Researcher:
Adsay, Nazmi Volkan

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Nazmi Volkan

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Adsay

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Adsay, Nazmi Volkan

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2018 - 2019162020 - 202356

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    Whipple-ables: clinicopathologic comparison of 1032 cancers removed by pancreatoduodenectomy based on pathologic re-review using refined site-specific criteria
    (Springer Nature, 2020) Balci, Serdar; Reid, Michelle; Seven, Ipek Erbarut; Saka, Burcu; Pehlivanoglu, Burcin; Memis, Bahar; Bagci, Pelin; Basturk, Olca; N/A; Adsay, Nazmi Volkan; Faculty Member; School of Medicine; Koç University Hospital; 286248
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    Poorly cohesive (signet ring cell) carcinoma of the ampulla of vater
    (Sage, 2020) Tuncel, Deniz; Basturk, Olca; Bradley, Kyle T.; Kim, Grace E.; Xue, Yue; Reid, Michelle D.; Balci, Serdar; Erbarut, Ipek; N/A; Adsay, Nazmi Volkan; Faculty Member; School of Medicine; 286248
    In the ampulla of Vater, carcinomas with "diffuse-infiltrative"/"signet ring cell" morphology, designated as "poorly cohesive carcinoma" (PCC) in the WHO classification, are very rare and poorly characterized. Nine cases with a classical PCC morphology constituting >50% of the tumor were identified. Mean age was 64.8 years (vs 64.6 in ampullary carcinomas [ACs]) and 6 were males, 3 females. The mean invasive tumor size was 2.5 cm (vs 1.9 in ACs). Other morphologic patterns displayed included cord-like infiltration (n=2), plasmacytoid cells (n=2), and microglandular component (n=4), including goblet cell adenocarcinoma-like foci. None of the cases were associated with dysplasia. By immunohistochemistry, the carcinomas did not show intestinal differentiation (CDX2 0/9, CK20 1/9, MUC2 3/9), MUC1 was positive in 4/9, MUC5AC was positive in 7/8. E-cadherin loss was noted in 4/9. All cases were advanced stage (6/9-pT3, 3/9-pT4) (vs 43% in ACs). Lymph node metastases were identified in 44% (vs 45% in AC). Six patients (67%) died of disease at a median of 25 months, 3 were alive at 13, 15, and 60 months. Overall median survival was significantly worse than that of intestinal-type ACs (26 vs 122 months, P = .006) and trended toward worse than pancreatobiliary type (26 vs 42 months, P = .1). In conclusion, PCCs constitute 2.45% of all ACs. These present as advanced tumors and express upper-gastrointestinal immunoprofile with frequent MUC5AC labeling, which may be helpful in identifying subtle infiltration in the surface mucosa since MUC5AC is not expressed in the ampullary mucosa. Patients have poor prognosis.
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    Medullary carcinoma of the ampulla has distinct clinicopathologic characteristics including common association with microsatellite instability and PD-L1 expression
    (Elsevier, 2023) Xue, Yue; Balci, Serdar; Pehlivanoglu, Burcin; Muraki, Takashi; Memis, Bahar; Saka, Burcu; Kim, Grace; Bandyopadhyay, Sudeshna; Knight, Jessica; El-Rayes, Bassel; Kooby, David; Maithel, Shishir K.; Sarmiento, Juan; Basturk, Olca; Reid, Michelle D.; Md, Volkan Adsay; N/A; Adsay, Nazmi Volkan; Faculty Member; School of Medicine; Koç University Hospital; 286248
    Medullary carcinomas have not yet been fully characterized in the ampulla. Here, 359 ampullary carcinomas (ACs) were reviewed and 11 medullary-type carcinomas (3%) were found and analyzed. In addition to the diagnostic medullary pattern, 6 showed focal mucinous and 8 had focal abortive gland-like formations. They occurred in younger patients (57 versus 65 y; P = .02), had larger invasion size (mean, 3.2 versus 1.9 cm; P = .01), formed nodular polypoid or plaque-like tumors, and often lacked preinvasive component. In addition to the lymphoplasmacytic infiltrates, they also had prominent eosinophils in 5 of 11 cases. Eight were papilla Vateri-NOS (not otherwise specified) tumors, 2 were ampullary-duodenal origin, 1 had a minor intra-ampullary papillary tubular neoplasm component, and none were ampullary-ductal. Although they had pushing-border infiltration, perineural and vascular invasion was common. They were strongly associated with DNA mismatch repair (MMR) protein deficient ( 7/11, 64%). The 5-yr survival rate (53%) appeared to be comparable with, and perhaps even better than that of nonmedullary ACs (47%), although this did not reach statistical significance (P =.47). Programmed cell death ligand-1 (PD-L1) expression levels were assessed in 8, and all 4 that were MMR deficient were positive both by combined positive score (CPS) >= 1 and tumor proportion score (TPS) >= 1, and of the 4 MMR proficient cases, 3 were positive by CPS; 2 by TPS. Overall, only 1 of the 8 available for analysis failed to show PD-L1 positivity by CPS. In contrast, non-medullary MMR-deficient carcinomas expressed PD-L1 in only 33% of tumors by CPS, and none by TPS. One medullary carcinoma was also EBV associated. Unlike 'medullary carcinomas' of the kidney, INI1 was retained in all 8 cases tested. In conclusion, medullary carcinomas are 3% of ACs, have a strong association with MMR-D, and may be less aggressive despite their larger size. PD-L1 expression appears to be closely associated with medullary ACs regardless of MMR status, and thus targeted therapies can be considered for all medullary carcinomas of this site. (c) 2022 Elsevier Inc. All rights reserved.
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    The efficacy and safety of endoscopic ultrasound-guided ablation of pancreatic cysts with alcohol and paclitaxel: a systematic review
    (Lippincott Williams and Wilkins, 2019) Faigel, Douglas O.; N/A; Attila, Tan; Adsay, Nazmi Volkan; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 118342; 286248
    Endoscopic ultrasound (EUS)-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens are investigative modalities. To evaluate the safety and efficacy of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens. A systematic review of computerized bibliographic databases was carried out for studies of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens from January 1980 to February 2018. EUS-guided cyst ablation-related outcomes (cyst resolution) and complications. Data were extracted from six studies (N=207 patients) for EUS-guided cyst ablation with alcohol lavage and eight studies (N=347 patients) for EUS-guided cyst ablation with paclitaxel-based regimens. The pooled proportion of patients with complete cyst resolution was 68/207 (32.8%) for EUS-guided cyst ablation with alcohol lavage and 221/347 (63.6%) for EUS-guided cyst ablation with paclitaxel. Postablation adverse events with EUS-guided ablation with alcohol lavage were 44/207 (21.7%), and those with EUS-guided ablation with paclitaxel-based regimens were 52/347 (15%). Limitations of this study are because of the variability in study design and regimens tested, paucity of randomized trials, and differences in pancreatic cyst types receiving treatment. EUS-guided cyst ablation appears to be effective and safe. The effect on pancreatic cancer incidence is unknown; EUS-guided pancreatic cyst ablation modalities require further improvement and validation to determine their role in the treatment of patients with pancreatic cystic lesions.
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    Histopathologic infiltration pattern predicts metastasis and progression better than pT-Stage and grade in well-differentiated pancreatic neuroendocrine tumors: a proposal for an infiltration-based morphologic grading system
    (SPRINGERNATURE, 2021) Reid, Michelle; Culci, Pelin Bağcı; Balcı, Serdar; Demirtaş, Deniz; Pehlivanoğlu, Burçin; Saka, Burcu; Memiş, Bahar; Bozkurtlar, Emine; Leblebici, Can Berk; Corobea, Adelina Birceanu; Xue, Yue; Sökmensüer, Cenk; Scarpa, Aldo; Luchini, Claudio; Baştürk, Olca; Taşkın, Orhun Çığ; Armutlu, Ayşe; Erkan, Murat Mert; Kapran, Yersu; Adsay, Nazmi Volkan; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 166686; 133567; 214689; 168101; 286248
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    Is it justifiable to move the grade-1 Ki67 index cut-off from 3% to 5% for pancreatic neuroendocrine tumors as has been proposed? The cases that fall to 3-5% category have clinicopathologic characteristics closer to those > 5%
    (Springer, 2020) Reid, Michelle; Balci, Serdar; Bagci, Pelin; Saka, Burcu; Pehlivanoglu, Burcin; Seven, Ipek Erbarut; Basturk, Olca; N/A; Adsay, Nazmi Volkan; Faculty Member; School of Medicine; Koç University Hospital; 286248
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    MCL1 as putative target in pancreatoblastoma
    (SPRINGER, 2022) Reissig, Timm M.; Uhrig, Sebastian; Jost, Philipp J.; Luchini, Claudio; Vicentini, Caterina; Liffers, Sven-Thorsten; Allgaeuer, Michael; Scarpa, Aldo; Lawlor, Rita Teresa; Froehling, Stefan; Stenzinger, Albrecht; Kloeppel, Gunter; Schildhaus, Hans-Ulrich; Siveke, Jens T.; N/A; Adsay, Nazmi Volkan; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 286248
    Pancreatoblastoma (PB) is a rare tumor of the pancreas. In case of metastases, the treatment options are sparse and targeted approaches are not developed. We here evaluate MCL1 amplification as a putative target in PB. Thirteen samples from adult (10/13) and pediatric patients (3/13) were collected. Three of these samples had been previously subjected to whole-exome sequencing (2 cases) or whole-genome sequencing (1 case) within a precision oncology program (NCT/DKTK MASTER), and this analysis had shown copy number gains of MCL1 gene. We established a fluorescence in situ hybridization (FISH) test to assess the copy number alterations of MCL1 gene in 13 formalin-fixed paraffin-embedded PBs, including the 3 cases assessed by genome sequencing. FISH analysis showed the amplification of MCL1 in 2 cases (both were adult PB), one of which was a case with the highest copy number gain at genomic analysis. In both cases, the average gene copy number per cell was >= 5.7 and the MCL1/1p12 ratio was >= 2.4. Our data support MCL1 as a putative target in PB. Patients with MCL1-amplified PB might benefit from MCL1 inhibition. Sequencing data is useful to screen for amplification; however, the established FISH for MCL1 can help to determine the level and cellular heterogeneity of MCL1 amplification more accurately.
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    Intraductal tubulopapillary neoplasms of the bile ducts: identity, clinicopathologic characteristics, and differential diagnosis of a distinct entity among intraductal tumors
    (W.B. Saunders, 2023) Pehlivanoğlu, Burçin; Adsay, Nazmi Volkan; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; 286248
    Among the mass-forming preinvasive (tumoral intraepithelial) neoplasms of the biliary tract, intraductal tubulopapillary neoplasms (ITPN-Bs) are increasingly being recognized as a separate category. By being intramucosal polypoid proliferations of dysplastic/neoplastic cells, they are highly similar to other members of the “intraductal neoplasms (IDNs)” category (namely, intraductal papillary neoplasms [IPNBs], and intraductal oncocytic papillary neoplasms [IOPNs]); however, they are distinguished by MUC6-expressing nonmucinous cells that lack intestinal differentiation and form striking tubular configuration. Their molecular/genetic profile is also proving to be different with frequent alterations in cell cycle and chromatin remodeling genes, which are quite uncommon in other IDNs and cholangiocarcinomas. Despite the conceptual overlaps, they are also very different from intracholecystic nonmucinous tubular neoplasms (ICTN) of the gallbladder with the latter being associated with Wnt/beta-catenin pathway alterations, and almost never invasive. In contrast, ITPN-Bs are invasive in an estimated 80% of the cases, although even invasive examples often exhibit a protracted course. Invasive carcinomas arising from ITPN-Bs are overall similar to cholangiocarcinomas (including small duct and large duct patterns) but also often have peculiar characteristics such as more nodular-compact (blunt invasion) pattern. Like other IDNs, the ITPN-Bs have also been classified in the past as intraductal-spreading type of cholangiocarcinomas (and they are still regarded as such in some publications). In small biopsies, they are prone to be mistaken as ordinary adenocarcinomas because of their tubular pattern and pancreatobiliary cytology although their relatively monotonous cytology and zones of back-to-back tubule formation can help in their correct identification. Clinical presentation of ITPN-Bs is generally similar to other intraductal neoplasms; however, in the intrahepatic component, they tend to be more nodular than cystic, and their snake-like intraductal growth pattern is often more striking. In the management (diagnosis and treatment) of these tumors that are in essence adenoma-carcinoma sequence, the invasive and noninvasive components ought to be evaluated separately. Minimally invasive examples are commonly curable, and even those more extensively invasive may have a surprisingly good prognosis. In summary, biliary ITPNs form a distinct category not only clinicopathologically, immunophenotypically, and molecular-wise but regarding their biological behavior as well.
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    Evaluation and pathologic classification of choledochal cysts clinicopathologic analysis of 84 cases from the west
    (Lippincott Williams & Wilkins, 2021) Hacıhasanoğlu, Ezgi; Muraki, Takashi; Pehlivanoğlu, Burçin; Memiş, Bahar; Mittal, Pardeep; Polito, Humbert; Everett, Rhonda; Sarmiento, Juan; Kooby, David; Maithel, Shishir K.; Baştürk, Olca; Reid, Michelle D.; N/A; Meriçöz, Çisel Aydın; Saka, Burcu; Erkan, Murat Mert; Adsay, Nazmi Volkan; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; School of Medicine; School of Medicine; 162418; 222921; 214689; 286248
    Choledochal cyst (CC) is believed to be a mostly Asian disorder. As a clinically defined entity, its pathologic correlates are poorly characterized. Eighty-four resected CCs from the West were reanalyzed. After applying established Japanese criteria, 9/66 with available imaging were disqualified and 10/39 with preoperative cyst typing had to be recategorized. None had been diagnosed with, or evaluated for, pancreatobiliary maljunction, but on retrospective analysis of radiologic images, 12/66 were found to have pancreatobiliary maljunction. The clinical findings were: F/M=5.7; mean age, 48; most (77%) presented with abdominal pain; mean size, 2.9 cm; choledocholithiasis 11%. Gross/histologic examination revealed 3 distinct pathology-based categories: (I) Cystic dilatation of native ducts (81%). (II) Double bile duct (13%), almost all of which were found in women (10/11); all were diagnosed by pathologic examination, and not preoperative diagnosis. (III) Gastrointestinal (GI) duplication type (6%). Microscopic findings of the entire cohort included mucosal-predominant lymphoplasmacytic inflammation (50%), follicular cholangitis (7%), mucosal hyperplasia (43%; 13% with papillae), intestinal metaplasia (10%), BilIN-like hyperplasia (17%), erosion/ulceration (13%), and severe dysplasia-mimicking atypia including "detachment atypia" and micropapillary degeneration (11%). Carcinomatous changes were seen in 14 cases (17%) (high-grade dysplasia/carcinoma in situ in 7, intraductal papillary neoplasm 1, and invasive carcinoma 6); and 13/14 of these occurred in pathologic category I, all with cyst size >1 cm. In conclusion, diagnostic imaging guidelines used in Asia are not routinely used (but should be adopted) in the West. Pathologically, cases designated as CC are classifiable in 3 groups: category 1 (dilated native duct type), more prone to carcinomatous change; category 2, double-duct phenomenon (all but 1 being female in this study); and category 3, GI-type duplication. Overall, 17% of CCs show carcinomatous change (50% of them invasive). CC specimens should be carefully examined with this classification and submitted entirely for assessment of at-risk mucosa and cancerous transformation.
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    Pancreatobiliary maljunction-associated gallbladder cancer is as common in the West, shows distinct clinicopathologic characteristics and offers an invaluable model for anatomy-induced reflux-associated physio-chemical carcinogenesis
    (Lippincott Williams and Wilkins (LWW), 2022) Muraki, Takashi; Pehlivanoglu, Burcin; Memis, Bahar; Reid, Michelle D.; Uehara, Takeshi; Basturk, Olca; Pernicka, Jennifer Golia; Klimstra, David S.; Jarnagin, William R.; Ito, Tetsuya; Hasebe, Osamu; Okaniwa, Shinji; Horigome, Naoto; Hisa, Takeshi; Mittal, Pardeep; Sarmiento, Juan M.; Maithel, Shishir K.; Koshiol, Jill; Tsai, Susan; Evans, Douglas; N/A; Erkan, Murat Mert; Adsay, Nazmi Volkan; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; 214689; 286248
    Objective: To determine the associations of pancreatobiliary maljunction (PBM) in the West. Background: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan. Results: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.