indicate the importance of prudent surveillance and the aggressive application of adjuvant chemotherapy.

Ampulla of Vater (AoV) carcinoma has a relatively good prognosis. The 5-year recurrence rate for AoV is still around 40%-50% however, and most recurrences occur in the early period. The aim of this study was to identify predictors of an early recurrence in AoV patients following a curative resection.

The clinicopathological data for 501 consecutive patients that underwent a resection for AoV in our institute between January 2000 and December 2015 were retrospectively reviewed. The characteristics of any recurrences and early recurrence patients were analyzed accordingly. Early recurrence was defined as occurring within one year of resection.

There were 170 diagnosed recurrences in our study population, 57.1% of whom were men, with a mean age of 60.1 years (range, 30-94 years). Almost all of the study patients underwent a pancreaticoduodenectomy, and 9% underwent minimally invasive surgery. Of the 170 recurrent cases, 107 were diagnosed with an early recurrence and had 1-, 3-, and 5-year overall survival rates of 77.7%, 18.4%, 10.5%, respectively. The factors that significantly influenced early recurrences, determined by multivariate analysis, lymphovascular invasion (LVI), lymph node ratio (LNR), and poor differentiation were found to be independent determinants of a recurrence within 1 year.

An early recurrence in AoV patients is ultimately lethal even though this cancer has a good prognosis. LVI, LNR, and poor differentiation are powerful predictors of an early recurrence in AoV. Hence, intensive surveillance and new therapeutic strategies should be considered for AoV patients with these predictors following a curative resection.

The definition of "early recurrence (ER)" after rectal cancer surgery is currently unclear.

To determine an evidence-based cut-off to distinguish early and late recurrence (LR) for patients with rectal cancer and compare the clinicopathological factors between the two groups.

Patients who underwent neoadjuvant chemoradiotherapy (nCRT) and radical resection for locally advanced rectal cancer were included. A minimum p-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into ER and LR groups based on overall survival. A logistic regression model was used to assess risk factors for ER.

A total of 763 patients were included, of which 167 (21.9%) experienced recurrence. The optimal cut-off value of recurrence-free survival to differentiate between ER (n = 125, 74.9%) and LR (n = 42, 25.1%) was 24 months (P = 0.000001). The median postrecurrence survival of ER and LR was 12 months and 22 months, respectively (p = 0.028). The most common recurrent sites in patients with ER and LR were lung metastases, the incidence of liver metastases, however, differed considerably in ER and LR (27.2% vs 9.5%, P = 0.019). Risk factors including elevated preoperative carcinoembryonic antigen (CEA), higher ypTNM stage, positive circumferential resection margin (CRM), and perineural invasion were significantly associated with ER.

A recurrence-free interval of 24 months is the optimal cut-off value for defining ER versus LR. Elevated preoperative CEA, higher ypTNM staging, positive CRM, and perineural invasion were associated with ER of locally advanced rectal cancer.

Some locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (CRT) prior to total mesorectal excision (TME) show early recurrence with a short disease-free interval. This is unacceptable for patients and their families, necessitating re-evaluation of the treatment process. We aimed to evaluate the risk factors and prognostic impact of early recurrence in patients who received preoperative CRT (pCRT) followed by TME for LARC.

Of 714 patients who underwent curative resection after pCRT for LARC from January 2010 to December 2016, we included 139 who developed recurrence after resection. Patients were divided into an early recurrence group, diagnosed <12 months after primary surgery, and a late recurrence group, diagnosed ≥12 months after primary surgery.

Forty-nine patients experienced early recurrence and 90 experienced late recurrence. Multivariate analysis revealed that tumor regression grade (hazard ratio [HR] 2.962, 95% confidence interval [CI] 1.434-6.119, P = 0.003) and positive ypN stage (HR 2.110, 95% CI 1.144-3.892, P = 0.017) correlated with early recurrence. The 5-year overall survival rates for early and late recurrences were not significantly different (P = 0.121).

In patients with early recurrence after pCRT followed by TME, tumor regression grade and ypN stage positivity were independent predictors of the early recurrence.

The current standard treatment for locally advanced rectal cancer (LARC) in Korea and Western countries is a multimodal approach incorporating preoperative long-course chemoradiotherapy (LCRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy. This approach has significantly improved local control and reduced recurrence rates; however, the overall survival benefit has not been established. Although LCRT is a good option, there remain challenging unresolved problems for colorectal surgeons. We focused on four challenging issues in this review article. The first is LARC with resectable liver metastases, for which there has been no consensus regarding optimal management and practice thus far. The second is cancer progression at the time of restaging after completion of preoperative LCRT. To date, there have been few reports on this issue. The third is early recurrence after TME following preoperative LCRT, the reason for which is thought to be the delayed systemic chemotherapy in the preoperative LCRT protocol. The fourth is cost-effectiveness. The preoperative LCRT protocol takes 5 weeks. After a 6-8-week waiting period, surgery is performed. Therefore, it is more time-consuming than short-course chemoradiotherapy. To overcome these issues, total neoadjuvant treatment (TNT) modalities, performed using various protocols, have been conducted globally based on cumulative experience. We also attempted to discuss previous TNT protocols in this article. One treatment strategy is not sufficient for patients with varying clinical characteristics. Therefore, we should revisit current treatment strategies based on recent clinical experience.

To date, there have been many studies on postoperative complications and oncologic outcomes, but the findings remain controversial. The purpose of the study was to determine the prognostic value of serum inflammatory markers as pretreatment in curatively resected colorectal cancer. The effects of serum inflammatory marker levels on postoperative morbidity were also examined.

Prospectively collected data from 1590 patients with primary sporadic colorectal adenocarcinoma who underwent curative resection between September 2012 and December 2013 at our institution were retrospectively analyzed. White blood cell count (× 10³/mcl), neutrophil/lymphocyte ratio, C-reactive protein, erythrocyte sedimentation rate (ESR), and Glasgow prognostic score (GPS) were evaluated. GPS was determined as follows: GPS of 2, elevated CRP level (> 1.0 mg/dl) and hypoalbuminemia (< 3.5 g/dl); GPS of 1, elevated CRP or hypoalbuminemia; and GPS of 0, neither elevated CRP nor hypoalbuminemia.

The median follow-up period for the 1590 patients was 59 months. The overall postoperative morbidity rate was 24.8%. In multivariate analysis, female sex (P = 0.006), rectal cancer other than colon cancer (P < 0.001), CEA level > 5 ng/ml (P < 0.001), ESR > 27 mm/h (P = 0.014), and a GPS of 1 or 2 (P < 0.001) were independent risk predictors for morbidity. A GPS of 1 or 2 (P < 0.001) and postoperative morbidity (P < 0.001) significantly affected both overall survival and disease-free survival in multivariate analyses.

A GPS of 1 or 2 is a significant risk factor for postoperative morbidity and a prognostic factor for long-term survival.

Neoadjuvant chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer. CRT leads to a better local control; however, this does not translate into a survival benefit. Long-term survival is mostly affected by the development of distant metastases after surgery. This study aimed to evaluate predictive clinical factors for the development of early metastatic disease after CRT.

Clinical data of patients with stage II/III rectal cancer submitted to CRT between January 2000 and October 2014 were collected from prospectively maintained electronic databases of three Italian institutes. Patients were divided into two groups: those who developed metastasis within 12 months from surgical resection (Group A) and patients without or with late distant relapse (Group B).

Among 635 patients, 86 (13.5%) had early distant relapse within 1 year from surgery (Group A), and 549 (86.5%) did not (Group B). A higher rate of early distant relapse was associated with CEA levels above 3 ng/dL (20% vs. 10%; p <0.001), tumor lying under 5 cm from anal verge (20% vs. 9%; p <0.001), and age under 63 years (17% vs. 11%; p = 0.036). Multivariate analysis confirmed these factors to be independently correlated with a higher risk of early metastasis.

Younger age, low tumors, and high serum CEA may be associated with unfavorable early oncological outcomes after CRT and surgery for rectal cancer. These clinical factors could be useful to select patients for more aggressive therapeutic strategies.

The follow-up schedule for colorectal cancer patients after curative surgery is inconsistent among the guidelines. Evaluation of time to recurrence (TTR) and survival after recurrence (SAR) may provide evidence for appropriate follow-up.

We assessed 3039 colon cancer (CC) and 1953 rectal cancer (RC) patients who underwent curative surgery between 2007 and 2008. We evaluated the pre- and post-recurrent clinicopathological factors associated with TTR and SAR in each stage of CC and RC.

The recurrence rates of stages I, II, and III were 1.2%, 13.1%, and 26.3%, respectively, for CC, and 8.4%, 20.0%, and 30.4%, respectively, for RC. In CC patients, high carcinoembryonic antigen (CEA) level and lymphovascular invasion were independent predictors of short TTR. In RC patients, metastatic factors (liver metastasis in stage III) and venous invasion (stage III) were independent predictors of short TTR. The prognostic factors of SAR were age (stage II CC and stage III RC), female gender (stage III RC), high CEA level (stage II RC), histological type (stage III CRC), nodal status (stage III CC), recurrence within 1 year (stage III RC), M1b recurrence (stage II CRC), local recurrence (stage II CC), and no surgical resection after recurrence (stage II and III CRC).

The follow-up schedule for stage I should be different from that for the other stages. We recommend that intensive follow-up is appropriate in stage III CC patients with undifferentiated adenocarcinoma or N2 nodal status, stage II RC patients with high preoperative CEA level, and stage III RC patients.

Local recurrence is common after radical surgery. However, the factors that contribute to survival after local recurrence remain unclear. In this retrospective study we analyzed the relationship between time to recurrence and survival after recurrence in 74 patients with locally recurrent gastric cancer. All patients received palliative radiotherapy with or without chemotherapy. The patients were divided into two groups according to the time between gastrectomy and local recurrence: early local recurrence (ELR, < 12 months after primary surgery), and late local recurrence (LLR, ≥12 months after primary surgery). The median overall survival (OS) time was 15 months for patients with ELR and 25 months for LLR patients. Univariate and multivariate analysis revealed that time to local recurrence was significantly associated with OS after local recurrence (P = 0.001). The hazard ratio of ELR compared with LLR patients was 0.442 (95% confidence interval: 0.264-0.741). These results indicate that early local recurrence predicted poor prognosis in gastric cancer patients with unresectable local recurrence.

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stages III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.

To explore the correlations between DCE-MRI quantitative parameters and synchronous distant metastasis and the clinicopathological factors in rectal cancers.

Sixty-three patients with rectal cancer (synchronous distant metastasis, n = 31; non-metastasis, n = 32) were enrolled in this study. Student's t test and ANOVA were used to compare DCE-MRI parameters (K ^trans , K _ep and V _e ). The receiver operating characteristic (ROC) analysis was used to find the reasonable threshold of DCE-MRI parameters to differentiate lesions with synchronous distant metastasis from those without metastasis.

The K ^trans , K _ep , and V _e value were significantly higher in the lesions with distant metastasis than in the lesions without distant metastasis (0.536 ± 0.242 vs. 0.299 ± 0.118 min^-1, p < 0.001; 1.598 ± 0.477 vs. 1.341 ± 0.390 min^-1, p = 0.022; and 0.324 ± 0.173 vs. 0.249 ± 0.091, p = 0.034; respectively). The K ^trans showed the highest AUCs of 0.788 (p < 0.001), with sensitivity of 61.29 % and specificity of 87.5 %, respectively.

DCE-MRI parameters may represent a prognostic indicator for synchronous distant metastases in patients with rectal cancer.

• The K ^trans , K _ep and V _e values correlated with synchronous distant metastasis. • Higher K ^trans , K _ep and V _e values were noted among patients with metastasis. • DCE-MRI parameters might represent a prognostic indicator for synchronous distant metastases.

To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) METHODS: Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis.

In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59%, and 89.47%, respectively) were significantly higher than those of LVI (64.86%, and 61.76%), but sensitivity and negative predictive value were not significantly different between MVI (60.71%, and 76.09%) and LVI (75.00%, and 77.42%).

While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI.

• Mesorectal vascular invasion (MVI) may be a radiologic prognostic factor for rectal cancer. • Specificity of MVI was higher than lymphovascular invasion in predicting early metastasis. • Mesorectal vascular invasion may be a better predictor for early distant metastasis.

Survival after the local recurrence of rectal cancer is influenced by several factors. The aim of this study was to ascertain whether the time interval from primary surgery for rectal cancer to local recurrence diagnosis has any impact on survival.

Population-based data was collected from the Swedish Colorectal Cancer Registry. 7410 patients were operated with radical abdominal surgery for rectal cancer during the period 1995-2002. Of these, 386 (5%) developed a local recurrence as a first event. The patients were divided into two groups: early local recurrence (ELR), diagnosed <12 months after primary surgery, and late local recurrence (LLR), diagnosed ≥12 months after primary surgery. Kaplan-Meier curves and hazard ratios were calculated for survival analyses. Survival was calculated from the date of the local recurrence diagnosis to death or end of follow-up.

Ninety-five patients had ELR and 291 patients LLR. Median time to local recurrence was 1.7 (0.1-7.9) years. Patients with a stage III primary tumour and non-irradiated patients were more common in the ELR compared with the LLR group. Factors that influenced survival were age at diagnosis of local recurrence (p < 0.001), stage of primary tumour (p = 0.027), and surgical resection of local recurrence (p < 0.001). Time to diagnosis of local recurrence had no influence on survival.

No difference in survival from date of diagnosis of local recurrence was seen between patients with ELR and patients with LLR. All patients with local recurrence should therefore be assessed for potential curative surgery, disregarding time to local recurrence.

The role of postoperative radiation therapy (RT) after local excision (LE) of deep submucosal invasive rectal cancer remains unclear. We evaluated the efficacy of adjuvant RT after LE of early rectal cancer with deep submucosal invasion.

We screened 227 patients who underwent transanal excision or endoscopic removal of deep submucosal invasive rectal cancer between 1992 and 2012, of which 66 did not undergo radical surgery owing to the patient's preference or poor medical conditions. Of these, 35 (53 %) underwent LE alone (LE group) and 31 (47 %) received adjuvant RT after LE (LE + RT group). Nine patients in the RT group received concurrent adjuvant chemotherapy with 5-fluorouracil. Two independent pathologists reviewed histological data.

The mean age of patients in the LE + RT and LE groups was 59.5 ± 9.6 and 55.3 ± 11.2 years, respectively. The mean follow-up duration was 78.7 ± 66.7 months in the LE + RT group and 70.5 ± 45.7 months in the LE group. Cancer eventually recurred in six patients (9.1 %; two in the LE + RT group and four in the LE group). In five of these patients, recurrence occurred within 4 years after the initial treatment. The other patient, who was in the LE group, exhibited multiple lymph node metastases at the 116-month follow-up. Kaplan-Meier estimates of recurrence-free survival at 5 years after treatment were 96.8 % in the LE + RT group and 97 % in the LE group (P = 0.657).

RT after LE of early rectal cancer with deep submucosal invasion might not improve recurrence-free survival compared with LE alone.

Despite intended curative resection, colorectal cancer will recur in ∼45% of the patients. Results of meta-analyses conclude that frequent follow-up does not lead to early detection of recurrence, but improves overall survival. The present literature shows that several factors play important roles in development of recurrence. It is well established that emergency surgery is a major determinant of recurrence. Moreover, anastomotic leakages, postoperative bacterial infections, and blood transfusions increase the recurrence rates although the exact mechanisms still remain obscure. From pathology studies it has been shown that tumors behave differently depending on their location and recur more often when micrometastases are present in lymph nodes and around vessels and nerves. K-ras mutations, microsatellite instability, and mismatch repair genes have also been shown to be important in relation with recurrences, and tumors appear to have different mutations depending on their location. Patients with stage II or III disease are often treated with adjuvant chemotherapy despite the fact that the treatments are far from efficient among all patients, who are at risk of recurrence. Studies are now being presented identifying subgroups, in which the therapy is inefficient. Unfortunately, only few of these facts are implemented in the present follow-up programs. Therefore, further research is urgently needed to verify which of the well-known parameters as well as new parameters that must be added to the current follow-up programs to identify patients at risk of recurrence.