Search

Ana Paróla,1 Fátima da Silva Mousinho de Palhares Falcão,1,2 Helena Farinha,1 André Caetano,3 Luís Santos,3 Elmira Medeiros,3 Miguel Viana-Baptista3,4 1Pharmacy Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; 2Department of Social Pharmacy, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; 3Neurology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; 4Faculty of Medical Sciences, Nova University of Lisbon, Lisbon, Portugal Purpose: Riluzole is indicated to prolong life or delay the institution of mechanical ventilation in patients with amyotrophic lateral sclerosis (ALS). Clinical studies have shown that this drug prolongs survival, defined as living patients who are not intubated for mechanical ventilation and without tracheotomy. The purpose of this study is to characterize riluzole’s use as well as the user population in order to contribute to a rational and safe use.Patients and methods: Descriptive, observational, retrospective study describing and characterizing the use of riluzole in ALS patients between July 2006 and December 2016 conducted in a Lisbon’s Central Hospital.Results: Over the course of the study period, 77 patients with different phenotypes of ALS received riluzole. The majority of patients (63%, n=49) were male. The median survival was 10.1 months, but 12 patients (16%) remained on therapy for more than 3 years; 65% of patients were lost to follow-up. The mean adherence rate was 91.2%, and the median adherence rate was 99.3%. One patient discontinued therapy due to gastrointestinal intolerance. Dyspnea and cough were the most common side effects, with roughly one third of patients experiencing each, followed by asthenia and hepatic effects.Conclusion: Despite the extended enrollment period, only 77 patients met the criteria for study inclusion. Nonetheless, statistical data regarding our population is in accordance with reported international data. High adherence rates were observed, but 14% of patients discontinued riluzole. In such cases, assessment by a multidisciplinary team is warranted. Keywords: riluzole, adherence rate, amyotrophic lateral sclerosis, safety profile, drug interactions

The current case report is about spontaneous non-traumatic rupture of a splenic artery aneurysm (SAA) in a 53-year-old woman with no particular medical history. An emergent laparotomy with splenectomy was required, unfortunately without success as the patient died. SAA is the most common visceral artery aneurysm. Most of SAA remain asymptomatic and are discovered incidentally on imaging. The overall risk of rupture increases with the size of SAA, especially when above 2 cm. Initial presentation of SAA has been associated with acute rupture and hemodynamic instability leading to substantial perioperative morbidity and mortality. [ABSTRACT FROM AUTHOR]

What is known and Objective Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. Main issues The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. What is new and conclusion The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies. [ABSTRACT FROM AUTHOR]

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Background In Europe, 15—38% of HIV infections are diagnosed at advanced stages. Late presentation is associated with increased morbidity and mortality, greater burden for the healthcare system and higher risk [...]

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Purpose of the study Since the use of more tolerable and less toxic combined antiretroviral (ARV) therapy, most drug‐naïve HIV patients achieve viral suppression and immunologic recovery, combined with less [...]

Background: Esophageal cancer posed significant global health challenges, particularly due to poor survival rates, especially in advanced stages. Primary endoscopic resection had emerged as an alternative treatment for early esophageal cancer, aiming to preserve organ function and reduce surgical morbidity., Methods: This retrospective multicenter cohort study included 334 patients with early esophageal cancer (T1a-b, N0) from 30 French-speaking European centers between 2000 and 2010. Patients underwent either primary endoscopic resection followed by esophagectomy (E group, n = 36) or esophagectomy alone (S group, n = 298). Cox proportional hazards models adjusted for TNM stage and propensity score weighting were used to assess the impact of primary endoscopic resection on recurrence-free survival (RFS), overall survival (OS), and postoperative complications., Results: Primary endoscopic resection did not significantly influence RFS (adjusted HR 0.92, 95% CI 0.31 to 2.68, p = 0.88) or OS (adjusted HR 1.06, 95% CI 0.35 to 3.13, p = 0.92) compared to esophagectomy alone. Initial higher thromboembolic complications in the endoscopic resection group were not significant after adjustment (adjusted OR 4.73, 95% CI 0.34 to 64.27, p = 0.24)., Conclusions: Primary endoscopic resection followed by esophagectomy for early esophageal cancer did not alter oncological outcomes or overall survival in this retrospective cohort. These findings supported the role of primary endoscopic resection as a safe initial treatment strategy, warranting validation in larger prospective studies., Registration: Our study was registered retrospectively on the Clinicaltrials.com website under the identifier NCT01927016. We acknowledge the importance of prospective registration and regret that this was not done before the commencement of the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS)., Methods: Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted., Results: Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance., Conclusions: TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS., (© 2024. The Author(s).)

Gastrointestinal Stromal Tumors (GISTs) account for 1 to 2% of gastrointestinal malignant tumors. They are characterized by overexpression of the tyrosine kinase (KIT). 60% of GISTs originate in the stomach. Managing them remains complex and varies depending on several factors such as location, size, molecular biology, type of clinical presentation, and the risks/benefits of surgical treatment. Surgery remains the only curative treatment, while tyrosine kinase inhibitors have demonstrated their efficacy as systemic treatment in the perioperative context. Risk stratification for recurrence guides the choice of adjuvant treatment, with a recommended duration of 3 years for high-risk patients., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose: Paraoesophageal hernias (PEH) are associated with a high complication rate and often occur in elderly and fragile patients. Surgical gastropexy without fundoplication is an accepted alternative procedure; however, outcomes and functional results are rarely described. Our study aims to evaluate short-term outcomes and the long-term quality of life after gastropexy as treatment for PEH., Methods: Single center cohort analysis of all consecutive patients who underwent gastropexy for PEH without fundoplication. Postoperative outcomes and functional results were retrospectively collected. Reflux symptoms developed postoperatively were reported using the validated quality of life questionnaire: GERD-Health Related Quality of Life Qestionnaire (GERD-HRQL)., Results: Thirty patients (median age: 72 years (65-80)) were included, 40% classified as ASA III. Main PEH symptoms were reflux (63%), abdominal/thoracic pain (47%), pyrosis (33%), anorexia (30%), and food blockage (26%). Twenty-six laparoscopies were performed (86%). Major complications (III-IVb) occurred in 9 patients (30%). Seven patients (23%) had PEH recurrence, all re-operated, performing a new gastropexy. Median follow-up was 38 (17-50) months. Twenty-two patients (75%) reported symptoms resolution with median GERD-HRQL scale of 4 (1-6). 72% (n = 21) reported operation satisfaction. GERD-HRQL was comparable between patients who were re-operated for recurrence and others: 5 (2-19) versus 3 (0-6), p = 0.100., Conclusion: Gastropexy without fundoplication was performed by laparoscopy in most cases with acceptable complications rates. Two-thirds of patients reported symptoms resolution, and long-term quality-of-live associated to reflux symptoms is good. Although the rate of PEH recurrence requiring a new re-intervention remained increased (23%), it does not seem to affect long-term functional results., (© 2024. The Author(s).)

Background: Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy., Methods: A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS., Results: The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34)., Conclusions: At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer., (© 2023. Society of Surgical Oncology.)

Primary surgical indications for the esophagus and stomach mainly involve cancer surgeries. In recent years, significant progress has been made in the field of esogastric surgery, driven by advancements in surgical techniques and improvements in perioperative care. The rate of resectability has increased, and surgical strategies have evolved to encompass a broader patient population. However, despite a reduction in postoperative mortality and morbidity, malnutrition remains a significant challenge after surgery, leading to weight loss, muscle mass reduction, and deficiencies in essential nutrients due to digestive complications. Malnutrition worsens quality of life and increases the risk of tumor recurrence, significantly affecting prognosis. Nevertheless, the nutritional consequences following surgery are frequently overlooked, mainly due to a lack of awareness regarding their long-term effects on patients who have undergone digestive surgery, extending beyond six months. Micronutrient deficiencies are frequently observed following both partial and total gastrectomy, as anticipated. Surprisingly, these deficiencies appear to be similarly prevalent in patients who have undergone esophagectomy with iron, vitamins A, B1, B12, D, and E deficiencies commonly observed in up to 78.3% of the patients. Recognizing the distinct consequences associated with each type of intervention underscores the importance of implementing preventive measures, early detection, and prompt management.

Objectives: Cytology of ascites or peritoneal washing is a routine part of staging of peritoneal metastases (PM). We aim to determine value of cytology in patients undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC)., Methods: Single-center retrospective cohort study included consecutive patients having PIPAC for PM of different primary between January 2015 and January 2020., Results: A total of 75 patients (median 63 years (IQR 51-70), 67 % female) underwent a total of 144 PIPAC. At PIPAC 1 59 % patients had positive and 41 % patients had negative cytology. Patients with negative and positive cytology only differed in terms of symptoms of ascites (16% vs. 39 % respectively, p=0.04), median ascites volume (100 vs. 0 mL, p=0.01) and median PCI (9 vs. 19, p<0.01). Among 20 patients who completed 3 PIPACs (per protocol), cytology changed in one from positive to negative, and in two from negative to positive. Median overall survival was 30.9 months in the per protocol group and 12.9 months in patients having <3 PIPACs (=0.519)., Conclusions: Positive cytology under PIPAC treatment is more frequently encountered in patients with higher PCI and symptomatic ascites. Cytoversion was rarely observed and cytology status had no impact on treatment decisions in this cohort., Competing Interests: Competing interests: Martin Hübner: ENCARE: Consultant fee (institution); Nestlé: Research funding. Capnomed: Sponsoring of scientific meetings; MSD, Fresenius: Speaker honorary (institution); ERAS society: Board member, chair education; ISSPP: Board member, chair education. Mélina Deban, Julien Châtelain, Daniel Clerc, Laura Toussaint and Hugo Teixeira Farinha declare no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7-12.8; 14.9-17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients., (© 2023. The Author(s).)

Gastric adenocarcinoma remains associated with a poor long-term survival, despite recent therapeutical advances. In most parts of the world where systematic screening programs do not exist, diagnosis is often made at advanced stages, affecting long-term prognosis. In recent years, there is increasing evidence that a large bundle of factors, ranging from the tumor microenvironment to patient ethnicity and variations in therapeutic strategy, play an important role in patient outcome. A more thorough understanding of these multi-faceted parameters is needed in order to provide a better assessment of long-term prognosis in these patients, which probably also require the refinement of current staging systems. This study aims to review existing knowledge on the clinical, biomolecular and treatment-related parameters that have some prognostic value in patients with gastric adenocarcinoma.

During 2022 a lot of efforts were developed to reduce health-costs by reducing complications and length of hospital stay. Same-day surgery is becoming the standard for all patients scheduled for elective surgery in CHUV. Outpatient colectomy also become a new standard. During 2022, endoscopic bariatric surgery became increasingly used. Not widely performed yet in Switzerland, these treatments deserve to be recognized and considered in various situations. Finally, 2022 saw a promising development of robotic surgery with the acquisition of Da Vinci and Dexter robots after allowing various high-precision surgical procedures., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background : Locally advanced gastroesophageal junction adenocarcinoma (GEJ) is treated with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. The aim of this study was to compare pathologic response and long-term outcomes in junction adenocarcinoma treated with neoadjuvant RCT versus CT. Methods : All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 were retrospectively analyzed. Results : A total of 94 patients were included, 67 (71.2%) RCT and 27 (28.8%) CT. Complete pathologic response was more frequent in RCT patients (13.4% vs. 7.4%, p = 0.009) with a trend to better lymph node control (ypN0) (55.2% vs. 33.3%; p = 0.057). RCT offered no benefit in R0 resection (66.7% vs. 72.1% CT, p = 0.628) and was related to higher postoperative cardiovascular complications (35.8% vs. 11.1%; p = 0.017). Long-term overall and disease-free survival were similar (5-year OS 61.1% RCT vs. 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs. 22.8% CT; p = 0.763). NAT type was neither independently associated with pathologic response nor long-term survival. Discussion : Patients with locally advanced GEJ adenocarcinoma treated with RCT had more postoperative cardiovascular complications but higher rates of complete pathologic response and a trend to superior locoregional lymph node control. This did not translate in a survival or recurrence benefit.

The objective of this study is to analyze oncological outcomes of patients with peritoneal metastases (PM) of colorectal origin treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)., Background: PIPAC has been demonstrated to be a feasible and safe novel treatment for patients with PM of various origins. Only small series reports on survival after PIPAC by disease entity., Methods: International retrospective cohort study of consecutive patients with PM of colorectal origin. Outcome measures were overall survival (OS), radiological response according to Response Evaluation Criteria in Solid Tumors (RECIST), histological response (peritoneal regression grading score [PRGS]: complete response: 1-4: no response), change of peritoneal cancer index (PCI), and symptom control., Results: Seventeen eligible centers compiled 256 non-selected patients (mean age 61 [50.6-69.2], 43% female) and 606 procedures. Sixty-three percent were treated after 2 lines of chemotherapy, median PCI at PIPAC1 was 18 (interquartile range [IQR] = 10-27). Median OS was 19.00 months (IQR = 12.9-29.8) from diagnosis and 9.4 months (IQR = 4.5-16.8) from PIPAC1. One hundred and four of 256 patients (40.6%) had ≥3 procedures (per protocol [pp]) with the following outcomes at PIPAC3: RECIST: 59.3% partial response/stable, 40.7% progression; mean PRGS: 2.1 ± 0.9. Median PCI was 21 (IQR = 15-29) at baseline and 20 (IQR = 12-27) at PIPAC3 ( P = 0.02). Fifty-six (54%) and 48 (46%) patients were symptomatic at baseline and PIPAC3, respectively ( P = 0.267). Median OS for the pp cohort was 11.9 months (IQR = 10.7-15.0) from PIPAC1. Independent predictors for survival were radiological response (HR = 3.0; 95% CI = 1.6-5.7) and no symptoms (HR = 4.5, 95% CI = 2.2-9.1) at PIPAC3., Conclusions: Objective treatment response and encouraging survival were demonstrated after PIPAC for colorectal PM. Prospective registry data and comparative studies are now needed in to confirm these data., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background The aim of this study was to analyse survival and surrogates for oncological response after PIPAC for appendiceal tumours. Methods This retrospective cohort study included consecutive patients with appendiceal peritoneal metastases (PM) treated in experienced PIPAC centers. Primary outcome measure was overall survival (OS) from the date of diagnosis of PM and from the start of PIPAC. Predefined secondary outcome included radiological response (RECIST criteria), repeat laparoscopy and peritoneal cancer index (PCI), histological response assessed by the Peritoneal regression grading system (PRGS) and clinical response. Results Final analysis included 77 consecutive patients (208 PIPAC procedures) from 15 centres. Median OS was 30 months (23.00-46.00) from time of diagnosis and 19 months (13.00-28.00) from start of PIPAC. 35/77 patients (45%) had ≥3 procedures (pp: per protocol). Objective response at PIPAC3 was as follows: RECIST: complete response 4 (11.4%), 11 (31.4%) partial/stable; mean PRGS at PIPAC3: 1.8 ± 0.9. Median PCI: 21 (IQR 18-27) vs. 22 (IQR 17-28) at baseline ( p = 0.59); 21 (60%) and 18 (51%) patients were symptomatic at baseline and PIPAC3, respectively ( p = 0.873). Median OS in the pp cohort was 22.00 months (19.00-NA) from 1st PIPAC. Conclusion Patients with PM of appendiceal origin had objective treatment response after PIPAC and encouraging survival curves call for further prospective evaluation.

Background: This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L)., Methods: Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group)., Results: In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group (p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group (p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups., Conclusions: The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies., (© 2022. Society of Surgical Oncology.)

Objectives: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care., Methods: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice., Results: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years., Conclusions: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care., (© 2021 British HIV Association.)

Background: The standard treatment protocol for PIPAC consists of three procedures. Completion of treatment has been shown to be prognostic of improved survival. The aim of this study was to identify predictors for completion of treatment. Methods: Retrospective multicentric cohort study of patients with peritoneal metastases undergoing PIPAC in three PIPAC expert centers. Per protocol (PP) treatment was defined as patients receiving ≥3 PIPACs and was compared to patients receiving <3. Results: Overall, 183 patients had 517 PIPACs. The main reasons for stopping PIPAC were disease progression in 50% patients, bowel obstruction in 15%, patient’s refusal to pursue in 10%, conversion to cytoreductive surgery in 7%, and medical reasons in 8%. Overall, 95 patients (52%) had PP treatment. The PP median OS was 17 vs. 7 months, p = 0.001. PP patients had r ascites (410 ± 100 mL vs. 960 ± 188 mL, p = 0.001), no prior history of bowel obstruction (12% vs. 24%, p = 0.028), and more bimodal treatment (39% vs. 13%, p < 0.001). After multiple regression, bimodal treatment was found as an independent predictive factor for completing PP (OR = 4.202, 95%CI [1.813, 10.630], p < 0.001), along with prior bowel obstruction (OR = 0.389, 95%CI [0.153, 0.920], p = 0.037). Conclusion: The absence of ascites and prior bowel obstruction can help to select patients suitable for PIPAC. Best results seem to be achieved when PIPAC is combined with systemic chemotherapy.

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for palliative treatment of peritoneal surface malignancies (PSM) and is currently tested also in the neoadjuvant and prophylactic setting. The aim was therefore to compare safety and tolerance of staging laparoscopy with or without PIPAC., Methods: This retrospective analysis compared consecutive patients undergoing staging laparoscopy alone for oesogastric cancer with patients having PIPAC for suspected PSM of various origins from January 2015 until January 2020. Safety was assessed by use of the Clavien classification for complications and CTCAE for capturing of adverse events. Pain and nausea were documented by use of a visual analogue scale (VAS: 0-10: maximal intensity)., Results: Overall, 25 PIPAC procedures were compared to 24 staging laparoscopies. PIPAC procedures took a median of 35 min (IQR: 25-67) longer. Four patients experienced at least one complication in either group (p = 0.741). No differences were noted for postoperative nausea (p = 0.961) and pain levels (p = 0.156). Median hospital stay was 2 (IQR: 1-3) for PIPAC and 1 (IQR: 1-2) for the laparoscopy group (p = 0.104)., Conclusions: The addition of PIPAC did not jeopardize safety and postoperative outcomes of staging laparoscopy alone. Further studies need to clarify its oncological benefits., (© 2022. The Author(s).)

The management of esophageal cancer (EC) has experienced manifold changes during the last decades. Centralization of EC treatment has been introduced in many countries, subsequently allowing the development of specialized high-volume centers. Minimal invasive surgery has replaced open surgery in many centers, whereas more potent systemic treatments have been introduced in clinical practice. Newer chemotherapy regimens increase long-term survival. Nevertheless, the overall survival of EC patients remains dismal for advanced tumor stages. In this direction, a wide range of targeted biologic agents (immunotherapy) is currently under assessment. Anti- Human Epidermal Growth Factor Receptor-2 (HER-2) monoclonal antibodies are used in HER2 (+) tumors, predominantly well-differentiated adenocarcinomas, and are currently assessed in the neoadjuvant setting (TRAP, INNOVATION trials). Immune checkpoint inhibitors Nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181), have demonstrated a survival benefit compared with conventional chemotherapy in heavily pre-treated progressive disease. More recently, CheckMate-577 showed very promising results for nivolumab in a curative adjuvant setting, improving disease-free survival mainly for esophageal squamous cell carcinoma. Several ongoing trials are investigating novel targeted agents in the preoperative setting of locally advanced EC. In addition, other immunomodulatory approaches such as peptide vaccines and tumor infiltrating lymphocytes (TILs) are currently under development and should be increasingly integrated into clinical practice.

Background Although clinical pharmacy is a crucial part of hospital pharmacist's day-to-day activity, its performance is not usually subject to a holistic assessment. Objective To define a set of relevant and measurable clinical pharmacy and support activities key performance indicators (cpKPI and saKPI, respectively). Setting Portuguese Hospital Pharmacies. Method After a comprehensive literature review focusing on the metrics already in use in other countries, several meetings with directors of hospital pharmacies were conducted to obtain their perspectives on hospital pharmacy practices and existing metrics. Finally, five rounds with a panel of 8 experts were performed to define the final set of KPIs, where experts were asked to score each indicator' relevance and measurability, and encouraged to suggest new metrics. Main outcome measure The first Portuguese list of KPIs to assess pharmacists' clinical and support activities performance and quality in hospital pharmacies. Results A total of 136 KPIs were assessed during this study, of which 57 were included in the original list and 79 were later added by the expert panel. By the end of the study, a total of 85 indicators were included in the final list, of which 40 are considered to be saKPI, 39 cpKPI and 6 neither. Conclusion A set of measurable KPIs was established to allow for benchmarking within and between Portuguese hospital Pharmacies and to elevate professional accountability and transparency. Future perspectives include the use of both cpKPIs and saKPIs on a national scale to identify the most efficient performances and areas of possible improvement., (© 2021. The Author(s).)

Purpose: Intraoperative estimated blood loss (EBL) is often reported in nearly all surgical papers; however, there is no consensus regarding its measurement. The aim of this study was to determine whether EBL (ml) is as reliable and reproducible in predicting complications as a simple binary grading of EBL., Methods: All consecutive patients undergoing colectomies between January 2015 and December 2018 were included. EBL was assessed prospectively by the surgeon and anaesthesiologist in ml and with a binary scale: bleeding "as usual" versus "more than usual" by the surgeon. Differences between pre- and post-operative haemoglobin levels (ΔHb g/dl) were correlated to EBL. Blood loss impact on 30-day postoperative morbidity was analysed., Results: A total of 270 patients were included, with a mean age of 65 years (SD 17). Mean EBL documented by surgeons correlated to EBL by anaesthesiologists (79.5 ml, SD 99 vs. 84.5 ml, SD 118, ϱ = 0.926, p < 0.001). Surgeons and anaesthesiologists' EBL correlated also with ΔHb (ϱ = - 0.273, p = 0.01 and ϱ = - 0.344, p = 0.01, respectively). Patient with surgeon EBL ≥ 250 ml or graded as "more than usual" bleeding had significantly more severe complications (8% vs. 20%, p = 0.02 and 8% vs. 27%, p = 0.001, respectively)., Conclusion: Anaesthesiologist and surgeon's EBL correlated with ΔHb. Simple grading of blood loss as "usual" and "more than usual" predicted severe complications and higher mortality rates. This simple binary grading of blood loss in colon surgery could be an alternative to the estimation of blood loss in ml as it is easy to apply but needs to be validated externally., (© 2021. The Author(s).)

Objectives: Since the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pressure to minimise its impact on public health has led to the implementation of different therapeutic strategies, the efficacy of which for the treatment of coronavirus disease 2019 (COVID-19) was unknown at the time. Remdesivir (REM) was granted its first conditional marketing authorisation in the EU in June 2020. The European Medicines Agency (EMA) and local health authorities all across the EU have since strongly recommended the implementation of pharmacovigilance activities aimed at further evaluating the safety of this new drug. The objective of this study was to evaluate adverse drug reactions (ADRs) attributed to either REM or hydroxychloroquine (HCQ) in patients hospitalised for COVID-19 in Centro Hospitalar de Lisboa Ocidental, a Portuguese hospital centre based in Lisbon. We present the preliminary results reporting plausible adverse effects of either HCQ or REM., Methods: An observational cohort study was carried out between 16 March and 15 August 2020. Participants were divided into two cohorts: those prescribed an HCQ regimen, and those prescribed REM. Suspected ADRs were identified using an active monitoring model and reported to the Portuguese Pharmacovigilance System through its online notification tool. The ADR cumulative incidence was compared between the two cohorts., Results: The study included 149 patients, of whom 101 were treated with HCQ and the remaining 48 with REM. The baseline characteristics were similar between the two cohorts. A total of 102 ADRs were identified during the study period, with a greater incidence in the HCQ cohort compared with the REM cohort (47.5% vs 12.5%; p<0.001). Causality was assessed in 81 ADRs, all of which were considered possible., Conclusions: Real-world data are crucial to further establish the safety profile for REM. HCQ is no longer recommended for the treatment of COVID-19., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Peritoneal metastases (PM) are relatively resistant to systemic chemotherapy, and data on histological response to therapy is rare. The aim of this study was to quantify the treatment response of PM after systemic chemotherapy., Methods: Retrospective monocentric cohort study of 47 consecutive patients with PM from gastrointestinal origin undergoing surgery (cytoreduction: CRS + Hyperthermic IntraPEritoneal Chemotherapy [HIPEC] or Pressurized IntraPeritoneal Aerosol Chemotherapy [PIPAC]) after prior systemic chemotherapy from 1.2015 to 3.2019. Tumor response was assessed using the 4-scale Peritoneal Regression Grading System (PRGS) (4: vital tumor to 1: complete response)., Results: Patients had a median of 2 (range: 1-7) lines and 10 (3-39) cycles of prior systemic chemotherapy. A median of four biopsies (range: 3-8) was taken with a total of 196 analyzed specimens. Twenty-four biopsies (12%) showed no histological regression (PRGS4), while PRGS 3, two and one were diagnosed in 37 (19%), 39 (20%), and 69 (49%) specimens, respectively. A significant heterogeneity was found between peritoneal biopsies in 51% patients. PRGS correlated strongly with peritoneal spread (PCI, p<0.0001), and was improved in patients with more than nine cycles of systemic chemotherapy (p=0.04). Median survival was higher in patients with PRGS < 1.8 (Quartiles one and 2) than higher (Q3 and Q4), but the difference did not reach significance in this small cohort., Conclusions: PRGS is an objective too to describe histological response of PM of GI origin after systemic chemotherapy. This response differs significantly between patients, allowing to distinguish between chemosensitive and chemoresistant tumors., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Laura Toussaint et al., published by De Gruyter, Berlin/Boston.)

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new mode of intraperitoneal chemotherapy administration that can potentially be improved by the addition of electrostatic precipitation (ePIPAC). This study aimed to describe the procedural details of ePIPAC and to analyze its safety for patients with nonresectable peritoneal metastasis as well as their tolerance and response to this treatment., Methods: This retrospective cohort study included consecutive patients treated with ePIPAC in three centers from April 2019 to April 2020. The toxicities of each patient were assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Complications were documented according to the Clavien classification. Quality of life (QoL) was assessed using EORTC-QLQ-C30, and the peritoneal regression grading score (PRGS) was used to grade histologic responses. Further surrogates for responses were the Peritoneal Cancer Index (PCI), ascites, and symptoms., Results: Overall, 69 patients received 147 ePIPACs with oxaliplatin (n = 34) or cisplatin/doxorubicin (n = 35) mainly for colorectal (n = 25), ovarian (n = 14), and gastric (n = 13) primary cancers. Systemic chemotherapy was used in the treatment of 54 patients (76%). The median electrostatic therapy time was 12 min (range 6-30 min). The overall and major CTCAE toxicity rates were respectively 24.6% and 15.9%. The postoperative complications rate according to Clavien classification was 4.7%. The responses of 22 patients who had three or more ePIPAC treatments were evaluated as follows: PCI (16 vs 14; p = 0.4), ascites (320 vs 98 ml; p = 0.1), and PRGS (2.23 vs 1.73; p = 0.15). The complete (PRGS1) and major (PRGS2) histologic responses at the third ePIPAC were respectively 38.5% and 53.8%. Overall QoL was stable during the first ePIPACs., Conclusion: Repetitive ePIPACs were safe and well tolerated for patients with unresectable peritoneal metastasis.