Endoscopic surveillance with systematic random biopsy for the early diagnosis of hereditary diffuse gastric cancer: a prospective 16-year longitudinal cohort study

Lee, Colin Y C; Olivier, Adriaan; Honing, Judith; Lydon, Anne-Marie; Richardson, Susan; O’Donovan, Maria; Tischkowitz, Marc; Fitzgerald, Rebecca C.; Pietro, Massimiliano di

doi:10.1016/s1470-2045(22)00700-8

Cited by 20 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In patients not undergoing PTG, endoscopic surveillance remains the unique option. 34 In our analysis of 15 pedigrees, only 1 documented DGC was reported and none of the remaining 14 women with LBC developed GC within a median 5 years of follow-up. In accordance with the latest IGCLC indications, 7 the benefits and risks of different preventive options (including PTG) were discussed in a multidisciplinary evaluation.…”

Section: Discussionmentioning

confidence: 72%

“…The 2020 IGCLC guidelines reduce the emphasis on PTG if GC family history is weak, as in HLBC syndrome. In patients not undergoing PTG, endoscopic surveillance remains the unique option . In our analysis of 15 pedigrees, only 1 documented DGC was reported and none of the remaining 14 women with LBC developed GC within a median 5 years of follow-up.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype

Corso,

Marino,

Zanzottera

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportancePathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation.ObjectivesTo evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers’ tumor samples, and the association of genetic profiles with clinical-pathological data and survival.Design, Setting, and ParticipantsThis single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers.Main Outcomes and MeasuresAccurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis.ResultsOf 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03).Conclusions and RelevanceIn this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

show abstract

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype

Corso,

Marino,

Zanzottera

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

show abstract

“…Random endoscopic gastric biopsies revealed occult, microscopic foci of signet ring cell carcinomas in approximately half (47.2%, 59/125) of the patients, which is consistent with the disease phenotype. 22 , 23 Total gastrectomy was conducted with an open surgical approach in all but two cases. Median operative duration was 168 minutes (range, 111-373 minutes) with a median estimated blood loss of 50 mL.…”

Section: Resultsmentioning

confidence: 99%

“…20,21 Although recent studies have demonstrated that endoscopic surveillance with random and targeted biopsies can be a reasonable alternative to surgery in some patients, the long-term safety of surveillance is not yet known. 22,23 Attempts to risk-stratify individuals on the basis of genotype or family cancer history to help guide clinical management have not been successful. 24,25 Total gastrectomy is an uncommon operation with a plethora of potential acute and chronic complications.…”

Section: Introductionmentioning

confidence: 99%

Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy

Gallanis,

Gamble,

Samaranayake

et al. 2024

JCO

View full text Add to dashboard Cite

PURPOSE Risk-reducing surgery for cancer prevention in solid tumors is a pressing clinical topic because of the increasing availability of germline genetic testing. We examined the short- and long-term outcomes of risk-reducing total gastrectomy (RRTG) and its lesser-known impacts on health-related quality of life (QOL) in individuals with hereditary diffuse gastric cancer syndrome. METHODS Individuals who underwent RRTG as part of a single-institution natural history study of hereditary gastric cancers were examined. Clinicopathologic details, acute and chronic operative morbidity, and health-related QOL were assessed. Validated questionnaires were used to determine QOL scores and psycho-social-spiritual measures of healing. RESULTS One hundred twenty-six individuals underwent RRTG because of a pathogenic or likely pathogenic germline CDH1 variant between October 2017 and December 2021. Most patients (87.3%; 110/126) had pT1aN0 gastric carcinoma with signet ring cell features on final pathology. Acute (<30 days) postoperative major morbidity was low (5.6%; 7/126) and nearly all patients (98.4%) lost weight after total gastrectomy. At 2 years after gastrectomy, 94% (64/68) of patients exhibited at least one chronic complication (ie, bile reflux, dysphagia, and micronutrient deficiency). Occupation change (23.5%), divorce (3%), and alcohol dependence (1.5%) were life-altering consequences attributed to total gastrectomy by some patients. In patients with a median follow-up of 24 months, QOL scores decreased at 1 month after gastrectomy and returned to baseline by 6-12 months. CONCLUSION RRTG is associated with life-changing adverse events that should be discussed when counseling patients with CDH1 variants about gastric cancer prevention. The risks of cancer-prevention surgery should not only be judged in the context of likelihood of death due to disease if left untreated, but also based on the real consequences of organ removal.

show abstract

“…We previously described the Cambridge criteria to aid endoscopic detection and characterisation of early SRCC in pale areas. 1 The criteria include six features: A, round shape (opposed to linear); B, well demarcated borders (opposed to faded margins); C, focally irregular microvessels; C++, diffusely irregular microvessels; D, irregular microsurface pattern; and E, reproducibility in dynamic view. The aim of this study was to validate the Cambridge criteria prospectively and to develop machine-learning (ML) tool based on these criteria to improve the effectiveness of the endoscopic diagnosis.…”

mentioning

confidence: 99%

Machine learning-based endoscopic classification for superficial mucosal lesions in hereditary diffuse gastric cancer

Wu,

Honing

et al. 2024

ESGE Days 2024

View full text Add to dashboard Cite

Endoscopic surveillance with systematic random biopsy for the early diagnosis of hereditary diffuse gastric cancer: a prospective 16-year longitudinal cohort study

Cited by 20 publications

References 30 publications

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype

Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy

Machine learning-based endoscopic classification for superficial mucosal lesions in hereditary diffuse gastric cancer

Contact Info

Product

Resources

About