Effect of chemotherapy on prognosis in patients with primary pancreatic signet ring cell carcinoma: A large real-world study based on machine learning.

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.

Contemporary outcomes for resected type 1-3 gastroesophageal junction adenocarcinoma: a single-center experience.

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.

A novel log odds of positive lymph nodes-based nomogram for predicting overall survival in patients with colorectal signet ring cell carcinoma: a SEER population-based study.

PURPOSE: Considering the poor prognosis and high lymph node (LN) involvement rate of colorectal signet ring cell carcinoma (SRCC), this study aimed to construct a prognostic nomogram to predict overall survival (OS) with satisfactory accuracy and utility, based on LN status indicators with superior predictability. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we obtained cases of colorectal SRCC patients and employed univariate and multivariate Cox analyses to determine independent prognostic factors. Kaplan-Meier curves were utilized to visualize survival differences among these factors. Receiver operating characteristic curves were generated to assess predictive performances of models incorporating various LN status indicators. A novel nomogram, containing optimal LN status indicators and other prognostic factors, was developed to predict OS, whose discriminatory ability and accuracy were evaluated using calibration curves and decision curve analysis. RESULTS: A total of 1663 SRCC patients were screened from SEER database. Older patients and those with grades III-IV, tumor sizes > 39 mm, T3/T4 stage, N1/N2 stage, M1 stage, and higher log odds of positive lymph nodes (LODDS) values exhibited poorer prognoses. Age, grade, tumor size, TNM stage, and LODDS were independent prognostic factors. The model containing N stage and LODDS outperformed the one relying solely on N stage as LN status indicator, resulting in a validated nomogram for accurately predicting OS in SRCC patients. CONCLUSION: The integration of LODDS, N stage, and other risk factors into a nomogram offered precise OS predictions, enhancing therapeutic decision-making and tailored follow-up management for colorectal SRCC patients.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

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.

A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study.

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.

Unusual Metastasis of Signet-Ring Cell Gastric Cancer That Could Not Be Detected With 18 F-FDG PET But With 68 Ga-FAPI PET/CT.

ABSTRACT: A 70-year-old man who was scheduled for surgery because of the recurrence of gastric cancer was referred to our clinic preoperatively. The patient underwent a comprehensive evaluation through 18 F-FDG and 68 Ga-FAPI ( 68 Ga-labeled FAP inhibitors) PET/CT scans. The 68 Ga-FAPI PET/CT scan was particularly valuable in this case because of its ability to detect recurrent mass lesions and identify unusual metastatic sites compared with the 18 F-FDG PET/CT scan.

Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer.

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.

Survival impact of gastrectomy and chemotherapy on gastric signet ring-cell carcinoma with different metastatic lesions: A population-based study.

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.

Invasive lobular carcinoma metastasis to pancreas mimicking pancreatic signet ring cell carcinoma: A case report and systematic review of the literature.

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.

Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

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.

Efficacy of Neoadjuvant Chemotherapy in Lobular and Rare Subtypes of Breast Cancer.

OBJECTIVE: To determine the predictive factors for the pathological complete response (pCR) in patients with non-ductal invasive breast cancer (ND-BC) receiving neoadjuvant chemotherapy. STUDY DESIGN: Observational study. Place and Duration of the Study: Departments of Medical Oncology, Tekirdag Namik Kemal University, Sirnak State Hospital, Aydin Adnan Menderes University, Marmara University, Bakirkoy Sadi Konuk Hospital, Basaksehir Cam and Sakura Hospital, Sakarya University, Balikesir Ataturk Hospital, Turkiye, from April 2016 to December 2022. METHODOLOGY: A total of 222 non-metastatic breast cancer patients who received neoadjuvant chemotherapy were included in this retrospective multicentric study. The clinicopathologic data were obtained from the hospitals' electronic-record-system. The logistic regression models were used to identify predictive factors for pCR. RESULTS: One hundred and twenty-six patients (56.8%) had invasive lobular carcinoma and 28 patients (12.6%) had signet ring cell/mucinous carcinoma. A total of 45 patients (20.3%) achieved pCR. The pCR rate was 14.3% for lobular carcinoma and 17.9% for signet ring cell/mucinous carcinoma. The univariate analysis showed that estrogen receptor-negative tumours (p = 0.017), high Ki-67 (p = 0.008), high histologic grade (p<0.001), HER2+ expression (p<0.001), and non-lobular histologic type (p = 0.012) were predictive factors for pCR. The multivariate model revealed that HER2 expression (p<0.001) and Ki-67 (p = 0.005) were independent predictors. CONCLUSION: Neoadjuvant chemotherapy demonstrated effectiveness in ND-BC patients, leading to favourable pCR rates and enabling breast-conserving surgery. Predictive markers for pCR varied depending on histologic types, with HER2 expression, ER status, Ki-67, and histologic grade showing significance in non-ductal subtypes, while HER2 status alone was predictive in lobular carcinoma. KEY WORDS: Neoadjuvant chemotherapy, Non-ductal breast cancer, Lobular carcinoma.

Atypical Histopathological Aspects of Common Types of Lung Cancer-Our Experience and Literature Review.

Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist's attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the "Marius Nasta" Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.

Comparison of 18 F-FDG and 18 F-FAPI PET/CT Findings of Signet-Ring Cell Carcinoma of the Stomach.

ABSTRACT: A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.

Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma.

AIM: Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective. METHOD: A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS ± HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery. RESULTS: Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p = 0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p = 0.039) and peritoneal carcinomatosis index >10 (p = 0.009), were factors independently associated with worse OS. CONCLUSION: Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.

Pseudomesotheliomatous Carcinoma of the Lung with Morphological Characteristics of Signet Ring Cell Carcinoma: An Autopsy Case Report.

A 50-year-old woman presented with left pleural effusion. A pleural fluid cell-block specimen and longitudinal lymph node needle biopsy suggested signet ring cell carcinoma (SRCC). Although computed tomography showed a consolidation shadow in the left lower lobe, a left lung biopsy could not be performed. Upper gastrointestinal endoscopy revealed no malignancies. We administered carboplatin, pemetrexed, ipilimumab, and nivolumab for lung cancer; however, she died due to progressive respiratory failure. Pathological autopsy revealed that the left pleura was thickened as in mesothelioma, based on which pseudomesotheliomatous carcinoma of the lung (PMCL) was diagnosed. PMCLs exhibiting an SRCC morphology are rare.

Hereditary Diffuse Gastric Cancer Treated by Prophylactic Total Gastrectomy.

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.