Management of Pain Medication in Patients With a History of Bariatric Surgery: A Systematic Review.

CONTEXT: Obesity prevalence is persistently increasing worldwide. Among surgical therapeutic procedures, bypass surgery and sleeve gastrectomy have shown the best results regarding weight loss, prevention, and treatment of secondary complications. However, these surgeries are associated with an increased risk of malabsorption and metabolic changes that could further affect the pharmacokinetics of drugs. On the other hand, patients with a history of such surgeries are more likely to experience pain and request analgesic initiation or adaptation. The question of how to manage pain medication in these patients is challenging due to their narrow therapeutic indexes. OBJECTIVES: To summarize the current literature on the impact of bariatric surgery on the subsequent pharmacokinetics of analgesics and propose a multidisciplinary therapeutic attitude to optimize pain management in these patients. METHODS: We conducted a systematic review that included all pharmacological studies published after 2000. RESULTS: Unexpectedly, these surgeries seem to increase the bioavailability of drugs by long-term improvement of hepatic function. Yet, the medical community drastically lacks robust guidelines for pain management in those patients. This systematic review aims to bring together pharmacological studies related to the use of pain treatments in patients who underwent bypass surgery or sleeve gastrectomy. CONCLUSIONS: Caution should be exercised regarding the risk of overdose in every circumstance: treatment initiation, change of doses, or change of molecule. More prospective trials comparing the pharmacokinetics of medications in obese patients with and without prior bariatric surgery are needed.

[Last year of residency for oncologists: Overview and perspectives]. / Premiers docteurs juniors d'oncologie médicale : état des lieux et perspectives.

CONTEXT: The reform of the third cycle of medical studies in France has introduced of the "Junior Doctor" status during the concluding year of residency. We wish to evaluate its implementation for the first promotion of medical oncology residents during 2021-2022 in correlation with the published guidelines. METHOD: AERIO conducted a cross-sectional study among French medical oncology residents. The survey was released via social networks and emails. RESULTS: Twenty-eight of 47 residents responded. The typical week involved one to two half-days of consultation, one dedicated to clinical research, one multidisciplinary team meetings, with the rest of time being occupied by day care (mostly) and hospitalization. Teaching and quality management activities were infrequent (monthly or less). The Junior Doctors rated their overall satisfaction at 8/10. A large majority (92.5 %) felt equipped to handle most of the situations they encountered. Almost all residents (92.9 %) had negotiated with their placement supervisor prior to the selection procedure. In one third of the cases (35.7 %), the principle of mismatch between the number of residents and the number of training sites was not respected. Only 42.9 % received training in scientific writing and 82.2 % of the residents agreed on the relevance of the post-internship training modules developed in other specialties. CONCLUSIONS: Junior doctors in medical oncology express overall satisfaction with this reform, which aligns with the recommendations. Nevertheless, certain concerns, such as selection procedure and inadequacy, along with areas requiring improvement, such as post-internship training and scientific writing, are clearly established.

Pathogenic alterations in PIK3CA and KMT2C are frequent and independent prognostic factors in anal squamous cell carcinoma treated with salvage abdominoperineal resection.

The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)KMT2C = 2.54, 95%CI = [1.25,5.17], P value = .010; HRPIK3CA = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials.

Medical oncologist stereotypes among medical students, residents and physicians: a national cross-sectional study.

OBJECTIVES: The perception of oncologists could impact the attractiveness of the specialty and dialogue between oncologists and other physicians. The aim of the study was to describe and understand the stereotypes and social representation (SR) associated with oncologists among medical students, residents and physicians in France. METHODS: This nationwide web-based survey conducted in 2021 was based on hierarchical evocation methods. Qualitative analyses were based on the Reinert method with factorial analyses. Each respondent's SR was graded from 1 to 5 (from 1: very positive SR to 5: very negative SR). RESULTS: Oncologists suffer from a rather negative SR. The negative representation was mostly related to difficulties in practising and the proximity with death and end of life. Oncologists were also associated with more positive notions like interdisciplinarity or intellectual complexity. Attendance to an oncology course was associated with a better SR of oncology (p=0.036), whereas having someone in the family practising oncology had a negative impact (p=0.028). CONCLUSIONS: SR of oncologists is rather contrasted. It was positively influenced by attendance to an oncology course, which could be an option to correct stereotypes and update on this rapidly evolving specialty.

The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy.

Pancreatic ductal adenocarcinoma is associated with a poor prognosis and there are few treatment options. The development of immunotherapy in pancreatic ductal adenocarcinoma has been difficult, and immune checkpoint inhibitors are only effective in a very small subset of patients. Most obstacles for treatment have been related to intertumoural and intratumoural heterogeneity, the composition of tumour stroma, and crosstalk with cancer cells. Improved molecular characterisation of pancreatic ductal adenocarcinoma and a better understanding of its microenvironment have paved the way for novel immunotherapy strategies, including the identification of predictive biomarkers, the development of rational combinations to optimise effectiveness, and the targeting of new mechanisms. Future immunotherapy strategies should consider individual characteristics to move beyond the traditional immune targets and circumvent the resistance to therapies that have been developed so far.

Obesity, cancer, and response to immune checkpoint inhibitors: Could the gut microbiota be the mechanistic link?

Immune checkpoint inhibitors (ICI) have deeply changed the therapeutic management of a broad spectrum of solid tumors. Recent observations showed that obese patients receiving ICIs might have better outcomes than those with normal weight, while obesity was historically associated with a worse prognosis in cancer patients. Of note, obesity is associated with alterations in the gut microbiome profile, which interacts with immune and inflammatory pathways, both at the systemic and intratumoral levels. As the influence of the gut microbiota on the response to ICI has been repeatedly reported, a specific gut microbiome profile in obese cancer patients may be involved in their better response to ICI. This review summarizes recent data on the interactions between obesity, gut microbiota, and ICIs. In addition, we highlight possible pathophysiological mechanisms supporting the hypothesis that gut microbiota could be one of the links between obesity and poor response to ICIs.

Onco-nephrology: Physicians' Expectations About a New Subspecialty.

INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.

Inclusion of patients with chronic kidney disease in randomized phase 3 clinical trials in patients with prostate, breast, lung, and colorectal cancer.

The objective of this study was to determine the proportion of phase 3 clinical trials investigating a systemic therapy for patients with prostate, breast, lung, or colorectal cancer that excluded patients with Chronic Kidney Disease (CKD) and the exclusion criteria chosen, if any. A search was conducted using the ClinicalTrials.gov database to identify eligible studies. Of the 268 included trials, 185 (69%) had at least one renal exclusion criteria. Of these 185 trials, 116 (63%) had an undefined exclusion criterion. Only disease site was associated with exclusion of patients with CKD in the univariate analysis, but no factors in the multivariate analysis. There are several potential barriers to including patients with CKD in clinical trials. Nevertheless, solutions can be proposed to allow the inclusion of these patients. This would allow them to access to innovative therapeutic strategies, but also allow a better applicability of trial results to this patient population.

Cytomegalovirus lymphadenitis mimicking a relapsed diffuse large B-cell lymphoma.

Cytomegalovirus (CMV) reactivation is frequent after autologous stem cell transplantation (ASCT), but generalized CMV lymphadenitis is rare. We report a CMV lymphadenitis after an ASCT mimicking a relapse of a diffuse large B-cell lymphoma. After histopathological documentation, CMV lymphadenitis should be treated to avoid systemic progression.

Apport de l'immunothérapie dans le traitement des cancers des voies biliaires avancés.

Contribution of immunotherapy in the treatment of advanced biliary tract cancer Biliary tract cancers (BTC) are rare tumors with a poor prognosis. Their treatment, at an advanced stage, relies on combinations of chemotherapies, which have a limited range and duration of benefit. Immunotherapy has emerged in recent years as a new therapeutic approach for BTC. However, the benefit with currently available treatments seems more modest than in other tumor locations and the predictive markers of response to these treatments remain to be identified. This review article summarizes the rationale, current data, and prospects and challenges for the development of immunotherapy in BTC.

État des lieux des pratiques de prise en charge des cancers des voies biliaires en France : résultats de l'enquête nationale ACABi.

Overview of biliary tract cancer management practices in France: results of the ACABi national survey INTRODUCTION: Biliary tract cancers (BTC) are rare. Their management has evolved in recent years. ACABi conducted a survey on the management practices of CVB in France. METHODS: A questionnaire was developed by a multidisciplinary team and distributed (June-July 2021) by the French digestive oncology societies. The data were analyzed according to the type of practice center (group A: university hospital or cancer comprehensive center, group B: general hospital or private hospital) RESULTS: 172 physicians (hepato-gastroenterologists: 58.0%, oncologists: 19.5% and surgeons: 18.3%), representing all French regions, responded. Access to echo-endoscopy and endoscopic retrograde cholangio-pancreatography was identical between the groups (> 80%), unlike cholangioscopy (group A: 82.9%, group B: 63.6%). In the adjuvant setting, capecitabine was proposed in the majority (> 65%). For non-operable tumors, the most commonly used first-line chemotherapy was cisplatin/gemcitabine (CISGEM, 66.3%). In 38.5% of cases, it was not performed in the day hospital and only 13.6% proposed a break after a fixed number of courses. The most commonly used second-line treatment was 5FU/oxaliplatin (FOLFOX, 52.3%). Molecular profiling was performed in more than half of the patients for 41.1% of respondents in group A and 18.8% in group B. DISCUSSION: This survey shows the application of therapeutic standards but also certain practices diverging from the recommendations as well as disparities between centers.

[Cancer imaging and prevention of renal failure]. / Imagerie des cancers et prévention de l'insuffisance rénale.

The risk of acute renal failure (ARF) following iodinated contrast media injection has long been overestimated because of the previous use of more toxic ICPs and uncontrolled studies. Nowadays, this concept is being questioned. Patients with severe renal failure and/or ARF are the only group still considered at risk. In these patients, it is necessary to discuss an alternative without an iodinated contrast agent. Contrast-enhanced ultrasound, MRI, spectral CT or PET-CT scan can be used instead of contrast-enhanced CT. Preventive measures should be applied when appropriate substitute to CT is not available or not diagnosed (minimum necessary dose of ICP, interruption of some treatments and prior hydration). These recommendations formalized by the European Society of Urogenital Radiology (ESUR) in 2018 address most situations faced by clinicians. In complex situations, an opinion from a nephrologist remains necessary after asking the radiologist about the availability of acceptable substitutes.

Discussion on methadone initiation protocols: A case report.

Through a concrete case, we discuss the main published protocols to initiate methadone and illustrate the advantages and disadvantages of rapid or gradual initiation and on-demand or fixed doses with rescue doses. Daily doses can vary widely depending on the protocol chosen. An on-demand administration could lead to an overdose as illustrated in our case. A better understanding of particularities and limitations of these protocols could lead to safer methadone initiation. Systematic comparison of different protocols and calculation of the daily dose should be a standard in clinical practice.

Decisions about treatment with targeted therapies in a palliative care unit: A case series.

BACKGROUND: Early palliative care integration into the oncologic treatment pattern is recognized and strongly recommended to anticipate end-of-life issues and avoid disproportionate care. Targeted therapies (TTs), with their very rapid onset of action and relatively good tolerance, may have an effect on cancer-related symptoms, which could be beneficial in the context of palliative care. METHODS: Data were extracted from a cohort of all patients hospitalized in an acute palliative care unit between 03.04.2019 and 07.04.2020. Data for all consecutive patients for which a decision on a TT was made during hospitalization were retrospectively analyzed. RESULTS: Forty-two patients were identified. Thirty-one patients were currently receiving TT on admission. For 19/31 (61.3%) patients, the treatment was discontinued. The remaining 12 patients had TT after discharge from the palliative care unit (continuation of the same TT or modification of the TT during the stay), with an average duration of 208 days and an average of 46 days between the last TT and death. TT was introduced or reintroduced in 7 patients of the 11 patients hospitalized without treatment at admission. In this group, the average duration of treatment was 28 days, with an average of 28 days between the last TT and death. Five of the patients who received re-challenged TT experienced a subjective improvement of their symptom. SIGNIFICANCE OF RESULTS: TT was discontinued in the majority of our patients. However, in some cases, the treatment was maintained because it was effective on cancer-related symptoms even at the end of life. However, this should not overshadow the palliative process. The continuation or introduction of a specific oncological treatment requires close cooperation between oncologists and palliative care physicians and an honest and clear explanation to patients and their families.

[Formation of French oncology resident: A national survey]. / État des lieux de la formation initiale de l'internat d'oncologie après la quatrième vague pandémie de la COVID-19 : une enquête AERIO-SFJRO.

BACKGROUND: COVID-19 pandemic troubled hospital and university's organization. Previous study showed oncology resident's formation has been impacted by pandemic. One year later, we aimed to evaluate the state of oncology resident's formation. METHODS: We conducted a transversal study written by AERIO and SJRO, released via social networks and mail to the French oncology residents. RESULTS: One hundred and sixty-four residents answered. Sixty-four (39%) were male and 99 (60.4%) were female, mean age was 26.8 years old, mean semester was 5.7. One hundred and five (64%) were medical oncologist and 53 (32.3%) were radiation oncologist. One hundred and forty residents (85.4%) had lectures during hospital internships, mainly in cancer center (77.1%) and academic hospitals (60.7%). One hundred and twenty-one residents (73.8%) had specialized diploma lectures, in 34.7% of case monthly. Respectively 42.7% and 18.3% of residents could access to their formation's day respectively rarely and never. Strengths of oncology residency were scientific dynamism (91.9%), clinical breadth (82%) and knowledge renewal (78.9%). Attractivity's obstacles to the residency were psychological arduousness (64%), administrative burden (48.2%) and too important worktime (47%). CONCLUSION: This survey shows the state of play of French oncology residency's formation at the end of 2021.

Rational testing for gene fusion in colorectal cancer: MSI and RAS-BRAF wild-type metastatic colorectal cancer as target population for systematic screening.

Gene fusions provide access to new therapeutic opportunities for patients treated for a colorectal cancer (CRC). However, they do not excess 1% of patients. A better identification of patients in whom gene fusions are highly prevalent is a major issue in a therapeutic and medico-economics perspective. This study assesses the rates of gene fusions in CRC patients with MSI/RAS-BRAFWT in our routine practice detected with a commercially available NGS-based fusion panel. Among the 130 MSI CRC tumors, 43 (33%) were KRAS-NRAS-BRAFWT. A gene fusion was detected in 7 (25.9%) of the 27 MSI/RAS-BRAFWT samples, which had RNA suitable for analysis after quality control. These fusions involved mainly NTRK1/3 (n = 5), as well as ALK (n = 1) and BRAF (n = 1). In the present study, we confirm that patients with MSI/RAS-BRAFWT CRCs represent a subpopulation in which targetable gene fusions are overrepresented. Our results support the use of a two-step algorithm for molecular screening, in which metastatic CRC patients would have routine MSI and RAS/BRAF testing, and then only those with MSI/RAS-BRAFWT would be screened with dedicated NGS RNA panel for gene fusions.