Central precocious puberty occurring in Bardet-Biedl syndrome-10 as a method for self-protection of human reproductive function: A case report.

Hypogonadism and obesity are primary features of Bardet-Biedl syndrome (BBS). Obesity is also an associated factor of central precocious puberty (CPP). The present report describes the case of a girl (age, 7 years and 6 months), with clinical manifestations of precocious puberty, progressive obesity, postaxial polydactyly, retinal degeneration and intellectual disability. The patient visited the clinic for the first time due to early breast development and progressive obesity. After 8 months of follow-up, the bone age had advanced almost 3 years, and the gonadotropin-releasing hormone (GnRH) stimulation test showed results that had changed from indicating pseudo precocious puberty to CPP. Whole-exome gene sequencing showed that there were two heterozygous mutations in the BBS type 10 (BBS10) gene, chr12:76739816(c.1949del) and chr12:76740374(c.1391C>G). The final diagnosis was of BBS10 and CPP. In order to protect the reproductive capacity of the patient, GnRH analogs were used for CPP treatment. After 15 months of treatment and follow-up, a physical examination revealed Tanner breast stage 1. Ultrasonography showed that the uterus and ovaries had reduced to their prepubertal size. In conclusion, the present report describes a case of CPP that occurred in a young girl with BBS10. We hypothesize that this was a prelude to gonad dysplasia, acting as a method for the self-protection of human reproductive function. However, more clinical data and molecular biological evidence are required to confirm the etiology and mechanism of this case.

Benefits of Prophylactic Cranial Irradiation in the MRI Era for Patients With Limited Stage Small Cell Lung Cancer.

Purpose: Previous studies have shown that prophylactic cranial irradiation (PCI) can improve the survival of patients with limited-stage small cell lung cancer (LS-SCLC). PCI is recommended for patients who respond well to chemoradiotherapy. However, whether PCI could be extrapolated to the LS-SCLC patients in the modern era of MRI is unknown. This study aimed to explore the value of PCI in patients with LS-SCLC in the era of brain MRI. Methods: This study included 306 patients with LS-SCLC at the Cancer Hospital of China Medical University. All patients received brain MRI at diagnosis and after radiochemotherapy to exclude brain metastases. A propensity score matching was performed to reduce the influence of potential confounders. Overall survival (OS), progression-free survival (PFS), and recurrence failure types were compared between PCI and non-PCI groups. Results: Among the 306 eligible patients, 81 underwent PCI, and 225 did not. After propensity score matching, there was no statistical difference in baseline data between the two groups, with 75 patients in each group. PCI did not achieve OS (median OS: 35 vs. 28 months, p = 0.128) or PFS (median PFS: 15 vs. 10 months, p = 0.186) benefits. During follow-up, 30 patients (20.0%) developed brain metastases, including 13 patients (17.3%) in the PCI group and 17 patients (22.7%) in the non-PCI group. Regarding death as a competitive risk, patients who received PCI had a lower cumulative incidence of brain metastasis than those who did not (3 years: 14.7% vs. 22.7%; Gray's test, p = 0.007). Conclusions: When brain MRI was performed at diagnosis and pre-PCI, PCI could reduce the cumulative rate of brain metastases, but it did not achieve survival benefits for LS-SCLC patients.

Optimizing Whole Brain Radiotherapy Treatment and Dose for Patients With Brain Metastases From Small Cell Lung Cancer.

PURPOSE: This study aimed to evaluate the survival outcomes of whole brain radiotherapy (WBRT) compared to whole brain radiotherapy plus local radiation boost (WBRT + boost), and further identify whether higher biologically effective dose (BED) of WBRT + boost translates into a survival benefit in small cell lung cancer (SCLC) patients with brain metastasis (BM). METHODS: SCLC patients with BM from January 1, 2012, to December 31, 2019, were retrospectively analyzed. Overall survival (OS) and intracranial progression-free survival (iPFS) were evaluated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate regression analyses of prognostic factors for OS were performed using Cox proportional hazards regression models. The cutoff value of BED was determined by the receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 180 eligible patients, 82 received WBRT + boost and 98 received WBRT. Both OS and iPFS in the WBRT + boost group were significantly superior to those in the WBRT group (median OS: 20 vs. 14 months, p = 0.011; median iPFS: 16 vs. 10 months, p = 0.003). At a cutoff value of 58.35 Gy in the WBRT + boost group, 52 for the high-BED (>58.35 Gy) group, 30 for the low-BED (≤58.35 Gy) group. High BED was significantly associated with improved OS and iPFS compared with low BED in the WBRT + boost group (median OS: 23 vs. 17 months, p = 0.002; median iPFS: 17 vs. 10 months, p = 0.002). CONCLUSIONS: Compared with WBRT alone, WBRT + boost improved OS and iPFS in SCLC patients with BM. High BED (>58.35 Gy) for WBRT + boost may be a reasonable consideration for SCLC patients with BM.

A rare case of 46, XX (SRY positive) testicular disorder of sex development with growth hormone deficiency: Case report.

RATIONALE: Chromosome karyotype analysis and SRY (sex determined region of Y chromosome) gene detection are routines for the diagnosis of growth hormone deficiency (GHD), but further whole exome gene sequencing occasionally leads to subversive results and unexpected conclusions. PATIENT CONCERNS: We report a single case of a 7-year-old Chinese boy who had stunted growth since he was 1 year old. He was short in height (height Standard Deviation Score (SDS) was less than 2.9), bilateral scrotal dysplasia and delayed bone age. DIAGNOSIS: His growth hormone (GH) stimulation tests showed GHD. His karyotype analysis and polymerase chain reaction (PCR) analyses indicated a 46, XX disorder of sex development (DSD) without the presence of the SRY gene. Nevertheless, considering that female gonad was not observed in the chest and abdominal magnetic resonance imaging, the whole exome gene sequencing was performed. Sequencing data confirmed the presence of SRY gene sequence and two copies of chromosome X. Later, using different primer sequences for PCR, it showed that the SRY gene was positive. The final diagnosis was a rare case of "46, XX (SRY positive) testicular DSD with GHD". INTERVENTIONS: The boy's parents agreed to use recombinant human growth hormone (rhGH) for GHD treatment, the starting dose was 0.035 mg / kg / day. But they disagreed with molecular diagnostics and genomic analysis of the Y chromosome. OUTCOMES: The boy was treated with rhGH for 3 months and his height increased by 2.2 cm. The patient will be followed-up until the end of his puberty. LESSONS: In summary, whole exome gene sequencing overturned the preliminary diagnosis results of karyotype analysis and SRY gene detection, and found that there may be a certain correlation between testicular DSD and GHD.