F1000Research F1000Research 2046-1402 F1000 Research Limited London, UK 10.12688/f1000research.140758.1 Systematic Review Articles Metastasis to the stomach: a systematic review

[version 1; peer review: 2 approved]

 Ibrahimli Arturan Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Resources Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0002-5527-4434 a 1 Aliyev Altay Conceptualization Data Curation Formal Analysis Funding Acquisition Investigation Methodology Project Administration Resources Software Supervision Validation Visualization Writing – Review & Editing 1 Majidli Aykhan Conceptualization Data Curation Formal Analysis Investigation Methodology Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0002-4332-7818 1 Kahraman Aysegul Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Galandarova Aysuna Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Khalilzade Emil Conceptualization Data Curation Formal Analysis Investigation Methodology Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Mammadli Heydar Conceptualization Data Curation Formal Analysis Investigation Methodology Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Huseynli Kamran Conceptualization Data Curation Formal Analysis Investigation Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Assaf Karam Data Curation Formal Analysis Investigation Methodology Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Kilinc Cagatay Conceptualization Data Curation Formal Analysis Investigation Methodology Software Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Muradov Nijat Data Curation Formal Analysis Funding Acquisition Investigation Methodology Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Alisan Omer F. Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Resources Software Supervision Validation Visualization 1 Abdullayev Sabir Conceptualization Data Curation Formal Analysis Investigation Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Sahin Yeliz I. Conceptualization Data Curation Formal Analysis Investigation Methodology Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Samadov Elgun Conceptualization Data Curation Formal Analysis Funding Acquisition Investigation Methodology Project Administration Resources Software Supervision Validation Visualization Writing – Review & Editing 1 Liv Bona Dea Hospital, Baku, Azerbaijan arturanibrahimli@yahoo.com

No competing interests were disclosed.

 18 10 2023 2023 12 1374 18 8 2023 Copyright: © 2023 Ibrahimli A et al. 2023 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: This study reviews the literature on gastric metastases (GM) in terms of diagnosis, treatment, and outcomes. The goal of this study was to provide clinicians with a reliable and beneficial source to understand gastric metastases arising from various primary tumors and to present the growing literature in an easily accessible form.

Methods: Articles published in English language from implementation of MEDLINE and Cochrane databases until May 2022 were considered for the systematic review. Articles other than English language, letters to the editor, posters, and clinical images were excluded. Hematogenous and lymphogenic metastases were included whereas direct tumoral invasion and seeding were excluded. Articles and abstracts were analyzed and last selection was done after cross-referencing and by use of defined eligibility criteria.

Results: In total 1,521 publications were identified and 170 articles were finally included totaling 186 patients with GM. The median age of patients was 62 years. Gynecologic cancer was the most common cancer type causing GM (67 patients), followed by lung cancer (33 patients), renal cancer (20 patients), and melanoma (19 patients). One of the main treatment methods performed for metastasis was resection surgery (n=62), sometimes combined with chemotherapy (ChT) or immunotherapy. ChT was the other most used treatment method (n=78). Also, immunotherapy was amongst the most preferred treatment options after surgery and ChT (n=10).

Conclusions: As 172 case reports were screened in the systematic review from different journals, heterogeneity was inevitable. Some articles missed important information such as complete follow-up or clinical information. Moreover, since all of the included articles were case reports quality assessment could not be performed. Among 172 case reports reviewed, resection surgery was performed the most and was sometimes combined with ChT and immunotherapy. Further research about what type of treatment has the best outcomes for patients with gastric metastases is needed.

 Metastasis to stomach gastric metastases gastric metastasis gastric cancer stomach cancer The author(s) declared that no grants were involved in supporting this work. Introduction

Metastases to the stomach are rare conditions with poor prognosis that may present with both gastrointestinal and systemic symptoms, such as loss of appetite, abdominal pain, fatigue, nausea, and vomiting, with a reported incidence of 0.2-0.7% based on clinical and autopsy findings. 1 Gastrectomy is thought to be the only potentially curative treatment for metastatic gastric cancer but the primary site of the tumor is also considered along with the type and grade of the tumor when planning treatment in gastric metastases. Therefore, chemotherapy is also an option for patients with higher grades and multi-focal cancers. This study reviews the literature on gastric metastases in terms of diagnosis, treatment, and outcomes. The intended goal of this study was to provide clinicians with a reliable and beneficial source to understand gastric metastases arising from various primary tumors and to present the growing literature in an easily accessible form by reviewing the case reports of different primary tumors separately with consideration of diagnosis, treatment, and clinical presentation which may vary from patient to patient depending on primary site of the tumor.

 Methods

This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 172 A computerized literature search through MEDLINE/ PubMed and Cochrane databases was conducted until May 2022.

The following combination of keywords was used for the search: ({({gastric (MeSH Terms)} AND {neoplasm metastasis (MeSH Terms)}) OR (gastric metastasis)} OR {gastric metastases}) OR (metastasis to the stomach). The search was limited by filtering for “free full text” and “case reports.” After the decision of inclusion and exclusion criteria by the team, two of the reviewers independently screened and retrieved each report.

Hematogenous and lymphogenic metastases were included whereas direct tumoral invasion and seeding were excluded from the study. Articles other than the English language, letters to the editor, posters, and clinical images were excluded. After the studies were screened and separated based on the inclusion and exclusion criteria, reviewers were divided to groups based on primary tumor location. Each group contained two reviewers to collect the data from studies of its specific location for example metastasis from gynecologic cancers or lung cancers.

The following data were extracted from the databases: first author, number of cases, age, sex, site of the primary tumor, histology and treatment of primary tumor, treatment of metastasis, clinical presentation of gastric metastases (GM), synchronous or metachronous GM, the time between primary and secondary GM, diagnostic procedures, other metastasis, and overall survival.

Since the study only contains screening of case reports, assessment of bias risk was not performed and thus it is mentioned as a limitation of study in discussion section.

 Results

The PRISMA flow chart below illustrates details about data collection ( Figure 1).

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.

In total, 1,521 publications were identified and 170 articles were finally included totaling 186 patients with GM (101 female and 85 male). The median age of patients was 62 years (IQR: 55-70.5). Gynecologic cancer (including breast cancer) was the most common cancer type causing GM (66 patients), followed by lung cancer (33 patients), renal cancer (20 patients), and melanoma (19 patients) ( Figure 2). Results are presented below according to the origin of the primary tumor. The main treatment method performed for metastasis was resection surgery (n=62, total, subtotal or partial gastrectomy, proximal gastrectomy, radical total gastrectomy with Roux-en-Y, wedge gastrectomy, and laparoscopic resection of gastric metastasis), sometimes combined with chemotherapy (ChT) or immunotherapy. Chemotherapy was the other most used treatment method (n=78). Also, immunotherapy was among the most preferred treatment options after surgery and chemotherapy (n=10).

Pie chart demonstrating percentages of primary tumor sites of patients with metastasis to stomach. Gynecologic cancer

The median age of the 66 patients was 57 years. In total, 46 cases had metastases other than GM. Bone was the most common site of metastasis. Five cases had no other metastases. The total number of cases in the breast group was 54, and one of them was a male patient. The median age of the breast group is 56, the youngest patient was 36 years old and the oldest patient was 84 years old. Invasive lobular carcinoma (ILC) had the largest number of patients in comparison to ovarian and uterine groups. A total of 31 patients presented with ILC. The ovarian group had nine patients; the median age was 61 years. The oldest patient was 73 years old; the youngest patient was 47 years old. The uterine group had two patients with ages 49 and 80 years. In most cases, systemic therapy was more effective than surgery. Surgical treatment had a role in palliative treatment. As a systemic treatment, chemotherapy was the most utilized treatment. Overall survival was given in only 25 cases and ranged from a few days to nine years. Six of the total patients are still alive. Table 1 2 – 56 summarizes the findings of included studies regarding gynecologic cancers.

Illustrating the data regarding metastasis from gynecologic cancers.
First author No of cases Age Sex Site of primary tumor Histology type of primary Treatment of primary Treatment of metastasis Clinical presentation of GM
Fousekis et al. 2 1 64 F Breast Lobular Ca ChT ChT Dysphagia, dyspepsia
Watanabe et al. 3 1 71 F Breast Ductal Ca Mastectomy and axillary lymph adenectomy, ChT Endocrine therapy Asymptomatic
Husain et al. 4 1 47 F Left breast Ductal Ca Neoadjuvant ChT, mastectomy with a left axillary lymph adenectomy, adjuvant endocrine therapy N/S Dyspepsia, weight loss, vomiting
Zhang et al. 5 1 46 F Bilateral breast Lobular Ca N/A N/A Epigastric discomfort
Jabi et al. 6 1 60 F Right breast Lobular Ca Palliative ChT Palliative ChT Epigastralgia, gastric bleeding, Anemia
Johnson et al. 7 1 50 F Breast Ductal Ca Lumpectomy, adjuvant RT, ChT N/S N/S
Okamoto et al. 8 1 51 F Breast Ductal Ca ChT ChT Melena, presyncope
Nehmeh et al. 9 1 58 F Right breast Ductal Ca Right modified mastectomy, left prophylactic mastectomy, adjuvant ChT N/S Perforated ulcer
Hanafiah et al. 10 1 71 F Left breast Lobular Ca Left mastectomy, axillary clearance, ChT, RT Ch Hoarseness, weight loss, early satiety
Teixeira et al. 11 1 40 F Right breast Lobular Ca Neoadjuvant ChT, RT, conservative surgery for right breast and right axillary lymph node Total gastrectomy Nausea, epigastric discomfort, early satiety, weight loss
Kutasovic et al. 12 1 52 F Left breast Invasive Ca of no special type Local excision, adjuvant RT, ChT, hormone therapy Subtotal gastrectomy N/S
Abdallah et al. 13 1 53 F Breast Lobular Ca ChT, hormone therapy N/S Abdominal pain, diffuse tenderness, abdominal distention
Liu et al. 14 1 82 F Left breast Phyllodes tumors Total mastectomy for recurrent tumor local excision, RT Excision surgery, RT Anemia, melena
Tang et al. 15 1 67 F Left breast Ductal Ca Left breast-conserving surgery, axillary lymphadenectomy, adjuvant ChT, RT N/S Stomach pain
De Gruttola et al. 16 1 61 F Breast Lobular Ca Mastectomy, adjuvant ChT, RT Total gastrectomy due to gastric perforation Gastric perforation
Mohy-Ud-Din et al. 17 1 83 F Breast Lobular Ca Mastectomy, sentinel lymph nodes excision, adj. ChT N/A Nausea, vomiting
Güler et al. 18 1 42 F Breast Ductal Ca N/A Total gastrectomy due to gastric perforation, ChT Acute Abdomen
Cui et al. 19 1 42 F Endometrium Endometrial Aca Total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy Neoadjuvant ChT, partial gastrectomy N/S
Asmar et al. 20 1 84 F Breast Lobular Ca Left mastectomy, adjuvant ChT, RT, hormone therapy Hormone therapy Dyspepsia
Klair et al. 21 1 60 F Ovary Ovarian granulosa cell tumor Total hysterectomy, bilateral salpingo-oophorectomy N/A Reflux, abdominal pain, nausea, anorexia
Yang 22 1 47 F Ovary Ovarian serous cystadenocarcinoma Total hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy, total omentectomy Laparoscopic resection, adjuvant ChT Abdominal pain
Bushan et al. 23 1 68 F Left breast Lobular Ca Wide excision of breast lesion, ChT, RT, hormone therapy Distal gastrectomy with D2 lymphadenectomy, left axillary excision, ChT Weight loss, dysphagia
Zhang et al. 24 2 45 F Breast Lobular Aca Lumpectomy, RT, ChT N/S N/S
64 F Breast Lobular Aca N/A N/A Weight loss
Jin et al. 25 1 55 F Breast Lobular Ca Neoadjuvant ChT, radical mastectomy, ChT, RT ChT N/S
Buka et al. 26 1 58 F Breast Invasive lobular Ca ChT, hormone therapy, RT Neoadjuvant ChRT, total gastrectomy, adjuvant ChT Abdominal pain, weight loss
Dória et al. 27 1 66 F Breast Invasive lobular Ca Letrozole Total gastrectomy, lymphadenectomy, esophagojejunostomy with a Roux loop technique Epigastric pain, vomiting, weight loss
Hwangbo et al. 28 1 73 F Ovary Serous Aca Cytoreductive surgery, adjuvant ChT Distal gastrectomy with Billroth I anastomosis, lymphadenectomy Epigastric pain, dyspepsia
Shetty et al. 29 2 56 F Breast Invasive ductal Ca Breast conservation therapy, adjuvant ChT ChT Epigastric discomfort, non-bilious vomiting
61 F Breast Invasive ductal Ca Left breast modified radical mastectomy, adjuvant RT Palliative ChT Abdominal pain, melena, abdominal distension
Geredeli et al. 30 1 47 F Breast Invasive lobular Ca Palliative ChT Subtotal stomach resection, ChT Asymptomatic
Kim et al. 31 1 58 F Ovary Serous Aca Total hysterectomy with salpingo-oophorectomy, lymphadenectomy with total omentectomy, adjuvant ChT Subtotal gastrectomy, lymphadenectomy, ChT Asymptomatic
Fernandes et al. 32 1 51 F Breast Invasive lobular Ca Quadrantectomy, adjuvant ChT, adjuvant RT, hormone therapy Total gastrectomy, adjuvant ChT, hormone therapy Dyspepsia
Moldovan et al. 33 1 49 F Cervix uteri SCC Surgery, ChRT Subtotal gastrectomy, lymphadenectomy D2, anastomotic layout shaped as Y Roux, omentectomy, adjuvant ChRT Pyloric stenosis, epigastric pains, late postprandial emesis, weight loss
Zhou and Miao 34 1 61 F Ovary Serous Aca Optimal debulking cytoreductive surgery, adjuvant ChT Gastric antrectomy Asymptomatic
Critchley et al. 35 1 62 F Breast Invasive lobular Ca Mastectomy, level 2 axillary clearance, adjuvant ChT, adjuvant RT, adjuvant hormone therapy ChT Loose stool, normocytic anemia, weight loss
Hara et al. 36 1 74 F Breast Invasive ductal Ca Breast-conserving surgery Paclitaxel Chronic gastritis
Ciulla et al. 37 1 70 F Breast Lobular Ca Postoperative hormone therapy Total gastrectomy, lymphadenectomy R1, esophagojejunostomy with Roux loose technique Asymptomatic
Jones et al. 38 2 51 F Breast Lobular Ca Wide local excision, axillary dissection, adjuvant RT Total gastrectomy with Roux-en-Y reconstruction, hormone therapy Weight loss, epigastric pain
61 F Breast Lobular Ca Mastectomy, axillary dissection, adjuvant ChT, RT, tamoxifen ChT, RT Progressive dysphagia, weight loss
Yim et al. 39 1 48 F Breast SRCC ChT ChT Epigastric discomfort
Wong et al. 40 1 72 F Breast Invasive lobular Ca Wide local excision, adjuvant RT Hormone therapy Acute abdomen, rebound tenderness, generalized peritonitis
Ricciuti et al. 41 1 65 M Breast Invasive ductal Ca Total mastectomy, complete axillary dissection, adjuvant hormone therapy Gastrectomy with Roux-en-Y esophagojejunostomy anastomosis Hematemesis, epigastric pain
Fernandes et al. 42 4 56 (the mean age) F Breast Invasive lobular Ca ChT, hormone therapy Total gastrectomy Ulcerated lesion, major bleeding
56 (the mean age) F Breast Invasive lobular Ca ChT, RT, hormone therapy ChRT Diffuse infiltration
56 (the mean age) F Breast Invasive ductal Ca ChT, hormone therapy ChT Infiltrative, ulcerated, stenotic lesion
56 (the mean age) F Breast Invasive ductal Ca ChT, hormone therapy ChRT Flat erosive lesion
Zullo et al. 43 3 49 F Ovary Serous Aca Hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, adjuvant ChT ChT Abdominal pain, vomiting, weight loss
80 F Cervix uteri Leiomyosarcoma Total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, adjuvant ChT N/A Epigastric pain
70 F Breast N/A Radical left mastectomy, adjuvant ChT ChT Dysphagia, epigastric pain
Villa Guzman et al. 44 1 58 F Breast Invasive lobular Ca Quadrantectomy, lymphadenectomy, adjuvant ChT, RT ChT, hormone therapy Nausea, epigastric pain
Mizuguchi et al. 45 1 71 F Ovary Serous Aca Total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, ChT ChT, hormone therapy Asymptomatic
Jmour et al. 46 4 51 F Breast Mixed Radical mastectomy with lymphadenectomy ChT, RT Nausea, vomiting, abdominal pain
47 F Breast Lobular infiltrating Ca Radical mastectomy with lymphadenectomy ChT, RT Nausea, vomiting, abdominal pain
51 F Breast Ductal infiltrating Ca N/A ChT, RT Nausea, vomiting, abdominal pain
36 F Breast Lobular infiltrating Ca Radical mastectomy with lymphadenectomy ChT, RT Nausea, vomiting, abdominal pain
Yim 47 1 65 F Breast Invasive lobular Ca Modified radical mastectomy, adjuvant ChT, adjuvant RT ChT Dyspepsia, anorexia, indigestion, epigastric discomfort, early satiety, weight loss
Choi et al. 48 1 44 F Breast Phyllodes tumor Right lumpectomy, axillary lymphadenectomy, RT, right total mastectomy Endoscopic hemostasis with cauterization Dizziness, anemia, melena
Khan et al. 49 1 56 F Breast Signet ring Aca ChT ChT Anemia
Mullally et al. 50 1 46 F Breast Invasive ductal Ca Left mastectomy, adjuvant ChT, hormone therapy, RT Palliative laparoscopic gastroduodenostomy, hormone therapy, palliative ChT Epigastric and left shoulder pain, epigastric tenderness, upper abdominal rigidity
Kliiger and Gorbaty 51 1 60 F Breast Invasive ductal Aca Systemic therapy, ChT N/A Nausea, diarrhea, vomiting, weight loss
Antonini et al. 52 1 61 F Ovary Serous Ca ChT, cytoreductive surgery ChT Dyspepsia
Kono et al. 53 1 64 F Ovary Mucinous Ca Bilateral salpingo-oophorectomy, simple hysterectomy, pelvic and para-aortic lymphadenectomy, partial omental resection ChT Back pain
Kim et al. 54 1 39 F Breast Invasive lobular Ca Right breast-conserving surgery, lymphadenectomy Duodenal stent, systemic ChT Upper abdominal discomfort and pain, indigestion
Woo et al. 55 1 51 F Breast Invasive lobular Ca Bilateral modified radical mastectomy, ChT, RT Radical subtotal gastrectomy with Billroth II anastomosis, D2 lymphadenectomy, ChT Epigastric pain
Ulmer et al. 56 1 55 F Breast Invasive lobular Ca Bilateral mastectomy, adjuvant ChT, RT, hormone therapy Palliative pyloric stent Nausea, vomiting, early satiety, weight loss

Aca: adenocarcinoma; Ca: carcinoma; SCC: squamous cell carcinoma; GM: gastric metastasis; RT: radiotherapy; ChT: chemotherapy; SRCC: signet ring cell adenocarcinomas; ER: estrogen receptor; HER: human epidermal growth factor receptor; PGR: progesterone receptor; Syn: synchronous; Met: metachronous; EGD: esophagogastroduodenoscopy; FNA: fine-needle aspiration.

 Gastrointestinal cancer

Median age of the 16 patients (11 male, five female) was 69 years, ranging from 22 years to 85 years. Overall survival of the seven patients whose data were given ranged from two months to 16 months. Although, there were six cases who were still alive and the survival of three cases was not reported. Among histological types of gastrointestinal cancers, adenocarcinoma (Adeno Ca) was the most common cancer type (seven patients), followed by hepatocellular cancer (HCC) (four patients) and squamous cell carcinoma (two patients). Endoscopy is the most frequently used method in the diagnosis of metastases. Methods such as computer tomography (CT), positron emission tomography and computed tomography (PET-CT), and endoscopic ultrasound were also used for diagnosis. One patient underwent laparotomy and biopsy. According to this research nine of these patients had surgery. Transcatheter left gastric artery embolization was performed in one patient. On the other hand, seven patients received chemotherapy and one patient had palliative radiotherapy. Nevertheless, one patient is unknown. Findings regarding gastrointestinal cancers are summarized in Table 2. 57 – 72

Illustrating data regarding metastasis from gastrointestinal cancers.
First author No of cases Age Sex Site of primary tumor Histology type of primary Treatment of primary Treatment of metastasis Clinical presentation of GM
Iwai et al. 57 1 76 F Transverse colon Poorly differentiated Aca with a partial component of signet-ring Ca ChT ChT Anemia, anorexia
Yang et al. 58 1 74 F Head of pancreas Poorly differentiated invasive Aca ChT ChT RUQ pain
Lee and Lee 59 1 82 M Right colon Moderately differentiated Aca Extended right hemicolectomy (declined adjuvant ChT) Radical total gastrectomy (declined adjuvant ChT) with Roux-en-Y and D2 dissection Asymptomatic
Rothermel et al. 60 1 61 M Body of pancreas Well-differentiated ductal Aca Distal pancreatectomy, splenectomy, adjuvant ChT ChT, palliative radiation, and wedge gastrectomy Asymptomatic
Terashima et al. 61 1 61 F Transverse colon Poorly differentiated Aca Extended right hemicolectomy, ChT Partial gastrectomy and D3 dissection, ChT Diarrhea, vomiting
Sasajima et al. 62 1 72 M Head and tail of pancreas IPMN ChT ChT (terminated after 2 courses) N/A
Tomonari et al. 63 1 78 M Body and distal pancreas Moderately differentiated ACa T3N0M0 Surgery, adjuvant ChT Subtotal gastrectomy Follow-up
Adachi 64 1 67 F Pancreas Well-differentiated SCC Distal pancreatectomy and splenectomy Total gastrectomy Anorexia, back pain
Nakazawa et al. 65 1 59 M Esophagus Mucosal SCC Subtotal esophagectomy, left lateral segmentectomy of liver, pancreatosplenectomy, adjuvant ChT Proximal gastrectomy Asymptomatic
Abouzied et al. 66 1 69 M Liver HCC Right hepatectomy ChT Iron-deficiency anemia
Ito et al. 67 1 78 M Liver ICC Lateral hepatectomy Proximal gastrectomy and lymphadenectomy Fatigue
Imai et al. 68 1 62 M Liver HCC N/A Transcatheter left gastric artery embolization Abdominal mass
Kim et al. 69 1 75 M Liver HCC Right hemihepatectomy, TACE Gastric wedge resection Melena, mild dyspnea
Peng et al. 70 1 22 M Liver HCC Right hemihepatectomy combined with left lateral tumor local resection, cholecystectomy, splenectomy Gastric tumor local resection Anemia, FOBT 4+
Kanthan et al. 71 1 85 M Colon Aca N/A N/A Anemia
Wang et al. 72 1 63 F Gallbladder Melanoma Surgery, ChT ChT Postprandial nausea, vomiting

Aca: adenocarcinoma; IPMN: intraductal papillary mucinous neoplasm; HCC: hepatocellular carcinoma; ChT: chemotherapy; RUQ pain: right upper quadrant pain; Syn: synchronous; EUS: endoscopic ultrasound; EUS-FNA: endoscopic ultrasound fine-needle aspiration; Ca: carcinoma; SCC: squamous cell carcinoma; ICC: intrahepatic cholangiocarcinoma; TACE: trans arterial chemoembolization; FOBT: fecal occult blood test; Met: metachronous; EGD: esophagogastroduodenoscopy; FDG: fluorodeoxyglucose; PET: positron emission tomography.

 Lung cancer

The median age of the 33 patients (25 male, eight female) was 62, ranging from 39 years to 78 years. Twenty- seven of the total cases had other metastases in addition to gastric ones. The survival time of the 22 patients whose data were given ranged from two weeks to 30 months. Yet, there were two cases that were still alive four and five years after metastases were found, respectively. Among histological types of primary lung cancers that lead to gastric metastases, adenocarcinoma was the most typical diagnosis (13 patients), followed by small cell lung cancer (SCLC) and squamous cell carcinoma (SCC). Regarding the treatment of GM, different combinations of chemotherapy were the most common choice (15 patients). On the other hand, seven of the total cases received surgical treatment (one esophagogastrostomy, two total, and four partial gastrectomies). However, since one patient’s metastasis was diagnosed after an autopsy, he could not receive any gastric treatment. Moreover, one patient refused any metastasis treatment, while six other cases’ treatments are unknown. Data pertaining to GM originating from primary lung cancers are summarized in Table 3. 73 – 102

Illustrating data regarding metastasis from lung cancers.
First author No of cases Age Sex Site of primary tumor Histology type of primary Treatment of primary Treatment of metastasis Clinical presentation of GM
Catalano et al. 73 1 78 M Lung - right upper lobe Poorly differentiated Aca Upper right lobectomy Total gastrectomy Asymptomatic
Shih-Chun et al. 74 1 55 M Lung - right upper lobe NSCLC Concurrent chemoradiotherapy Palliative total gastrectomy, ChT Gastric bleeding, ulcerative mass
Das Majumdar et al. 75 1 72 M Lung Poorly differentiated Aca Palliative RT Immunotherapy, ChT Identified with body CT after pathological fracture
Liu et al. 76 1 58 M Lung Aca Middle right lobectomy, neoadjuvant therapy, ChT ChT, partial gastrectomy N/S
Nemoto et al. 77 1 64 M Lung - right lower lobe SCC Adjuvant ChT Esophagogastrostomy Epigastric pain, progressive dysphagia
He et al. 78 1 61 M Lung SCLC Left lower lobectomy Cardia resection Progressive dysphagia
Yang et al. 79 1 59 M Lung - left upper lobe Poorly differentiated metastatic carcinoma ChT Anti-PD1 immunotherapy Right upper limb pain, epigastric discomfort
Li et al. 80 1 61 M Lung - right lower lobe SCC ChT ChT, gastrectomy Progressive abdominal distention
Bhardwaj et al. 81 1 39 F Lung SCC ChT, nivolumab RT Dizziness, melena
Badipatla et al. 82 1 65 M Lung Aca ChT, palliative care ChT, palliative care Bilateral flank pain, nausea, vomiting, change in bowel habit
Qasrawi et al. 83 1 69 F Lung - left upper lobe Aca RT Hospice care Melena, hypotension
Kim et al. 84 1 70 F Lung Pleomorphic carcinoma Right bronchial artery embolization, right upper lobectomy, adjuvant ChT Partial gastrectomy, immunotherapy Abdominal pain
Maeda et al. 85 1 60 F Lung SCLC ChT N/A Nausea, vomiting
Struyf et al. 86 1 68 M Lung Aca ChT ChT Severe epigastric pain
Altintas et al. 87 1 55 M Lung Aca ChT ChT Epigastric pain, hematemesis, melena
Casella et al. 88 1 63 M Lung SCLC Supportive care Supportive care Fever, weight loss, epigastric pain, constipation
Ohashi et al. 89 1 62 M Lung Large cell carcinoma Right upper lobectomy ChT Abdominal pain
Aokage et al. 90 2 69 M Lung - right upper lobe Pleomorphic carcinoma Right upper lobectomy, parietal pleura resection Partial gastrectomy, splenectomy Fatigue, anemia
62 M Lung - left upper lobe Pleomorphic carcinoma Left upper lobectomy Distal gastrectomy, splenectomy N/A
Katsenos and Archondakis 91 1 61 M Lung - left upper lobe Aca ChT ChT Upper GIS bleeding
Diem et al. 92 1 62 F Lung - right upper lobe Aca N/A ChT Epigastric pain
Hu et al. 93 1 54 M Lung SCC RT, right middle lobectomy None (patient refused) Dysphagia
Koh et al. 94 1 46 M Lung Pleomorphic carcinoma Antibiotics N/A Abdominal pain, tenderness
Hung et al. 95 1 47 M Lung SCC RT, ChT ChT Weight loss, dysphagia
Taira et al. 96 1 64 M Lung Pleomorphic carcinoma, Aca Left upper lobectomy ChT Anemia
Gao et al. 97 1 66 M Lung SCLC ChT ChT, supportive care Epigastric pain
Kim et al. 98 1 68 M Lung Poorly differentiated Aca Left lower lobectomy, posterior segmentectomy right upper lobe (2004), left upper lobe wedge resection (2007), palliative chemotherapy Palliative ChT Epigastric pain, dyspepsia
Chen et al. 99 1 59 F Lung Sarcomatoid carcinoma Supportive treatment Supportive treatment Abdominal pain, anorexia, weight loss
Dong et al. 100 1 60 F Lung Glomus tumor N/A N/A Hemoptysis, melena, abdominal distension
Kim et al. 101 2 66 M Lung SCLC N/A N/A Epigastric pain, epigastric tenderness, fatigue
68 M Lung SCLC N/A N/A Hemoptysis, weight loss
Del Rosario et al. 102 1 77 F Lung Aca ChT Palliative care N/A
Kanthan et al. 71 1 75 M Lung Aca N/A N/A Epigastric pain, RUQ pain

Aca: adenocarcinoma; SCC: squamous cell carcinoma; RT: radiotherapy; GIS: gastrointestinal; EGD: esophagogastroduodenoscopy; EUS: endoscopic ultrasound; GDS: gastroduodenoscopy; NSCLC: non-small-cell lung cancer; SCLC: small-cell lung cancer; ChT: chemotherapy; RUQ: right upper quadrant; ChT: chemotherapy; USG: ultrasonography; Syn: synchronous; Met: metachronous.

 Malign melanoma

The median age of the 19 patients (seven female, 12 male) was 67, ranging from 28 years to 89 years. In 16 patients, other organ metastases were also discovered in addition to malign melanoma. Overall survival was not mentioned in 10 cases. Two of these cases deceased two and four days after hospital admission respectively, and one patient died after a year. Moreover, one of these patients was alive at five years, and another was alive at six months. Overall survival of three cases is three, 27, and four months, respectively. One of these patients refused treatment, and one of them did not receive treatment. However, immunotherapy was applied to six patients, surgery to five patients, radiotherapy to two patients, and only supportive treatment to three patients. In addition, the treatment of GM was not mentioned in three cases. Table 4 summarizes the findings of included studies regarding malign melanoma. 103 – 121

Illustrating data regarding metastasis from malignant melanoma.
First author No of cases Age Sex Site of primary tumor Histology type of primary Treatment of primary Treatment of metastasis Clinical presentation of GM
Zhu et al. 103 1 36 M Right plantar Nodular Mohs microsurgery N/A Anorexia, nausea, vomiting
Yoshimoto et al. 104 1 82 F Fourth left toe Acral lentiginous Surgery Palliative RT Melena
Okamoto et al. 105 1 79 M Esophagus Pigmented submucosal tumor-like growth in the esophagus Nivolumab Nivolumab Gross hematuria, weight loss, cough, exertional dyspnea
Cortellini et al. 106 1 81 M N/A N/A N/A N/A Weakness, hyporexia, anemia
Groudan et al. 107 1 66 F Vulva N/A N/A Palliative RT, immunotherapy Fatigue, exertional dyspnea, hematemesis, weight loss, nausea
Syed et al. 108 1 49 F Back N/A Surgery Immunotherapy, supportive care, SRS Anorexia, abdominal pain, fatigue, weight loss, nausea, vomiting
Genova et al. 109 1 80 M Scalp Lentigo RT Immunotherapy Hypochromic anemia
Wong et al. 110 1 81 F Foot Acral lentiginous Amputation, CT Denied the treatment Dyspnea, fatigue, anemia
Grander et al. 111 1 67 M Right hypochondrium, back, scalp Superficial spreading Surgery Total gastrectomy, radiosurgery Melena
Carcelain et al. 112 1 65 F N/A N/A Surgery Surgery N/S
Lestre et al. 113 1 67 M Lower back Superficial spreading Excision, adjuvant immunotherapy No N/S
Rana et al. 114 1 72 M N/A N/A N/A N/A Weight loss, anorexia
Rovere et al. 115 1 68 M N/A N/A N/A Supportive care N/S
Eivazi-Ziaei et al. 116 1 56 M Right heel-ALM N/A Surgery Supportive care Epigastric pain
El-Sourani et al. 117 1 43 F Right breast N/A Surgery Sleeve gastrectomy after atypical resection, complete locoregional lymphadenectomy Melena, anemia
Buissin et al. 118 1 63 M Anorectal Hyperplastic polyp Abdominoperineal resection Supportive care Tenderness in the RUQ
Bankar et al. 119 1 41 F N/A N/A N/A Surgery N/S
Mohan et al. 120 1 28 M N/A N/A N/A Temozolomide Abdominal pain, anorexia, weight loss
Farshad et al. 121 1 89 M Chest wall N/A Local excision Nivolumab Fatigue, rigors, fever

ALM: acral lentiginous melanoma; ChT: chemotherapy; RUQ: right upper quadrant; EGD: esophagogastroduodenoscopy; NBI: narrow band imaging; RT: radiotherapy; SRS: stereotactic radiosurgery; IHC: immunohistochemistry; CT: computed tomography; EMG: electromyography; Syn: synchronous; Met: metachronous; FDG: fluorodeoxyglucose; PET: positron emission tomography.

 Urogenital cancers

The median age of 20 patients (11 male and nine female) with kidney cancer was 68.5 years old. A total of 11 patients had metastases other than GM. Overall survival was mentioned only in four cases and ranged from two months to one year. One of the 20 patients did not receive any therapy for GM, whereas 13 patients underwent surgical treatment (four endoscopic mucosal resections, nine gastrectomies), four patients had chemotherapy and one patient was treated with radiotherapy. Regarding prostate cancer, the median age of the affected individuals was 67 years old. Concerning the GM treatment four patients received chemotherapy, one patient underwent mucosal resection, and one patient refused treatment. Overall survival was mentioned for three patients ranging from four months to 19 months. All four patients with testis cancer had other metastases and two of them received chemotherapy. One study included bladder cancer without other metastases and the patient was referred to palliative care. Data pertaining to gastric metastases originating from primary urogenital cancers are summarized in Table 5. 71 , 122 – 151

Illustrating data regarding metastasis from urogenital cancers.
First author No of cases Age Sex Site of primary tumor Histology type of primary Treatment of primary Treatment of metastasis Clinical presentation of GM
Tapasak and Mcguirt 122 1 77 M Kidney RCC Nephrectomy, ChT Roux-en-Y gastric bypass Gastrointestinal bleeding, anemia
Podzolkov et al. 123 1 30 M Testis Choriocarcinoma ChT N/A Epigastric pain, dyspnea
Koterazawa et al. 124 1 70 F Kidney RCC Nephrectomy Endoscopic submucosal resection Weight loss
Hakim et al. 125 1 86 F Kidney RCC Nephrectomy, ChT RT Gastrointestinal bleeding
Yoshida et al. 126 1 85 F Kidney RCC Nephrectomy Endoscopic resection Anemia, melena
Bernshteyn et al. 127 1 68 M Kidney RCC Nephrectomy N/A Dyspnea, melena
Weissman et al. 128 2 70 M Kidney RCC Nephrectomy ChT Dyspepsia, malaise, weight loss
85 M Kidney RCC Nephrectomy ChT Dyspepsia, malaise, weight loss
Chaar et al. 129 1 30 M Testis Choriocarcinoma Orchiectomy ChT (patient refused) Melena, anemia
Arakawa et al. 130 1 80 F Kidney RCC Cht ChT Anorexia, pyrexia, malaise
Uehara et al. 131 1 73 M Kidney RCC Nephrectomy, ChT Endoscopic mucosal resection, immunotherapy Gastric mass
O'Reilly et al. 132 1 59 F Kidney Clear cell RCC Nephrectomy Laparoscopic sleeve gastrectomy Asymptomatic
Abu Ghanimeh et al. 133 1 67 M Kidney Clear cell RCC Nephrectomy No treatment initiated Gastrointestinal bleeding
Mazumdar et al. 134 1 49 M Testis Seminoma N/A N/A Abdominal pain
Barras et al. 135 1 53 M Kidney RCC Nephrectomy Partial gastrectomy Hematochezia
Riviello et al. 136 1 68 M Kidney RCC Nephrectomy Gastrectomy, ChT Melena, postural dizziness, weakness
Hong et al. 137 1 60 M Bladder Clear cell urothelial Ca ChT, RT Palliative care Projectile vomiting
Onitilo et al. 138 2 57 M Prostate Aca LHRH agonist ChT Weakness, nausea, vomiting, hematemesis
89 M Prostate Aca LHRH agonist ChT Weakness, nausea, vomiting, hematemesis
Tiwari et al. 139 1 58 F Kidney Clear cell RCC N/A Roux-en-Y subtotal gastrectomy Melena, hematemesis, fatigue
Yodonawa et al. 140 1 73 M Kidney Leiomyosarcoma Nephrectomy Distal gastrectomy Melena, weakness
Chibbar et al. 141 1 69 F Kidney Clear cell RCC Nephrectomy Endoscopic mucosal resection Fatigue, lightheadedness, anemia
Sakurai et al. 142 1 61 M Kidney RCC Nephrectomy Partial gastrectomy, ChT Melena, anemia
Patel et al. 143 1 71 M Prostate Aca Surgery, RT N/A Weakness, dizziness, anemia
Sharifi et al. 144 1 17 F Kidney Primitive neuroectodermal ChT ChT Abdominal pain, distention
Greenwald et al. 145 1 62 M Kidney Clear cell RCC Nephrectomy Partial gastrectomy Testicular pain
Costa et al. 146 1 66 F Kidney RCC Nephrectomy Palliative laparoscopic wedge resection Anemia
Soe et al. 147 1 64 M Prostate N/A LHRH agonist Palliative care (patient refused chemotherapy) Anemia, melena
Bhandari and Pant 148 1 58 M Prostate Aca LHRH agonist ChT Abdominal pain
Lowe et al. 149 1 18 M Testis Choriocarcinoma ChT, orchidectomy ChT Melena, lethargy, dizziness
Inagaki et al. 150 1 75 M Prostate Aca LHRH agonist Endoscopic mucosal resection, hormone therapy Epigastric pain
Tavukcu et al. 151 1 67 M Prostate Mixed 55% ductal 45% acinar Prostatectomy, RT Androgen deprivation therapy, ChT Ascites, vomit
Kanthan et al. 71 1 19 M Testis Predominantly choriocarcinoma, embryonal Ca Orchiectomy Partial gastrectomy聽 Melena, anemia

Ca: carcinoma; ChT: chemotherapy; EUS: endoscopic ultrasound; Aca: adenocarcinoma; RT: radiotherapy; EGD: esophagogastroduodenoscopy; RCC: renal cell carcinoma; LHRH: luteinizing hormone releasing hormone; Syn: synchronous; Met: metachronous.

 Others

The median age of the four patients with Merkel cell carcinoma was 73 years old. Two patients had other metastases in addition to GM. Three patients underwent surgery, chemotherapy, and radiotherapy, whereas one patient was treated with chemotherapy and radiotherapy. One patient with squamous cell carcinoma had other metastases in addition to GM and received chemotherapy and radiotherapy for the primary tumor.

Regarding bone cancers (n=3) one of the patients was 14 years old and stood out as the youngest patient in this group. Concerning the GM therapy, one of the patients with a known treatment underwent surgery and chemotherapy the other received only surgery. In all patients, GM was discovered metachronous. Three studies were included for soft tissue cancer. All three patients had metastases in addition to GM and underwent different types of GM treatment (including radiotherapy, chemotherapy, excision with snare, and cautery). For the thyroid cancer group, the median age was 71 years old. Overall survival (OS) was only mentioned for one patient (2.5 months). Regarding diffuse large B-cell lymphoma (DLBCL) (n=2), patients received chemotherapy for primary cancer and for GM. GM was discovered synchronously. Kovecsi et al., described the only case of GM from adrenocortical carcinoma of the adrenal gland. 152 The patient underwent adrenalectomy for primary and total gastrectomy with splenectomy and end-to-side Roux-en-Y esophagojejunal anastomosis for GM. One patient with choriocarcinoma from retroperitoneum underwent chemotherapy for primary cancer and GM. Table 6 summarizes the findings of included studies regarding gastrointestinal cancers. 151 – 171

Illustrating data regarding metastasis from other cancers.
First author No of cases Age Sex Site of primary tumor Histology type of primary Treatment of primary Treatment of Metastasis Clinical presentation of GM
Kovecsi et al. 152 1 71 M Adrenal gland Adrenocortical carcinoma Right adrenalectomy Total gastrectomy, splenectomy, with end-to-side Roux-en-Y eso-jejunal anastomosis Weight loss, epigastric pain, vomiting, fatigue
Koti et al. 153 1 14 F Bone Ewing sarcoma ChT, local excision ChT, total gastrectomy, RT Abdominal mass, low-grade fever, weight loss
Dodis et al. 154 1 72 F Bone Ewing sarcoma Total knee replacements, RT, ChT N/A Anemia
Urakawa et al. 155 1 73 M Bone Osteosarcoma ChT, surgery Partial gastrectomy Anemia, hematemesis
Shibuya et al. 156 1 27 M Extragonadal retroperitoneal Choriocarcinoma Cht ChT Abdominal pain, melena, vomiting
Tarangelo et al. 157 1 65 M Head, neck SCC Cht, RT, robotic excision N/A Melenic bowel movements
Kamihara et al. 158 1 70 M Lymph nodes DLBC R-CHOP ChT R-CHOP ChT N/A
Zepeda-Gomez et al. 159 1 39 F Lymph nodes DLBC ChT, omeprazole ChT Melena, weight loss, retroperitoneal mass
Teh et al. 160 1 37 F Oropharynx SCC Surgery, adjuvant RT Palliative RT Weight loss, LUQ pain, melena
Elkafrawy et al. 161 1 67 M Skin MCC Surgery, consolidative Atezolizumab, RT Melena
Ha et al. 162 1 82 M Skin MCC Surgery, RT No Anorexia, weight loss
Idowu et al. 163 1 79 F Skin MCC Surgery, ChT, RT N/A Anemia
Parikh et al. 164 1 60 M Skin MCC ChT, RT ChT Maroon colored stools
Subramanian et al. 165 1 62 M Soft tissue Leiomyosarcoma Surgery, RT RT, ChT Melena, abdominal pain, nausea, vomiting
Dent et al. 166 1 60 M Soft tissue Sarcoma Surgery Remove with snare and cautery Upper abdominal pain, melena
Samuel et al. 167 1 56 M Soft tissue Synovial sarcoma Surgery, RT Doxorubicin N/A
Thorburn et al. 168 1 56 M Supraglottic larynx, hypopharynx Advanced SCC Surgery, tracheostomy, radical RT N/A Anemia, hematemesis
Fuladi et al. 169 1 71 F Thyroid Anaplastic carcinoma Total thyroidectomy, left modified radical neck dissection, RT N/A Nausea, vomiting
Ayaz et al. 170 1 72 M Thyroid Anaplastic carcinoma N/A N/A Melena
Karrasch et al. 171 1 53 F Thyroid Medullary thyroid cancer Complete thyroidectomy ChT N/A Fatigue, anorexia, epigastric pain radiating to the back

SCC: squamous cell carcinoma; MCC: merkel cell carcinoma; RT: radiotherapy; EGD: esophagogastroduodenoscopy; DLBC: diffuse large B cell; ChT: chemotherapy; LUQ: left upper quadrant; Met: metachronous; EGD: esophagogastroduodenoscopy; FDG: fluorodeoxyglucose; PET: positron emission tomography; Syn: synchronous.

 Discussion

Gastric metastases are uncommon and give information about the progressed stage of malignant disease, with a reported incidence of 0.2-0.7% based on clinical and autopsy findings. 1 Furthermore, metastasis to the stomach frequently indicates short survival. These metastases are observed rarely due to clinical problems regarding their diagnosis and treatment. 2 Progressively, with improvements in prognosis for cancer patients, metastatic tumors in the stomach are being detected more frequently. 1 There are several symptoms of gastric metastases, such as abdominal pain, diarrhea, nausea, vomiting, weight loss, and dyspepsia. The most preferred treatment method for gastric metastasis is surgical resection of the tumor. Also, chemotherapy is the most applied alternative option.

This systematic review has a few potential limitations that need to be mentioned. As 172 case reports were screened in the systematic review from different journals the heterogeneity was inevitable. Some articles missed important information such as complete follow-up or clinical information. Moreover, since all of the included articles were case reports, quality or bias assessment could not be performed.

Gynecologic cancer

Gastric metastasis mainly occurs due to breast cancer. Both ovarian and uterine metastases are distinctly less frequent. 38 Invasive lobular carcinoma is the type with the highest affinity to the digestive system with an incidence of 4.5% compared to 0.2% in ductal carcinoma. 26 Breast cancer metastases to the gastrointestinal tract are rare, with a median time interval from the diagnosis of the primary tumor to metastasis up to seven years. 21 The longest disease-free interval is 22 years after the initial diagnosis 17 of 24. 10 Some metastatic tumors may have a similar presentation as primary gastric cancer. 38 The detailed immunohistochemical analysis will allow the most accurate diagnosis to differentiate between primary gastric cancer and gastric metastasis from breast cancer. 26 Most gastric metastatic breast cancers are estrogen receptor (ER)-positive, progesterone receptor (PR)-positive/negative, and human epidermal growth factor receptor (HER2)-negative. However, in primary gastric adenocarcinoma, ER and PR can be positively expressed in 20-28% of patients. 19 In a few cases, metastatic breast cancer is negative for ER and PR, so a diagnosis cannot be made based on these two investigations alone. 59 ER and PR can be used as markers; however, they are not always suitable diagnostic markers to confirm if a tumor has originated. 11 Treatment of gastrointestinal metastases from breast cancer is discussed frequently in the literature. Systemic therapy is the first option. 36 The effective rate of systemic treatment is about 46%. 60 Surgical treatment may have a role in palliative treatment. 34 Surgical treatment is considered in cases with obstruction or bleeding. 36 Metastasis to the gastrointestinal tract can be the first presentation of breast cancer, therefore it is imperative to consider the possibility of breast cancer metastasis to the gastrointestinal metastasis. 26 , 46

Gastrointestinal cancer

Among cancers that metastasize to the stomach, gastrointestinal system cancers are encountered in a minority. Gastric metastases gave unspecific findings, such as anemia, bleeding, and pain. Pancreas, liver, and colon account for the majority of primary cancers. Nine of the cases had other metastases in addition to gastric ones. Since pancreatic cancers are usually caught at an advanced stage, the chances of surgical treatment and their response to treatment are low. We see that three of five patients died within a year. 2 , 6 , 8 Among these cases, the prognosis of pancreatic head cancers was worse than body and tail cancers.

 Lung cancer

In fact, lung cancer is the most mortal type of all cancers. However, the stomach is not a common site for primary lung cancers’ metastases, especially compared with brain, liver, adrenal glands, and bones. 74 Yet, the expected lifespan after diagnosis of metastasis is found to be relatively low. The median survival time was four months (average 6.8 months) among 16 cases who died. On the other hand, data showed that endoscopy is the gold standard in diagnosis. In addition, pathology and immunohistochemistry are considered important factors to differentiate gastric metastases from primary cancers. 81 Regarding the treatment of gastric metastases of the pulmonary origin, although non-invasive chemotherapy treatments were the most common choice, patients who received surgery, particularly partial gastrectomy, but also esophagogastrostomy and laparotomy, tended to have relatively much longer survival time. 77 , 90 , 95 However, this conclusion is not definitive, since in some cases surgeries may be avoided when the patient’s condition is extremely severe and the number of cases with given surgical treatments is scarce. So the potential benefit of surgeries to the expected lifespan of the patients needs further investigation.

 Malign melanoma

Although melanoma accounts for only 5% of cutaneous malignancies, it makes up nearly 75% of skin cancer- related deaths. 103 , 107 Malignant melanoma ranks as the most common metastatic tumor of the gastrointestinal (GI) tract. 103 , 110 , 120 It takes an average of 52 months for a primary cutaneous melanoma to spread to the gastrointestinal tract. 107 , 110 Only 1-4% of patients with malignant melanoma deceased before gastrointestinal metastases are diagnosed. On the other hand, GI tract metastasis was observed in more than 60% of melanoma patients by autopsy. 103 , 110 , 111 , 114 , 121 The most commonly involved sites include the small and large bowels and rectum; however, gastric metastasis is a rare case 110 , 111 , 117 , 119 , 121 due to the non-specificity of its symptoms, such as epigastric discomfort, nausea, vomiting, weight loss, hematemesis, and melena. 103 , 107 , 110 , 111 , 114 , 117 , 121 The average survival is four to six months. 103 , 107 , 121 Endoscopy is an effective method for detecting melanoma metastases due to pigmentation, which can then be confirmed by histology and immunohistochemistry. 114 , 121 Treatment options include surgical resection, immunotherapy, chemotherapy, and targeted therapy. If a patient is symptomatic, surgical excision can be a palliative technique that can also prolong survival. 103 , 121

Urogenital cancer

Regarding urogenital metastases GM is uncommon and the incidence is reported to vary between 0.2% and 0.7%. 123 The most common clinical presentations are gastrointestinal bleeding (melena and hematemesis), anemia, and malaise. Whereas two patients had no symptoms associated with the gastrointestinal system. 131 , 140 Esophagogastroduodenoscopy is often necessary for diagnosis and localized treatment. 131 The presence of gastric metastases is considered an important indicator of advanced disease. 149 Treatment options varied depending on the stage of the metastasis including endoscopic resection, partial or total gastrectomy, chemotherapy, and palliative care. Even though overall survival seems to be longer in patients who underwent surgery, the main reason for this may be that these patients have early-stage diseases suitable for surgery. Therefore, treatment options should be decided upon the stage of the disease and the general well-being of the patient.

 Others

The most common symptoms, in terms of frequency, are melena, abdominal pain, vomiting, weight loss, anemia, fatigue, and loss of appetite. Gastrointestinal endoscopy plays an important role in the diagnosis of GM if suspected. 162 Tumor seeding after endoscopic gastrostomy tube replacement was observed in two cases. 161 , 169 Even though surgery is the frequent treatment for solid organ cancer metastasis, chemotherapy is the chosen treatment for DLBCL, skin cancer, and sarcoma. Overall survival was only mentioned for four cases; therefore, it is difficult to comment on which treatment method is more beneficial. Metastasis to the stomach is not reported frequently. Thus, determining the prognosis and planning the treatment based on scientific evidence seems to be problematic for clinicians.

In conclusion, among 172 case reports reviewed, resection surgery was performed the most for treatment and was sometimes combined with chemotherapy and immunotherapy. However, the literature regarding the management of patients with secondary gastric cancer is limited. Therefore, further multi-centric research to reach a consensus about what type of treatment has the best outcomes for patients with gastric metastases is needed.

 Data availability Underlying data

All data underlying the results are available as part of the article and no additional source data are required.

 Extended data

OSF: Tables for ‘Metastasis to the stomach: a systematic review’. https://doi.org/10.17605/OSF.IO/Y4QD5. 172

Reporting guidelines

OSF: PRISMA checklist for ‘Metastasis to the stomach: a systematic review’. https://doi.org/10.17605/OSF.IO/Y4QD5. 172

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).

 Acknowledgements

The abstract of this paper was presented in 41 st congress of the European Society of Surgical Oncology and was published by the journal of the same society (EJSO) on February 2023 ( https://doi.org/10.1016/j.ejso.2022.11.492).

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J Med Case Rep. 2016;10:208–210. 27461534 10.1186/s13256-016-0981-9 PMC4962496 Ibrahimli A : Metastasis to the Stomach: A Systematic Review.[Dataset]. OSF. 2023. 10.17605/OSF.IO/Y4QD5 10.5256/f1000research.154145.r261964 Reviewer response for version 1 Grizzi Fabio 1 2 Referee https://orcid.org/0000-0003-0925-742X Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Rozzano, Italy

Competing interests: No competing interests were disclosed.

 2 5 2024 Copyright: © 2024 Grizzi F 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve

I found Ibrahimii et al.'s manuscript on systematically reviewing stomach metastasis quite compelling. Their study stands out for its clarity and significance within its research domain. While I have some minor suggestions for the authors, such as delving deeper into the heterogeneity noted across the included studies and exploring its implications for managing gastric metastasis, I also recommend addressing the variations in terminology among studies, particularly in distinguishing between the term “studies” and “case reports”. This attention to detail will enhance the coherence and applicability of their findings, advancing our understanding of the underlying biology of this neoplastic process.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes

Is the statistical analysis and its interpretation appropriate?

Yes

If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Yes

Are sufficient details of the methods and analysis provided to allow replication by others?

Yes

Are the conclusions drawn adequately supported by the results presented in the review?

Yes

Reviewer Expertise:

My primary area of research lies in investigating cancers originating from unrelated histologies as intricate systems. I am particularly driven by the pursuit of novel prognostic, predictive, and therapeutic biomarkers.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

 10.5256/f1000research.154145.r232517 Reviewer response for version 1 Sarı Murat 1 Referee https://orcid.org/0000-0003-0596-1559 Marmara University, Istanbul, Turkey

Competing interests: No competing interests were disclosed.

 2 1 2024 Copyright: © 2024 Sarı M 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve

The stomach is a rare organ in terms of metastasis sites. It would be valuable to write a review evaluating this issue. The review is clearly the result of extensive research. Figures and tables are adequate and informative. Therefore, acceptance of this article will provide impact and citations to the journal.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes

Is the statistical analysis and its interpretation appropriate?

Yes

Are sufficient details of the methods and analysis provided to allow replication by others?

Yes

Are the conclusions drawn adequately supported by the results presented in the review?

Yes

Reviewer Expertise:

Medical oncology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.