Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network.

BACKROUND: Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy. METHODS: A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared. RESULTS: Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420). CONCLUSIONS: Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.

Analysis of contributing factors influencing thromboembolic events after total knee arthroplasty.

BACKGROUND: Venous thromboembolic events (VTE) are a known and well-described complication following total knee arthroplasty (TKA). We sought to validate the American College of Chest Physicians thromboprophylaxis recommendations after elective TKA, paying special attention to our dose adjustments for weight, and their impact on VTE in our population. METHODS: We retrospectively investigated risk factors in patients undergoing TKA, focusing mainly on symptomatic VTE occurrence rates from deep vein thrombosis (DVT) or pulmonary embolism (PE). The anticoagulation protocol consisted of starting low molecular-weight heparin (LMWH) therapy, with dalteparin administered 12 h after surgery in patients who received general anesthesia or 24 h later in patients who received single-dose regional anesthesia. RESULTS: Data from 346 patients (mean age 66.8 [range 24-91] yr) who underwent primary or revision TKA depicted an overall symptomatic VTE rate of 15%. The proximal DVT rate was 1.7%, and the nonfatal PE rate was 0.9%. The mean time to VTE diagnosis was 5.6 days. The first dalteparin dose was administered 19.5 (range 10-48) h after surgery in patients without VTE and 22.6 (range 11.5-52) h after surgery in patients with VTE (p = 0.003). With a first dose of dalteparin administered 12 h postoperatively, patients presented significantly lower DVT and PE rates than if it was administered 24 h postoperatively (8.5% v. 16.3%, p = 0.048). CONCLUSION: Delayed administration of LMWH has deleteriously impacted the VTE rate after TKA at our institution. Prompt initiation of LMWH (≤ 12 h after surgery) is appropriate, without increasing the risk of major bleeding.

CONTEXTE: Les événements thromboemboliques veineux (ETV) sont une complication connue et bien décrite de la chirurgie pour prothèse totale du genou (PTG). Nous avons voulu valider les recommandations de l'American College of Chest Physicians en matière de thromboprophylaxie après la PTG non urgente en portant une attention particulière à l'ajustement des doses selon le poids et à leur impact sur les ETV dans notre population. MÉTHODES: Nous avons analysé de manière rétrospective les facteurs de risque chez des patients soumis à une PTG en nous attardant principalement aux taux d'ETV symptomatiques sous forme de thrombose veineuse profonde (TVP) ou d'embolie pulmonaire (EP). Le protocole d'anticoagulothérapie prévoyait l'administration d'une héparine de bas poids moléculaire (HBPM), la daltéparine, 12 h après la chirurgie chez les patients ayant reçu une anesthésie générale, ou 24 h après chez les patients ayant reçu une anesthésie locorégionale à dose unique. RÉSULTATS: Les données provenant de 346 patients (âgés en moyenne de 66,8 and [éventail 24-91 and]) ayant subi une PTG primaire ou une révision de PTG ont révélé un taux d'ETV symptomatique global de 15 %. Le taux de TVP proximal a été de 1,7 % et le taux d'EP non fatale a été de 0,9 %. Le temps moyen avant le diagnostic d'ETV a été 5,6 jours. La première dose de daltéparine avait été administrée 19,5 h (éventail 10-48 h) après la chirurgie chez les patients n'ayant pas présenté d'ETV et 22,6 h (éventail 11,5-52 h) après la chirurgie chez les patients ayant manifesté un ETV (p = 0,003). Avec une première dose de daltéparine administrée 12 h après l'intervention, les patients ont présenté des taux de TVP et d'EP significativement moindres que si elle leur avait été administrée 24 h après l'intervention (8,5 % c. 16,3 %, p = 0,048). CONCLUSION: L'administration retardée de l'HBPM a produit des effets défavorables pour ce qui est des taux d'ETV après la PTG dans notre établissement. L'instauration rapide de l'HBPM (≤ 12 h après la chirurgie) est appropriée et n'accroît pas le risque d'hémorragie majeure.

Survival and recurrence patterns after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophagogastric adenocarcinoma.

INTRODUCTION: We have previously identified Docetaxel, Cisplatin, and 5FU (DCF) as a safe, tolerable, and effective regimen in the neoadjuvant setting for locally advanced adenocarcinoma (ADC) of the esophagus and esophagogastric junction (EGJ). We hypothesized that DCF combined with enhanced surgical control would result in a low rate of local or regional recurrence, and thus reviewed our outcomes with this treatment regimen. METHODS: A prospectively entered database of all esophageal and EGJ ADC patients resected at a high-volume referral center over 6 years (9/07-9/13) was reviewed for cases treated with curative intent neoadjuvant DCF followed by en bloc resection with extended lymphadenectomy (D2/D3). Recurrences was defined as locoregional (biopsy on endoscopy/regional lymph nodes (LNs)) and distant. Standard statistical techniques were used. RESULTS: Of 279 patients with ADC, 86 (85% male, mean age 63 years (interquartile range 56-70)) underwent preoperative DCF and curative intent resection for locally advanced ADC (cT3 93%; cN+ 69%) of the EGJ (54%) or distal esophagus (46%). After median follow-up of 40 months, the overall 5-year survival was 54% and 43 (52%) had recurred at a median time of 14 months. Sites of recurrence included locoregional only in 2 of 45 (4%), distant only in 40 of 45 (89%), and locoregional and distant in 3 of 45 (7%). DISCUSSION: The present study demonstrates favourable oncologic outcomes with low local/regional recurrence and an excellent overall 5-year survival after neoadjuvant DCF for esophageal and EGJ ADCs. Because the majority of recurrences were distant, our data support the notion that efforts to improve outcomes in these patients should concentrate on enhancing systemic, rather than local, therapy.

The impact of endocrine therapy on sexual dysfunction in postmenopausal women with early stage breast cancer: encouraging results from a prospective study.

The goal of this project was to investigate the contentious issue of a possible effect of endocrine therapy (ET) on sexual dysfunction (SD) in postmenopausal early stage breast cancer survivors. To date, few studies have assessed sexual functioning prior to initiating ET and none have taken sexual distress into account when reporting the prevalence of ET-induced SD. We report the findings of a study on the change in SD (defined as experiencing sexual problems causing distress) during the first 6 months of ET usage. Between January 2009 and May 2011, 118 patients entered the study and 66 completed questionnaires prior to initiation of ET and after 6 months of use. Sexual functioning (SF) was evaluated with the female sexual function index while sexual distress was assessed with the female sexual distress scale (FSDS-R). Gynecological symptoms were measured with the FACT-B ES subscale. Over time, the level of gynecological symptoms increased (p < 0.001), whereas no decline in SF was observed. The percentage of women who reported experiencing at least one sexual problem (85 %) and the percentage who were sexually distressed (30 %) remained the same across time. Importantly, the change in the prevalence of SD between baseline (24 %) and 6 months (29 %) was not statistically significant. Women experiencing SD at baseline were more likely to experience SD after 6 months of ET usage (OR = 7.4, 95 % CI = 1.5-36.9) than women who had no SD prior to initiating ET. The observation that SF remained stable across time is encouraging news. However, longer follow-up and the inclusion of women who were premenopausal at diagnosis are needed to determine the potential influence of extended duration of ET (e.g., at least 5 years) on SD. Further studies, including assessing the impact of early identification of patients at risk of developing SD and timely intervention, are warranted.