ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC. Objectives RCC. RCC . (RCC) prostatespecific prostate specific PSMA PETCT PET tumors However 68GaPSMA11 GaPSMA 68Ga 11 Ga 68Ga-PSMA-1 18Ffluorodeoxyglucose Ffluorodeoxyglucose 18F fluorodeoxyglucose F 18FFDG FFDG FDG (18F-FDG clearcell clear (ccRCC Methods 3 included recorded therapy scanning nonccRCC non excluded characteristics pvalue p 0017 0 017 0.017 Results Seventytwo Seventy two analysis all 0.05. 005 0.05 05 0.05) (SUVmax 085 85 0.8 cutoff value2526 25 26 value=25.26 p<0.001 p0001 001 z2709 z 2 709 z=2.709 p=0.007 p0007 007 090 90 0.9 z3433 433 z=3.433 091 91 vs075 vs 75 vs.0.75 z1998 1 998 z=1.998 p=0.046. p0046 p=0.046 046 p=0.046) age sex location diameter WHOISUP WHO ISUP intraclass ICC (ICC 0.80, 080 0.80 , 80 0.80] Conclusions (RCC 68GaPSMA1 68Ga-PSMA- 01 0.01 00 0.0 08 8 0. value252 value=25.2 p<0.00 p000 z270 70 z=2.70 p=0.00 09 9 z343 43 z=3.43 vs07 7 vs.0.7 z199 99 z=1.99 p004 p=0.04 04 68GaPSMA 68Ga-PSMA value25 value=25. p<0.0 p00 z27 z=2.7 p=0.0 z34 4 z=3.4 vs0 vs.0. z19 z=1.9 value2 value=25 p<0. p0 z2 z=2. p=0. z3 z=3. vs.0 z1 z=1. value=2 p<0 z=2 p=0 z=3 vs. z=1 value= p< z= p=

SUMMARY A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease. 71yearold yearold 71 year old (PTC hospital neck vein clavicle skin involved noticed unresectable however surgery Therefore mg po p o p.o 2week week 2 on/1week on1week onweek on/1 on 1 regimen withdrawal performed BRAFVE BRAFV E NGS observed increased withdraw taken metastasis longterm long term disease 7 1week on1 on/

Abstract X-linked intellectual disability (XLID) has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID), is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID). The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T), which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1) gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI) protein from glycine to valine (p. Gly237Val). Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

ABSTRACT Objective: To evaluate the efficacy and safety of bipolar transurethral enucleation and resection of the prostate (B-TUERP) versus bipolar transurethral resection of the prostate (B-TURP) in the treatment of prostates larger than 60g. Material and Methods: Clinical data for 270 BPH patients who underwent B-TUERP and 204 patients who underwent B-TURP for BPH from May 2007 to May 2013 at our center were retrospectively analyzed. Outcome measures included operative time, decreased hemoglobin level, total prostate specific antigen (TPSA), International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), quality of life (QoL) score, post void residual urine volume (RUV), bladder irrigation duration, hospital stay, and the weight of resected prostatic tissue. Other measures included perioperative complications including transurethral resection syndrome (TURS), hyponatremia, blood transfusion, bleeding requiring surgery, postoperative acute urinary retention, urine incontinence and urinary sepsis. Patients in both groups were followed for two years. Results: Compared with the B-TURP group, the B-TUERP group had shorter operative time, postoperative bladder irrigation duration and hospital stay, a greater amount of resected prostatic tissue, less postoperative hemoglobin decrease, better postoperative IPSS and Qmax, as well as lower incidences of hyponatremia, urinary sepsis, blood transfusion requirement, urine incontinence and reoperation (P<0.05 for all). Conclusions: B-TUERP is superior to B-TURP in the management of large volume BPH in terms of efficacy and safety, but this finding needs to be validated in further prospective, randomized, controlled studies.