Variations in the Density and Distribution of Cajal Like Cells Associated With the Pathogenesis of Ureteropelvic Junction Obstruction: A Systematic Review and Meta-Analysis.

Introduction: Cajal like cells (CLCs) in the upper urinary tract have an ability to generate coordinated spontaneous action potentials and are hypothesized to help propel urine from renal pelvis into the ureter. The objective of this review was to describe the variations in the density and distribution of CLCs associated with ureteropelvic junction obstruction (UPJO). Materials and Methods: Studies comparing the density and distribution of CLCs in the human upper urinary tract in patients with UPJO and healthy controls were included in this systematic review. We searched online electronic databases; Ovid MEDLINE, Scopus, PubMed and Cochrane reviews for the studies published before October 31, 2020. A meta-analysis was conducted to compare the density of CLCs at the ureteropelvic junction (UPJ) in patients with UPJO and matched controls. Results: We included 20 and seven studies in the qualitative and quantitative synthesis, respectively. In majority (55%) CLCs were located between the muscle layers of the upper urinary tract. The CLC density in the UPJ gradually increased with aging in both healthy subjects and patients with UPJO. The pooled analysis revealed that the density of CLCs at the UPJ was significantly low in patients with UPJO compared to the controls (SMD = -3.00, 95% CI = -3.89 to -2.11, p < 0.01). Conclusions: The reduction in CLC density at the UPJ in patients with UPJO suggests a contribution from CLCs in the pathogenesis of UPJO. Since age positively correlates with CLC density, it is imperative to carefully match age when conducting case control studies comparing the CLC density and distribution. Protocol Registration Number: CRD42020219882.

A closer look at NIFTP.

Despite the rise in the incidence of papillary thyroid carcinoma (PTC) during the last 30 years, the mortality rate due to PTC has remained static. One reason for this phenomenon is the indolent nature of some of the tumors that are diagnosed as PTC. A subgroup of tumors, which often exhibited such indolent behavior, was encapsulated/well-circumscribed follicular lesions that showed PTC nuclear features. Despite their indolent behavior, these tumors were managed as was any other PTC, often with total thyroidectomy and radioactive iodine (RAI) treatment. In order to prevent overtreatment of these tumors, they were recently reclassified as "non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)." Since it is proposed that NIFTP be managed in a more conservative manner, its diagnosis is now based on strict histological criteria. The genetic basis of these diagnostic criteria and the utility of molecular markers in the diagnosis of NIFTP are currently being scrutinized. The aim of this review is to discuss the events that led to the emergence of the term NIFTP, as well as its histological and molecular background.

Star fruit nephrotoxicity: a case series and literature review.

BACKGROUND: Star fruit is a popular medicinal fruit in the tropics. Its hypoglycaemic properties are considered useful in achieving glycaemic control in diabetes. Star fruit induced nephrotoxicity is a rare cause of acute kidney injury in individuals with both normal and reduced baseline renal function. We present three cases of acute kidney injury due to star fruit nephrotoxicity from Sri Lanka, and discuss the published literature on this topic. CASE PRESENTATION: Three Sri Lankan patients, all with a background of diabetes, presented to us with acute nausea and anorexia following recent consumption of star fruit. Two patients complained of diarrhoea and one patient complained of intractable hiccoughs. They all had elevated serum creatinine on admission. Two were known to have normal baseline serum creatinine levels. On renal biopsy two had evidence of oxalate crystal deposition. One did not show crystal deposition but had acute interstitial nephritis for which no alternate cause could be identified. Two were treated with short courses of prednisolone and two required acute haemodialysis. All recovered renal function, with both patients with known baselines approaching their premorbid serum creatinine levels. CONCLUSION: Consumption of star fruit, especially on an empty stomach or in a state of dehydration may precipitate acute kidney injury. A history of star fruit ingestion must be actively looked for in patients presenting with unexplained acute kidney injury. The use of star fruit as a therapy for diabetes should be discouraged.

BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma.

Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6, respectively.

In situ immunopathological changes in cutaneous leishmaniasis due to Leishmania donovani.

Cutaneous leishmaniasis in Sri Lanka is a newly established parasitic disease caused by the usually visceralizing Leishmania donovani. Skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. In situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. Skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines, namely interferon (IFN)-γ, interleukin (IL)-12A, tumor necrosis factor (TNF)-α, IL-4 and IL-10 by real-time RT-PCR. Significant up-regulation of the Th1 cytokine IFN-γ and down-regulation of the Th2 cytokine IL-4 were seen in patients compared to healthy controls. Significantly elevated tissue expression of IFN-γ and TNF-α was seen in lesions that presented later than 6 months from the time of onset, while IL-4 expression was more prominent in lesions that responded poorly to antimony therapy. A prominent Th1 response appears to support resolving of lesions, whereas a Th2-biased milieu tends to favor poor responsiveness to antimony and delayed lesion healing in L. donovani infections in Sri Lanka.

Metastatic invasive lobular carcinoma of the breast masquerading as a primary renal malignancy.

Breast cancer is known to metastasise to different organs in the body, but an initial presentation of breast cancer with loin pain secondary to a metastatic renal mass is extremely rare. We report a 58-year-old woman who presented with recurrent left loin pain due to a metastatic deposit of invasive lobular carcinoma of the breast. The detection of a renal mass on computed tomography led to the assumption of a renal pelvic malignancy. The diagnostic dilemma posed by the detection of a breast mass during staging and the usefulness of immunohistochemistry in the confirmation of diagnosis are discussed.

Incidence of bladder cancer in sri lanka: analysis of the cancer registry data and review of the incidence of bladder cancer in the South asian population.

PURPOSE: To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). MATERIALS AND METHODS: The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. RESULTS: A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. CONCLUSIONS: Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan.

Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant.

A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses.

Incidence of prostate cancer in Sri Lanka using cancer registry data and comparisons with the incidence in South Asian men in England.

OBJECTIVE: •To investigate the incidence of carcinoma of the prostate (CaP) in Sri Lanka and compare the rates with the migrant population in the UK. METHODS: •The Sri Lanka cancer registry data were used to determine the rates of CaP in Sri Lanka from 2001 to 2005. •The incidence of CaP in 8,426,000 men, aged ≥30 years, was analysed using 5-year age bands and age-standardized rates were calculated using European standard population data. •The relative risk was calculated by comparison with the South Asian migrant population in the UK using the Prostate Cancer in Ethnic Subgroups (PROCESS) study data, a population-based retrospective cohort study of 2140 men carried out over a 5-year period in four predefined areas of southern England. •Data from incidental findings of CaP in Sri Lanka on transurethral resection of the prostate (TURP) specimens were also analysed. RESULTS: •In all, 1378 new cases of CaP were diagnosed during the 5-year period with a mean age of 69.2 years at diagnosis. •Compared with the previous 5 years, the incidence of CaP had doubled to 5.7 per 100,000, but was significantly lower than in the PROCESS study (relative risk 0.25). •Districts with a higher population density had higher adjusted rates of CaP in Sri Lanka (5.8-12.4 per 100,000). •For TURP specimens, 16.8-18.75% had incidental diagnoses of CaP in Sri Lanka, higher than other published studies. CONCLUSIONS: •The Sri Lankan cancer registry data showed a low rate of CaP, similar to other South Asian countries, but the actual incidence of CaP in Sri Lanka is probably higher than reported, as seen in the densely populated districts and the high rate of incidental diagnosis of CaP in TURP specimens. •The incidence of CaP in migrant South Asians in the UK was much higher than in Sri Lanka. •Further studies are required to examine the environmental and genetic components which may be responsible for the low incidence of CaP in Sri Lanka.

Large-cell calcifying sertoli cell tumour of the testis detected at screening of a family with Carney syndrome.

We report the detection of a large-cell calcifying Sertoli cell tumour (LCCSCT) in a 34-year-old male during screening of a family with Carney syndrome. The patient had ignored the testicular swelling for 7 years. He also had a cardiac myxoma. The LCCSCT in this patient had prognostically unfavourable features such as large size (>6 cm) and a high mitotic rate. There is only one previous report of a malignant LCCSCT in a patient with Carney syndrome.