Browsing by Author "Pehlivanoglu, Burcin"

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    Adenomyomas of the Gallbladder An Analysis of Frequency, Clinicopathologic Associations, and Relationship to Carcinoma of a Malformative Lesion
    (2024) Dursun, Nevra; Memis, Bahar; Pehlivanoglu, Burcin; Taskin, Orhun Cig; Okcu, Oguzhan; Akkas, Gizem; Bagci, Pelin; Balci, Serdar; Saka, Burcu; Araya, Juan Carlos; Bellolio, Enrique; Roa, Juan Carlos; Jang, Kee-Taek; Losada, Hector; Maithel, Shishir K.; Sarmiento, Juan; Reid, Michelle D.; Jang, Jin-Young; Cheng, Jeanette D.; Basturk, Olca; Koshiol, Jill; Adsay, N. Volkan
    Context.-The nature and associations of gallbladder (GB) "adenomyoma"(AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs. Objective.-To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM. Design.-Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM. Results.-Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio =1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat -type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma arose from AM (invasion was confined to AM, and dysplasia was predominantly in AM). Conclusions.-AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component (ie, the name "adeno-myoma"is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flattype high-grade dysplasia or carcinoma in situ, and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.
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    Follicular Cholecystitis: Reappraisal of Incidence, Definition, and Clinicopathologic Associations in an Analysis of 2550 Cholecystectomies
    (SAGE PUBLICATIONS INC, 2020) Saka, Burcu; Memis, Bahar; Seven, Ipek Erbarut; Pehlivanoglu, Burcin; Balci, Serdar; Bagci, Pelin; Reid, Michelle; Dursun, Nevra; Tapia Escalano, Oscar; Carlos Roa, Juan; Carlos Araya, Juan; Kong, So Yeon; Basturk, Olca; Koshiol, Jill; Adsay, N. Volkan
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    Non-steroidal anti-inflammatory drug use and inflammatory markers associated with gallbladder dysplasia: A case-control analysis within a series of patients undergoing cholecystectomy
    (2024) Rosa, Lorena; Cook, Paz; Pfeiffer, Ruth M.; Kemp, Troy J.; Hildesheim, Allan; Pehlivanoglu, Burcin; Adsay, Volkan; Bellolio, Enrique; Araya, Juan Carlos; Pinto, Ligia; Ferreccio, Catterina; Aguayo, Gloria; Vinuela, Eduardo; Koshiol, Jill
    Inflammation has been associated with the development of gallbladder cancer (GBC). However, little is known about the associations of both, inflammation and the use of non-steroidal anti-inflammatory drugs (NSAIDs), with preneoplastic lesions. We analyzed the association of NSAIDs and gallbladder dysplasia in 82 patients with dysplasia and 1843 patients with gallstones among symptomatic patients from a high-risk population. We also analyzed associations for 33 circulating immune-related proteins in a subsample of all 68 dysplasia cases diagnosed at the time of sample selection and 136 gallstone controls. We calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Biliary colic was reported among most cases (97.6%) and controls (83.9%). NSAID use was inversely associated with gallbladder dysplasia (OR: 0.48, 95%CI: 0.26-0.83). Comparing the highest versus lowest category of each immune-related protein, eight proteins were inversely associated with dysplasia with sex- and age-adjusted ORs ranging from 0.30 (95%CI: 0.12-0.77) for IL-33 to 0.76 (95%CI: 0.59-0.99) for MIP-1B. Of those, GRO remained associated with dysplasia (OR: 0.64, 95%CI: 0.45-0.91) and BCA-1 was borderline associated (OR: 0.74, 95%CI: 0.54-1.01) after adjusting the logistic regression model for sex, age, and NSAIDs. In conclusion, NSAID users were less likely to have gallbladder dysplasia, suggesting that NSAIDs might be beneficial for symptomatic gallstones patients. The inverse association between immune-related markers and dysplasia requires additional research, ideally in prospective studies with asymptomatic participants, to understand the role of the inflammatory response in the natural history of GBC and to address the biological effect of NSAIDs.
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    T2 gallbladder cancer shows substantial survival variation between continents and this is not due to histopathologic criteria or pathologic sampling differences
    (2021) DeSimone, Mia S.; Goodman, Michael; Pehlivanoglu, Burcin; Memis, Bahar; Balci, Serdar; Roa, Juan Carlos; Jang, Kee-Taek; Jang, Jin-Young; Hong, Seung-Mo; Lee, Kyoungbun; Kim, Haeryoung; Choi, Hye-Jeong; Muraki, Takashi; Araya, Juan Carlos; Bellolio, Enrique; Sarmiento, Juan M.; Maithel, Shishir K.; Losada, Hector F.; Basturk, Olca; Reid, Michelle D.; Koshiol, Jill; Adsay, Volkan
    Published data on survival of T2 gallbladder carcinoma (GBC) from different countries show a wide range of 5-year survival rates from 30-> 70%. Recently, studies have demonstrated substantial variation between countries in terms of their approach to sampling gallbladders, and furthermore, that pathologists from different continents apply highly variable criteria in determining stage of invasion in this organ. These findings raised the question of whether these variations in pathologic evaluation could account for the vastly different survival rates of T2 GBC reported in the literature. In this study, survival of 316 GBCs from three countries (Chile n = 137, South Korea n = 105, USA n = 74), all adequately sampled (with a minimum of five tumor sections examined) and histopathologically verified as pT2 (after consensus examination by expert pathologists from three continents), was analyzed. Chilean patients had a significantly worse prognosis based on 5-year all-cause mortality (HR: 1.89, 95% CI: 1.27-2.83, p = 0.002) and disease-specific mortality (HR: 2.41, 95% CI: 1.51-3.84, p < 0.001), compared to their South Korean counterparts, even when controlled for age and sex. Comparing the USA to South Korea, the survival differences in all-cause mortality (HR: 1.75, 95% CI: 1.12-2.75, p = 0.015) and disease-specific mortality (HR: 1.94, 95% CI: 1.14-3.31, p = 0.015) were also pronounced. The 3-year disease-specific survival rates in South Korea, the USA, and Chile were 75%, 65%, and 55%, respectively, the 5-year disease-specific survival rates were 60%, 50%, and 50%, respectively, and the overall 5-year survival rates were 55%, 45%, and 35%, respectively. In conclusion, the survival of true T2 GBC in properly classified cases is neither as good nor as bad as previously documented in the literature and shows notable geographic differences even in well-sampled cases with consensus histopathologic criteria. Future studies should focus on other potential reasons including biologic, etiopathogenetic, management-related, populational, or healthcare practice-related factors that may influence the survival differences of T2 GBC in different regions.
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    TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern
    (2024) Pehlivanoglu, Burcin; Araya, Juan Carlos; Lawrence, Scott; Roa, Juan Carlos; Balci, Serdar; Andersen, Jesper B.; Rashid, Asif; Hsing, Ann W.; Zhu, Bin; Gao, Yu-Tang; Koshiol, Jill; Adsay, Volkan
    A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPPBRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastropancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubularspindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.