Publications by authors named "Arnold J Markowitz"

48 Publications

Characterization and Clinical Outcomes of DNA Mismatch Repair-deficient Small Bowel Adenocarcinoma.

Clin Cancer Res 2021 Mar 16;27(5):1429-1437. Epub 2020 Nov 16.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: The prevalence and clinical characteristics of small bowel adenocarcinomas (SBA) in the setting of Lynch syndrome have not been well studied. We characterized SBA according to DNA mismatch repair and/or microsatellite instability (MMR/MSI) and germline mutation status and compared clinical outcomes.

Experimental Design: A single-institution review identified 100 SBAs. Tumors were evaluated for MSI via MSIsensor and/or corresponding MMR protein expression via IHC staining. Germline DNA was analyzed for mutations in known cancer predisposition genes, including MMR (, and ). Clinical variables were correlated with MMR/MSI status.

Results: Twenty-six percent (26/100; 95% confidence interval, 18.4-35.4) of SBAs exhibited MMR deficiency (MMR-D). Lynch syndrome prevalence was 10% overall and 38.5% among MMR-D SBAs. Median age at SBA diagnosis was similar in non-Lynch syndrome MMR-D versus MMR-proficient (MMR-P) SBAs (65 vs. 61; = 0.75), but significantly younger in Lynch syndrome (47.5 vs. 61; = 0.03). The prevalence of synchronous/metachronous cancers was 9% (6/67) in MMR-P versus 34.6% (9/26) in MMR-D SBA, with 66.7% (6/9) of these in Lynch syndrome ( = 0.0002). In the MMR-P group, 52.2% (35/67) of patients presented with metastatic disease, compared with 23.1% (6/26) in the MMR-D group ( = 0.008). In MMR-P stage I/II patients, 88.2% (15/17) recurred, compared with 18.2% (2/11) in the MMR-D group ( = 0.0002).

Conclusions: When compared with MMR-P SBA, MMR-D SBA was associated with earlier stage disease and lower recurrence rates, similar to observations in colorectal cancer. With a 38.5% prevalence in MMR-D SBA, germline Lynch syndrome testing in MMR-D SBA is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2892DOI Listing
March 2021

Discordant DNA mismatch repair protein status between synchronous or metachronous gastrointestinal carcinomas: frequency, patterns, and molecular etiologies.

Fam Cancer 2020 Oct 9. Epub 2020 Oct 9.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

The widespread use of tumor DNA mismatch repair (MMR) protein immunohistochemistry in gastrointestinal tract (GIT) carcinomas has unveiled cases where the MMR protein status differs between synchronous/metachronous tumors from the same patients. This study aims at examining the frequency, patterns and molecular etiologies of such inter-tumoral MMR discordances. We analyzed a cohort of 2159 colorectal cancer (CRC) patients collected over a 5-year period and found that 1.3% of the patients (27/2159) had ≥ 2 primary CRCs, and 25.9% of the patients with ≥ 2 primary CRCs (7/27) exhibited inter-tumoral MMR discordance. We then combined the seven MMR-discordant CRC patients with three additional MMR-discordant GIT carcinoma patients and evaluated their discordant patterns and associated molecular abnormalities. The 10 patients consisted of 3 patients with Lynch syndrome (LS), 1 with polymerase proofreading-associated polyposis (PAPP), 1 with familial adenomatous polyposis (FAP), and 5 deemed to have no cancer disposing hereditary syndromes. Their MMR discordances were associated with the following etiologies: (1) PMS2-LS manifesting PMS2-deficient cancer at an old age when a co-incidental sporadic MMR-proficient cancer also occurred; (2) microsatellite instability-driven secondary somatic MSH6-inactivation occurring in only one-and not all-PMS2-LS associated MMR-deficient carcinomas; (3) "compound LS" with germline mutations in two MMR genes manifesting different tumors with deficiencies in different MMR proteins; (4) PAPP or FAP syndrome-associated MMR-proficient cancer co-occurring metachronously with a somatic MMR-deficient cancer; and (5) non-syndromic patients with sporadic MMR-proficient cancers co-occurring synchronously/metachronously with sporadic MMR-deficient cancers. Our study thus suggests that inter-tumoral MMR discordance is not uncommon among patients with multiple primary GIT carcinomas (25.9% in patients with ≥ 2 CRCs), and may be associated with widely varied molecular etiologies. Awareness of these patterns is essential in ensuring the most effective strategies in both LS detection and treatment decision-making. When selecting patients for immunotherapy, MMR testing should be performed on the tumor or tumors that are being treated.
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http://dx.doi.org/10.1007/s10689-020-00210-4DOI Listing
October 2020

NCCN Guidelines Insights: Colorectal Cancer Screening, Version 2.2020.

J Natl Compr Canc Netw 2020 10 1;18(10):1312-1320. Epub 2020 Oct 1.

National Comprehensive Cancer Network.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age to initiate screening in average risk individuals and follow-up for low-risk adenomas.
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http://dx.doi.org/10.6004/jnccn.2020.0048DOI Listing
October 2020

Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies.

JAMA Surg 2020 11;155(11):1050-1057

Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer.

Objectives: To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy.

Design, Setting, And Participants: This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution.

Interventions: Genetic counseling, esophagogastroduodenoscopy, and possible total gastrectomy.

Main Outcomes And Measures: CDH1 variant classification, family cancer history, findings of signet ring cell carcinoma at esophagogastroduodenoscopy and surgery, postoperative events and weight changes, and follow-up.

Results: Of 181 individuals with CDH1 germline variants (mean [SD] age at time of testing, 44 [15] years; 126 [70%] female), 165 harbored a pathogenic or likely pathogenic variant. Of these patients, 101 underwent open (n = 58) or minimally invasive (n = 43) total gastrectomy. Anastomotic leaks that required drainage were infrequent (n = 3), and median long-term weight loss was 20% (interquartile range [IQR], 10%-23%). In those undergoing minimally invasive operations, more lymph nodes were retrieved (median, 28 [IQR, 20-34] vs 15 [IQR, 9-19]; P < .001) and the hospital stay was 1 day shorter (median, 6 [IQR, 5-7] vs 7 [IQR, 6-7] days; P = .04). Signet ring cell cancer was identified in the surgical specimens of 85 of 95 patients (89%) with a family history of gastric cancer and 4 of 6 patients (67%) who lacked a family history. Among the latter 6 patients, 4 had a personal or family history of lobular breast cancer, including 2 with signet ring cell cancer. Of the 16 patients with pathogenic or likely pathogenic CDH1 variants who presented with locally advanced or metastatic gastric cancer, 3 (19%) had no family history of gastric cancer or personal or family history of lobular breast cancer.

Conclusions And Relevance: Total gastrectomy may be warranted for patients with pathogenic or likely pathogenic CDH1 variants and a family history of gastric or lobular breast cancer and may be appropriate for those without a family history. A minimally invasive approach is feasible and may be preferred for selected patients.
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http://dx.doi.org/10.1001/jamasurg.2020.3356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527942PMC
November 2020

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019.

J Natl Compr Canc Netw 2019 09;17(9):1032-1041

National Comprehensive Cancer Network.

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.
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http://dx.doi.org/10.6004/jnccn.2019.0044DOI Listing
September 2019

Colorectal carcinoma with double somatic mismatch repair gene inactivation: clinical and pathological characteristics and response to immune checkpoint blockade.

Mod Pathol 2019 10 7;32(10):1551-1562. Epub 2019 Jun 7.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Double somatic mismatch-repair-gene mutation/alteration is a recently recognized molecular mechanism that underlies microsatellite instability-high in some colorectal carcinomas. It remains to be determined whether and how microsatellite instability-high tumors with this molecular defect differ from their counterparts caused by other mechanisms, specifically, Lynch syndrome-associated and MLH1-promoter hypermethylated. In this study, we evaluated the clinical and pathological characteristics of a series of 15 double somatic mutation/alteration-associated microsatellite instability-high colorectal carcinomas identified from our genetics service and 68 such cases reported in the literature. We observed that these cases presented at an age similar to MLH1-promoter hypermethylated (n = 20) and microsatellite-stable (n = 39) cases but older than Lynch syndrome-associated cases (n = 20, p < 0.05). While these tumors simulated other microsatellite instability-high tumors in their prevalent right-sided location, they appeared to differ in TNM stages at presentation (73% stage III/IV versus 25% stage III/IV in other microsatellite instability-high tumors, p = 0.04). Histologically, 40% of them had a dominant solid growth pattern. Inter-tumoral heterogeneity was a striking feature, spanning the spectrum from medullary type (with a tumor-infiltrating-lymphocyte/high-power-field count as high as 59) to conventional-type with only few tumor-infiltrating-lymphocytes (1/high-power-filed). As a group, these tumors seemed less likely to show robustly high lymphocytic infiltration than other microsatellite instability-high tumors (only 20% had ≥10 tumor-infiltrating-lymphocytes/high-power-filed, whereas this rate in Lynch syndrome-associated and MLH1-promoter hypermethylated tumors was 60% and 75%, respectively). Three double somatic mutation/alteration-associated tumors were treated with a PD1/PD-L1 checkpoint inhibitor. While all three had an elevated tumor-mutation-burden (>47 mut/megabase), only one had tumor-infiltrating-lymphocytes >10/high-power-field, yet all three exhibited measurable response. In summary, microsatellite instability-high colorectal carcinomas caused by double somatic mismatch-repair-gene mutation/alteration may have varied clinical and pathological characteristics, and some may have relatively low tumor-infiltrating-lymphocytes; response to immune checkpoint inhibitors can be achieved in this group even when the lymphocytic infiltration is not abundant.
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http://dx.doi.org/10.1038/s41379-019-0289-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849386PMC
October 2019

Cellular localization of PD-L1 expression in mismatch-repair-deficient and proficient colorectal carcinomas.

Mod Pathol 2019 01 30;32(1):110-121. Epub 2018 Aug 30.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Blockade of the interaction between PD-1 and its ligands PD-L1 has shown clinical efficacy across several tumor types, especially in mismatch-repair-deficient colorectal carcinoma. The aim of this study was to examine the pattern and cellular localization of PD-L1 expression in the different molecular subtypes of mismatch-repair-deficient colorectal cancers vs. their mismatch-repair-proficient counterparts. PD-L1/SATB2 double-antibody-immunohistochemistry was utilized to distinguish tumor cell from immune cell staining. We observed in our series of 129 colorectal adenocarcinomas that PD-L1 expression occurred primarily in tumor-associated-immune cells and most prominently at the tumor-stroma-interface of the invasive front. The level of invasive front immune cell staining was significantly higher in mismatch-repair-deficient tumors compared to mismatch-repair-proficient tumors (p < 0.001), but no difference was observed among the different subtypes of mismatch-repair-deficient tumors: Lynch syndrome-associated vs. MLH1-methylated vs. unexplained. While selected mismatch-repair-proficient tumors exhibited unusually high tumor-infiltrating-lymphocytes and had high level immune cell PD-L1 expression, a positive correlation between PD-L1 expression and high lymphocyte count was detected only in mismatch-repair-deficient tumors (r = 0.39, p < 0.001) and not in mismatch-repair-proficient tumors. Notably, true tumor cell PD-L1 expression in colorectal carcinoma was rare, present in only 3 of 129 tumors (2.3%): 2 MLH1-methylated and 1 mismatch-repair-proficient with high tumor-infiltrating-lymphocytes; and the staining in the tumor cells in all 3 was diffuse (>=50% of the tumor). These findings may serve to inform further efforts aiming to evaluate PD-L1 immunohistochemistry vis-à-vis molecular sub-classification as predictive biomarkers in the treatment of colorectal carcinoma.
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http://dx.doi.org/10.1038/s41379-018-0114-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309293PMC
January 2019

NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2018.

J Natl Compr Canc Netw 2018 08;16(8):939-949

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.
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http://dx.doi.org/10.6004/jnccn.2018.0067DOI Listing
August 2018

Direct Percutaneous Endoscopic Jejunostomy: Procedural and Nutrition Outcomes in a Large Patient Cohort.

JPEN J Parenter Enteral Nutr 2018 Jul 27;42(5):898-906. Epub 2017 Dec 27.

Gastroenterology and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Direct percutaneous endoscopic jejunostomy (DPEJ) is used for enteral nutrition (EN) in patients with postoperative anastomotic leaks after esophagectomy/gastrectomy and at high risk for aspiration. We characterized the indications, technical success, procedural/nutrition outcomes, and adverse events in a large cohort of patients undergoing DPEJ insertion.

Methods: Patients undergoing DPEJ insertion between January 2009 and March 2015 were identified from an institutional endoscopy database. Demographic, procedural, and nutrition outcome data were collected from electronic medical records. Regression analyses were used to identify predictors of adverse events and procedural success.

Results: A total of 452 patients underwent 480 attempts at DPEJ insertion. Indications included preoperative or postoperative weight loss (64%), postoperative upper gastrointestinal (UGI) anastomotic leak (13%), aspiration prevention (10%), and other (13%). Of attempted procedures, 398 (83%) were successful. Feeding was initiated in 389 (98%) of patients; a median of 1775 calories was delivered daily. Median body mass index (BMI) at baseline was 22.9 (11.4-44.7) and did not change over follow-up. Median change in BMI after DPEJ was similar in groups that received EN with palliative and curative intent. Adverse events following 480 attempted DPEJ insertions included 13 (3%) immediate and 74 (15%) delayed, 13 (3%) of which were serious. Patients with head and neck cancer had more adverse events than those with esophageal cancer (P = .020).

Conclusion: DPEJ is a successful and safe procedure that effectively provides access for EN support in malnourished patients and patients with postoperative UGI cancer.
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http://dx.doi.org/10.1002/jpen.1023DOI Listing
July 2018

Endoluminal high-dose-rate brachytherapy for locally recurrent or persistent esophageal cancer.

Brachytherapy 2018 May - Jun;17(3):621-627. Epub 2018 Feb 26.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Purpose: Management of locally recurrent or persistent esophageal cancer (EC) after standard chemoradiation is challenging. This study updates our experience of treating medically inoperable EC patients with endoluminal high-dose-rate brachytherapy (EHDRBT) including the patients treated with a novel multiballoon channel centering esophageal applicator.

Methods And Materials: Thirty-three consecutive patients with early-stage primary (n = 7), posttreatment persistent (n = 7), and recurrent (n = 19) EC treated with EHDRBT at our institution were included. Median dose and treatment lengths were 14 Gy (range 10-17.5 Gy) and 6 cm (3.5-9.0 cm), respectively. Endoscopy and biopsy were performed 3 months after EHDRBT and then every 3-6 months thereafter.

Results: Median followup was 17.4 months (range 5.0-88.3). Grade 1 and 2 toxicities were observed in 13 (44.8%) and 11 (37.9%) patients, respectively. Grade 3 toxicity (tracheoesophageal fistula) was observed in 1 patient who had previously received two courses of external beam radiotherapy as well as a stent insertion. Median overall survival (OS) for entire cohort was 20.9 months, and 1-year OS was 78%. Complete response was achieved in 58.6% of patients with median time to failure and 1-year disease-free survival of 10.3 months (range 5.4-28.2) and 27%, respectively.

Conclusions: For medically inoperable patients with early-stage primary or local posttreatment residual or recurrent EC, EHDRBT is a well-tolerated treatment option with minimal Grade ≥3 toxicity. Brachytherapy in our hands continues to be a safe treatment option. Although 58.6% of patients achieved a complete response and the OS of this cohort is relatively good, long-term local control and cure remains a challenge.
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http://dx.doi.org/10.1016/j.brachy.2018.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746417PMC
February 2019

Clinical Value of CT Colonography Versus Preoperative Colonoscopy in the Surgical Management of Occlusive Colorectal Cancer.

AJR Am J Roentgenol 2018 Feb 20;210(2):333-340. Epub 2017 Dec 20.

1 Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.

Objective: CT colonography (CTC) has been recognized as a complementary approach to evaluating the entire colon after incomplete colonoscopy (IC) in patients with occlusive colorectal cancer (CRC). The objective of this study is to evaluate changes in preoperative surgical planning after CTC is performed for patients with occlusive CRC and IC in an oncologic hospital.

Materials And Methods: This retrospective study included 65 consecutive patients with occlusive CRC who underwent CTC after IC at our institution from February 2000 to April 2016. CTC examinations and radiology reports were reviewed by an abdominal radiologist. Clinical information was obtained from a review of the electronic medical record.

Results: CTC contributed to a change in the initial surgical plan of the surgeon for 14 of 65 patients (21.5%). In these 14 patients, CTC detected five synchronous proximal colon polyps (35.7%), five synchronous proximal cancers (35.7%), two imprecise CRC locations (14.3%), one case of proximal colon ischemia (7.1%), and one instance of tumor infiltration of the urinary bladder (7.1%). All CTC findings were confirmed at surgery, and all proximal colon polyps were subsequently confirmed to be advanced adenomas.

Conclusion: The preoperative CTC findings optimized the surgical management plan for 21.5% of patients with occlusive CRC and IC.
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http://dx.doi.org/10.2214/AJR.17.18144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473453PMC
February 2018

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017.

J Natl Compr Canc Netw 2017 12;15(12):1465-1475

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.
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http://dx.doi.org/10.6004/jnccn.2017.0176DOI Listing
December 2017

Computed Tomography Colonography vs Colonoscopy for Colorectal Cancer Surveillance After Surgery.

Gastroenterology 2018 03 22;154(4):927-934.e4. Epub 2017 Nov 22.

Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Background & Aims: Recommendations for surveillance after curative surgery for colorectal cancer (CRC) include a 1-year post-resection abdominal-pelvic computed tomography (CT) scan and optical colonoscopy (OC). CT colonography (CTC), when used in CRC screening, effectively identifies colorectal polyps ≥10 mm and cancers. We performed a prospective study to determine whether CTC, concurrent with CT, could substitute for OC in CRC surveillance.

Methods: Our study enrolled 231 patients with resected stage 0-III CRC, identified at 5 tertiary care academic centers. Approximately 1 year after surgery, participants underwent outpatient CTC plus CT, followed by same-day OC. CTC results were revealed after endoscopic visualization of sequential colonic segments, which were re-examined for discordant findings. The primary outcome was performance of CTC in the detection of colorectal adenomas and cancers using endoscopy as the reference standard.

Results: Of the 231 participants, 116 (50.2%) had polyps of any size or histology identified by OC, and 15.6% had conventional adenomas and/or serrated polyps ≥6 mm. No intra-luminal cancers were detected. CTC detected patients with polyps of ≥6 mm with 44.0% sensitivity (95% CI, 30.2-57.8) and 93.4% specificity (95% CI, 89.7-97.0). CTC detected polyps ≥10 mm with 76.9% sensitivity (95% CI, 54.0-99.8) and 89.0% specificity (95% CI, 84.8-93.1). Similar values were found when only adenomatous polyps were considered. The negative predictive value of CTC for adenomas ≥6 mm was 90.7% (95% CI, 86.7-94.5) and for adenomas ≥10 mm the negative predictive value was 98.6% (95% CI, 97.0-100).

Conclusions: In a CRC surveillance population 1 year following resection, CTC was inferior to OC for detecting patients with polyps ≥6 mm. Clinical Trials.gov Registration Number: NCT02143115.
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http://dx.doi.org/10.1053/j.gastro.2017.11.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847443PMC
March 2018

Endoscopic Ultrasound as a Pretreatment Clinical Staging Tool for Gastric Cancer: Association with Pathology and Outcome.

Ann Surg Oncol 2017 Nov 16;24(12):3658-3666. Epub 2017 Aug 16.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Endoscopic ultrasound (EUS) is a guideline-recommended diagnostic test to estimate pretreatment clinical stage in gastric cancer. The impact of EUS to discriminate long-term outcomes has not been established.

Objectives: The objectives of our study were to (1) evaluate the association between EUS and pathologic stage; (2) evaluate the ability of EUS to predict disease-specific survival (DSS); and (3) determine how neoadjuvant chemotherapy (NCT) affects these relationships.

Methods: A prospective gastric cancer database at a tertiary care cancer center identified 734 patients who underwent curative intent resection. Patients were separated into EUS low-risk (T1-2, N0) and EUS high-risk (T3-4 Nany, or Tany N+) groups. Agreement statistics and 5-year DSS were estimated stratified by NCT.

Results: Between 1987 and 2015, 68% (502/734) of patients were not treated with NCT. Among these patients, percentage agreement between EUS and pathology was moderate (individual T stage: 52%; N stage: 70%; risk group: 73%). EUS accurately estimated pathologic risk group in 73% (365/502) of patients, whereas it overestimated pathologic risk group in 19% (93/502) of patients and underestimated risk in 8% (41/502) of patients. EUS in non-NCT staging was able to discriminate DSS for T stage (hazard ratio [HR] 5.07, p < 0.05), N stage (HR 3.58, p < 0.05), and risk group (HR 6.35, p < 0.05). Among patients treated with NCT, EUS was unable to discriminate DSS for T stage (HR 0.94, p > 0.05), N stage (HR 1.46, p > 0.05) and risk group (HR 0.50, p > 0.05).

Conclusions: Pretreatment clinical staging based on EUS alone could lead to over- or under treatment in 27% of patients and can discriminate DSS in NCT-naive patients. EUS should be used in the context of other validated clinical risk tools.
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http://dx.doi.org/10.1245/s10434-017-6050-9DOI Listing
November 2017

Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma.

Mod Pathol 2016 11 22;29(11):1433-1442. Epub 2016 Jul 22.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation. To address these questions, we performed a pilot study to evaluate the patterns of PD-L1 and PD-1 immunohistochemical expression on colorectal carcinoma cells and their tumor-infiltrating lymphocytes, respectively. Using tissue microarray, we found that 5% (19/394) of colorectal carcinomas exhibited high tumor PD-L1 expression, and 19% (76/392) had elevated numbers of PD-1-positive tumor-infiltrating lymphocytes. PD-L1 levels correlated with PD-1 levels (P<0.001), and mismatch-repair-deficient tumors had significantly higher rates of high PD-L1 and PD-1 expression when compared with mismatch-repair-proficient tumors (18% vs 2% and 50% vs 13%, respectively; P<0.001 for both). Staining intensity was also stronger for both markers in mismatch-repair-deficient tumors. Furthermore, we observed that among patients with mismatch-repair-deficient colorectal carcinoma, PD-1/PD-L1 expression stratified recurrence-free survival in an inter-dependent manner: an association between high PD-1-positive tumor-infiltrating lymphocytes and improved recurrence-free survival (P=0.041) was maintained only when the tumors had low-level PD-L1 expression (P=0.006); patients whose tumors had both high PD-1-positive tumor-infiltrating lymphocytes and high PD-L1 expression had a significantly worse recurrence-free survival (P<0.001). Thus, our results not only provide a foundation for further assessment of PD-L1 immunohistochemistry as a predictive marker for anti-PD-1 therapy in colorectal carcinoma, they also shed light on the prognostic impact of tumor-infiltrating lymphocytes in different subsets of mismatch-repair-deficient colorectal carcinomas.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083129PMC
http://dx.doi.org/10.1038/modpathol.2016.139DOI Listing
November 2016

Educational and Psychosocial Support Needs in Lynch Syndrome: Implementation and Assessment of an Educational Workshop and Support Group.

J Genet Couns 2017 Apr 12;26(2):232-243. Epub 2016 Oct 12.

Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 295, New York, NY, 10065, USA.

Few reports of educational and counseling support resources exist for Lynch syndrome (LS), a disorder requiring multi-organ cancer screening and specialized medical care throughout adult life. Here we describe the development and efficacy of two resources designed to address this need, the Memorial Sloan Kettering Cancer Center Clinical Genetics Service annual Lynch Syndrome Educational Workshop (LSEW), and a quarterly Lynch Syndrome Patient Advocacy Network (LSPAN) support group. The LSEW and LSPAN were implemented beginning in 2012. Participant survey data evaluating satisfaction, clarity, and unmet needs for each event were retrospectively analyzed and summarized using descriptive statistics. Annual LSEW attendance ranged from 53 to 75 total participants. LSEW year 1 participants indicated a need for a support group, and preferred in-person meetings at a frequency of every 3-6 months. For LSEW year 2-5 participants, >96 % reported satisfaction with the LSEW, and >82 % expressed interest in secure online support. Common themes for improvement included increased time for question and answer sessions and additional introductory genetics education. Responding LSPAN participants (n = 57 total survey responses in 11 meetings) found the meetings helpful (100 %), information clear (91 %), and presence of a genetic counselor useful (67 %). Desired discussion topics included coping with stress and anxiety, development of a support network, family communication about LS, genetic testing decisions, and bereavement. Following genetic counseling, a need exists for ongoing educational and emotional support in LS. Implementation of resources such as the LSEW and LSPAN is feasible and perceived as helpful by participants.
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http://dx.doi.org/10.1007/s10897-016-0015-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383525PMC
April 2017

A Positive Prospective Trial of Antibiotic Therapy in Advanced Stage, Non-Bulky Indolent Lymphoma.

Tumor Microenviron Ther 2015 Feb 18;2(1):14-18. Epub 2015 Feb 18.

Memorial Sloan Kettering Cancer Center, Department of Medicine, 1275 York Avenue New York, NY, 10065 USA.

Background: We have prospectively studied a three month course of clarithromycin (substituted by Prevpac, lansoprazole/ amoxicillin/ clarithromycin, in the first two wks when stool H pylori+) for non-bulky, advanced stage indolent lymphoma. These patients are often candidates for expectant monitoring and it is during this period that a window of opportunity may exist to identify and treat associated infections.

Methods: All previously untreated patients with a new diagnosis of indolent lymphoma (FL and non-FL) meeting GELF criteria were treated with 12 weeks of clarithromycin. There were 32 evaluable patients, 4 of whom had stool H pylori.

Results: At one month post-antibiotic therapy, we have observed lymphoma responses in 7 of 32 patients (21.9%). Two additional patients had objective response during followup (28.1% overall response). The median treatment free survival for antibiotic responders is 69.9 months and for non-responders, 30.6 months (p = 0.019).

Conclusion: Three response patterns have been noted, perhaps suggestive of an immune-mediated response -- prompt PET negative; flair with delayed PET negative response; and gradual continuous improvement. This prospective study appears promising, may be a step toward developing a lymphoma prevention strategy by reducing "antigen drive," and deserves further clinical/biological study. http://clinicaltrials.gov/show/NCT00461084.
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http://dx.doi.org/10.1515/tumor-2015-0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718606PMC
February 2015

A proposed staging system and stage-specific interventions for familial adenomatous polyposis.

Gastrointest Endosc 2016 Jul 6;84(1):115-125.e4. Epub 2016 Jan 6.

Center for Hereditary Tumors, HELIOS Klinikum Wuppertal, University Witten-Herdecke, Wuppertal, Germany.

Background And Aims: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis.

Methods: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments.

Results: The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode.

Conclusions: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.
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http://dx.doi.org/10.1016/j.gie.2015.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570515PMC
July 2016

Endoscopic Management of Esophageal Anastomotic Leaks After Surgery for Malignant Disease.

Ann Thorac Surg 2016 Jan 28;101(1):301-4. Epub 2015 Sep 28.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Background: Esophageal anastomotic leaks after cancer surgery remain a major cause of morbidity and mortality. Endoscopic interventions, including covered metal stents (cSEMS), clips, and direct percutaneous endoscopic jejunostomy (dPEJ) tubes are increasingly used despite limited published data regarding their utility in this setting. This study aimed to determine the efficacy and safety of a multimodality endoscopic approach to anastomotic leak management after operation for esophageal or gastric cancer.

Methods: We performed a retrospective review of prospectively maintained databases of gastric and esophageal operations at our hospital between January 2003 and December 2012. Included patients had an operation for esophageal or gastric cancer, demonstrated evidence of an anastomotic leak at the esophageal anastomosis, and underwent attempted endoscopic therapy. Healing was defined as clinical and radiographic leak resolution.

Results: Forty-nine patients with leaks underwent endoscopic management. Of the 49 patients, 31 (63%) received cSEMS, 40 (82%) had dPEJ tubes inserted, and 3 (6%) received clips. Twenty-three (47%) patients underwent a combined approach. Overall, 88% of patients achieved healing in a median of 83 days. Twenty-two of 23 patients (96%) who underwent a multimodality endoscopic approach healed. Only 1 patient had a major complication associated with stent erosion into the pulmonary artery, which was successfully treated with operative repair.

Conclusions: Esophageal anastomotic leaks after esophageal and gastric cancer operations can be managed successfully and safely with endoscopic therapy. Combining cSEMS for leak control and dPEJ tube placement for nutritional support was highly effective in achieving healing, without the need for surgical repair.
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http://dx.doi.org/10.1016/j.athoracsur.2015.06.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910386PMC
January 2016

Palliation of malignant gastric outlet obstruction with simultaneous endoscopic insertion of afferent and efferent jejunal limb enteral stents in patients with recurrent malignancy.

Surg Endosc 2016 Feb 20;30(2):521-525. Epub 2015 Jun 20.

Gastroenterology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.

Background: Patients with prior pancreaticobiliary or distal gastric cancer treated surgically may have local anastomotic recurrence with obstruction of the afferent and efferent jejunal limbs. This report describes the efficacy and safety of simultaneous endoscopic insertion of self-expanding metal stents into the afferent and efferent jejunal limbs in patients with gastric outlet obstruction (GOO) of post-surgical anatomy for palliation of recurrent malignancy.

Methods: Patients were identified from an endoscopic database at a specialized cancer center between September 2007 and March 2014. Technical success was defined as single-session insertion of afferent and efferent jejunal limb enteral stents. Clinical success was defined as immediate symptom relief and ability to advance diet. A durable response was defined as symptom relief of at least 60 days or until hospice placement or death.

Results: Twenty-three patients were identified who underwent insertion of two 22-mm-diameter uncovered duodenal stents. Stent length varied from 60 to 120 mm. Stents were placed under endoscopic and fluoroscopic guidance. Three patients required balloon dilation to facilitate stent insertion. Average procedure time was 58.8 min (range 28-120). Technical success was achieved in 23/24 (96%) patients. Clinical success was achieved in 19/23 (83%) patients. Following initial stent insertion and prior to subsequent re-intervention, 11/19 (58%) patients had a durable response with a median duration of 70 days (range 4-315). Eight (42%) patients underwent subsequent re-intervention at a median of 22 days (range 11-315). Five patients had stent revision and were able to tolerate oral intake. Two patients had percutaneous endoscopic gastrostomy/jejunostomy insertion. One patient required surgical diversion for persistent obstruction. Complications included stent migration and post-stent insertion bacteremia due to food bolus obstruction.

Conclusions: Recurrent malignant GOO in patients with post-surgical anatomy treated with simultaneous endoscopic enteral stenting of afferent and efferent jejunal limbs has a high rate of technical and clinical success and low rate of complications and provides effective palliation.
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http://dx.doi.org/10.1007/s00464-015-4234-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027626PMC
February 2016

Mismatch repair deficient-crypts in non-neoplastic colonic mucosa in Lynch syndrome: insights from an illustrative case.

Fam Cancer 2015 Mar;14(1):61-8

Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA,

Mono-allelic germline mutations in DNA mismatch repair (MMR) genes lead to Lynch syndrome (LS). Questions remain as to the timing of the inactivation of the wild-type allele in LS-associated tumorigenesis. Speculation exists that it happens after the neoplasia has been initiated. However, a recent study reported the presence of MMR-deficiency in non-neoplastic colonic crypts in LS; thus the possibility can be raised that these crypts may be tumor precursors, and as such, biallelic loss of MMR may occur prior to neoplasia. Here we report a unique case that showed findings supporting both of the two seemingly conflicting notions. The patient was a 40-year-old female with LS, MSH2 type, who underwent a segmental colectomy for an adenocarcinoma. By immunohistochemistry, the carcinoma lost MSH2/MSH6. Interestingly, there was also complete loss of MSH2/MSH6 in a distinct focus of 20 colonic crypts that were morphologically non-neoplastic, thus supporting the possibility of biallelic loss of MMR before initiation of neoplasia. However, in a separate adenoma, MMR was preserved in neoplastic glands with low grade dysplasia and lost only in glands with high grade dysplasia, i.e., MMR loss after tumor initiation. These are relevant findings with regard to the timing of MMR deficiency in LS tumorigenesis, and bring forth the possibility that varied tumorigenic pathways may exist. Additionally, we observed that the MMR-deficient non-neoplastic crypts harbored increased intraepithelial CD8-positive T-lymphocytes similar to the patient's carcinoma, providing a potential new venue for the study of the natural antitumor immune responses in LS individuals.
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http://dx.doi.org/10.1007/s10689-014-9751-2DOI Listing
March 2015

Results of a prospective thyroid ultrasound screening program in adenomatous polyposis patients.

Am J Surg 2014 Nov 20;208(5):764-769. Epub 2014 Jun 20.

Department of Surgery, Colorectal Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address:

Background: Patients with adenomatous polyposis may be at increased risk for developing thyroid cancer (TC). However, screening guidelines for TC in these patients are not well established.

Methods: Patients with a diagnosis of familial adenomatous polyposis, attenuated familial adenomatous polyposis, and gene mutation-negative adenomatous polyposis enrolled in our Hereditary Colorectal Cancer Family Registry were eligible for a screening thyroid ultrasound (US). Findings were reviewed by the study endocrinologist and intervention and/or follow-up determined.

Results: Fifty patients underwent screening thyroid US. Thirty-four (68%) patients had abnormal findings on US, including 27 (79%) with thyroid nodules. In 7 patients, US-detected thyroid nodules met established criteria for fine-needle aspiration. Of the 6 patients who underwent fine-needle aspiration, 2 (4%) were diagnosed with papillary TC. Both of these patients were female.

Conclusions: A large proportion of adenomatous polyposis patients will have abnormal results on thyroid US, including suspicious-appearing thyroid nodules that when biopsied are malignant. Female patients have an apparently greater risk of developing TC. Polyposis patients, especially women, should be offered participation in a thyroid US screening program.
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http://dx.doi.org/10.1016/j.amjsurg.2014.03.012DOI Listing
November 2014

Cribriform-morular variant of papillary thyroid carcinoma: an indication to screen for occult FAP.

Fam Cancer 2014 Dec;13(4):547-51

Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Room C-1077, New York, NY, 10065, USA.

Cribriform-morular variant (CMV) is a rare subtype of papillary thyroid carcinoma (PTC) that is associated with familial adenomatous polyposis (FAP). Given the high likelihood for multi-organ malignancies in FAP patients, this study explores the yield of diagnosing occult FAP among CMV-PTC patients. Institutional database was searched in order to identify patients with pathologically-confirmed CMV-PTC from 2000 to 2012. Medical records were reviewed, and clinical and pathological features were analyzed. Eleven cases of CMV were identified from 6,901 patients with PTC, for a prevalence of 0.16 %. All 11 patients were female. The median age at CMV-PTC diagnosis was 36 years (range 18-46). Two patients had pre-existing FAP at the time of PTC diagnosis. The other nine patients were referred for colonoscopy and/or genetic testing. Six patients underwent colonoscopy and one (17 %) was diagnosed with FAP based on polyposis phenotype and genetic testing. The mean age of patients at the time of CMV-PTC diagnosis was younger in the FAP group (23 years, range 18-34) than in the sporadic group (37 years, range 25-46). All three patients with FAP-associated CMV-PTC had multicentric tumors, while all five sporadic patients did not. Our study found that approximately one-sixth of patients with CMV-PTC may have occult FAP. Patients with FAP-associated CMV-PTC appear to be younger and more likely to have multicentric tumors than those with sporadic CMV-PTC. Due to the increased risk of malignancy in patients with FAP, patients with CMV-PTC should be referred for colonoscopy and/or genetic evaluation for FAP.
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http://dx.doi.org/10.1007/s10689-014-9732-5DOI Listing
December 2014

Utilization of colonoscopy and pathology reports for identifying patients meeting the world health organization criteria for serrated polyposis syndrome.

Dis Colon Rectum 2014 Jul;57(7):846-50

1Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 2Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 3Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Serrated polyposis syndrome is a rare syndrome associated with an increased risk for colorectal cancer. The World Health Organization criteria were established to standardize the diagnosis and management of patients afflicted with serrated polyposis. Although useful, the criteria may not be ideal for the initial screening of at-risk populations.

Objective: The aim of this study was to examine the use of a minimal cutoff point of serrated lesions to increase the yield of serrated polyposis cases.

Design: This was a retrospective review of colonoscopy and pathology reports to identify patients who met the World Health Organization criteria for serrated polyposis.

Setting: This study was conducted at a tertiary cancer care referral center.

Patients: Five hundred patients who had at least 2 pathologically confirmed hyperplastic polyps and/or sessile serrated adenomas/polyps diagnosed between 1999 and 2009 were assessed.

Main Outcome Measures: The primary outcome measure was the number of serrated polyposis cases.

Results: Forty of the 500 (8%) patients met the World Health Organization criteria for serrated polyposis syndrome. Patients underwent a median of 4 colonoscopies (range, 1-23) before satisfying the criteria, and only 1 (3%) patient met the criteria for diagnosis during the initial colonoscopy. All 16 patients with a history of colorectal cancer were only diagnosed with serrated polyposis either at the time of their cancer diagnosis or during postoperative colonoscopies. Only 5 of the 40 (13%) patients were enrolled in our institutional Hereditary Colorectal Cancer Family Registry before our study for prospective serrated lesion tracking and colorectal cancer screening.

Limitations: This tool requires validation in a prospective setting.

Conclusions: The cutoff point of at least 2 pathologically confirmed serrated lesions can serve as a screening tool for identifying patients meeting the World Health Organization criteria for serrated polyposis syndrome who would otherwise go undetected.
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http://dx.doi.org/10.1097/DCR.0000000000000140DOI Listing
July 2014

Mosaic partial deletion of the PTEN gene in a patient with Cowden syndrome.

Fam Cancer 2014 Sep;13(3):459-67

Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 295, New York, NY, 10065, USA.

Cowden syndrome is an autosomal dominant condition caused by pathogenic mutations in the phosphatase and tensin homolog (PTEN) gene. Only a small proportion of identified pathogenic mutations have been reported to be large deletions and rearrangements. We report on a female patient with a previous history of breast ductal carcinoma in situ who presented to our institution for management of gastrointestinal hamartomatous polyposis. Although several neoplastic predisposition syndromes were considered, genetic evaluation determined that the patient met clinical diagnostic criteria for Cowden syndrome. Array-based comparative genomic hybridization was performed and revealed a mosaic partial deletion of the PTEN gene. Follow-up clinical history including bilateral thyroid nodules, dermatological findings, and a new primary "triple-negative" adenocarcinoma of the contralateral breast are discussed. We highlight the need for recognition and awareness of mosaicism as it may provide an explanation for variable phenotypic presentations and may alter the genetic counseling risk assessment of affected individuals and family members.
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http://dx.doi.org/10.1007/s10689-014-9709-4DOI Listing
September 2014

Endoluminal high-dose-rate brachytherapy for early stage and recurrent esophageal cancer in medically inoperable patients.

Brachytherapy 2013 Sep-Oct;12(5):463-70. Epub 2013 Feb 20.

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY.

Purpose: The management of superficial primary and recurrent esophageal cancer (EC) in medically inoperable patients is complex. Endoluminal high-dose-rate (HDR) brachytherapy has shown mixed results in terms of toxicity and local control. In this study, we examined the outcomes and toxicities in a set of patients with superficial primary and recurrent EC treated with a consistent HDR technique.

Methods And Materials: Between 8/2008 and 7/2011, 14 patients were treated with HDR intraluminal brachytherapy, 10 (71.4%) with recurrent disease, and 4 (28.6%) with previously unirradiated lesions. Patients received three weekly fractions to a median dose of 12 Gy (range, 10-15 Gy); dose was prescribed to 7-mm median depth with mucosal dose limited to 8-10 Gy using a 12-14-mm applicator.

Results: Median followup was 15.4 months. Overall freedom from failure (OFFF) and overall survival (OS) at 18 months were 30.8% (95% confidence interval [CI]: 5.2, 56.4) and 72.7% (95% CI: 45.3, 100), respectively. For patients with recurrent disease, OFFF and OS at 18 months were 11.1% (95% CI: 0, 32.1) and 55.6% (95% CI: 15.4, 95.8), respectively. For patients with previously unirradiated disease, OFFF and OS at 18 months were 75.0% (95% CI: 31.6, 100) and 100.0%, respectively. Eight (57.1%) patients had Grade 1 acute adverse effects; 6 (42.9%) patients had chronic Grade 1 adverse effects; 1 (7.1%) patient developed Grade 2 stricture. Grade 3 tracheoesophageal fistula occurred in 1 (7.1%) patient. One patient died before completion of treatment of unrelated causes.

Conclusions: HDR endoluminal brachytherapy is a well-tolerated treatment for superficial primary and recurrent EC in medically inoperable patients.
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http://dx.doi.org/10.1016/j.brachy.2012.12.001DOI Listing
May 2014

Patients with colorectal and renal cell carcinoma diagnoses appear to be at risk for additional malignancies.

Clin Colorectal Cancer 2013 Mar 29;12(1):23-7. Epub 2012 Sep 29.

Department of Surgery, Colorectal Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Unlabelled: Patients with colorectal cancer (CRC) and renal cell carcinoma (RCC) may be at risk for additional primary malignancies. A review of 101 patients with these concurrent diagnoses was performed. Forty-two percent of patients had 1 or more additional malignancies; none appeared to be associated with Lynch syndrome (LS). This suggests the need for careful follow-up in these patients and further study.

Background: Small studies have demonstrated that patients who have both colorectal and renal cell carcinoma may be at increased risk for the development of additional malignancies. A possible genetic basis has been suggested. Our study describes the clinicopathologic features of these patients and clarifies the relationship of this cohort with Lynch syndrome (LS).

Methods: Patients with primary CRC and RCC treated at our institution were identified. Medical records were reviewed for demographic and clinical information. Immunohistochemical staining for mismatch repair (MMR) proteins was performed on tumor tissue when possible.

Results: During the study period, 24,642 patients were treated for CRC and 7,366 were treated for RCC at our institution. One hundred seventy-nine patients had both diagnoses, with 101 patients eligible for inclusion in our cohort. Tumors were typically early stage. The 2 cancers presented as synchronous lesions in 42% of patients. Thirty-two patients had 1 additional primary malignancy, 7 patients had 2 additional primary malignancies, and 3 patients had 3 additional primary malignancies. No patient had a family history that met the Amsterdam II criteria (AC) for LS, but 50% had family members with 1 malignancy. One of 10 colorectal tumors analyzed for the absence of MMR protein expression demonstrated the absence of MSH6, but the corresponding RCC demonstrated intact expression of all 4 MMR proteins.

Conclusion: It is rare for patients to be diagnosed with both CRC and RCC. The clinicopathologic features of this cohort and the results of immunohistochemical analysis performed on a sample of these patients do not suggest LS. However, the high rate of additional carcinomas suggests a need for careful follow-up. Multicenter longitudinal studies are warranted to further understand the natural history and possible genetic basis for this entity.
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http://dx.doi.org/10.1016/j.clcc.2012.07.004DOI Listing
March 2013

Covered esophageal self-expandable metal stents in the nonoperative management of postoperative colorectal anastomotic leaks.

Gastrointest Endosc 2012 Aug;76(2):431-5

Dr. Henry D. Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, New York 10029, USA.

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http://dx.doi.org/10.1016/j.gie.2012.03.1393DOI Listing
August 2012

Endoscopic management of complete colonic obstruction.

J Interv Gastroenterol 2011 Oct 1;1(4):179-181. Epub 2011 Oct 1.

Division of Gastroenterology and Hepatology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA.

A patient with metastatic rectal cancer underwent a diverting transverse loop colostomy due to rectal obstruction. 16 months later, he underwent a low anterior resection to resect his rectal cancer along with reversal of his transverse colostomy, and creation of a temporary loop ileostomy. Six months later, he was brought to the operating room for closure of his ileostomy. Post-operatively, the patient developed nausea, vomiting, and abdominal distention and imaging revealed a large bowel obstruction, confirmed by colonoscopy. The patient refused surgical diversion and a cecostomy tube was placed for decompression. After maturation of the cecostomy fistula, a rendezvous colonoscopy was performed, retrograde through the rectum and antegrade through the cecostomy fistula. The obstructing mucosa was traversed and the site of obstruction was balloon dilated, relieving the obstruction endoscopically.
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http://dx.doi.org/10.4161/jig.1.4.19969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350891PMC
October 2011

The prevalence of thyroid cancer and benign thyroid disease in patients with familial adenomatous polyposis may be higher than previously recognized.

Clin Colorectal Cancer 2012 Dec 15;11(4):304-8. Epub 2012 Mar 15.

Department of Surgery, Colorectal Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Purpose: Patients with familial adenomatous polyposis (FAP) are at increased risk for colorectal cancer and extracolonic neoplasms. The prevalence of thyroid cancer (TC) and benign thyroid disease in this patient population is unclear, and guidelines for screening for TC in these patients are not well established. The purpose of this study was to report the prevalence of TC and benign thyroid disease in patients with FAP.

Methods: The prospectively maintained Hereditary Colorectal Cancer Family Registry at Memorial Sloan-Kettering Cancer Center was queried to identify patients with FAP and with TC and/or benign thyroid disease.

Results: Sixty-six patients with FAP were identified. There were 30 men and 36 women, with a median age of 38.6 years. Four (6.1%) patients had a history of TC. All were women, with a mean age at TC diagnosis of 36.5 years. Three of the 4 TCs were papillary thyroid cancer. Two patients with TC presented with palpable nodules. An additional 6 (9.1%) patients with FAP had a history of benign thyroid disease, including nodules (3), hypothyroidism (2), cysts (2), goiter (1), and thyroiditis (1). Three of 4 patients with TC and all 6 patients with benign thyroid disease had other extracolonic manifestations associated with FAP.

Conclusions: The prevalences of TC (6.1%) and benign thyroid disease (9.1%) are increased in our patients with FAP and are higher than noted in some previous reports. Periodic thyroid ultrasound screening should be considered in patients with FAP to further elucidate the prevalence and for possible early detection of TC and benign thyroid disease in this population.
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http://dx.doi.org/10.1016/j.clcc.2012.01.006DOI Listing
December 2012