Journal of Kidney Cancer and VHL最新文献

Primary synovial sarcoma (PSS) of the kidney is considered the rarest type of all renal sarcomas with specific chromosomal translocation t (X; 18) (p11.2; q11.2). We report the case of a 65-year-old man with no medical conditions who presented to the emergency department with sudden severe right flank pain associated with haemodynamic instability and haemorrhagic shock. Computed tomography (CT) of the abdomen and pelvis revealed a right renal mass. A right open radical nephrectomy was performed. Histopathology revealed a monophasic synovial sarcoma. The patient received six cycles of docetaxel and gemcitabine as adjuvant chemotherapy. No sign of recurrence was seen on a follow-up CT urogram. This rare tumour often presents atypically, and clear guidelines regarding appropriate treatment are lacking. Our case showed that treatment with docetaxel/gemcitabine after an open radical nephrectomy is promising.

Obesity has been established as a risk factor for renal cell carcinoma (RCC). Recently, studies have described obesity as a probable protecting factor in the metastatic stage of RCC. In this study, we assessed the relationship between body mass index (BMI) and overall survival in patients under systemic therapy. The correlation between BMI and overall median survival was studied in 76 patients diagnosed with metastatic RCC under systemic therapy. The groups were divided into overweight and obesity (BMI > 25 kg/m²) and underweight or normal (BMI < 25 kg/m²). Statistical analysis was performed using the Cox regression model adjusted by gender. A total of 76 patients were studied: 16 women (21%) and 60 men (79%). The median BMI was 27.96 kg/m²; 24 patients (31.6%) had low BMI and 52 (68.4%) had high BMI. Median overall survival in the group with BMI > 25 kg/m² was 17 months (95% confidence interval [CI]: 13-34 months), while in the group with BMI ≤ 25 kg/m², it was 14 months (95% CI: 8-20 months). When adjusted by gender, the group with BMI > 25 kg/m² presented a hazards ratio of 0.54 (95% CI: 0.30-0.96), P = 0.044 (Log Rank). A high BMI significantly acts as a protecting factor. We observed an increased overall survival of overweight and obese patients within the context of metastatic RCC under systemic treatment. These data confirm the findings published in other studies that suggest the role of lipid metabolism in this type of tumors.

Wilms' tumor (WT) in adults is a rare neoplasm. Only a few reports are available in the literature. The tumor often masquerades as renal cell carcinoma (RCC). For accurate reporting, histopathological examination (HPE) plays a vital role in early diagnosis and prompt administration of multimodality treatment helps to improve the prognosis. We comprehensively analyzed five cases of adult WT presenting in the third to fifth decade with flank pain, hematuria, fever, and palpable lump. After complete clinical, biochemical, radiological, and HPE evaluation, tumor was staged and treatment was planned accordingly. Patients with low-stage WT were treated with open radical nephrectomy and chemotherapy. One of the patients diagnosed with inferior vena cava (IVC) thrombus apart from the above treatment also underwent IVC thrombectomy. Another young male presenting with distant metastasis (stage IV) and focal anaplasia on histology received preoperative chemotherapy and then planned for surgery. Unfortunately, the tumor being unresectable, second-line chemotherapy was given but he ultimately succumbed to death. All other patients are on regular follow-up and disease-free. Adult nephroblastoma is a rare clinical entity with hostile behavior. The presence of IVC thrombus is not a contraindication to surgery. Although the management strategy as per pediatric protocol by the inclusion of multimodality approach improves survival, still the overall prognosis in adults is dismal. There is a need for a standardized treatment protocol to encourage a homogenous approach for this rare disease and thereby improve survival.

Kidney cancer, with 4% of all malignancies, is one of the most common malignancies occurring among in adults. In Saudi Arabia, kidney cancer comprises 2.3% of all cancers, and its incidence has increased by 33%. Partial nephrectomy (PN) is considered as the gold standard for T1 renal masses. In this retrospective study, we did a chart review for all patients who underwent PNs between April 2013 and February 2019. Data comprised presentation, tumor size, type of procedure (open vs. laparoscopic vs. robotic), and intra- and post-operative complications. Chi-square, ANOVA, and cross-tabulation were done using SPSS software. P > 0.05 was considered significant. Approval was obtained from the institutional review board of King Abdullah International Medical Research Center. In all, 69 patients were identified: 26 (37.7%) males and 43 (62.3%) females, with mean age = 54.53 ± 13.21 years; mean body mass index = 32.36 ± 7.03, and mean tumor size = 3.7 ± 1.72 cm. In terms of presentation, most patients (50, 72.4%) presented incidentally as opposed to symptomatic presentation. Of these patients, 18 (26.1%) underwent open partial nephrectomy (OPN), 29 (42%) laparoscopic partial nephrectomy (LPN), and 22 (31.9%) robotic partial nephrectomy (RPN). On comparing minimally invasive surgery (MIS) PN with OPN, we found that OPN had more blood loss and a longer hospital stay but a shorter operating room (OR) time. Results of PN irrespective of the procedure type, whether it was OPN, LPN, or RPN, were similar if performed by experienced surgeons. However, open procedures involved a higher blood loss, more operative time, and longer hospital stay when compared with minimally invasive techniques.

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary outcome was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson-Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15-1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson-Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04-1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.

Renal angiomyolipoma is a rare cause of renal tumor in children. Most are associated with tuberous sclerosis, and the classic type is observed more commonly. Epithelioid angiomyolipoma is even rarer with only limited case reports and series published in literature, most of which are of adult patients. We describe a 12-year-old boy, a diagnosed patient of tuberous sclerosis, who presented with pain in the left flank. On evaluation, it was found to have a left renal mass with the clinical picture suggestive of renal cell carcinoma. Partial nephrectomy was performed and histopathology revealed epithelioid angiomyolipoma. The child was asymptomatic at follow-up after 3 months. Only a few such cases in children are found in literature, which are discussed alongside. Differential diagnosis of this rare tumor must be kept in mind in a renal tumor as surgery is generally curative in this possibly malignant tumor. Metastasis confers a poor prognosis. Chemotherapy is generally not effective, although various regimens have been tried. Tumor recurrence must be kept in mind and a follow-up after apparent complete remission is of paramount importance.

Lynch syndrome (LS) is an autosomal dominant inherited disorder due to pathogenic variations in the mismatch repair genes, which predisposes to malignancies, most commonly colon and endometrial carcinoma. Muir-Torre syndrome is a subset of LS with cutaneous sebaceous adenoma and keratoacanthoma in addition to the malignancies. Renal cell carcinoma (RCC) in patients with LS is extremely rare. Only 26 cases have been reported and among them, only two cases of papillary RCC. We report a case of synchronous papillary RCC and colonic adenocarcinoma in an 85-year-old male with Lynch/Muir-Torre syndrome. The LS was diagnosed when he presented with multiple sebaceous adenomas and genetic testing showed a pathogenic variant in MSH6 mismatch repair gene. A colonoscopy at that time showed multiple tubular adenomas with high-grade dysplasia. He was lost to follow-up and presented with gastrointestinal bleeding after 20 years. A right colonic mass, and a solid mass in the lower pole of the right kidney, was detected by imaging. Right Colectomy showed a T3N0 mucin-producing adenocarcinoma. Right nephrectomy showed a T3a papillary RCC which was microsatellite stable with MSH6, and KRAS mutation. The 36-month follow-up exams showed additional sebaceous neoplasms, and an absence of metastatic carcinoma. Analysis of the reported cases of RCC in LS show clear cell RCC as the most common type. These tumors showed MLH1 mutation most commonly, unlike the urothelial malignancies in LS which involve MSH2. Among the 4 cases of RCC with MSH6 mutation, three were in females, indicating some gender differences.

Hypoxia-inducible factor (HIF), an important mediator of hypoxia response, is implicated in tumorigenesis in the setting of pseudohypoxia, such as in the inactivation of von Hippel-Lindau tumor suppressor protein (pVHL), leading to development and progression of clear cell renal cell carcinoma (ccRCC). Targeting downstream molecules in HIF pathway, such as vascular endothelial growth factor (VEGF), has led to improvement in clinical outcome for patients with advanced ccRCC, but such therapy thus far has been limited by eventual resistance and treatment failure. Following the discovery of HIF-2α playing a key role in ccRCC carcinogenesis, inhibitors targeting HIF-2α have been developed and have demonstrated encouraging efficacy and safety profile in clinical trials. This review discusses HIF-2α as a promising therapeutic target for ccRCC.

Thrombotic microangiopathy (TMA) is characterised by abnormalities in the walls of arterioles and capillaries, precipitated by hereditary or acquired characteristics, and culminating in microvascular thrombosis because of dysregulated complement activity. A number of drugs can precipitate TMA, including vascular endothelial growth factor (VEGF) inhibitors, because of their effects on endothelial repair. Pazopanib is a VEGF inhibitor used for the treatment of renal cell carcinoma (RCC); it is uncommonly associated with TMA. A 52-year-old male, 5 years post his second kidney transplant secondary to immunoglobulin (Ig) A nephropathy, presented with hypertension, fluid overload, and worsening graft function (peak creatinine 275 µmol/L, baseline 130-160 µmol/L) and nephrotic range proteinuria 2 months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters were unremarkable. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA, with overlying features of borderline cellular rejection. He was treated with intravenous methylprednisolone 250 mg for 3 days and commenced on irbesartan 75 mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented association with other tyrosine kinase inhibitors (TKIs). In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained <200 µmol/L 3 months after admission. This is the first reported biopsy-proven case of TMA attributed to pazopanib in a kidney transplant recipient. With increasing clinical indications for and availability of TKIs, clinicians need to be aware of their association with TMA events in kidney transplant recipients, who are already susceptible to TMA due to abnormal vasculature, infectious triggers, ischaemia-reperfusion injury, and use of calcineurin inhibitor.

The aim of this study was to evaluate germline variant frequencies of pheochromocytoma and paraganglioma targeted susceptibility genes with next-generation sequencing method. Germline DNA from 75 cases were evaluated with targeted next-generation sequencing on an Illumina NextSeq550 instrument. KIF1B, RET, SDHB, SDHD, TMEM127, and VHL genes were included in the study, and Sanger sequencing was used for verifying the variants. The pathogenic/likely pathogenic variants were in the VHL, RET, SDHB, and SDHD genes, and the diagnosis rate was 24% in this study. Three different novel pathogenic variants were determined in five cases. This is the first study from Turkey, evaluating germline susceptibility genes of pheochromocytoma and paraganglioma with a detection rate of 24% and three novel variants. All patients with pheochromocytoma and paraganglioma need clinical genetic testing with expanded targeted gene panels for higher diagnosis rates.