Spital STS

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

ABSTRACTRelapsed/refractory multiple myeloma (RRMM) patients with dialysis‐dependent renal impairment face limited therapeutic options due to exclusion from clinical trials, a lack of evidence‐based guidelines, and inferior outcomes. Bispecific antibodies targeting B‐cell maturation antigen (BCMA) have shown promise in RRMM treatment but remain understudied in this vulnerable population. To illustrate this issue, we introduce the case of a 68‐year‐old female with triple‐class RRMM and end‐stage renal disease requiring hemodialysis, treated with elranatamab as a second line treatment following progression after therapy with daratumumab, bortezomib, lenalidomide, and dexamethasone. Despite experiencing grade I cytokine release syndrome during the initial administrations, symptoms were managed effectively with tocilizumab and dexamethasone, allowing treatment continuation. The patient achieved a very good partial remission within 7 weeks. Although hemodialysis dependence persisted, the therapy was well‐tolerated with manageable adverse events. According to the literature, BCMA‐directed immunotherapies, including teclistamab, belantamab mafodotin, and idecabtagene vicleucel, have shown efficacy in dialysis‐dependent RRMM patients, though data remain limited. Pharmacokinetic analyses indicate that mild or moderate renal impairment does not have a significant impact on the pharmacokinetics of elranatamab. Although no retrospective studies or case series have investigated the use of elranatamab in dialysis‐dependent patients, a single case report suggests that its administration is both feasible and well‐tolerated in this population despite the absence of comprehensive pharmacokinetic data. This review highlights feasibility, safety, and encouraging efficacy of elranatamab in managing RRMM in a dialysis‐dependent patient, representing the second case report in the literature. By providing real‐world evidence for the use of bispecific antibodies in end stage renal disease patients, this review emphasizes the potential for expanding therapeutic options to this vulnerable population while highlighting the need for vigilant monitoring of infection prevention and management. Prospective studies are warranted to validate these findings and optimize therapeutic strategies for patients with RRMM and severe renal impairment.

The WHO classifications of 2017 and 2022 recommend the use of pituitary transcription factors PIT-1, T-PIT and SF-1 as well as GATA3 and ERα for histopathological diagnosis. The aim of this study is to demonstrate their diagnostic impact in a large retrospective cohort. 921 PitNETs/PAs diagnosed in our department between October 2004 and April 2018 were retrospectively reassessed according to the WHO classifications 2017 and 2022. The original classification (WHO 2004) and the clinical data were retrieved from the patient records. Hormone-immunonegative null cell adenomas represented the largest subgroup (397 of 921) in the WHO 2004 classification. Of these, 377 were reclassified as gonadotroph PitNETs/PAs, and 14 were assigned to a non-gonadotroph hormone-producing cell line. Only 6 cases remained null cell tumors. 27 of 35 plurihormonal adenomas were assigned to a specific cell line in the 2017 and 2022 WHO classifications. Of 489 adenomas formerly classified as expressing of 1 or 2 hormones, the histopathological diagnosis was confirmed in 459 cases with the use of TP. Of the remaining 30 cases, 12 cases with positive immunostaining of 2 hormones could be assigned to a single cell line, and 18 cases changed their lineage. The correct correlation with clinical data significantly improved from 75.4% (WHO 2004) to 96.2% (WHO 2017 and 2022). Corticotroph PitNETs showed the highest risk for recurrence (21.9%) and progression (55.8%). The new classification enables more accurate (sub)classification and significantly improves clinicopathological correlation. In individual cases, it is essential to consider the reclassification to predict the clinical prognosis and to schedule the follow-up accordingly.

We assessed the benefit of adjuvant aspirin in patients with resected phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated colon cancer. This was a phase III, prospective, randomized, placebo-controlled, double-blind, multicenter, and multinational trial. Patients with resected colon cancer stage II and III harboring an activating PIK3CA mutation were included. Because of financial constraints, the trial was prematurely closed. Randomization was 2:1 to aspirin 100 mg versus placebo daily for 3 years. The primary endpoint was disease-free survival (DFS). Secondary endpoints included the time to disease recurrence (TTR), overall survival, and adverse events. Overall, 1,040 patients were screened for PIK3CA mutations, with 112 randomized to aspirin (N = 74) and placebo (N = 38). The median age was 66 years, and 42.9% were female. After a median follow-up of 4 years, 19 DFS events occurred, including 10 in the aspirin and nine in the placebo arm. The HR for DFS was 0.57 [90% confidence interval (CI), 0.27-1.22], in favor of aspirin (P = 0.11). DFS rates at 5 years were 86.5% (90% CI, 77.7%-92.0%) in the aspirin and 72.9% (90% CI, 55.7%-84.3%) in the placebo arm. The HR for TTR was 0.49 (90% CI, 0.21-1.19, P = 0.089) in favor of aspirin. No patient experienced aspirin-related serious adverse events. The SAKK 41/13 is the first randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in patients with resected PIK3CA-mutant colon cancer, with clinically relevant DFS and TTR improvements. Although results were not statistically significant because of premature study closure, adjuvant aspirin warrants individual consideration in patients with resected PIK3CA-mutant colon cancer stage II and III. See related commentary by Drew et al., p. 3107.

The excision of oropharyngeal carcinoma of more than 50% of the soft palate followed by static reconstruction may result in functional deficits, including velopharyngeal insufficiency, swallowing, and speech difficulties. We describe a functional soft palate reconstruction technique aimed at restoring aeromechanical and acoustic functions, enabling swallowing without nasal regurgitation and speech with low nasalance. We developed a new operative technique, using muscle transfer and a free flap to create a dynamic reconstruction. To prove the distinct nerve innervation of the two digastric bellies and the feasibility of the technique, we first performed an anatomical study, and then implemented the technique in our clinic. The surgical technique included transfer of the anterior and posterior bellies of the digastric muscle in association with a folded radial forearm free flap. A retrospective analysis of patients who underwent this soft palate functional reconstruction after cancer resection between 2007 and 2017 was performed, and a subjective analysis of nasalance and swallowing was done to evaluate the functional outcomes. Eight patients (six males, two females) with a mean age of 56 years (range 43-69) who were affected by oropharynx carcinoma (stage T1-3) infiltrating the soft palate were included. Analysis of the reconstruction showed that seven of the eight patients had satisfactory swallowing function, and all patients were able to speak in an understandable manner with minimal nasalance. Our surgical approach provided a functional reconstruction with outcomes close to normality, making it a suitable technique for patients with large soft palate defects.

Myeloproliferative neoplasms can cause primary Budd-Chiari-Syndrome with acute or chronic liver failure necessitating liver transplantation. However, preventing the recurrence remains challenging and the need for post-transplant anticoagulant and cytoreductive treatment is not sufficiently clear. We analyzed the treatment regimens for all patients who presented to our department with PBCS from MPN between 2004 and 2021. Eight patients underwent liver transplantation - 6 of them due to an acute liver failure. Post-transplant, all patients received anticoagulant and 7 patients cytoreductive medication. The mean survival after transplantation was 13.25 years. Liver transplantation shows favorable long-term outcome when combined with post-transplant anticoagulant and cytoreductive treatment.