Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer.

BACKGROUND: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody-drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown. METHODS: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC. RESULTS: One hundred and seventy-nine patients were included: the majority with HR-negative tumours received SG first (ADC1) (n = 100/108) while most with HR-positive tumours received T-DXd first (n = 56/71). Median progression-free survival 2 was short: 2.7 months (95% CI: 2.4-3.3) in the whole population, respectively, 3.1 (95% CI: 2.6-3.6) and 2.2 months (95% CI: 1.9-2.7) for patients receiving T-DXd or SG second (ADC2). Intermediary lines of chemotherapy between ADC1 and ADC2 had no impact. Primary resistance to ADC2 occurred in 54.4% of patients. Certain patients showed initial response to ADC2. CONCLUSIONS: Clinical benefit of sequentially administered SG and T-DXd is limited for most patients. Nevertheless, a subset of patients might benefit-on the short term-from a second ADC. Additional studies are needed to identify patients who could benefit from two ADCs with similar payloads.

Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.

Salvage reirradiation for local prostate cancer recurrence after radiation therapy. For who? When? How?

PURPOSE: Literature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. MATERIALS AND METHODS: A total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy. RESULTS: Late genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. CONCLUSION: Despite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.

Risk management in outpatient surgery.

Outpatient surgery has become a national policy priority set by health care authorities (targets for more than 70% of outpatient procedures by 2022), making ambulatory hospitalization the new standard of care. This practice introduces new risks along the patient's course. Even though these risks are low and although the literature and data from insurance databases is reassuring, the risks in outpatient surgery remain poorly understood. Risks can be organizational in view of the many stages of the patient journey that must be formalized-medical, anesthetic or surgical-in view of planned discharge the same evening as the procedure, and medico-legal because of the importance of the discharge authorization and the information provided to the patient. A risk management approach (a priori or a posteriori) has become a mandatory part of a policy of continuous quality improvement and safety of care. The coordination of all the team members (surgeon, anesthesiologist, nursing and administrative staff and the patient's accompanying person) as well as the patient's active participation are essential to minimize risks and prevent complications.

Risk management for surgical energy-driven devices used in the operating room.

Complications related to energy sources in the operating room are not well-recognized or published, despite occasionally dramatic consequences for the patient and the responsible surgeon. The goal of this study was to evaluate the risks and consequences related to use of energy sources in the operating room. PATIENTS AND METHODS: Between 2009 and 2015, 876 adverse events related to health care (AERHC) linked to energy sources in the operating room were declared in the French experience feedback data base "REX". We performed a descriptive analysis of these AERHC and analyzed the root causes of these events and of the indications for non-elective repeat operations, for each energy source. RESULTS: Five different energy sources were used, producing 876 declared AERHC: monopolar electrocoagulation: 614 (70%) AERHC, advanced bipolar coagulation (thermofusion): 137 (16%) AERHC, ultrasonic devices: 69 (8%) AERHC, traditional bipolar electrocoagulation: 32 AERHC, and cold light: 24 AERHC. The adverse events reported were skin burns (27.5% of AERHC), insulation defects (16% of AERHC), visceral burns or perforation (30% of AERHC), fires (11% of AERHC), bleeding (7.5% of AERHC) and misuse or miscellaneous causes (8% of AERHC). For the five energy sources, the root causes were essentially misuse, imperfect training and/or cost-related reasons regarding equipment purchase or maintenance. One hundred and forty-six non-elective procedures (17% of AERHC) were performed for complications related to the use of energy sources in the operating room. CONCLUSION: This study illustrates the risks related to the use of energy sources on the OR and their consequences. Most cases were related to persistent misunderstanding of appropriate usage within the medical and paramedical teams, but complications are also related to administrative decisions concerning the purchase and maintenance of these devices.

[Regional anaesthesia for head and neck surgery]. / Anesthésie locorégionale pour la chirurgie esthétique de la face et du cou.

Plastic surgery is more and more developing. Facial blocks are adapted to surgical procedures performed in this setting. They are easy to perform and may prolong postoperative analgesia. Facial blocks may be used in ambulatory surgery as a single technique or combined with general anaesthesia or intravenous sedation. After a reminding of facial nerve anatomy, facial and cervical blocks are described with their indications. Guidelines for performance and monitoring are also indicated.

Prevalence of postoperative bladder distension and urinary retention detected by ultrasound measurement.

BACKGROUND: Postoperative bladder distension and urinary retention are commonly underestimated. Ultrasound enables accurate measurement of bladder volume and thus makes it possible to determine the prevalence of postoperative bladder distension. METHODS: Using ultrasound, we measured the volume of the bladder contents at the time of discharge from the recovery room in 177 adult patients who had undergone thoracic, vascular, abdominal, orthopaedic or ENT surgery. RESULTS: Forty-four per cent of the patients had a bladder volume >500 ml and 54% of the 44%, who had no symptoms of bladder distension, were unable to void spontaneously within 30 min. The risk factors for urinary retention were age >60 yr (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.01-4.38), spinal anaesthesia (OR 3.97, 95% CI 1.32-11.89) and duration of surgery >120 min (OR 3.03, 95% CI 1.39-6.61). CONCLUSION: Before discharge from the recovery room it seems worthwhile to systematically check the bladder volume with a portable ultrasound device in patients with risk factors.

One hundred laparoscopic choledochotomies with primary closure of the common bile duct.

BACKGROUND: Several technical approaches for laparoscopic CBD exploration (LCBDE) exist. Laparoscopic choledochotomy is required in some situations and whenever a transcystic approach fails. Biliary drainage after choledochotomy has a 5% morbidity rate and avoidance of biliary drains might therefore further improve the results of LCBDE. The authors report a prospective multicentric evaluation of laparoscopic choledochotomy with completion choledochoscopy and primary duct closure without any biliary drainage. METHODS: Between October 1991 and December 1997, 100 patients from four surgical centers underwent this approach for CBD stones. Choledocholithiasis had been demonstrated preoperatively in 35 patients (35%), suspected in 52 and was incidentally found during routine intraoperative cholangiography in 13 patients. External ultrasound was the only preoperative imaging investigation in 87 patients. LCBDE was attempted irrespective of age, ASA score, or the circumstances leading to the preoperative diagnosis or suspicion of CBD stones (acute cholecystitis in 33% of patients, cholangitis in 10%, or mild acute pancreatitis in 6% of all patients). RESULTS: The technique was equally feasible in all participating centers (University hospital, general hospital, or private practices). Vacuity of the CBD was achieved in all patients without mortality. Eleven patients had complications and 3 patients required a laparoscopic reintervention. Median postoperative hospital stay was 6 days (range: 1-26). No patient required additional CBD procedures during follow-up. CONCLUSIONS: In case of LCBDE, choledochotomy with primary closure without external drainage of the CBD is a safe and efficient alternative, even in patients with acute cholecystitis, cholangitis, or pancreatitis, provided that choledochoscopy visualizes a patent CBD. This technique is applicable in all types of medical institutions if required laparoscopic skills and equipment are available.

An outbreak of imipenem-resistant Acinetobacter baumannii in critically ill surgical patients.

OBJECTIVE: To describe an outbreak of imipenem-resistant Acinetobacter baumannii (IR-Ab) and the measures for its control, and to investigate risk factors for IR-Ab acquisition. DESIGN: An observational and a case-control study. SETTING: A surgical intensive care unit (ICU) in a university tertiary care hospital. METHODS: After admission to the ICU of an IR-Ab-positive patient, patients were prospectively screened for IR-Ab carriage upon admission and then once a week. Environmental cleaning and barrier safety measures were used for IR-Ab carriers. A case-control study was performed to identify factors associated with IR-Ab acquisition. Cases were patients who acquired IR-Ab. Controls were patients who were hospitalized in the ICU at the same time as cases and were exposed to IR-Ab for a similar duration as cases. The following variables were investigated as potential risk factors: baseline characteristics, scores for severity of illness and therapeutic intervention, presence and duration of invasive procedures, and antimicrobial administration. RESULTS: Beginning in May 1996, the outbreak involved 17 patients over 9 months, of whom 12 acquired IR-Ab (cases), 4 had IR-Ab isolates on admission to the ICU, and 1 could not be classified. Genotypic analysis identified two different IR-Ab isolates, responsible for three clusters. Ten of the 12 nosocomial cases developed infection. Control measures included reinforcement of barrier safety measures, limitation of the number of admissions, and thorough environmental cleaning. No new case was identified after January 1997. Eleven of the 12 cases could be compared to 19 controls. After adjustment for severity of illness, a high individual therapeutic intervention score appeared to be a risk factor for IR-Ab acquisition. CONCLUSION: The outbreak ended after strict application of control measures. Our results suggest that high work load contributes to IR-Ab acquisition.