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1.
J Gastrointest Surg ; 28(5): 634-639, 2024 May.
Article in English | MEDLINE | ID: mdl-38704200

ABSTRACT

BACKGROUND: Surgical resection remains the mainstay of treatment for tumors of the gastroesophageal junction (GEJ). However, contemporary analyses of the Western experience for GEJ adenocarcinoma are sparsely reported. METHODS: Patients with GEJ adenocarcinoma undergoing resection between 2012 and 2022 at a single institution were grouped based on Siewert subtype and analyzed. Pathologic and treatment related variables were assessed with relation to outcomes. RESULTS: A total of 302 patients underwent resection: 161 (53.3%) with type I, 116 (38.4%) with type II, and 25 (8.3%) with type III tumors. Most patients received neoadjuvant therapy (86.4%); 86% of cases were performed in a minimally invasive fashion. Anastomotic leak occurred in 6.0% and 30-day mortality in only 0.7%. The rate of grade 3+ morbidity was lower for the last 5 years of the study than for the first 5 years (27.5% vs 49.3%, P < .001), as was median length of stay (7 vs 8 days, P < .001). There was a significantly greater number of signet ring type tumors among type III tumors (44.0%) than type I/II tumors (11.2/12.9%, P < .001). Otherwise, there was no difference in the distribution of pathologic features among Siewert subtypes. Notably, there was a significant difference in 3-year overall survival based on Siewert classification: type I 60.0%, type II 77.2%, and type III 86.3% (P = .011). Siewert type I remained independently associated with worse survival on multivariable analysis (hazard ratio, 4.5; P = .023). CONCLUSIONS: In this large, single-institutional series, operative outcomes for patients with resected GEJ adenocarcinoma improved over time. On multivariable analysis, type I tumors were an independent predictor of poor survival.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Esophagogastric Junction , Stomach Neoplasms , Humans , Esophagogastric Junction/surgery , Esophagogastric Junction/pathology , Adenocarcinoma/surgery , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Male , Female , Middle Aged , Aged , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Treatment Outcome , Neoadjuvant Therapy , Retrospective Studies , Anastomotic Leak/etiology , Anastomotic Leak/epidemiology , Gastrectomy/methods , Esophagectomy/methods , Length of Stay/statistics & numerical data , Adult , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/mortality , Aged, 80 and over , Survival Rate
2.
PLoS One ; 19(5): e0302685, 2024.
Article in English | MEDLINE | ID: mdl-38739633

ABSTRACT

BACKGROUND: Primary pancreatic signet ring cell carcinoma (PSRCC), an extremely rare histologic variant of pancreatic cancer, has a poor prognosis. This study aimed to investigate the prognostic value of chemotherapy in PSRCC. METHODS: Patients with PSRCC between 2000 and 2019 were identified using the Surveillance Epidemiology and End Results (SEER) database. The main outcomes in this study were cancer-specific survival (CSS) and overall survival (OS). The baseline characteristics of patients were compared using Pearson's Chi-square test. Kaplan-Meier analysis was used to generate the survival curves. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression models, and Random Survival Forest model were used to analyze the prognostic variables for OS and CSS. The variance inflation factors (VIFs) were used to analyze whether there was an overfitting problem. RESULTS: A total of 588 patients were identified. Chemotherapy was an independent prognostic factor for OS and CSS, and significantly associated with OS (HR = 0.33, 95% CI = 0.27-0.40, P <0.001) and CSS (HR = 0.32, 95% CI = 0.26-0.39, P <0.001). CONCLUSIONS: Chemotherapy showed beneficial effects on OS and CSS in patients with PSRCC and should be recommended in clinical practice.


Subject(s)
Carcinoma, Signet Ring Cell , Machine Learning , Pancreatic Neoplasms , Humans , Carcinoma, Signet Ring Cell/drug therapy , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/mortality , Female , Male , Middle Aged , Prognosis , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Aged , Kaplan-Meier Estimate , SEER Program , Adult , Proportional Hazards Models
3.
Front Immunol ; 15: 1365834, 2024.
Article in English | MEDLINE | ID: mdl-38660300

ABSTRACT

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors. Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use. Results: Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/. Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.


Subject(s)
Carcinoma, Signet Ring Cell , Nomograms , Stomach Neoplasms , Humans , Carcinoma, Signet Ring Cell/mortality , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/diagnosis , Stomach Neoplasms/mortality , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Male , Female , Middle Aged , Retrospective Studies , Prognosis , Aged , Internet , Neoplasm Staging , Adult , SEER Program
4.
World J Surg Oncol ; 22(1): 107, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644507

ABSTRACT

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. PATIENTS AND METHODS: The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. RESULTS: In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. CONCLUSION: TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.


Subject(s)
Carcinoma, Signet Ring Cell , Colorectal Neoplasms , Neoplasm Staging , Nomograms , SEER Program , Humans , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/mortality , Female , Male , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Middle Aged , Prognosis , Survival Rate , Follow-Up Studies , Aged , Retrospective Studies , China/epidemiology , Neoplasm Invasiveness , Adult
5.
Eur J Surg Oncol ; 50(6): 108343, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38640606

ABSTRACT

BACKGROUND: Advances in perioperative chemotherapy have improved outcomes in patients with gastric cancers (GC). This strategy leads to tumour downstaging and may result in a pathologic complete response (pCR). The study aimed to evaluate the predictors of pCR and determine the impact of pCR on long-term survival. METHODS: At the Department of Gastrointestinal and HPB Oncology at the Tata Memorial Centre, Mumbai, 1001 consecutive patients with locally advanced GCs undergoing radical resection following neoadjuvant chemotherapy from January 2005 to June 2022 were included. RESULTS: At a median follow-up of 61 months, the median OS was 53 months with a 5-year OS of 46.8 %. Ninety-five patients (9.49 %) realized pCR. Non-signet and well-differentiated histology were associated with pCR. pCR was significantly associated with improved OS, 5-year OS 79.2 % vs 43.2 % (HR 0.30, p < 0.001). On multivariable analysis, the realization of pCR and completion of adjuvant chemotherapy had superior OS. Whereas, signet-ring histology, linitis-like tumours, and high lymph node ratio had adverse outcomes. CONCLUSION: Tumour grade and signet-ring histology predict achievement of pCR in locally advanced GCs after neoadjuvant chemotherapy. Patients with pCR have significantly improved survival. Future neoadjuvant strategies should focus on enhancing pCR rates to improve overall outcomes.


Subject(s)
Lymph Node Excision , Neoadjuvant Therapy , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/therapy , Male , Female , Middle Aged , Aged , Chemotherapy, Adjuvant , Adult , Gastrectomy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Staging , Survival Rate , Neoplasm Grading , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/drug therapy , Retrospective Studies , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adenocarcinoma/genetics
7.
J Gastrointest Surg ; 28(5): 694-702, 2024 May.
Article in English | MEDLINE | ID: mdl-38458911

ABSTRACT

PURPOSE: This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). METHODS: A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. RESULTS: The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. CONCLUSION: The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.


Subject(s)
Adenocarcinoma , Antigens, Tumor-Associated, Carbohydrate , Biomarkers, Tumor , CA-19-9 Antigen , Carcinoembryonic Antigen , Carcinoma, Signet Ring Cell , Stomach Neoplasms , alpha-Fetoproteins , Humans , Stomach Neoplasms/blood , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Female , Middle Aged , Prognosis , Biomarkers, Tumor/blood , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adenocarcinoma/mortality , alpha-Fetoproteins/analysis , alpha-Fetoproteins/metabolism , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Carcinoma, Signet Ring Cell/blood , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/mortality , Antigens, Tumor-Associated, Carbohydrate/blood , Aged , CA-125 Antigen/blood , Adult , Retrospective Studies
9.
Clin J Gastroenterol ; 17(3): 412-418, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38520641

ABSTRACT

In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.


Subject(s)
Adenocarcinoma , Carcinoma, Signet Ring Cell , Gastric Mucosa , Gastritis , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Male , Middle Aged , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/microbiology , Gastritis/pathology , Gastritis/microbiology , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Gastric Mucosa/pathology , Gastric Mucosa/microbiology , Helicobacter Infections/pathology , Helicobacter Infections/complications , Endoscopic Mucosal Resection
10.
Asian J Surg ; 47(4): 1769-1775, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38302357

ABSTRACT

BACKGROUND: A comprehensive understanding of gastric signet ring cell carcinoma (SRCC) is limited. The aim of our study was to analyze metastatic patterns of gastric SRCC and evaluate impacts of gastrectomy and chemotherapy for metastatic gastric SRCC. METHODS: We obtained data of gastric cancer patients between 2010 and 2017 in the Surveillance, Epidemiology, and End Results database. Chi-square tests were used to compare data significance. Kaplan-Meier, Cox proportional hazards regression and Fine-Gray competing risk analysis were used to analyze the difference in the overall survival (OS) and cancer-specific survival (CSS). Propensity-score matching was used to adjust numerical difference. RESULTS: Among 36,459 eligible gastric cancer patients, 6264 (17.2 %) were SRCC patients. Bone metastasis was more common in SRCC patients than in non-SRCC patients. The multivariate analysis showed that chemotherapy (HR = 0.30, 95 %CI = 0.27-0.33, p < 0.01) and gastrectomy (HR = 0.51, 95 %CI = 0.45-0.59, p < 0.01) were protective prognostic factors in certain stage Ⅳ SRCC patients. For the effect of gastrectomy, survival benefits could be found in patients with liver metastasis. The gastrectomy was not associated with improved OS in patients with lung or multiple metastases. In subgroup analysis, SRCC patients with metastasis who received gastrectomy and chemotherapy (HR = 0.17, p < 0.01; HR = 0.03, p < 0.01) had a better OS and CSS than those who had chemotherapy only (HR = 0.30, p < 0.01; HR = 0.18, p < 0.01). CONCLUSION: Our study analyzed the unique metastatic patterns of gastric SRCC and recommended chemotherapy as the first choice in metastatic SRCC. For patients with liver metastasis, gastrectomy plus chemotherapy can be considered.


Subject(s)
Carcinoma, Signet Ring Cell , Liver Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Carcinoma, Signet Ring Cell/drug therapy , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/pathology , Gastrectomy , Prognosis , Liver Neoplasms/surgery
11.
Dig Dis ; 42(3): 221-229, 2024.
Article in English | MEDLINE | ID: mdl-38342087

ABSTRACT

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.


Subject(s)
Carcinoma, Signet Ring Cell , Nomograms , SEER Program , Stomach Neoplasms , Humans , Carcinoma, Signet Ring Cell/mortality , Carcinoma, Signet Ring Cell/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Male , Female , Middle Aged , Prognosis , Aged , Adult , Neoplasm Staging , ROC Curve , Proportional Hazards Models
12.
Pathol Res Pract ; 253: 155049, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38176311

ABSTRACT

Metastasis to the gastrointestinal tract is a rare instance in the natural history of breast cancer, usually in association with lobular histology and widespread dissemination of disease. We report the case of a 74-year-old woman with a history of invasive lobular carcinoma presenting with a pancreatic metastasis mimicking a primary pancreatic adenocarcinoma; we also present a systematic review of the relevant literature. The presentation of pancreatic metastasis in the setting of breast cancer is unspecific, and histology is of paramount importance for a correct diagnosis; surgical metastasectomy could be of some benefit in the correct clinical setting.


Subject(s)
Adenocarcinoma , Breast Neoplasms , Carcinoma, Lobular , Carcinoma, Signet Ring Cell , Pancreatic Neoplasms , Female , Humans , Aged , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/pathology , Pancreatic Neoplasms/diagnosis , Breast Neoplasms/pathology , Carcinoma, Signet Ring Cell/diagnosis , Carcinoma, Signet Ring Cell/pathology , Pancreas/pathology
13.
J Gastroenterol Hepatol ; 39(5): 893-901, 2024 May.
Article in English | MEDLINE | ID: mdl-38273469

ABSTRACT

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.


Subject(s)
Colitis, Ulcerative , Propensity Score , Humans , Male , Female , Middle Aged , Colitis, Ulcerative/pathology , Colitis, Ulcerative/complications , Colitis, Ulcerative/epidemiology , Aged , Japan/epidemiology , Crohn Disease/pathology , Crohn Disease/epidemiology , Crohn Disease/complications , Colitis-Associated Neoplasms/pathology , Colitis-Associated Neoplasms/etiology , Colitis-Associated Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Adult , Adenocarcinoma/pathology , Adenocarcinoma/epidemiology , Adenocarcinoma/etiology , Neoplasm Staging , Neoplasm Grading , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/epidemiology , Adenocarcinoma, Mucinous/etiology , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Diagnosis, Differential , Prevalence
14.
J Natl Cancer Inst ; 116(2): 299-308, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-37699004

ABSTRACT

BACKGROUND: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer . METHODS: We reviewed the Memorial Sloan Kettering Cancer Center gastric, esophageal, and gastroesophageal junction cancer database. Associations between baseline characteristics and tumor and germline molecular alterations were compared between those with early-onset and average-onset esophagogastric cancer using Fisher exact tests and the Benjamini-Hochberg method for multiple-hypothesis correction. RESULTS: We included 1123 patients with early-onset esophagogastric cancer (n = 219; median age = 43 years [range = 18-49 years]) and average-onset esophagogastric cancer (n = 904; median age = 67 years [range = 50-94 years]) treated between 2005 and 2018. The early-onset group had more women (39% vs 28%, P = .002). Patients with early-onset esophagogastric cancer were more likely to have a gastric primary site (64% vs 44%, P < .0001). The signet ring cell and/or diffuse type was 3 times more common in the early-onset esophagogastric cancer group (31% vs 9%, P < .0001). Early-onsite tumors were more frequently genomically stable (31% vs 18%, P = .0002) and unlikely to be microsatellite instability high (2% vs 7%, P = .003). After restricting to adenocarcinoma and signet ring cell and/or diffuse type carcinomas, we observed no difference in stage (P = .40) or overall survival from stage IV diagnosis (median = 22.7 vs 22.1 months, P = .78). CONCLUSIONS: Our study supported a preponderance of gastric primary disease sites, signet ring histology, and genomically stable molecular subtypes in early-onset esophagogastric cancer. Our findings highlight the need for further research to define the underlying pathogenesis and strategies for early detection and prevention.


Subject(s)
Adenocarcinoma , Carcinoma, Signet Ring Cell , Esophageal Neoplasms , Stomach Neoplasms , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/epidemiology , Stomach Neoplasms/genetics , Adenocarcinoma/epidemiology , Adenocarcinoma/genetics , Cardia/metabolism , Esophagogastric Junction/metabolism , Esophagogastric Junction/pathology , Carcinoma, Signet Ring Cell/metabolism , Carcinoma, Signet Ring Cell/pathology , Retrospective Studies
15.
Intern Med ; 63(2): 235-239, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37225495

ABSTRACT

We herein report a rare case of hereditary diffuse gastric cancer in a Japanese man. A 41-year-old man underwent esophagogastroduodenoscopy which revealed a small gastric erosion. Biopsy specimens showed signet ring cell carcinoma, and endoscopic submucosal dissection was performed. The patient's elder sister had died of gastric cancer at 38 years old. Considering the family history, a genetic test was conducted and revealed a CDH1 germline mutation. Although no carcinomatous lesion was detected endoscopically, prophylactic total gastrectomy was performed. The resection specimen showed seven microlesions of signet ring cell carcinoma confined to the lamina propria mucosae.


Subject(s)
Adenocarcinoma , Carcinoma, Signet Ring Cell , Stomach Neoplasms , Male , Humans , Aged , Adult , Stomach Neoplasms/genetics , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Genetic Predisposition to Disease , Gastrectomy , Adenocarcinoma/surgery , Carcinoma, Signet Ring Cell/genetics , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/pathology , Germ-Line Mutation , Cadherins/genetics
17.
Ann Surg Oncol ; 31(2): 783-791, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37991582

ABSTRACT

BACKGROUND: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. METHODS: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). RESULTS: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. CONCLUSIONS: A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.


Subject(s)
Carcinoma, Signet Ring Cell , Stomach Neoplasms , Humans , Neoplasm Staging , Retrospective Studies , Lymph Nodes/surgery , Lymph Nodes/pathology , Prognosis , Stomach Neoplasms/pathology , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/pathology
19.
Clin Colorectal Cancer ; 23(1): 35-45, 2024 03.
Article in English | MEDLINE | ID: mdl-37980215

ABSTRACT

BACKGROUND: Colonic signet ring cell carcinoma (SRCC) is a mucinous adenocarcinoma subtype often associated with poor prognosis. This study assessed the survival benefits of adjuvant therapy after curative resection of stage II-III colonic SRCC. METHODS: This was a retrospective analysis of outcomes of adjuvant therapy in colonic SRCC using National Cancer Database (2010-2019) data. Patients who received adjuvant therapy were matched to those who did not use the nearest neighbor propensity-score matching. The primary outcome was 5-year overall survival (OS). RESULTS: The unmatched cohort included 3530 patients. Patients who received adjuvant therapy were significantly younger, more often male, and more often had Charlson scores 0-1, left-sided cancers, stage III disease, lymphovascular invasion, and perineural invasion. The matched cohort included 958 patients (53.6% female); 479 received adjuvant therapy and 479 did not. Adjuvant therapy was associated with longer mean OS (39.9 vs. 29.2 months; P < .001). Survival benefit of adjuvant therapy was evident in stage III disease (37.5 vs. 24.7 months; P < .001), right-sided colon cancer (40.2 vs. 27.7 months; P < .001), and transverse colon cancer (40.6 vs. 31.1 months; P = .002), but not stage II disease (52.1 vs. 53.1 months; P = .694) or left-sided colon cancer (35.8 vs. 32.6 months; P = .417). Independent predictors of improved OS were adjuvant therapy (HR: 0.539; P < .001), laparoscopic surgery (HR: 0.829; P = .001), robotic-assisted surgery (HR: 0.63; P = .007), and number of harvested lymph nodes (HR: 0.976; P < .001). CONCLUSIONS: Adjuvant therapy was associated with improved OS in stage III, right-sided, and transverse colon SRCC. The survival benefit of adjuvant therapy in stage II and left-sided colon SRCC was limited.


Subject(s)
Carcinoma, Signet Ring Cell , Colonic Neoplasms , Robotic Surgical Procedures , Humans , Male , Female , Retrospective Studies , Carcinoma, Signet Ring Cell/therapy , Carcinoma, Signet Ring Cell/pathology , Colonic Neoplasms/pathology , Neoplasm Staging , Chemotherapy, Adjuvant , Prognosis
20.
Hum Cell ; 37(2): 511-522, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38143259

ABSTRACT

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.


Subject(s)
Adenocarcinoma, Mucinous , Carcinoma, Signet Ring Cell , Peritoneal Neoplasms , Pseudomyxoma Peritonei , Animals , Mice , Humans , Pseudomyxoma Peritonei/therapy , Pseudomyxoma Peritonei/metabolism , Pseudomyxoma Peritonei/pathology , Mice, Nude , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/therapy , Adenocarcinoma, Mucinous/pathology , Carcinoma, Signet Ring Cell/therapy , Carcinoma, Signet Ring Cell/pathology , Myelin P2 Protein
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