Normal kidney size and its influencing factors - a 64-slice MDCT study of 1.040 asymptomatic patients

<p>Abstract</p> <p>Background</p> <p>Normal ultrasound values for pole-to-pole kidney length (LPP) are well established for children, but very little is known about normal kidney size and its influencing factors in adults. The objectives of this study were thus to establish normal CT values for kidney dimensions from a group of unselected patients, identify potential influencing factors, and to estimate their significance.</p> <p>Methods</p> <p>In multiphase thin-slice MDCTs of 2.068 kidneys in 1.040 adults, the kidney length pole to pole (LPP), parenchymal (PW) and cortical width (CW), position and rotation status of the kidneys, number of renal arteries, pyelon width and possible influencing factors that can be visualized, were recorded from a volume data set. For length measurements, axes were adjusted individually in double oblique planes using a 3D-software. Analyses of distribution, T-tests, ANOVA, correlation and multivariate regression analyses were performed.</p> <p>Results</p> <p>LPP was 108.5 ± 12.2 mm for the right, and 111.3 ± 12.6 mm for the left kidney (p < 0.0001 each). PW on the right side was 15.4 ± 2.8 mm, slightly less than 15.9 ± 2.7 mm on the left side (p < 0.0001), the CW was the same (6.6 ± 1.9 mm). The most significant independent predictors for LPP, CW, and PW were body size, BMI, age, and gender (p < 0.001 each). In men, the LPP increases up to the fifth decade of life (p < 0.01). It is also influenced by the position of the kidneys, stenoses and number of renal arteries (SRA/NRA), infarctions suffered, parapelvic cysts, and absence of the contralateral kidney; CW is influenced by age, position, parapelvic cysts, NRA and SRA, and the PW is influenced in addition by rotation status (p < 0.05 each). Depending on the most important factors, gender-specific normal values were indicated for these dimensions, the length and width in cross section, width of the renal pelvis, and parenchyma-renal pyelon ratio.</p> <p>Conclusions</p> <p>Due to the complex influences on kidney size, assessment should be made individually. The most important influencing factors are BMI, height, gender, age, position of the kidneys, stenoses and number of renal arteries.</p

Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma

STUDY QUESTION: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma? SUMMARY ANSWER: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable. WHAT IS KNOWN ALREADY: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs). STUDY DESIGN, SIZE, DURATION: The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7-30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman's rho 0.853, P &lt; 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases. LARGE SCALE DATA: Datasets are available in the supplementary tables. LIMITATIONS, REASONS FOR CAUTION: Even though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association. WIDER IMPLICATIONS OF THE FINDINGS: The observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events. STUDY FUNDING/COMPETING INTEREST(S): The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE-A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad's Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden's Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.CC BY-NC 4.0 DeedPublished: 09 March 2024Correspondence address: Karin Sundfeldt, Department of Obstetrics and Gynecology, Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academyat University of Gothenburg, SE-405 30 Gothenburg, Sweden. E-mail: [email protected] (K.S.) https://orcid.org/0000-0002-7135-3132;Division of Oncology,Department of Clinical Sciences Lund, Lund University, SE-223 81 Lund, Sweden. E-mail: [email protected] (I.H.) https://orcid.org/0000-0002-6840-3The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE—a strategic research area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad’s Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden’s Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021- 01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.).</p