Oncological monitoring after transanal total mesorectal excision (TaTME) for rectal neoplasia.

BACKGROUND: The surgical treatment of choice for rectal neoplasia is total mesorectal excision (TME). The transanal approach enables a better approach in male and obese patients and/or those with a narrow pelvis and in patients with small tumors. Short-term results are comparable with those for laparoscopy or the open approach, but the medium- and long-term oncological data are sparse. The aim of the present study was to evaluate our early experience with transanal TME (TaTME). METHODS: This was a retrospective study conducted on patients who underwent TaTME at our center between August 2013 and April 2017 with a follow-up ≥ 3 years. Histopathology, complications, mortality, neoplastic recurrence and disease-free survival were analyzed. RESULTS: One hundred patients (68 men and 32 women,, median age 66.8 years [range 29.6-91.2 years]) were included. There were 67 T3 cases (67%) with 74 N0 cases (74%), the mesorectal quality was graded optimal for 87.6% and only 2 cases of radial margin involvement were detected (2%). The median follow-up period was 47.6 months (range 11.8-78.9 months). Eighteen cases of recurrence were diagnosed, of which 3 (3%) recurred locally with an average disease-free period of 43.1 months. Overall survival was 80% and mortality due to progression of disease was 13%. CONCLUSIONS: TaTME is a safe surgical procedure with surgical, anatomopathological and oncological results at 3 years (medium-term) comparable with those for the laparoscopic and open approaches. Better monitoring is required with studies of the long-term functional and quality of life outcomes, i.e., at 5 or 10 years.

Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling.

This corrects the article DOI: 10.1038/onc.2016.209.

Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling.

Canonical Wnt signaling induces the stabilization of ß-catenin, its translocation to the nucleus and the activation of target promoters. This pathway is initiated by the binding of Wnt ligands to the Frizzled receptor, the association of the LRP5/6 co-receptor and the formation of a complex comprising Dvl-2, Axin and protein kinases CK1α, ɛ, γ and GSK3. Among these, activation of CK1ɛ, constitutively bound to LRP5/6 through p120-catenin, is required for the association of the rest of the components. We describe here that CK1ɛ is activated by the PP2A/PR61ɛ phosphatase. Binding of Wnt ligands promotes the interaction of LRP5/6-associated CK1ɛ with Frizzled-bound PR61ɛ regulatory subunit, facilitating the access of PP2A catalytic subunit to CK1ɛ and its activation, what enables the recruitment of Dvl-2 to the receptor complex and the initiation of the Wnt pathway. Our results uncover the mechanism of activation of the canonical Wnt pathway by its ligands.

A feasibility study of the efficacy and tolerability of the combination of Exemestane with the COX-2 inhibitor Celecoxib in post-menopausal patients with advanced breast cancer.

BACKGROUND: This was a feasibility study of the combination of Exemestane and the cyclooxygenase-2 (COX-2) inhibitor Celecoxib in advanced breast cancer. PATIENTS AND METHODS: Post-menopausal women with histologically proven, hormone receptor positive, advanced breast cancer who had progressive disease, normal blood counts, liver and renal function were eligible. Exemestane was given at a dose of 25 mg daily and Celecoxib at a dose of 400 mg bd. Responses were assessed according to RECIST criteria and toxicity was accessed according to CTC. The primary end-point was the percentage of patients who had neither discontinued therapy nor progressed at 6 months ('treatment successes'). RESULTS: Fifty-three eligible patients were enrolled. Of 30 patients with target lesions, 4 (13%) had a complete response (CR), 12 (40%) a partial response (PR) and 5 (17%) stable disease (SD). The best response in 18 of the 23 patients with no target lesions at baseline was stable disease. The clinical benefit (CR, PR+SD) for the whole group was therefore 39/53 (74%). The 'treatment success' rate was 60%. There were two non-malignant deaths which may have been associated with treatment. CONCLUSION: The combination of Exemestane and Celecoxib shows promising activity and tolerability and these results support the use of this combination in phase III clinical trials of short duration treatments.

Primary cutaneous extraskeletal osteosarcoma under a previous electrodessicated actinic keratosis.

Extraskeletal osteosarcoma represents approximately 1% of soft tissue sarcomas and approximately 4% of all osteosarcomas. It is therefore much rarer than osteosarcoma arising primarily in bone. Skin as a primary site has seldom been reported. This report describes an extraskeletal osteosarcoma of the skin under a previously electrodessicated actinic keratosis.

Squamous cell carcinoma arising in long-standing necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a disease of collagen. Squamous cell carcinomas developing in areas of chronic ulceration and scarring have been well documented in a variety of skin diseases but rarely in areas of necrobiosis lipoidica. The case history of a 76-year-old female is presented, whose squamous cell carcinoma appeared 30 years after the diagnosis of necrobiosis lipoidica. The clinical and histopathological picture is described, stressing the importance of the unusual association of the two pathologies in the prognostic.

Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study.

BACKGROUND: A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients. PATIENTS AND METHODS: Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles). RESULTS: In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64). CONCLUSION: This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.

[Risk factors involved in presbyacusis]. / Factores de riesgo involucrados en la presbiacusia.

INTRODUCTION: Presbyacusis is a disease whose prevalence tends to increase in Europe, due to the aging of the population. Our purpose is to evaluate the prevalence of presbyacusis, as well as the implication of sex, cardiovascular risk factors and relation with home and its geographical location. PATIENTS AND METHOD: We started a cross-sectional study with 61 patients coming from different retirement homes, being able to finally test 59 subjects, after two abandonments. RESULTS: The prevalence of presbyacusis was of 16.9%, predominating in female sex, although it was not a statistically significant association, with an average age at the moment of the study of 75.7 years. None of the presbyacusis patients referred smoking habits in the last 30 years, and only sporadic alcohol. A significantly negative statistical relation with the hypertension was verified. There was no significant statistical association with the location and type of home, neither with other risk factors. CONCLUSIONS: The high prevalence of the disease is confirmed, without a real significant predominance in women. The time of evolution of the disease is variable at the moment of the diagnosis. We emphasized the absence of relation between the arterial hypertension, the consumption of tobacco and alcohol and presbyacusis, as well as the rest of studied risk factors.

Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up.

Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up.

Orthopaedic treatment in tibial diaphyseal fractures. Risk factors affecting union.

A retrospective of 216 tibial fractures treated orthopedically was carried out. The aim was to analyze a set of clinicobiological parameters that owing to their assumed action on the physiological model of consolidation can be considered as risk factors to be taken into account in all kinds of orthopedic treatment, because they may lead to a lengthening of the normal consolidation time of the fracture. The variables analyzed were the following: type of immobilization, causative agent of the fracture, location of the focus of the fibular fracture, initial displacement, degree of conminution, type of wound, type of fracture, appearance of radiologically observable callus, commencement of weight-bearing, post-fracture hematoma, secondary displacement, and infection of soft tissues. In the particular case of immobilization by an ischiopedic plaster cast, the following parameters showed a greater degree of prognostic significance: initial displacement, secondary displacement, and age.

Mitomycin C as an adjuvant in resected gastric cancer.

As a result of their previous experience with mitomycin C at high discontinuous doses in advanced gastric cancer, the authors studied its role as an adjuvant for locally advanced cases after surgical complete resection. Results from 70 evaluable patients are presented. Patients were allocated randomly to receive mitomycin C, 20 mg/m2 I.V. direct once every 6 weeks, four courses, or a placebo. After a follow-up period of 250 weeks, seven patients of treatment arm and 23 controls have already relapsed (p less than 0.001). Toxicity was moderate and controllable by symptomatic measures. The authors consider this investigation a positive contribution in the field of adjuvant therapy of gastric cancer.