Individuals with acquired cystic kidney disease (ACKD) in the setting of end-stage renal disease (ESRD) have a high risk of developing renal cell carcinoma (RCC). ACKD-RCC is considered a distinct renal neoplasm in the International Society of Urologic Pathologists (ISUP)-World Health Organization (WHO) classification of kidney tumors which may behave aggressively. Since its original description, there have been multiple case reports and series published; however, the pathogenesis of this neoplasm is uncertain and there is limited data on the genetic aberrations of this tumor. Herein, we present our experience with ESRD kidneys, with emphasis on ACKD-RCC, associated cysts, and the somatic mutation analysis of a subset of ACKD-RCCs using next-generation sequencing. Our data on 59 cases with ESRD that underwent nephrectomy, shows that ACKD-RCC represents more than half of the tumors (25/46; 54%) developing in ESRD, followed by papillary RCC (13; 28%). History of dialysis, male sex, and African American race were potential risk factors for developing ACKD-RCCs. Further, ACKD-RCC–like cysts are possible precursors of RCCs in the ACKD setting noted in 40 of 46 (87%) cases with tumors. Next-generation sequencing analysis revealed recurrent mutations in the KMT2C gene in 4 of 5 ACKD-RCCs (80%), exclusively exhibiting cribriform “sieve-like” morphology; whereas the case negative for KMT2C mutations exhibited “type 2” papillary RCC morphology and lacked “sieve-like” growth pattern. Pathogenic mutations in TSC2 were the second common abnormality (3/5; 60%), often coexisting with KMT2C mutations. Deleterious mutations in additional genes such as CBL, PDGFRA, and SYNE1, etc. were noted but were nonrecurrent and always coexisted with mutations in KMT2C or TSC2. To conclude, our study highlights that mutations in a chromatin-modifying gene KMT2C may potentially be oncogenic drivers for the development of ACKD-RCC with classic sieve-like morphology. In addition, pathogenic mutations in TSC2 possibly play a role in the development of cysts/tumors in a subset of ACKD patients. If corroborated in larger cohorts, these findings would be useful in planning surveillance and early intervention in ESRD patients developing ACKD.
Objectives To characterize the tumor microenvironment of testicular germ cell tumors (GCTs) using immunohistochemical markers. Methods Seventy-seven orchiectomies, including 36 nonmetastatic (NM) seminomas, 15 metastatic (M) seminomas, 13 nonmetastatic nonseminomatous germ cell tumors (NSGCTs), and 13 metastatic NSGCTs, were studied with PD-1, PD-L1, FOXP3, CD68, CD163, and mismatch repair (MMR) immunohistochemistry. FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) expressing CD68 and CD163 were enumerated. PDL-1 expression was evaluated on tumor cells and macrophages. Results GCTs primarily express PD-L1 on TAMs, except choriocarcinoma, where true tumor cell positivity was noted. Seminomas reveal increased intratumoral PD-L1+ TAMs compared with NSGCTs (P < .05). Activated TILs are increased in NM-seminomas compared with M-seminomas (P < .05). All GCTs retained MMR expression. Conclusions Robust PD-L1+ TAMs are significantly expanded in seminomas compared with NSGCTs. Among all GCTs, only choriocarcinoma cells reveal true positivity for PD-L1. These findings expand the realm of potentially targeted treatments for GCTs.
BACKGROUND Laparoscopic cholecystectomy is difficult in acute cholecystitis because the gall bladder is usually thick walled and tensely distended. If the inflammation of the gall bladder extends to the porta hepatis the dissection becomes difficult. The normally thin minimally adherent tissue that invest the cystic duct and artery is markedly thickened and oedematous and may not readily separate from these structures with the usual blunt dissection technique. The duct wall also may be oedematous, thus making its external diameter similar to gall bladder neck and common bile duct. Moreover, operative difficulty substantially increases with time. It is believed that laparoscopic cholecystectomy in acute cholecystitis is having more operative time, more conversion rate and more chance of injury. METHODS We did an observational study to determine the safety, benefits and drawbacks of laparoscopic cholecystectomy within 72 hours of symptoms (and beyond that). RESULTS Total 325 patients underwent laparoscopic cholecystectomy in acute cholecystitis. Among them 110 patients were operated within 72 hours of appearance of symptoms while 215 patients were operated upon after 72 hours of appearance of symptoms. The mean duration of surgery was significantly (p< 0.001) less in early surgery group. There was no conversion. There was no serious intra operative complication (injury) in early group. There was no statistically significant post-operative complication in either group. Post-operative stay was significantly less (p<0.004) in early laparoscopic cholecystectomy group. Period of return to work was also significantly less (p<0.001) in early group. CONCLUSIONS Early (within 72 hours of appearance of symptoms) laparoscopic cholecystectomy can be safely advocated in patients of acute cholecystitis. It does not result in increased conversion rate or increased intra operative complication. Moreover it offers benefits shorter post-operative hospital stay and early return to work than laparoscopic cholecystectomy after 72 hours of appearance of symptoms.
Multinodular goiters are more often looked upon as potentially benign type. But the incidence of malignancy in MNG is on the rise. The objective of this study was to determine the incidence of malignancy in multinodular goiter. In this prospective study total 40 patient of thyroid swellings (MNG, STN & diffuse goitre) were seen in the M.K.C.G. Medical College Hospital, Southern Orissa, during August 2011-July 2013. Thyroid hormone profile and FNAC was done in all cases while, USG was done in 28 cases and all cases underwent surgery and subsequently histopathological examination. In our series 62.5% of patients were found to have MNG and 3 (12%) of them were found to harbor malignant lesions in their glands after histopathological studies.
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