Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.
Humans ; Stomach Neoplasms/pathology* ; Peritoneal Neoplasms/secondary* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Hyperthermia, Induced/methods* ; Peritoneum/pathology* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures/methods* ; Survival Rate

Peritoneal metastasis of gastric cancer serving as the most frequent form of metastasis, is one of the leading causes of death. A portion of surgically treated patients often suffer from small peritoneal residual metastasis, which will lead to recurrence and metastasis of gastric cancer patients after surgery. Given these, the prevention and treatment of peritoneal metastasis of gastric cancer deserves more attention. Molecular residual disease (MRD) refers to the molecular abnormalities of tumor origin that cannot be found by traditional imaging or other laboratory methods after treatment, but can be found by liquid biopsy, representing the possibility of tumor persistence or clinical progress. In recent years, the detection of MRD based on ctDNA has gradually become a research hotspot in the prevention and treatment of peritoneal metastasis. Our team established a new method for MRD molecular diagnosis of gastric cancer, and reviewed the research achievements in this field.
Humans ; Stomach Neoplasms/pathology* ; Peritoneal Neoplasms/secondary* ; Liquid Biopsy ; Neoplasm, Residual/genetics*

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

Brain Diseases ; Humans ; Immune Checkpoint Inhibitors ; Peritoneal Neoplasms/secondary* ; Peritoneum/pathology* ; Stomach Neoplasms/surgery*

Gastric cancer is one of the most common malignancy in China. Most of the patients of gastric cancer treated clinically are in advanced stage. In the past years, with the progress of anti-cancer drug therapy, after the comprehensive treatment based on drugs therapy of inoperative stage IV gastric cancer, some cases can reduce the tumor stage and get the opportunity of radical operation. Some of the patients who underwent surgical treatment can get the chance of long-term survival. The results of REGATTA trial confirmed that palliative surgery plus chemotherapy could not improve the long-term survival of patients with stage IV gastric cancer. Neoadjuvant intraperitoneal plus intravenous chemotherapy can reduce the tumor stage of some cases of stage IV gastric cancer with peritoneal metastasis and receive surgical treatment, so as to gain the chance of long-term survival. Regimen of intraperitoneal hyperthermia chemotherapy combined with PHOENIX trial is expected to improve the conversion operation rate of gastric cancer with peritoneal metastasis. Paclitaxel-based three-drug chemotherapy can reduce the tumor stage of some inoperable advanced gastric cancer and obtain the opportunity of radical operation, improving the disease-free survival rate and overall survival rate of patients, thus has become the cornerstone of conversion therapy for stage IV gastric cancer. Antiangiogenic targeted drug apatinib combined with paclitaxel is safe and reliable, and can be used as an alternative for the conversion therapy of stage IV gastric cancer, which provides a new idea for cytotoxic drugs combined with targeted drugs. In the era of immunotherapy, the combined application and first-line application of immunosuppressive drugs has become a clinical consensus. For advanced Her-2 positive esophagogastric junction adenocarcinoma cases, the successful exploration of the four-drug combination of chemotherapy+ anti-Her-2 targeted drugs+ anti-PD1 monoclonal antibody combined with the first-line therapy has opened up a new era of transformational therapy for stage IV gastric cancer. Gastric cancer is a malignant tumor with high heterogeneity, the classification of stage IV gastric cancer represented by Yoshida classification is based on imaging, and a more reasonable classification method should be developed in combination with gene detection in the future. Based on this, an individualized and accurate conversion therapy plan is formulated, so as to effectively improve the long-term survival of patients with stage IV gastric cancer.
Adenocarcinoma/surgery* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; China ; Combined Modality Therapy ; Esophagogastric Junction ; Gastrectomy ; Humans ; Hyperthermic Intraperitoneal Chemotherapy ; Infusions, Parenteral ; Neoadjuvant Therapy ; Neoplasm Staging ; Peritoneal Neoplasms/secondary* ; Stomach Neoplasms/surgery*

Rapid aging, economic development, lifestyle westernization, hygiene improvement, and scientific development have contributed for the epidemiologic changes of gastric cancer. This study aimed to review the descriptive epidemiology, risk factors, and prevention of gastric cancer in Korea. Age-standardized incidence and mortality of gastric cancer have decreased and showed age effect and cohort effect. Annual percent change in the incidence of gastric cancer has been prominent in recent years. Major risk factor of gastric cancer is Helicobacter pylori infection. Although H. pylori infection was associated with only non-cardia gastric cancer in meta-analysis, H. pylori infection was associated with both non-cardia and cardia gastric cancer in Asian studies. The estimated population attributable fraction of H. pylori regarding gastric cancer incidence was about 76% in Korean. Cigarette smoking and alcohol drinking was associated with gastric cancer regardless of cardia and non-cardia gastric cancer. Cigarette smoking was estimated to be responsible for 28% of gastric cancer incidence in men and 2% in women. Obesity was risk factor for cardia gastric cancer but not non-cardia gastric cancer. This discrepancy between cardia and non-cardia gastric cancer was consistently shown in epidemiologic studies in Korea. Salt intake was also well-known risk factor of gastric cancer and prevalence of high sodium intake more than 2,000mg in Korean was 81.5%. For primary prevention of gastric cancer, eradication of H. pylori and life-style modification including no smoking, no alcohol drinking, weight control, and low sodium intake are important. Gastric endoscopy is recommended for secondary prevention of gastric cancer.
Aging ; Alcohol Drinking ; Asian Continental Ancestry Group ; Cardia ; Cohort Effect ; Economic Development ; Endoscopy ; Epidemiologic Studies ; Epidemiology ; Female ; Helicobacter pylori ; Humans ; Hygiene ; Incidence ; Korea ; Life Style ; Male ; Mortality ; Obesity ; Prevalence ; Primary Prevention ; Risk Factors ; Secondary Prevention ; Smoke ; Smoking ; Sodium ; Stomach Neoplasms

INTRODUCTIONSporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours.

METHODSEight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis.

RESULTSAll the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation.

CONCLUSIONThe results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers.

Colorectal Neoplasms ; genetics ; pathology ; Female ; Humans ; Male ; Microsatellite Instability ; Mutation ; Neoplasm Metastasis ; Peritoneal Neoplasms ; pathology ; secondary ; Proto-Oncogene Proteins B-raf ; genetics ; Stomach Neoplasms ; pathology ; secondary

After World War II, the incidence of gastric cancer decreased rapidly in most of the developed countries; however, it remained high in countries where secondary prevention of gastric cancer is practiced without primary prevention (Helicobacter pylori eradication). In such countries, changes in gastric microbiota contribute to gastric carcinogenesis, and the composition of gastric microbiota is mainly determined by the status of H. pylori infection. In non-infected individuals with no history of H. pylori infection, gastric microbiota includes various bacteria, creating ideal microbial diversity. Because it is difficult for most bacteria to proliferate in an acidic environment in stomach, only few bacteria are present in non-infected individuals. Conversely, microbial dysbiosis with H. pylori predominance is often observed in infected individuals with unimpaired gastric secretory ability, because other bacteria cannot survive at low intragastric pH. Such microbial dysbiosis may rapidly lead to gastric carcinogenesis, resulting in diffuse-type gastric cancer. It is more frequent in young patients with unimpaired gastric secretory ability than in elderly patients with gastric atrophy and metaplasia. Lastly, bacteria producing carcinogenic N-nitrosamine compounds are often detected in individuals with past or chronic H. pylori infection, because of the loss of gastric secretory ability. Such an unideal microbial diversity observed at high intragastric pH may slowly lead to gastric carcinogenesis, in turn resulting in gastric adenoma or intestinal-type gastric cancer. To prevent gastric carcinogenesis, changes in the composition of gastric microbiota should be studied in conjunction with intragastric acidity, which depends on the status of H. pylori infection.
Adenoma ; Aged ; Atrophy ; Bacteria ; Carcinogenesis ; Developed Countries ; Dysbiosis ; Helicobacter pylori ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Metaplasia ; Microbiota ; Primary Prevention ; Secondary Prevention ; Stomach ; Stomach Neoplasms ; World War II

OBJECTIVETo assess the clinical value of the diagnostic laparoscopy in choosing treatment strategies for patients with gastric cancer.

METHODSRetrospective analysis was performed on clinical and pathological data collected from 2 023 patients undergoing gastric cancer surgery in the Zhongshan Hospital of Fudan University from 2009 to 2014. All the patients were diagnosed as gastric cancer by endoscopic biopsy and staged by imaging examination before surgery. During the diagnostic laparoscopy procedure, a small periumbilical incision was made and a pneumoperitoneum with COunder 10-15 mmHg was established through a port. A 10 mm trocar was put in, and the camera was inserted. Two 5 mm trocars were put in two ports which located in midclavicular line two fingers under the left and right costal margin and then the instruments were inserted. A thorough inspection included ascites, the abdominal cavity, liver, diaphragm, spleen, greater omentum, colon, small intestine, mesentery, adnexa (female) and pelvic floor. If the tumor located at the posterior part of the stomach, the gastrocolic ligament was opened in order to look for carcinomatosis in the omental bursa. The accuracy rate of diagnostic laparoscopy in diagnosing adjacent organ invasion and intra-abdominal metastasis was calculated, and the rate of adjusting treatment plans after diagnostic laparoscopy was also calculated.

RESULTSThere were 52.7%(1 067/2 023) of patients underwent diagnostic laparoscopy. The accuracy rate of diagnostic laparoscopy in evaluating adjacent organ invasion and intra-abdominal metastasis were 98.3%(1 049/1 067) and 98.1%(1 047/1 067) respectively. Besides, 14 patients with stage T4b and 32 with intra-abdominal metastasis, which were missed by imaging examination, were diagnosed by diagnostic laparoscopy. The treatment plans of 9.3% (99/1 067) of patients were changed after diagnostic laparoscopy, and 65 (6.1%) cases of non-therapeutic laparotomy were avoided. However, 18 cases of adjacent organ invasion and 20 cases of intra-abdominal metastasis were still missed by diagnostic laparoscopy, and 12 cases received non-therapeutic laparotomy.

CONCLUSIONDiagnostic laparoscopy has considerable value in assessing adjacent organ invasion and intra-abdominal metastasis and has great clinical significance in making precise treatment plans.

Abdominal Neoplasms ; diagnostic imaging ; secondary ; Digestive System ; pathology ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Laparoscopes ; Laparoscopy ; instrumentation ; methods ; statistics & numerical data ; Laparotomy ; statistics & numerical data ; Male ; Neoplasm Invasiveness ; diagnostic imaging ; Patient Care Planning ; statistics & numerical data ; Retrospective Studies ; Stomach Neoplasms ; diagnostic imaging ; surgery ; Surgical Instruments ; Unnecessary Procedures ; statistics & numerical data

OBJECTIVETo establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance.

METHODSClinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity.

RESULTSAmong 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28.2%). Neutrophil/lymphocyte ratio (NLR) of 26 patients was ≥ 2.37(26/231, 11.3%). Multivariate analysis showed that Lauren classification (HR=8.95, 95%CI:1.32-60.59, P=0.025), CA125(HR=17.45, 95%CI:5.54-54.89, P=0.001), CA72-4(HR=20.06, 95%CI:5.05-79.68, P=0.001), and NLR (HR=4.16, 95%CI:1.17-14.75, P=0.032) were independent risk factors of peritoneal metastasis in gastric cancer. In the nomogram, the highest score was 241, including diffuse or mixed Lauren classification (54 score), CA125 ≥ 35 kU/L (66 score), CA72-4 ≥ 10 kU/L (100 score), and NLR ≥ 2.37 (21 score), which represented a highest risk of peritoneal metastasis (more than 90%). The AUC of nomogram was 0.912, which was superior than any single variable (AUC of Lauren classification: 0.678; AUC of CA125: 0.720; AUC of CA72-4: 0.792; AUC of NLR: 0.613, all P=0.000). The total score of nomogram increased according to the TNM stage, and was highest in the peritoneal metastasis group (F=49.1, P=0.000). When the cut-off value calculated by ROC analysis was set at 140, the model could best balanced the sensitivity (0.79) and the specificity (0.87). Only 5% of patients had peritoneal metastasis when their nomogram scores were lower than 140, while 58% of patients had peritoneal metastasis when their scores were ≥ 140(χ=69.1, P=0.000).

CONCLUSIONThe risk evaluation model established with Lauren classification, CA125, CA72-4 and NLR can effectively predict the risk of peritoneal metastasis in gastric cancer, and provide the reference to preoperative staging and choice of therapeutic strategy.

Antigens, Tumor-Associated, Carbohydrate ; blood ; Area Under Curve ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Female ; Humans ; Leukocyte Count ; statistics & numerical data ; Logistic Models ; Lymphocytes ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; diagnosis ; Neutrophils ; pathology ; Nomograms ; Peritoneal Neoplasms ; secondary ; Prognosis ; ROC Curve ; Retrospective Studies ; Risk Assessment ; methods ; Risk Factors ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; classification ; diagnosis ; pathology