Short and long‐term outcomes of prophylactic total gastrectomy in 54 consecutive individuals with germline pathogenic mutations in the <i>CDH1</i> gene

Stillman, Mason D; Kusche, Nicole; Toledano, Sabrina; Hilfrank, Kimberly J.; Yoon, Changhwan; Gabre, Joel; Rustgi, Sheila D.; Hur, Chin; Kastrinos, Fay; Ryeom, Sandra; Yoon, Sam S.

doi:10.1002/jso.27084

Cited by 8 publications

(4 citation statements)

References 48 publications

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“…Furthermore, it is critically important to confirm both proximal and distal margins of the gastrectomy specimen to ensure that no gastric tissue remains. Recent reports have highlighted favourable safety outcomes amongst HDGC patients undergoing risk-reducing total gastrectomy 141 , 142 .…”

Section: Hereditary Gastric Cancermentioning

confidence: 99%

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

2023

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Background Inheritance patterns show familial clustering of gastrointestinal cancers, and multiple germline conditions have now been identified that predispose to colorectal, gastric, and pancreatic cancers. Methods A narrative review based on recent relevant literature was conducted. Results Lynch syndrome, formerly known as hereditary non-polyposis colorectal cancer, increases the risk of several abdominal cancers, with the highest population prevalence. Familial adenomatous polyposis and some of the more infrequent polyposis syndromes have distinct characteristics affecting various organ-specific cancer risks. Hereditary gastric and pancreatic cancer syndromes include those also causing colorectal cancer, while additional genetic disorders predisposing only to upper gastrointestinal malignancies have been recognized more recently. Diagnosing and managing hereditary cancer syndromes requires multidisciplinary expertise and may be best managed in tertiary centres, with a need to consider patient preference and ensure shared decision-making. Conclusion Several germline conditions predispose to colorectal, gastric, and pancreatic cancer, which inform identification, surveillance regimens, prevention, cascade screening, counselling, and surgical management. The authors describe developments in the hereditary origin of colorectal, gastric, and pancreatic cancer with current recommendations in surveillance and surgical management.

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Section: Hereditary Gastric Cancermentioning

confidence: 99%

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

2023

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“…A few molecular germline mutations are currently recognized as causal events related to these cases [ 29 ]. There are formal recommendations for carriers and their relatives in these situations [ 30 , 31 ]. Nonetheless, many young GC patients do not have such mutations, as is the case in the 95 GC patients under 50 years old discussed in this study.…”

Section: Discussionmentioning

confidence: 99%

Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported

Assumpção

Moreira

et al. 2022

Cancers

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Hereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world’s cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry’s contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventions.

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“…There were 15 studies reporting clinical outcomes following PTG in patients with CDH1 pathogenic variants, with a total of 353 patients (Table 1) [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The median age at the time of surgery was 42 years old (32-54), and there was a greater proportion of female patients at 62.2%.…”

Section: Surgical Outcomes Of Ptgmentioning

confidence: 99%

“…There were 19 studies that examined the histopathological outcomes following PTG in 414 patients (Table 2) [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Following PTG, 88.6% of patients had early lesions, including pagetoid 202 in situ lesions and foci of intramucosal signet ring cell adenocarcinoma.…”

Section: Histopathological Outcomes Of Ptgmentioning

confidence: 99%

A Systematic Review on Clinical and Health-Related Quality of Life Outcomes following Total Gastrectomy in Patients with Hereditary Diffuse Gastric Cancer

Lim,

di Pietro,

O’Neill

2024

Cancers

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Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant syndrome associated with early onset diffuse gastric cancer. Definitive treatment is prophylactic total gastrectomy (PTG) associated with significant morbidity. Studies published from January 2000 to December 2022 reporting clinical, histopathological or health-related quality of life outcomes in HDGC patients undergoing PTG were identified. The study quality was assessed by the “Newcastle–Ottawa scale”. Of the 257 articles screened, 21 were selected. A total of 353 patients were examined in 15 studies that reported surgical outcomes. The median age was 42 years old. The median major complication and mortality rates were 19.2% and 0.3%, respectively. The most common complications were wound infection at 4.8% followed by anastomotic leak and pulmonary complications at 4.5% each. Following PTG, 88.6% of patients had early lesions amongst 414 patients. The mean/median number of signet ring cell carcinoma foci in the gastrectomy specimens was from 2 to 78. All cases were stage 1 with no lymph node involvement. There was a wide range of psychosocial effects following PTG closely related to the physical symptoms. It is imperative for patients to receive comprehensive preoperative counselling to make an informed decision and be followed up under the care of a multidisciplinary team.

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Short and long‐term outcomes of prophylactic total gastrectomy in 54 consecutive individuals with germline pathogenic mutations in the CDH1 gene

Cited by 8 publications

References 48 publications

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported

A Systematic Review on Clinical and Health-Related Quality of Life Outcomes following Total Gastrectomy in Patients with Hereditary Diffuse Gastric Cancer

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