Exosomal long non-coding RNA MALAT1: a candidate of liquid biopsy in monitoring of Wilms' tumor.

PURPOSE: Wilms' tumor (WT) is a rare kidney cancer that primarily affects children. Exosomes are extracellular vesicles that cargo nucleic acids, proteins,etc. for cellular communication. Long non-coding RNAs (lncRNAs) have utility as biomarkers for cancer diagnosis, prognosis, and disease monitoring. We hypothesize that expression of lncRNA, metastasis-associated lung adenocarcinoma transcript-1(MALAT1), is dysregulated and possibly trafficked within exosomes to influence the tissue microenvironment for metastasis and recurrence of WT. METHODS: We investigated the expression of MALAT1 in thirty WT samples by qPCR. Exosomes were isolated using a precipitated and affinity-binding-based kit, and characterized using TEM, NTA, and DLS. RESULTS: Mean number of exosomes was 9.01×108/mL in primary culture, 1.64×108/mL in urine, and 4.65×108/plasma:400µl. Average yield of total RNA was 1.28µg (primary-culture supernatant:1ml), 1.47µg (Urine:1ml), 1.65µg (Plasma:400 µL). We quantified MALAT1 in exosomes derived from these sources in patients of WT. Expression of MALAT1 was significantly downregulated (p=0.008) in WT samples. CONCLUSION: This is the first study that demonstrated the presence of lncRNA MALAT1 in various invasive and non-invasive samples of patients with WT(primary tissue culture, urine, and plasma samples).

Cortical transit time: understanding utility and pitfalls in children with pelviureteric junction obstruction.

INTRODUCTION: Delayed cortical transit time (CTT) has been recently studied and proposed as a parameter that can predict the need for surgery in children with pelviureteric junction obstruction (PUJO). AIM: The aim of this study was to study the change in CTT, after surgery, in children with PUJO and to correlate CTT with intrapelvic pressure of the kidney. MATERIAL AND METHODS: A prospective study was performed, and all children who underwent pyeloplasty from January 2016 to December 2017 were included. Pre-operative and postoperative renal ultrasonography and Technetium-99m mercaptoacetyltriglycerine Tc-MAG3 renal scintigraphy were performed. Cortical transit time was measured by a visual method by two different observers. The renal intrapelvic pressure of the kidney was also measured during surgery after giving a diuretic to replicate the diuresis induced during the renal scan. The correlation was studied between the pre-operative CTT and intrapelvic pressures and between the pre-operative CTT and the renal function of the affected kidney. RESULTS: Thirty-one children were included in the study. The median age of children who underwent surgery was 50 months (2-168). In 71% of patients, the CTT was prolonged before surgery, whereas only 22.5% had delayed CTT after surgery. The mean CTT before surgery was 226.1 ± 74.8 s and decreased to 165.4 ± 55.9 s after surgery (p= <0.001). The mean intrapelvic pressure was 21 ± 7.5 cm H2O. There was no correlation noted between the intrapelvic pressure and the CTT. A significant negative correlation was noted between the CTT and the different renal function of the kidney. DISCUSSION: This is the first prospective study that studies the changes in CTT after surgery. Only retrospective studies had been conducted to date which concluded that CTT was delayed in most of the patients who had been operated. It has been proposed that the prolonged CTT is due to raised pressure in the kidney secondary to obstruction. This study did not find any correlation between the pressure and CTT. The significant negative correlation between CTT and renal function also emphasizes the need to take the renal function into consideration before interpreting and using the absolute value of CTT for guiding treatment. CONCLUSION: Cortical transit time assessment by the visual method is a useful parameter in the management of children with PUJO. There is a significant improvement in CTT after surgery.

Comparison of the renal dynamic scan performed with 99mTc-L,L-EC and 99mTc-MAG3 in children with pelviureteric junction obstruction.

The aim was to compare the renal dynamic scan (RDS) performed with technetium-99-L,L-ethylene dicysteine (Tc-L,L-EC) and technetium-99-mercaptoacetyltriglycine (Tc-MAG3) in children with pelviureteric junction (PUJ) obstruction. A retrospective study was carried out and children with PUJ obstruction who had RDS performed with both Tc-L,L-EC and Tc-MAG3. Children with any intervention in between the two scans or a gap of more than 2 months in between renal scans were excluded. The dose of each radiotracer used was 0.1 mCi/kg (3.7 MBq/kg), with a minimum dose of 1 mCi (37 MBq). RDS was performed using the F+0 protocol. The differential renal function, Tmax, T1/2, drainage pattern, and hepatic uptake of the radiotracer were recorded and compared. A Bland-Altman plot was used to assess agreement between the two radiotracers. Sixteen children were included in the study. A total of 18 obstructed and 14 normal renal units were available to us for study. The values of differential renal function as well as Tmax and T1/2 of the two radiotracers were in agreement. In three obstructed kidneys in which T1/2 on Tc-MAG3 was greater than 20 min, Tc-L,L-EC showed T1/2 values of 13.3 min or less. Tc-L,L-EC showed nonobstructive drainage in three patients who had shown partial obstruction on Tc-MAG3 scan. The hepatic uptake of Tc-L,L-EC was also lower compared with Tc-MAG3. To conclude Tc-L,L-EC is a useful radiotracer for the evaluation of children with PUJ obstruction, with better assessment of drainage and lower hepatic uptake compared with Tc-MAG3.

A Case of Peeling Skin Syndrome.

Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparing palm and soles. Histologically, there was epidermal separation at the level of stratum corneum, just above the stratum granulosum. This case is being presented due to its rarity.

Enteric Duplication Cysts in Children: A Clinicopathological Dilemma.

AIM: Enteric duplication cysts are rare and uncommon congenital malformations formed during the embryonic period of the development of human digestive system and are mainly encountered during infancy or early childhood, but seldom in adults. The clinical presentation is extremely variable depending upon its size, location and type. We present six cases of enteric duplication cysts with diverse clinico-pathological features. MATERIALS AND METHODS: This study was carried out in the Department of Pathology and Department of Paediatric Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India for a period of 2 years (January 2013 - December 2014). We retrospectively analyzed six patients of enteric duplication cysts based on data obtained, which consisted of patient's age, sex, clinical presentation, radiological features, operative findings and histopathology report. The data collected was analyzed by descriptive statistics. RESULTS: Six children between age range of 3 days to 10 years had enteric duplication cysts. Two had ileal and one each were of pyloroduodenal, colonic and rectal duplication cyst. In one patient a presumptive diagnosis of enteric duplication cyst was made. Radiology played an important contributory role in diagnosis of these cysts in all the patients but histopathology proved to be gold standard for its confirmation. All these patients were managed by surgical excision. The postoperative and follow up period in all the cases was uneventful. CONCLUSION: It is important to be aware and make a definitive diagnosis of this rare congenital anomaly as they can present in various clinical forms and can cause significant morbidity and even mortality if left untreated by causing life threatening complications.

Predictive factors for successful vessel-intact laparoscopic orchiopexy for intra-abdominal testes.

OBJECTIVE: To identify the predictive factors for successful vessel-intact laparoscopic orchiopexy (VILO) for nonpalpable intra-abdominal testes (NPIT). MATERIALS AND METHODS: 25 boys with 28 NPITs within 2 cm of the internal ring underwent VILO. They were divided into two groups based upon outcome, for statistical comparison. Group A (successful VILO): patients with testes pexed in scrotum during surgery, and maintained viability and scrotal position of testes at 3-month & 6-month postoperative follow up. Group B: failed VILO. RESULTS: Intrascrotal fixation at VILO was achievable for 17/28 NPITs. Postoperative follow up and final outcome data were available for 25/28 NPITs, of which 14 were successful (A) while 11 had failed VILO (B). The mean age of patients in group A differed significantly from that of patients in group B (4.16 years versus 6.64 years; p = 0.035). The mean testis-to-internal ring distance was 0.50 cm for group A and 1.05 cm for group B, but this was not statistically significant (p = 0.141). There was statistically a highly significant difference (p = 0.002) with respect to the mean internal ring-to-midscrotum distances in groups A and B: 5.56 cm and 7.05 cm, respectively. A scatter-plot of age or height against internal ring-to-midscrotum distance showed a fairly linear relationship. CONCLUSIONS: Age or height of the patient at surgery is an independent factor predicting the success of VILO for intra-abdominal testis. The internal ring-to-midscrotum distance increases with age/height, resulting in increased testis-to-midscrotum distance and higher failure rate of VILO in older children.

Management of female anterior perineal injuries with urethrovaginal disruption by anterior sagittal transanorectal approach.

OBJECTIVE: Urethrovaginal disruption injury poses a considerable challenge in surgical correction, mainly due to difficult access to the receded urethrovaginal unit deep in the scarred anterior perineum. We assessed the feasibility, safety and efficacy of the anterior sagittal transanorectal approach (ASTRA) in the repair of anterior perineal injury with urethrovaginal disruption in female children. MATERIALS AND METHODS: Three girls with urethrovaginal disruption following perineal injury were operated by ASTRA between March 2008 and December 2010. All of them had severe scarring of the anterior perineum at the time of definitive repair by this approach. One underwent ASTRA repair without a covering colostomy. RESULTS: Total urethrovaginal mobilization and anchorage of urethral and vaginal orifices at the vestibule were successfully achieved in all patients. One patient has developed vaginal stenosis at 1.5 years follow up. Despite the absence of a colostomy cover in one case, there were no wound complications in the early postoperative period. CONCLUSION: The ASTRA is safe and efficacious in the repair of traumatic urethrovaginal disruption in children.