Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes
Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation woul...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/728 |
| _version_ | 1797488705742569472 |
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| author | Joseph D. Forrester Deshka Foster James M. Ford Teri A. Longacre Uri Ladabaum Sara Fry Jeffrey A. Norton |
| author_facet | Joseph D. Forrester Deshka Foster James M. Ford Teri A. Longacre Uri Ladabaum Sara Fry Jeffrey A. Norton |
| author_sort | Joseph D. Forrester |
| collection | DOAJ |
| description | Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable. Methods: We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher’s exact test. Results: In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology (<i>p</i> = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue (<i>p</i> = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again. Conclusions: Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable. |
| first_indexed | 2024-03-10T00:06:08Z |
| format | Article |
| id | doaj.art-4afdac697fee4262a1b2ccbc787b0ccf |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:06:08Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4afdac697fee4262a1b2ccbc787b0ccf2023-11-23T16:07:39ZengMDPI AGCancers2072-66942022-01-0114372810.3390/cancers14030728Surgery for Hereditary Diffuse Gastric Cancer: Long-Term OutcomesJoseph D. Forrester0Deshka Foster1James M. Ford2Teri A. Longacre3Uri Ladabaum4Sara Fry5Jeffrey A. Norton6Department of Surgery, Stanford University Medical Center, Stanford, CA 94305, USADepartment of Surgery, Stanford University Medical Center, Stanford, CA 94305, USADepartments of Medical Oncology, Stanford University Medical Center, Stanford, CA 94305, USADepartment of Pathology, Stanford University Medical Center, Stanford, CA 94305, USADepartment of Gastroenterology, Stanford University Medical Center, Stanford, CA 94305, USADepartment of Surgery, Stanford University Medical Center, Stanford, CA 94305, USADepartment of Surgery, Stanford University Medical Center, Stanford, CA 94305, USAIntroduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable. Methods: We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher’s exact test. Results: In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology (<i>p</i> = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue (<i>p</i> = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again. Conclusions: Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable.https://www.mdpi.com/2072-6694/14/3/728hereditary diffuse gastric cancer (HDGC)CDH-1 mutationgastric cancer |
| spellingShingle | Joseph D. Forrester Deshka Foster James M. Ford Teri A. Longacre Uri Ladabaum Sara Fry Jeffrey A. Norton Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes Cancers hereditary diffuse gastric cancer (HDGC) CDH-1 mutation gastric cancer |
| title | Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes |
| title_full | Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes |
| title_fullStr | Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes |
| title_full_unstemmed | Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes |
| title_short | Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes |
| title_sort | surgery for hereditary diffuse gastric cancer long term outcomes |
| topic | hereditary diffuse gastric cancer (HDGC) CDH-1 mutation gastric cancer |
| url | https://www.mdpi.com/2072-6694/14/3/728 |
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