Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: A Problem with a Thousand Nuances—A Systematic Review of Oncological Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC). The guidelines have recognized various approaches, depending on the tumor stage and other risk factors such as histotype and lymphovascular positivity. Much more debate has centered around the boundary within which these treatments should be considered. Indeed, these are methods to be reserved for ECC, but tumor size may represent the most significant limitation. In particular, there is no consensus on the strategy to be adopted in the case of ECC ≥ 2 cm. Therefore, this systematic review was to collect the literature evidence regarding the management of these patients. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the Pubmed and Scopus databases was conducted in April 2022, from the date of the first publication. We made no limitation on the country. We included all studies containing data on disease-free survival, overall survival, recurrence rate (RR), or complete response rate (CRR) to chemotherapy. RESULTS: Twenty-six studies fulfilled the inclusion criteria, and 691 patients were analyzed regarding FST. Surgery-based FST showed an RR of between 0 and 42.9%, which drops to 12.9% after excluding the vaginal or minimally invasive approaches. Furthermore, papers regarding FST based on the neoadjuvant chemotherapy (NACT) approach showed a CRR of between 21.4 and 84.5%, and an RR of between 0 and 22.2% CONCLUSION: This paper focused on the significant heterogeneity present in the clinical management of FST of ECC ≥ 2 cm. Nevertheless, from an oncological point of view, approaches limited to the minimally invasive or vaginal techniques showed the highest RR. Vice versa, the lack of standardization of NACT schemes and the wealth of confounders to be attributed to the histological features of the tumor make it difficult, if not impossible, to set a standard of treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1245/s10434-022-12436-w

Laparoscopic uterosacral ligament suspension: a systematic review and meta-analysis of safety and durability

IntroductionPelvic organ prolapse (POP) is a widespread condition affecting from 40% to 60% of women. Reconstructive vaginal surgeries are the most commonly performed procedures to treat POP. Among those, uterosacral ligament suspension (USLS), which is usually performed transvaginally, preserves pelvic statics and dynamics and appears to be an effective method. Laparoscopic USLS is a valid alternative to vaginal approach, and the aim of our review is to confirm its safety and feasibility and to compare clinical outcomes among the procedures.Materials and methodsFollowing the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in December 2022. We made no restriction on the publication year nor on the country. Data about POP-Q recurrence rate (RR), intraoperative and postoperative complications (graded according to Clavien–Dindo classification), readmission rate, and reoperation rate were collected and analyzed. We used comparative studies for meta-analysis.ResultsA total of nine studies fulfilled inclusion criteria: two articles were non-comparative retrospective observational studies, three more articles were comparative studies where laparoscopic USLS was confronted with other surgical techniques (only data of laparoscopic USLS were analyzed), and four were comparative retrospective cohort studies between laparoscopic and vaginal USLS procedures. The comparative studies were enrolled in meta-analysis. Patients were analyzed concerning perioperative risks and the risk of recurrence. The meta-analysis highlighted that there was no clear inferiority of one technique over the other.DiscussionLaparoscopic USLS is a technique with a low complication rate and low recurrence rate. Indeed, laparoscopic procedure allows better identification of anatomical landmarks and access to retroperitoneum. Moreover, efficacy over time and durability of Laparoscopic (LPS) USLS was also observed. However, these data should be weighed in light of the length of follow-up, which was in a very short range. Further, focused and prospective studies will be necessary to confirm this finding

The position of nonsense mutations can predict the phenotype severity : A survey on the DMD gene

A nonsense mutation adds a premature stop signal that hinders any further translation of a protein-coding gene, usually resulting in a null allele. To investigate the possible exceptions, we used theDMDgene as an ideal model. First, because dystrophin absence causes Duchenne muscular dystrophy (DMD), while its reduction causes Becker muscular dystrophy (BMD). Second, theDMDgene is X-linked and there is no second allele that can interfere in males. Third, databases are accumulating reports on many mutations and phenotypic data. Finally, becauseDMDmutations may have important therapeutic implications. For our study, we analyzed large databases (LOVD, HGMD and ClinVar) and literature and revised critically all data, together with data from our internal patients. We totally collected 2593 patients. Positioning these mutations along the dystrophin transcript, we observed a nonrandom distribution of BMD-associated mutations within selected exons and concluded that the position can be predictive of the phenotype. Nonsense mutations always cause DMD when occurring at any point in fifty-one exons. In the remaining exons, we found milder BMD cases due to early 5' nonsense mutations, if reinitiation can occur, or due to late 3' nonsense when the shortened product retains functionality. In the central part of the gene, all mutations in some in-frame exons, such as in exons 25, 31, 37 and 38 cause BMD, while mutations in exons 30, 32, 34 and 36 cause DMD. This may have important implication in predicting the natural history and the efficacy of therapeutic use of drug-stimulated translational readthrough of premature termination codons, also considering the action of internal natural rescuers. More in general, our survey confirm that a nonsense mutation should be not necessarily classified as a null allele and this should be considered in genetic counselling.Peer reviewe

A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report

Background Mutations in RAB39B at Xq28 causes a rare form of X-linked intellectual disability (ID) and Parkinson’s disease. Neurofibromatosis type 1 (NF1) is caused by heterozygous mutations in NF1 occurring de novo in about 50% of cases, usually due to paternal gonadal mutations. This case report describes clinical and genetic findings in a boy with the occurrence of two distinct causative mutations in NF1 and RAB39B explaining the observed phenotype. Case presentation Here we report a 7-year-old boy with multiple café-au-lait macules (CALMs) and freckling, severe macrocephaly, peculiar facial gestalt, severe ID with absent speech, epilepsy, autistic traits, self-harming, and aggressiveness. Proband is an only child born to a father aged 47. Parents did not present signs of NF1, while a maternal uncle showed severe ID, epilepsy, and tremors.By RNA analysis of NF1, we identified a de novo splicing variant (NM_000267.3:c.6579+2T>C) in proband, which explained NF1 clinical features but not the severe ID, behavioral problems, and aggressiveness. Family history suggested an X-linked condition and massively parallel sequencing of X-exome identified a novel RAB39B mutation (NM_171998.2:c.436_447del) in proband, his mother, and affected maternal uncle, subsequently validated by Sanger sequencing in these and other family members. Conclusions The case presented here highlights how concurrent genetic defects should be considered in NF1 patients when NF1 mutations cannot reasonably explain all the observed clinical features

Efficacy of lamivudine to prevent hepatitis reactivation in hepatitis B virus-infected patients treated for non-Hodgkin lymphoma.

The association of hepatitis viruses with non-Hodgkin lymphomas (NHL) is not rare. Several authors have reported an exceeding prevalence of hepatitis C virus (HCV)1-3 or of hepatitis B virus (HBV)4,5 infection in patients affected by NHL. A sustained increase of alanine aminotransferase (ALT) associated with high levels of HBV viremia (HBV-DNA) 1 to 2 months after the suspension of chemotherapy has been described in patients suffering from NHL and infected by HBV.7,8 Recently, a nucleotide analogue (lamivudine) was shown to be beneficial in HBV-infected patients with signs of active replication.6 The aim of this study was to investigate the role of lamivudine to treat or to prevent hepatitis reactivation in HBV-infected subjects suffering from NHL and undergoing chemotherapy

Large mediastinal mass of heterotopic thyroid tissue: a case report and review of literature

Salvatore. Incidental detection of a mediastinal mass in a asymptomatic patient poses a not easy diagnostic problem. For solid masses or cysts, histology or cytology is often necessary. Although substernal extension of a cervical goiter is common, totally intrathoracic primary thyroidal mass is unusual. We describe a rare case of heterotopic accessory mediastinal thyroid in a patient completely asymptomatic both for signs of thyroid dysfunction and mechanical compression. Radiological and hormonal 6 and 12 months follow-up is reported

Oncological outcomes in fertility-sparing treatment in stage IA-G2 endometrial cancer

BACKGROUND: The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins. STUDY DESIGN: Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were “endometrial cancer” AND “fertility sparing” AND “oncologic outcomes” AND “G2 or stage IA”. RESULTS: A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months. CONCLUSIONS: Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased

Conservative Resectoscopic Surgery, Successful Delivery, and 60 Months of Follow-Up in a Patient with Endometrial Stromal Tumor with Sex-Cord-Like Differentiation

Uterine tumors with sex-cord-like differentiation are extremely rare types of uterine stromal neoplasm. These tumors were classified into two groups with considerable practical relevance because clinical behaviour of uterine tumor resembling ovarian sex cord tumor (UTROSCT) differs widely from its closely related endometrial stromal tumors with sex-cord-like elements (ESTSCLE). Treatment and prognosis of these tumors are unresolved issues because of the exiguous number of reported cases. We describe a rare case of endometrial stromal tumor with sex-cord-like differentiation successfully treated by resectoscopic surgery and conservation of the uterus, in an infertile patient affected by metrorrhagia. This procedure resulted in a pregnancy immediately after treatment and in a successful delivery. During 60 months of follow-up no evidence of recurrence was observed

A novel in-frame deletion in MYOT causes an early adult onset distal myopathy

Missense mutations in MYOT encoding the sarcomeric Z-disk protein myotilin cause three main myopathic phenotypes including proximal limb-girdle muscular dystrophy, spheroid body myopathy, and late-onset distal myopathy. We describe a family carrying a heterozygous MYOT deletion (Tyr4_His9del) that clinically was characterized by an early-adult onset distal muscle weakness and pathologically by a myofibrillar myopathy (MFM). Molecular modeling of the full-length myotilin protein revealed that the 4-YERPKH-9 amino acids are involved in local interactions within the N-terminal portion of myotilin. Injection of in vitro synthetized mutated human MYOT RNA or of plasmid carrying its cDNA sequence in zebrafish embryos led to muscle defects characterized by sarcomeric disorganization of muscle fibers and widening of the I-band, and severe motor impairments. We identify MYOT novel Tyr4_His9 deletion as the cause of an early-onset MFM with a distal myopathy phenotype and provide data supporting the importance of the amino acid sequence for the structural role of myotilin in the sarcomeric organization of myofibers