Evaluation of diagnostic algorithm and therapeutic interventions for intra-abdominal desmoid tumors

Desmoid-type fibromatosis (DF) is a distinctly rare condition, mostly of younger adults, characterized by the development of locally aggressive tumors of mesenchymal origin. Desmoid tumors (DT) arise either sporadically or in association with FAP (familial adenomatous polyposis), although certain risk factors have also been identified, including pregnancy and antecedent surgical trauma. They can emerge from any connective tissue including muscle, fascia and aponeurosis and are therefore classified, according to location, as intra-abdominal, of the abdominal wall and extra-abdominal. Despite the lack of metastasizing potential, the course can be unpredictable. Various mutations of APC and β-catenin genes, among others, play a catalytic role in the pathogenesis of this neoplastic entity. Surgery has lost its traditional role as first line treatment of the disease and several other treatment methods are being considered. Cytotoxic chemotherapy, non-cytotoxic systemic therapy and targeted therapy have been revealed as part of different treatment regimens. Recent progress regarding DT biology and molecular pathways has led to the development of promising novel biological agents. In any case, a multidisciplinary approach is required and is gradually employed, espe-cially in intra-abdominal DTs. In this review, we aim to present current knowledge on DF and summarize current treatment regimens as well as their effectiveness, with emphasis on the intraperitoneal type of DT.     

Minimally Invasive Treatments for Benign Prostatic Hyperplasia: Systematic Review and Network Meta-Analysis

PurposeTo review and to compare indirectly the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and MethodsA literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostatic artery embolization (PAE). Data on the following variables were included: International prostate symptom score (IPSS), maximum urinary flow rate, quality of life, and postvoid residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect.ResultsThere was no significant difference in outcomes between therapies for IPSS at the 3, 6, and 12-month follow ups. Although outcomes for Rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation versus PAE versus Rezum. TURP PVR was significantly better than Urolift at 3, 6, and 12 months. No significant differences in minor or major adverse events were noted.ConclusionAlthough significant differences in outcomes were limited, Aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while Aquablation has limited high quality data and has been associated with bleeding-related complications.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

An update in pathologic diagnosis of uterine mesenchymal tumours

Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

A comparison of mobilization and mobilization with movement on pain and range of motion in people with lateral ankle sprain: A randomized clinical trial

BackgroundMaitland and Mulligan mobilization techniques are two manual therapy methods to increase the range of motion following immobility treatment. The present study was conducted to compare two therapeutic methods, namely mobilization and mobilization with movement (MWM), on the pain and range of motion in people with lateral ankle sprain.MethodsA total of 40 individuals with grade two lateral ankle sprain were randomly divided into two groups, including the Maitland's mobilization intervention group, and the Mulligan's mobilization intervention group. Both groups underwent treatment every other day for two consecutive weeks. The pain intensity was measured using the Visual Analogue Scale (VAS), and the ankle dorsiflexion movement range using the Weight Bearing Lunge Test (WBLT) before and one day after the intervention.ResultsThere were no significant differences between the two groups in terms of pain (P = 0.297) and range of motion (P = 0.294) before the intervention. Meanwhile, after the intervention, a significant change was observed in both groups in terms of these variables, which indicates the effectiveness of both interventions (P < 0.001) and the greater effect of the mobilization with movement in reducing pain (P = 0.037) and increasing the range of motion (P = 0.021).ConclusionsBoth techniques significantly improved the range of motion and reduced pain in people with lateral ankle sprain, but Mulligan's technique was significantly more effective among the two, perhaps due to joining active and passive mobilizing tensile forces as well as interaction of afferents and efferents in the reflex arc.     

Effects of manual therapy on body posture: Systematic review and meta-analysis

BackgroundSeveral clinical trials investigated the effectiveness of MT on body posture, but a systematic review grouping the results of these studies was not found in the literature.Research questionDoes manual therapy (MT) cause postural changes?MethodsInclusion criteria were: randomized controlled trials in any population; studies in which the primary intervention was the use of any MT technique; studies that evaluated the immediate, short, medium, or long-term effects of interventions on body posture; and studies published in peer-reviewed scientific journals in any year and language. In March 2022, we conducted a search in the PUBMED, Cinahl, Embase, PEDro, and Cochrane Central databases that yielded 6627 articles, of which 38 including 1597 participants were eligible; of these, 35 could be grouped into 12 meta-analyses. The risk of bias was assessed using the PEDro scale and the certainty in the scientific evidence rated through the GRADE system.ResultsThe results allowed us to conclude with moderate certainty in the evidence that, when compared to no intervention or sham, in the short and medium term, MT reduced the forward head posture (14 studies, 584 individuals, 95%CI 0.38, 1.06), reduced thoracic kyphosis (5 studies, 217 individuals, 95%CI 0.37, 0.94), improved lateral pelvic tilt (5 studies, 211 individuals, 95%CI 0.11, 0.67) and pelvic torsion (2 studies, 120 individuals, 95%CI 0.44, 1.19) and increased plantar area (3 studies, 134 individuals, 95%CI 0.04, 0.74). With moderate certainty, there was no significant effect on shoulder protrusion (5 studies, 176 individuals, 95%CI −0.11, 0.61), shoulder alignment in the frontal plane (3 studies, 160 individuals, 95%CI −0.15, 0.52), scoliosis (2 studies, 26 individuals, 95%CI −1.57, 2.19), and pelvic anteversion (5 studies, 233 individuals, 95%CI −0.02, 0.51). With low certainty, MT had no effect on scapular upward rotation (2 studies, 74 individuals, 95%CI −0.76, 2.17). With low to very low certainty, it is possible to conclude that MT was not superior to other interventions in the short or medium term regarding the improvement of forward head posture (5 studies, 170 individuals, 95%CI −1.39, 0.67) and shoulder protrusion (3 studies, 94 individuals, 95%CI −4.04, 0.97).SignificanceMT can be recommended to improve forward head posture, thoracic kyphosis and pelvic alignment in the short and medium term, but not shoulder posture and scoliosis. MT reduces the height of the plantar arch and this must be taken into account in physical therapy planning. PROSPERO registration number: CRD42021244423.