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.

[Sufentanil in balanced anesthesia: need to predict concentrations for dose optimization]. / Sufentanil en anesthésie balancée: intérêt de prédire les concentrations pour optimiser les doses.

During balanced anaesthesia sufentanil may be difficult to use, as the required doses change over time depending on the patient and the noxious stimuli. Patient adjustment may be improved by using pharmacokinetic simulations that predict the concentration achieved in the body. In the first case report, sufentanil was given manually as repeated boluses, then by infusion. As haemodynamic status remained unstable, a simulation of the sufentanil concentration time course was started during the case. It showed that instability had pharmacokinetic explanation and allowed to determine the adequate sufentanil concentrations (0.30-0.40 ng.mL-1 + N2O + isoflurane 0.8-1 vol% for abdominal surgery). However, adjusting the doses manually required numerous human actions. In the second case, sufentanil was given as a computer-controlled infusion. The adequate concentrations were determined (0.15-0.20 ng.mL-1 + N2O + isoflurane 0.4 vol% for peripheral surgery in an aged cardiac patient). They were maintained with a limited number of human actions and resulted in satisfactory haemodynamic stability.

Routine intraoperative cholangiography is feasible and efficient during laparoscopic cholecystectomy.

BACKGROUND/AIMS: This is the evaluation of the feasibility and results of routine laparoscopic intraoperative cholangiography. PATIENTS AND METHODS: A multicentric prospective study in 315 consecutive patients undergoing elective or urgent laparoscopic cholecystectomy. RESULTS: The success rate was 94%. Mean duration of intraoperative cholangiography was 12 min. Sixteen of 18 failures were related to a narrow cystic duct. One cystic duct avulsion (ligated under laparoscopy) and 2 false positive cholangiograms (1 transcystic exploration, 1 conversion) were noted. Intraoperative cholangiography revealed aberrant bile ducts possibly at risk to injury from dissection in four patients (1.3 per cent). Intraoperative cholangiography disclosed unsuspected stones in 10 patients (4%). Forty-five patients had a preoperative suspicion of choledocholithiasis: choledocholithiasis were found at intraoperative cholangiography in 3 of 13 patients who had preoperative endoscopic sphincterotomy for stone extraction, in 1 of 11 patients with normal preoperative endoscopic cholangiography, and in 11 of 21 patients undergoing surgery alone (57%). CONCLUSION: If complete clearance of choledocholithiasis is to remain the objective of surgical treatment of biliary lithiasis including laparoscopic cholecystectomy, then routine intraoperative cholangiography is feasible and efficient.

Laparoscopic treatment for choledocholithiasis: a prospective evaluation in 247 consecutive unselected patients.

BACKGROUND/AIMS: Evaluation of the feasibility and results of the one-stage treatment combining routine intraoperative cholangiography and laparoscopic common bile duct exploration for choledocholithiasis. PATIENTS AND METHODS: Multicentric (5 centers-9 surgeons) prospective study in 247 consecutive patients (mean age 68 years; range 21-92) during a 50-month period (November 1991-December 1995). Laparoscopic treatment of choledocholithiasis was attempted irrespective of the circumstances leading to the diagnosis of biliary lithiasis or the preoperative suspicion of choledocholithiasis. RESULTS: One out of four patients (n = 61) had unsuspected choledocholithiasis disclosed by routine intraoperative cholangiography. A laparoscopic complete clearance of choledocholithiasis was achieved in 208 of 236 attempted cases (88%), with either transcystic duct extraction (n = 116) or choledochotomy (n = 92). Open surgery was required in 20 patients for failure of laparoscopic treatment and in 3 patients despite successful extraction. Twenty-one of 25 patients (84%) referred for failure of retrograde endoscopic stone extraction had successful laparoscopic choledocholithiasis clearance. The mean duration for the laparoscopic transcystic approach and choledochotomy were 108 min (range 50-300) and 173 min (range 70-480), respectively. Eleven patients had retained stones (4.4%). Minor and major complications were recorded in 9 and 22 patients respectively. The operative mortality was 0.4% (95% confidence interval: 0-1.2%). CONCLUSION: Intraoperative cholangiography during laparoscopic cholecystectomy and laparoscopic common bile duct exploration when required should be considered as the simplest and most efficient treatment for choledocholithiasis. The multicenter character of this study including consecutive patients from public and private practices, strengthens our conclusions and is consistent with a wide diffusion of this diagnostic and therapeutic strategy.

[Treatment of common bile duct lithiasis under laparoscopy. A prospective multicenter study in 189 patients]. / Traitement de la lithiase de la voie biliaire principale sous laparoscopie.

OBJECTIVES: The aim of this study was to assess the feasibility and results of common bile duct laparoscopic treatment and exploration in patients with choledocholithiasis. PATIENTS AND METHODS: From November 1991 to December 1994, 189 consecutive malades (120 females; mean age 68 years, range: 21-92) with choledocholithiasis identified during routine intraoperative cholangiogram underwent surgical exploration of common bile duct in 5 surgical centers. Twenty patients were referred to surgery after unsuccessful endoscopic sphincterotomy. RESULTS: Following laparoscopic exploration and intraoperative cholangiography, common bile duct stone extraction by laparoscopy was not attempted in 11 patients (5.8%). The common bile duct was successfully cleared of all stones in 153 patients (81% of the overall population and 86% of laparoscopic attempts), either via the transcystic route (n = 97) or through choledocotomy (n = 56). Eighteen patients required conversion to open surgery, 16 for unsuccessful stone extraction and 2 despite successful stone extraction. Postoperative endoscopic sphincterotomy was required in 7 patients (4.4%) for retained stones after laparoscopic treatment. There were no postoperative deaths (95% confidence interval 0-1.6%), and follow-up, ranging from 3 to 42 months, has shown no further clinical evidence of retained stones. CONCLUSION: Diagnosis and treatment of common bile duct stones is feasible by laparoscopy, and the results in this series compare favorably with those of conventional surgical treatment. Complete treatment of biliary lithiasis, in one operation, avoids the pitfalls of patient selection for preoperative endoscopic retrograde cholangiography and the risks of endoscopic sphincterotomy.

Prospective evaluation in 121 consecutive unselected patients undergoing laparoscopic treatment of choledocholithiasis.

Laparoscopic common bile duct (CBD) exploration was attempted in 115 of 121 consecutive unselected patients with choledocholithiasis (mean age 69 (range 21-92) years) found during routine intraoperative cholangiography. The CBD was successfully cleared of all stones in 100 patients (87 per cent). Ten of 11 patients referred for surgery after failure of endoscopic sphincterotomy had complete laparoscopic choledocholithiasis. Eleven patients (10 per cent) required conversion to open CBD exploration, and laparoscopic exploration was not attempted in six (5 per cent) because of inflammation or fibrosis. Postoperative endoscopic sphincterotomy was required in four patients (4 per cent) for retained stones after laparoscopic exploration. There were no postoperative deaths (39 per cent of patients were aged 75 years or more). Routine intraoperative cholangiography, and when required laparoscopic CBD exploration, should be compared in randomized trials with preoperative endoscopic retrograde cholangiography in patients with suspected choledocholithiasis.