Treatment Options for Signet Ring Cell Carcinoma of the Urinary Bladder: A Population-Based Study.

OBJECTIVES: Signet ring cell carcinoma (SRCC) of the urinary bladder is a rare and highly aggressive form of bladder cancer, with no widely agreed-upon treatment strategy. The aim of this study was to identify important factors influencing patient prognosis and to assess how various treatment approaches affect survival outcomes. METHODS: A retrospective study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) Program, including patients with bladder primary SRCC who were presented between 2000 and 2017. Univariate and multivariate Cox regression models were used to examine the impact of various factors on cancer-specific survival (CSS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to homogenize both groups. The impact of different treatment regimens on patient CSS and OS was analyzed using the Kaplan-Meier method. RESULTS: A total of 33 cases of non-muscular invasive SRCC and 210 cases of muscular invasive SRCC were included in this study. Multivariate analysis identified race, TNM stage, and surgical method as independent variables influencing both OS and CSS. In non-muscle invasive bladder SRCC patients, radical cystectomy showed no CSS benefit compared to transurethral resection of bladder tumors (P = 0.304). For muscle invasive SRCC, patients who underwent partial cystectomy had better OS and CSS compared to those who underwent radical cystectomy (P = 0.019, P = 0.024). However, after conducting a PSM analysis, the differences between the two surgical outcomes were not statistically significant (P = 0.504, P = 0.335). Lymphadenectomy, chemotherapy, and radiation did not show any benefit to the prognosis of patients. CONCLUSION: This study identified race, TNM stage, and surgical approach as significant independent predictors for SRCC outcomes. Simple radical cystectomy and partial cystectomy proved to be effective treatments for SRCC. The optimal treatment option still needs to be supported by a number of prospective research trials.

Signet ring cells and conditional survival after trimodality therapy for esophageal adenocarcinoma.

BACKGROUND AND METHODS: Although signet ring cell (SRC) histology is associated with resistance to neoadjuvant chemoradiotherapy and worse overall survival (OS) in esophageal adenocarcinoma (EAC), its prognostic relationship among patients who survive the early period following resection is unknown. EAC patients who underwent trimodality therapy at a single institution (2006-2018) were identified. Bayesian multivariable regression (BMR) analyses of OS and additional OS from a 3-year landmark were performed. RESULTS: Of 631 patients, SRCs were present in 16.0% (N = 101). SRC was associated with shorter median OS (45.8 [95% confidence interval: 31.0-96.7] vs. 79.8 [63.0-107.2] months; p = 0.014). In BMR analysis, the absence of an SRC component was moderately associated with improved OS (probability of beneficial effect, PBE = 0.879). Three-year conditional BMR analysis of additional OS (N = 357) showed that SRC status no longer had a prognostic effect (PBE = 0.546); higher pathological stage was strongly associated with worse additional OS (PBE < 0.001). CONCLUSIONS: The presence of SRC portends worse OS following trimodality therapy for EAC. However, this prognostic impact is dynamic and abates by 3 years postoperatively. In contrast, a higher pathological stage is strongly associated with poor overall and 3-year conditional survival. DISCUSSION: These findings may inform postoperative patient counseling and surveillance protocols.

Response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy.

Objectives: To determine the response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy. METHODS: The non-randomised, quasi-experimental retrospective cohort study was conducted at the Combined Military Hospital, Rawalpindi, Pakistan, and comprised data of patients treated between January 1, 2020, to September 30, 2021. The data retrieved related to histologically proven and locally advanced rectal cancer patients aged 18-70 years receiving neoadjuvant chemoradiotherapy. Radiotherapy dose was 45 gray to pelvis with a boost to gross tumour of 5.4 gray in 3 fractions by using volumetric arc therapy concurrently with capecitabine 625mg/m² daily. A magnetic resonance imaging scan of pelvis with contrast was done at 5-10 weeks before surgery. Histological response to neoadjuvant treatment of various histological types was evaluated using the Rectal Cancer Regression Grade. Data was analysed using SPSS 22. RESULTS: Of the 182 patients evaluated, 108(59.34%) were included; 64(59.3%) males and 44(40.7%) females. The overall mean age was 45.4±5.2 years. Regression status was grade 1 in 24(22%) patients, grade 2 in 43(40%) and grade 3 in 41(38%) (p=0.074). There were 12(11.11%) patients with signet ring cell and 10(83.3%) showed pathological tumour regression. There were 17(15.74%) patients with mucinous variant, and 12(70.5%) had tumour regression. There were 79(73.15%) patients with adenocarcinoma, and 59(74.6%) of them showed tumour regression. . CONCLUSIONS: There was less tumour regression in mucinous and signet ring cell variants of adenocarcinoma. Modification and intensification of neoadjuvant therapy may be required in such histologies.

A prognostic framework for predicting lung signet ring cell carcinoma via a machine learning based cox proportional hazard model.

PURPOSE: Signet ring cell carcinoma (SRCC) is a rare type of lung cancer. The conventional survival nomogram used to predict lung cancer performs poorly for SRCC. Therefore, a novel nomogram specifically for studying SRCC is highly required. METHODS: Baseline characteristics of lung signet ring cell carcinoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression and random forest analysis were performed on the training group data, respectively. Subsequently, we compared results from these two types of analyses. A nomogram model was developed to predict 1-year, 3-year, and 5-year overall survival (OS) for patients, and receiver operating characteristic (ROC) curves and calibration curves were used to assess the prediction accuracy. Decision curve analysis (DCA) was used to assess the clinical applicability of the proposed model. For treatment modalities, Kaplan-Meier curves were adopted to analyze condition-specific effects. RESULTS: We obtained 731 patients diagnosed with lung signet ring cell carcinoma (LSRCC) in the SEER database and randomized the patients into a training group (551) and a validation group (220) with a ratio of 7:3. Eight factors including age, primary site, T, N, and M.Stage, surgery, chemotherapy, and radiation were included in the nomogram analysis. Results suggested that treatment methods (like surgery, chemotherapy, and radiation) and T-Stage factors had significant prognostic effects. The results of ROC curves, calibration curves, and DCA in the training and validation groups demonstrated that the nomogram we constructed could precisely predict survival and prognosis in LSRCC patients. Through deep verification, we found the constructed model had a high C-index, indicating that the model had a strong predictive power. Further, we found that all surgical interventions had good effects on OS and cancer-specific survival (CSS). The survival curves showed a relatively favorable prognosis for T0 patients overall, regardless of the treatment modality. CONCLUSIONS: Our nomogram is demonstrated to be clinically beneficial for the prognosis of LSRCC patients. The surgical intervention was successful regardless of the tumor stage, and the Cox proportional hazard (CPH) model had better performance than the machine learning model in terms of effectiveness.

Characteristics and outcomes of rectal cancer in patients with inflammatory bowel disease: a single-center experience.

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) has been well documented in the literature. The present study aimed to assess the characteristics and outcomes of rectal cancer in patients with IBD. This study was a retrospective review of a prospectively maintained IRB-approved database at Cleveland Clinic Florida. Rectal cancer patients with or without IBD treated with curative surgery between 2016 and 2020 were compared for demographics, disease characteristics, and pathologic and oncologic outcomes. The primary outcomes were 3-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were clinicopathologic outcomes including disease stage, tumor histology and histologic features, and treatments received. 238 patients with rectal cancer were included, 15 (6.3%) of whom had IBD. IBD patients were significantly younger (52.9 vs 60.3 years, p = 0.033), presented more often with cT1-2 tumors (64.3% vs 30.4%, p = 0.008), and signet-ring cell pathology (14.3% vs 2%, p = 0.02). IBD patients received neoadjuvant chemoradiation less often (40% vs 72.6%, p = 0.029) and had shorter time between diagnosis and surgery (7.5 vs 25 weeks, p = 0.013) than did non-IBD patients. Both groups had similar OS (36 vs 34.7 months, p = 0.431) and DFS (36 vs 32.9 months, p = 0.121). IBD patients with rectal cancer tend to present at a younger age, with a less invasive disease, and signet-ring carcinomas, and receive neoadjuvant treatment less often than non-IBD patients. Based on low level of evidence, IBD and non-IBD rectal cancer patients might have similar survival.

Propensity-Score Matched Analysis of Survival Outcomes of Adjuvant Therapy in Stage II-III Signet-Ring Cell Carcinoma of the Colon.

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.

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.

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.

Microsatellite Instability-high Signet Ring Cell Carcinoma of the Colon Treated With Immunotherapy: Report of a Case.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are attracting increasing attention as a novel and potentially curative therapy for microsatellite instability-high (MSI-H) colorectal cancer (CRC). CASE REPORT: An 80-year-old female visited our hospital with complaints of lower abdominal pain due to bowel obstruction caused by descending colon cancer. After 1 month of metallic stent detention, she underwent radical surgery, although laparotomy showed broad peritoneal dissemination. Based on the genetic finding of MSI-H status, pembrolizumab therapy was administered in two cycles. Unfortunately, the therapy was ineffective, and the patient died after being discharged 5 months after surgery. CONCLUSION: The findings in this case of MSI-H CRC with a poor response to an ICI suggest the importance of confirming HLA status, including beta-2-microglobulin and HLA expression, before starting ICI therapy in cases of MSI-H CRC.

A case report of anterior mediastinal signet ring cell carcinoma.

RATIONALE: Anterior mediastinal signet ring cell carcinoma (SRCC) is a rare tumor that has only been reported in two cases of thymic cancer. Positive immunohistochemistry (IHC) staining for caudal-type homeobox (CDX) 2, cytokeratin (CK) 20 and special AT-rich binding protein (SATB) 2 usually indicate gastrointestinal tumors but begin to appear in thymic cancers with enteric differentiation. Here, we describe a case of the anterior mediastinal SRCC with enteric differentiation who was correctly treated with surgery and chemo-radiation and was alive after four months. PATIENT CONCERNS: A 48-year-old female presented without chest and lung symptoms had an anterior mediastinal mass during a routine physical examination. Laboratory examinations showed an elevated level of serum carbohydrate antigen (CA)-125 at 73.63 U/mL. Chest computed tomography (CT) showed an irregular soft tissue density shadow with heterogeneous enhancement in the anterior mediastinum. The tumor had invaded the pericardium, the left septal nerve and the innominate and was completely removed after anterior mediastinal surgery. Postoperative pathological examinations revealed signet ring cell features and positive staining for CDX2, CK20, SATB2 and Ki-67 (Li: 70%). The samples were negative for cluster of differentiation (CD)-5, CK7, thyroid transcription factor (TTF) 1, NapsinA, CerbB-2, P53 and PD-L1 by IHC examinations. The suspected diagnosis was an anterior mediastinal SRCC that had originated in the digestive system. DIAGNOSIS: The patient was diagnosed with anterior mediastinal SRCC. INTERVENTIONS: The patient was treated with surgery and combined chemo-radiotherapy. OUTCOMES: The patient had no recurrence or metastasis after five months. LESSONS: We describe a rare case of the anterior mediastinal SRCC of unknown origin. Our case, for the first time shows that surgery combined with chemo-radiotherapy is an effective treatment regimen for anterior mediastinal SRCC.

Epidemiology and prognostic analysis of patients with pancreatic signet ring cell carcinoma: a population-based study.

BACKGROUND: Pancreatic signet ring cell carcinoma (PSRCC) is a rare tumour subtype with poorly understood epidemiological characteristics and prognosis. We attempted to comprehensively characterise the epidemiology and survival outcomes of PSRCC. METHODS: Patients diagnosed with PSRCC between 2000 and 2018 were identified using Surveillance, Epidemiology and End Results Stat 8.3.9.2 software. Age-adjusted incidence and survival were calculated. Survival curves were plotted using the Kaplan-Meier method, and the differences between survival curves were compared using the log-rank test. Cox proportional hazards models were used to evaluate factors that independently predict overall survival. The primary analysis was a complete case analysis; multiple imputations were employed in a sensitivity analysis. RESULTS: We identified 585 eligible patients with PSRCC. The overall annual incidence from 2000 to 2018 was 0.349 (95% CI, 0.321-0.379) per million population. The incidence increased significantly in patients over 55 years of age and peaked at about 80 years of age (2.12 per million). Males and Black patients had the highest incidence. The observed survival rates at 1, 2 and 5 years were 20.1, 8.3 and 3.4%, respectively. Survival analysis revealed that primary surgery and chemotherapy are effective treatments for patients with PSRCC (P < 0.05). According to multivariate Cox regression analysis, early stage and receiving surgery and chemotherapy were favourable factors (P < 0.05). Similar conclusions were drawn from the interpolated data. CONCLUSIONS: PSRCC is a highly malignant tumour that predominates in elderly, male and Black patients. The prognosis is poor with a 5-year survival rate of 3.4%; however, multivariate analysis and adjusted models accounting for missing data revealed that early diagnosis, surgery and chemotherapy are effective in improving the prognosis.

Breast metastasis of signet ring cell carcinoma from the colon: a case report.

BACKGROUND: Colon cancer is one of the most common diagnosed malignancies. Despite the use of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and other comprehensive treatments, distant metastasis is still one of the main causes for dying of colon cancer. The common metastatic site of colon cancer is the liver, lung, and bone. In this article, we report a rare case of breast metastasis of signet ring cell carcinoma from the colon. CASE PRESENTATION: A 44-year-old woman was diagnosed with colon cancer and received a radical surgery of colon cancer in 2019. Combined with postoperative pathological and computed tomography (CT) images, a diagnosis of cT3N2M0 mucinous adenocarcinoma of colon (according to AJCC cancer staging manual, Version 8) was established. Adjuvant chemotherapy (XELOX: oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was performed followed by surgical resection. Fourteen months later, the patient underwent mastectomy for breast mass, which was diagnosed pathologically as metastasis of signet ring cell carcinoma from the colon. XELOX chemotherapy regimen (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) combined with bevacizumab (7.5 mg/kg on day 1) was used after the mastectomy. The patient had stable disease according to her last examination (RECIST criteria). CONCLUSION: It is rare to find a report of a patient of colon cancer that metastasizes to breast. We hope to increase treatment experience for patients with this rare metastasis.

Therapeutic plasma exchange in gastric signet ring cell carcinoma presenting as microangiopathic hemolytic anemia: A rare case report.

Microangiopathic hemolytic anemia (MAHA) defines a group of disorders characterized by the formation of microthrombi in capillaries and arterioles and the fragmentation of erythrocytes that pass through. Cancer-related MAHA is a rare but serious condition that is encountered in patients diagnosed with a malignancy. This clinical picture is thought to be linked to certain tumor characteristics; particularly, adenocarcinoma histology, vascular invasion, and bone marrow infiltration. MAHA is most commonly associated with tumors of gastric, prostate, and breast origin. The optimal treatment is not clear; however, there is evidence for the importance of promptly starting an effective antineoplastic regimen and it was also reported that administering therapeutic plasma exchange (TPE) therapy for immunocomplex removal could be beneficial for patients with symptoms of bleeding and thrombosis. Here, we present a case that presented a picture of MAHA secondary to gastric signet-ring cell adenocarcinoma (SRCC). The clinical picture was initially evaluated as thrombotic thrombocytopenic purpura and the patient benefited significantly from the TPE treatment administered before the adenocarcinoma diagnosis was confirmed. In this period, epistaxis stopped, platelet count increased from 25 × 109 /L to 162 × 109 /L, fragmented erythrocyte rate in the peripheral smear decreased by more than 75% and other laboratory findings of hemolysis (LDH, bilirubin, etc.) significantly improved.

Diagnosis and Management of Primary Prostatic Signet Ring Cell Carcinoma: Single-Center Experience.

The purpose of the study was to retrospectively summarize the diagnosis and management of 10 primary prostatic signet ring cell carcinoma (PPSRCC) cases in our center. Ten PPSRCC patients diagnosed at the First Affiliated Hospital of Nanjing Medical University from November 2014 to December 2020 were included. Clinical characteristics, image features, therapeutic procedures, histological diagnosis, and outcomes were retrospectively analyzed. All patients received prostate-specific antigen (PSA) examination preoperatively. Nine of them accepted multiparametric magnetic resonance imaging (mpMRI) due to elevated PSA value, and further biopsied. Among them, five patients were diagnosed as prostatic adenocarcinoma and the other four cases were found a mixture of signet ring cell carcinoma (SRCC) and adenocarcinoma. Furthermore, gastrointestinal endoscope and abdominal computed tomography (CT) did not find SRCC originating in gastrointestinal tract. Therefore, these cases were considered to be PPSRCC. Nine patients accepted laparoscopic or robot-assisted RP. Only one patient with normal PSA adopted transurethral resection of the prostate. Postoperative pathological results confirmed SRCC mixed with prostatic adenocarcinoma in nine cases, and only one patient with pure SRCC. After surgery, nine patients received adjuvant hormone therapy, one of which accepted radiotherapy simultaneously. The patient with pure SRCC did not accept any adjuvant therapy postoperatively. During a mean follow-up of 31.9 months, only four patients were alive without disease progression. In summary, PPSRCC is a rare malignant tumor with few specific symptoms, rapid disease progression, and poor prognosis and is frequently accompanied by high-grade prostate adenocarcinoma patterns. There is still no clear and effective strategy to improve the prognosis.

Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges.

PURPOSE: There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ. METHODS: A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated. RESULTS: This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC. CONCLUSION: Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.

Signet ring cell carcinoma of the gastrointestinal tract: National trends on treatment effects and prognostic outcomes.

BACKGROUND: Signet ring cell carcinoma (SRCC) is a distinct malignancy occurring across the tubular gastrointestinal tract (tGIT). We comprehensively examined the outcomes of patients diagnosed with SRCC across tGIT. METHODS: SRCC and not-otherwise-specified adenocarcinoma (NOS) patients reported to the National Cancer Database from 2004 to 2015 were included. Baseline characteristics, outcomes and site-specific adjusted hazard ratios (aHR) derived from Cox models of SRCC patients were compared to those of NOS patients. Overall survival (OS) was primary endpoint. RESULTS: A total of 41,686 SRCC (4.6%) and 871,373 NOS patients (95.4%) were included. SRCC patients were younger (63.1 ± 14.7 vs. 67.0 ± 13.4 y, p < 0.001) and more likely to present with Stage IV disease than NOS patients (42.5% vs. 24.5%, p < 0.001). Stomach (n = 24,433) and colon (n = 9,914) contributed highest frequency of SRCC. SRCC histology was associated with shorter OS (aHR = 1.377, p < 0.001) in multivariate model. There was an interaction between SRCC and chemotherapy effects on risk of death (interaction aHR = 1.072, pinteraction< 0.001) and between SRCC histology and disease site, suggesting that the effect of SRCC on OS is site-dependent, with a higher increased risk of death in patients with rectal SRCC (aHR = 2.378, pinteraction< 0.001). CONCLUSION: Significant negative prognostic effect associated with SRCC is site-dependent across the GIT. Surgical and or systemic therapy was associated with improved OS among SRCC patients, but remained lower than NOS patients. Further understanding of gastrointestinal SRCC molecular profile is needed to better inform future treatment strategies.

Clinicopathological and Molecular Characteristics of Colorectal Signet Ring Cell Carcinoma: A Review.

Colorectal signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) with unique characteristics. Due to the limited researches on it, a comprehensive and in-depth understanding of this subtype is still lacking. In this article, we summarize the clinicopathological features and molecular characteristics of colorectal SRCC based on a literature review. Clinically, SRCC has been associated with young age, proximal site preference, advanced tumor stage, high histological grade, high rate of lymph node involvement, frequent peritoneal metastasis, and a significantly poor prognosis. Regarding molecular characteristics, in SRCC, the mutation burden of the classic signaling pathways that include WNT/ß-catenin, RAS/RAF/MAPK, and PI3K/AKT/mTOR signaling pathways are generally reduced. In contrast, some genes related to the "epithelial-mesenchymal transition (EMT) process" and the "stem cell properties", including RNF43, CDH1, and SMAD4, as well as the related TGF-ß signaling pathway have been observed more frequently altered in SRCC than in conventional adenocarcinoma (AC). In many studies but not in others, SRCC showed a higher frequency of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype (CIMP) positive status compared to AC. It has been proposed that colorectal SRCC consists of two subtypes, in which the MSI+/CIMP+/BRAF +/CD3+/PD-L1+ hypermethylated genotype is more common in the proximal colon, and may represent the potential candidate for immunotherapy. Understanding the special molecular mechanisms related to the aggressive biology of SRCC is of great importance, which may provide a theoretical basis for the development of more targeted and effective treatments for this refractory disease.

Primary signet ring cell carcinoma of the uterine cervix: A case report.

RATIONALE: Primary signet ring cell carcinoma of the uterine cervix is extremely rare and the clinical characteristics and prognosis are not well known and there are no specific guidelines for treatment. PATIENT CONCERNS: A 43-year-old woman was referred to our hospital for abnormal uterine bleeding lasting 1 month. DIAGNOSES: Histological examination revealed a signet ring cell carcinoma of the uterine cervix. After evaluation of extragenital origin, the patient was diagnosed International Federation of Gynecology and Obstetrics stage IIIC1 primary signet ring cell carcinoma or the uterine cervix. INTERVENTION: The patient was prescribed concomitant chemo-radiation followed by intracavitary brachytherapy. OUTCOMES: She showed no evidence of disease after treatment but, it recurred after 7 months of last treatment. LESSONS: Different approaches to diagnosis and treatment of this rare disease are needed and molecular pathological studies related to the onset of the disease are required.

A Prognostic Model for Patients With Gastric Signet Ring Cell Carcinoma.

BACKGROUND: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). METHODS: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. RESULTS: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. CONCLUSION: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.

Risk of metachronous peritoneal metastases in patients with pT4a versus pT4b colon cancer: An international multicentre cohort study.

INTRODUCTION: With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. MATERIALS AND METHODS: From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). RESULTS: In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23-60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. CONCLUSION: Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies.