A multivariate model to define risk groups among patients with curatively resected stage I and II colon carcinoma: Final report of a retrospective cohort study.

696 Background: Patients with stage I or II colon carcinoma (CC) have a 10 or 20% risk, respectively, of presenting recurrent disease after a potentially curative surgical resection and adjuvant chemotherapy have not improved survival in this setting. In this study, we present a multivariate model to define risk groups. Methods: Consecutive cases with stage I and II CC treated at a single cancer center in Mexico City, from January 1992 to December 2016, were included in this 25-year cohort. Clinical history and biochemical data were registered, and colon resection was performed with curative intention with standard lymphadenectomy. Standard hematoxylin-eosin slides and CDX2 immunohistochemistry (IHC) slides were analyzed by two independent pathologists. The Kaplan-Meier method and Cox model were used to analyze the association of prognostic factors and overall survival (OS). Results: 3,301 cases of colorectal cancer were treated during this study, but only 556 patients with stage I and II CC were included in the database: 266 women (47.8%) and 290 males (52.2%) (mean age 57.9 years); 52 (9.4%), 431 (77.5%), 36 (6.5%) and 37 (6.7%) were pTNM stages I, IIa, IIb, and IIc, respectively. R0 resection was performed in 548 patients (98.6) and R1 in 8 (1.4%). Location in the left colon (HR 1.63), hemoglobin (HR 0.93), serum albumin (HR 2.45), prognostic nutritional index 0.915), platelet count (HR 0.998), body mass index (HR 0.94), basal carcinoembryonic antigen (HR 1.0), TNM stage [stage I reference category, IIa (HR 5.46), IIb (HR 4.42), IIc (HR 9.28)], R1 residual disease (HR 2.8), negative CDX2 IHC (HR 2.1), and use of adjuvant chemotherapy (HR 0.629) were included in the final model as independent predictors of OS (model p < 0.0001).Predicted survival functions using this model defined three distinct risk groups. Conclusions: This multivariate model adds significant prognostic value to the pTNM classification. This model can be useful for stratifying prognosis in patients with CC and will aid in the design of randomized clinical trials evaluating the usefulness of adjuvant chemotherapy in this subgroup of patients with CC.

Prognostic factors for intrathyroidal papillary carcinomas – a multivariate analysis

Aim: to examine prognostic significance of patient-related, tumor-related and treatment-related factors for intrathyroidal papillary thyroid carcinomas (PTC), via multivariate analysis.Material and methods. This study included 153 patients with intrathyroidal PTCs (pT1/pT2/pT3) surgically treated in our Institution during two-decade period. Patients with locally invasive tumors (pT4) and initial distant metastases (M1) were excluded. Parameters of interest were: gender (male; female), age (<=45; >45 years), tumor size (pTNM classification WHO 1984), multifocality (no; yes), histological type of PTC (pure; microcarcinoma; follicular; poorly differentiated), presence of lymphonodal metastases (pN1a; ipsilateral-pN1b; contralateral-pN1b; total), surgery extent (total thyroidectomy; total thyroidectomy with lymphonodal dissections). Univariate and multivariate analysis of all parameters was performed in order to distinguish factors of significance for disease-free survival (DFS) and cancer-specific overall survival (cs-OS).Results. In the follow-up, 10% of patients had locoregional or distant relapse, while 5.2% died due to PTC. Univariate analysis distinguished older age, male gender, tumors over 4cm in diameter, multifocality and poorly differentiated PTC-types as unfavorable prognostic factors for cs-OS. DFS was significantly shorter in males vs. females, as well as in patients with multifocal vs. solitary PTC. Tumor multifocality was unfavorable prognostic factor for both DFS and cs-OS. Independent prognostic factors for intrathyroidal PTCs, based on Cox multivariate analysis, were multifocality and gender for DFS, and multifocality and age at diagnosis for cs-OS.Conclusions. Prognostic factors define risk groups within population of differentiated PTCs providing timely, adequate treatment and opportunity for longer quality life of patients with PTCs.

Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d'étude des Tumeurs Endocrines (GTE) retrospective study

ObjectiveManagement of insulinomas in the context of MEN1 remains poorly studied. The aim of this study was to evaluate long-term results of various surgical approaches in a large cohort of insulinoma–MEN1 patients.Design and methodsConsecutive insulinoma–MEN1 patients operated on for a nonmetastatic insulinoma between 1957 and 2010 were retrospectively selected from the MEN1 database of the French Endocrine Tumor Group. The type of surgery was categorized as distal pancreatectomy (DP), total pancreatectomy/cephalic duodenopancreatectomy (TP/CDP), or enucleation (E). Primary endpoint was time until recurrence of hypoglycemia after initial surgery. Secondary endpoints were post-operative complications.ResultsThe study included 73 patients (median age=28 years). Surgical procedures were DP (n=46), TP/CDP (n=9), or E (n=18). After a median post-operative follow-up of 9.0 years (inter-quartile range (IQR): 2.5–16.5 years), 60/73 patients (82.2%) remained hypoglycemia free. E and TP/CDP were associated with a higher risk of recurrent hypoglycemia episodes (unadjusted hazard ratio: 6.18 ((95% CI: 1.54–24.8);P=0.010) for E vs DP and 9.51 ((95% CI: 1.85–48.8);P=0.007) for TP/CDP vs DP. After adjustment for International Union against Cancer pTNM classification, enucleation remained significantly associated with a higher probability of recurrence. Long-term complications had occurred in 20 (43.5%) patients with DP, five (55.6%) with TP/CDP, but in none of the patients who have undergone E (P=0.002).ConclusionIn the French Endocrine database, DP is associated with a lower risk for recurrent hypoglycemia episodes. Due to lower morbidity, E alone might be considered as an alternative.

Role of overexpressions of ALEX1 gene in human colorectal tumorigenesis.

443 Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo family which has several ARM repeat domain. Our studies have revealed that overexpression of ALEX1 suppressed colony formation ability of stable human colorectal carcinoma cell lines. But clinical significance of ALEX1 expression in colorectal cancer patients is largely unknown. Methods: We examined the expression level of ALEX1 mRNA in matched tissue pairs of normal colorectal mucosa and colorectal tumor tissue by quantitative real-time RT-PCR Tumor specimens along with adjacent normal tissues were obtained from 49 patients with primary colorectal cancer undergoing complete surgical resection of tumors and lymph nodes, followed by adjuvant systemic therapy in some cases. All tissue samples were stored at -80°C until use. The 49 colorectal specimens comprised 26 well-differentiated and 23 moderately-differentiated adenocarcinoma. Corresponding extraneoplastic normal colon tissues from the same 49 patients were also examined. The pathological stages of the patients were as follows: stage I, 9 patients; stage II, 16 patients and stage III, 24 patients by pTNM classification. The post-surgical treatment observation period was from 277 to 3,631 days (1625.0 ± 1033.0 days). Results: In 34 cases out of 49 (69%) colorectal tumor tissues, greater than a 50% reduction of the ALEX1 mRNA level was observed in comparison to adjacent normal mucosa tissues. ALEX1 mRNA was significantly reduced in colorectal tumor tissues than those in normal mucosa (p=0.01459, Mann–Whitney U-test). The 17 cases with higher ALEX1 gene expression (tumor/normal value ³a0.20) significantly revealed a better disease-free survival rate than the other 32 cases (< 0.20; p = 0.045, log-rank test), which showed significant correlations between ALEX1 expression and better prognosis. There was no significant relationship between ALEX1 expression and the other clinicopathological features. Conclusions: Our findings may support that ALEX1 functions as a tumor suppressor in colorectal cancer progression. Examination of ALEX1 expression might be helpful for predicting the prognosis of patients with curative resected colorectal cancer.

Scoring system for predicting recurrences in patients with papillary thyroid microcarcinoma

ContextPapillary thyroid microcarcinomas (PMC) defined as tumors ≤10 mm in diameter (including pT1a and pT3 according to the latest pTNM classification) have good prognosis, although recurrence is possible. Clinicians are interested in using a scoring system for predicting recurrences.ObjectiveTo identify the prognostic factors for recurrence in patients with PMC and to develop a scoring system based on lymph node involvement, multifocality, and sex. To determine the impact of extrathyroidal invasion (ETI) and a threshold value for analyzing multifocality.MethodsSingle-center retrospective study of a cohort of 1669 patients with PMC managed from 1960 to 2007. The Kaplan–Meier survival rate and prognostic factors of events were analyzed using log-rank tests and uni- and multivariate Cox model-based analyses. A scoring system was proposed.ResultsSixty-eight recurrences were observed. Initial lymph node metastases (P=0.0001), multifocality (P=0.05), and male sex (P=0.01) were significantly associated with recurrence, although there was a period effect (after 1990). PMC size was not a significant variable. Our scoring system allows us to separate patients into three risk groups according to their recurrence-free probability. For PMC Nx patients, total foci size of multifocal tumors >20 mm was significantly associated with recurrence (P<0.0001). Radioiodine (RAI) ablation was associated with better outcome only in PMC with ETI.ConclusionOur scoring system classifies recurrence risk. In PMC Nx patients, multifocality is important in planning therapeutic strategies. Recurrence probability of pT3 PMC appears lower if RAI ablation is performed.

Pre-Enucleation Chemotherapy for Eyes Severely Affected by Retinoblastoma Masks Risk of Tumor Extension and Increases Death From Metastasis

Purpose Initial response of intraocular retinoblastoma to chemotherapy has encouraged primary chemotherapy instead of primary enucleation for eyes with clinical features suggesting high risk of extraocular extension or metastasis. Upfront enucleation of such high-risk eyes allows pathologic evaluation of extraocular extension, key to management with appropriate surveillance and adjuvant therapy. Does chemotherapy before enucleation mask histologic features of extraocular extension, potentially endangering the child's life by subsequent undertreatment? Methods We performed retrospective analysis of 100 eyes with advanced retinoblastoma enucleated with, or without, primary chemotherapy, in Beijing Tongren Hospital, retrospectively, from October 31, 2008. The extent of retinoblastoma invasion into optic nerve, uvea, and anterior chamber on histopathology was staged by pTNM classification. The treatment groups were compared for pathologic stage (Cochran-Armitage trend test) and disease-specific mortality (competing risks methods). Results Children who received chemotherapy before enucleation had lower pTNM stage than primarily enucleated children (P = .01). Five patients who received pre-enucleation chemotherapy died as a result of extension into brain or metastasis. No patients who had primary enucleation died. For children with group E eyes, disease-specific survival (DSS) was lower with pre-enucleation chemotherapy (n = 45) than with primary enucleation (n = 37; P = .01). Enucleation longer than 3 months after diagnosis was also associated with lower DSS (P < .001). Conclusion Chemotherapy before enucleation of group E eyes with advanced retinoblastoma downstaged pathologic evidence of extraocular extension, and increased the risk of metastatic death from reduced surveillance and inappropriate management of high-risk disease, if enucleation was performed longer than 3 months after diagnosis.