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.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

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.

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.

Right-sided versus left-sided colorectal cancer in elderly patients: a sub-analysis of a large multicenter case-control study in Japan.

PURPOSE: This study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis. METHODS: In a sub-analysis of a multicenter case-control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon. RESULTS: Among the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS. CONCLUSION: RCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs.

Partial Gastrectomy is Associated with Improved Overall Survival in Signet-Ring Cell Gastric Cancer.

BACKGROUND: Signet-ring cell gastric cancer (SRGC) is a histological variant of gastric adenocarcinoma (GAC) with a worse prognosis compared to non-signet-ring cell gastric cancer (NSRGC). To our knowledge, the overall survival (OS) among patients with SRGC undergoing total/near-total (TG) versus partial gastrectomy (PG) has never been reported from a large-scale Western database. METHODS: We performed a retrospective analysis of patients with both SRGC and NSRGC using The National Cancer Database. RESULTS: In total, 17,086 patients were included. Patients who underwent TG versus PG were 25.5% (n = 770) versus 74.5% (n = 2246) for SRGC, and 20.9% (n = 2943) versus 79.1% (n = 11,127) for NSRGC, respectively. Patients who had SRGC were more likely to undergo TG (25.5% versus 20.9% P< 0.0001). Patients with distal gastric tumors were less likely to undergo TG (16.5% versus 25.4% P < 0.0001). Patients undergoing PG for the SRGC histological variant had better OS (HR = 0.68, CI=0.61-0.76; P < 0.0001) versus those who underwent TG. Similarly, NSRGC patients undergoing PG also had improved OS, but to a lesser extent (HR = 0.91, CI = 0.85-0.96; P= 0.002). Overall, PG for GAC was associated with improved OS compared to TG, although the OS benefit is more profound in the SRGC histological variant (P < 0.0001). CONCLUSIONS: Our results show that TG is not associated with improved OS in patients who undergo gastrectomy for GAC, even when adjusted for tumor location. The survival differences are more pronounced in the SRGC histology variant. The worst survival is observed in patients with SRGC who undergo TG after adjusting for different covariates.

Nomograms to Predict Overall and Cancer-Specific Survival in Gastric Signet-Ring Cell Carcinoma.

BACKGROUND: The objective of our study was to develop and validate nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with signet-ring cell carcinoma (SRCC) of the stomach. METHODS: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 1781 patients were randomly allocated to a training set (n = 1335) and a validation set (n = 446). Univariate and multivariate analyses were used to determine the prognostic effect of variables. Nomograms were developed to estimate OS and CSS and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC), and decision curve analyses (DCA). DCA was utilized to compare the nomograms and the Tumor-Node-Metastasis (TNM) staging system. RESULTS: Age, race, tumor size, T, N, M stage, and use of surgery and/or radiotherapy were included in the nomograms. C-indexes for OS and CSS were 0.74 and 0.75 in the training set, respectively. C-indexes for OS and CSS were 0.76 and 0.76 in the validation set. Calibration plots and receiver operating characteristic (ROC) curves showed good predictive accuracy. According to the decision curve analyses (DCA), the new model was more useful than the TNM staging system. CONCLUSIONS: We developed nomograms to predict OS and CSS in patients with SRCC of the stomach. Nomograms may be a valuable clinical supplement of the conventional TNM staging system.

Prognostic Outcomes of Signet Ring Cell Carcinoma of the Breast.

BACKGROUND: Signet ring cell breast carcinoma (SRCBC) is a rare variant of invasive lobular carcinoma and there are no large series characterizing its long-term prognosis. MATERIALS AND METHODS: The NCDB was queried from 2004-2016 to identify SRCBC patients. Patients were excluded if they had non-invasive tumors, multiple malignancies, or incomplete surgical data. Univariate analysis was performed utilizing chi-squared and Fischer's Exact tests. Kaplan-Meier and Cox proportional hazard models were used for survival analysis. RESULTS: 324 patients met inclusion criteria. Patients were mostly White (75.3%), ≥50 years of age (88.2%), female (98.5%), and had a low Charlson-Deyo score (82.7%). 34.5% had Stage IV disease and 78.1% had ER+ tumors. In patients with non-Stage IV disease, 91.5% received surgery: 49.5% had lumpectomy and 50.5% underwent mastectomy. Radiation therapy was used in 40.7% (71.4% with lumpectomy and 35.8% with mastectomy) and 50% received chemotherapy. Significant differences in unadjusted overall survival were seen at 5 and 10 years based on stage (P < 0.001). On multivariate analysis, ER+ patients showed an improved survival (HR 0.5, P < 0.01) but there was no difference in survival if ER+ patients received endocrine therapy (ET) (HR 0.9, P = 0.57). Non-metastatic patients who underwent surgery had improved overall survival compared to those that did not (HR 0.5, P = 0.02), but there was no survival difference based upon type of breast operation (P = 0.8). CONCLUSION: SRCBC frequently presents at an advanced stage. While ER+ patients appear to have improved survival, there was no clear survival benefit to receiving ET in ER+ patients.

Rare Histological Variants of Prostate Adenocarcinoma: A National Cancer Database Analysis.

PURPOSE: The American Joint Committee on Cancer recognizes 6 rare histological variants of prostate adenocarcinoma. We describe the contemporary presentation and overall survival of these rare variants. MATERIALS AND METHODS: We examined 1,345,618 patients who were diagnosed with prostate adenocarcinoma between 2004 and 2015 within the National Cancer Database. We focused on the variants mucinous, ductal, signet ring cell, adenosquamous, sarcomatoid and neuroendocrine. Characteristics at presentation for each variant were compared with nonvariant prostate adenocarcinoma. Cox regression was used to study the impact of histological variant on overall mortality. RESULTS: Few (0.38%) patients presented with rare variant prostate adenocarcinoma. All variants had higher clinical tumor stage at presentation than nonvariant (all p <0.001). Metastatic disease was most common with neuroendocrine (62.9%), followed by sarcomatoid (33.3%), adenosquamous (31.1%), signet ring cell (10.3%) and ductal (9.8%), compared to 4.2% in nonvariant (all p <0.001). Metastatic disease in mucinous (3.3%) was similar to nonvariant (p=0.2). Estimated 10-year overall survival was highest in mucinous (78.0%), followed by nonvariant (71.1%), signet ring cell (56.8%), ductal (56.3%), adenosquamous (20.5%), sarcomatoid (14.6%) and neuroendocrine (9.1%). At multivariable analysis, mortality was higher in ductal (HR 1.38, p <0.001), signet ring cell (HR 1.53, p <0.01), neuroendocrine (HR 5.72, p <0.001), sarcomatoid (HR 5.81, p <0.001) and adenosquamous (HR 9.34, p <0.001) as compared to nonvariant. CONCLUSIONS: Neuroendocrine, adenosquamous, sarcomatoid, signet ring cell and ductal variants more commonly present with metastases. All variants present with higher local stage than nonvariant. Neuroendocrine is associated with the worst and mucinous with the best overall survival.

miR-99a-5p as Possible Diagnostic and Prognostic Marker in Patients With Gastric Cancer.

BACKGROUND: The signet-ring cell carcinoma (SRC), one of the histological subtypes of gastric cancer, often exhibits aggressive behavior in clinical practice and is therefore a commonly found subtype in advanced gastric cancer. However, SRC, especially at the early stages, has recently been reported to show a lower potential for malignancy than other pathological subtypes. Because the detailed molecular mechanisms underlying SRC pathology remain unclear, we focused on microRNAs (miRs) and aimed to elucidate the molecular mechanisms involved in endowing early SRC with its characteristic properties. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples of patients diagnosed with various pathological subtypes of gastric cancer including SRC were used to purify and subsequently evaluate miRs. RESULTS: As expected, patients with SRC were observed to have significantly high miR-99a-5p expression. Further, high miR-99a-5p expression was found to closely correlate with less aggressive clinicopathological features, and functional studies probed by overexpression of miR-99a-5p resulted in inhibition of proliferation in two SRC cell lines. CONCLUSIONS: The present study reports that high levels of miR-99a-5p were observed in patients with SRC, particularly those with early stage SRC. In addition, miR-99a-5p expression was found to be related to cell proliferation. Therefore, miR-99a-5p could emerge as a diagnostic biomarker for early SRC and lymph node metastases or related adverse prognosis in patients.

The amount of signet ring cells is significantly associated with tumour stage and survival in gastric poorly cohesive tumours.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate whether the amount of signet ring cells (SRCs) affects clinicopathological characteristics and prognosis of poorly cohesive (PC) gastric tumours. STUDY DESIGN: One hundred seventy-three patients with PC tumours treated at three European centres from 2004 to 2014 were reclassified in three categories: (a) pure SRC cancers (SRC1) (≥90% SRCs); (b) PC carcinoma with SRC component (SRC2) (>10%, <90% SRCs); (c) PC carcinoma not otherwise specified (SRC3) (≤10% SRCs). RESULTS: The percentage of SRCs was inversely related to the pT stage (Spearman's ρ = -0.174, P < .001) and the number of positive nodes coded as a continuous variable (P = .009). Five year cancer-related survival was significantly higher (58%, 95% confidence interval [CI]: 36%-75%) in SRC1 compared with SRC2 (39%, 95% CI: 28%-50%) and SRC3 (38%, 95% CI: 22%-53%), (P = .048). In multivariable analysis, the impact of PC categories on cancer-related survival was significant when controlling for sex, age, pT, pN, and curativity (hazard ratio [HR] of sSRC2 vs SRC1 = 2.08, 95% CI: 1.01-4.29, P = .046; HR of SRC3 vs SRC1 = 2.38, 95% CI: 1.05-5.41, P = .039). CONCLUSION: The percentage of SRCs was inversely related to tumour aggressiveness, with long-term survival significantly higher in SRC1 compared with SRC2 and SRC3 tumours.

Significance of CT attenuation and F-18 fluorodeoxyglucose uptake of visceral adipose tissue for predicting survival in gastric cancer patients after curative surgical resection.

BACKGROUND: The purpose of this study was to investigate the prognostic significance of computed tomography (CT) attenuation and F-18 fluorodeoxyglucose (FDG) uptake of visceral adipose tissue (VAT) to predict peritoneal recurrence-free survival (RFS) as well as RFS and overall survival (OS) in patients with advanced gastric cancer (AGC). METHODS: We retrospectively enrolled 117 patients with AGC who underwent staging FDG positron emission tomography (PET)/CT and subsequent curative surgical resection. CT attenuation and FDG uptake (SUV) of VAT and maximum FDG uptake of primary tumor (SUVmaxT) were measured from PET/CT images. The relationship of VAT attenuation and SUV with clinico-histopathologic factors and survival was assessed. RESULTS: There was a significant positive correlation between VAT attenuation and SUV (p < 0.001, r = 0.799). In correlation analyses, both VAT attenuation and SUV showed significant positive correlations with T stage, TNM stage, tumor size, and platelet-to-lymphocyte ratio (p < 0.05), and patients who experienced recurrence during the first 3-year after surgery had significantly higher VAT attenuation and SUV than those who had no recurrence (p < 0.05). Patients with high VAT attenuation and SUV showed significantly worse RFS, peritoneal RFS, and OS than those with low values (p < 0.05). On multivariate survival analysis, VAT attenuation was significantly associated with peritoneal RFS and OS and VAT SUV was significantly associated with OS (p < 0.05). CONCLUSIONS: CT attenuation and FDG uptake of VAT on staging FDG PET/CT were correlated with tumor characteristics and were significant predictive factors for peritoneal RFS and OS in patients with AGC.

Incidence, risk factors, treatment, and survival of ovarian metastases of colorectal origin: a Dutch population-based study.

OBJECTIVE: The aim of this nationwide study was to provide insight in the incidence, risk factors, treatment, and survival of patients with ovarian metastases from colorectal cancer (CRC). METHODS: Data from the Netherlands Cancer Registry were used. All newly diagnosed female CRC patients between 2008 and 2016 were included. Treatment was categorized as follows: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); resection of the primary tumor; palliative treatment; and no treatment. Overall survival (OS) was investigated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Of 53,883 female CRC patients, 11,343 (21.1%) had metastases at time of diagnosis. Among them, 471 (4.2%) had ovarian metastases. Within latter group, 27.2% received CRS-HIPEC; 38.4% underwent resection of the primary tumor; 25.3% received palliative treatment; and 9.1% received no treatment. Median OS of all patients with ovarian metastases was 17.5 months. In patients receiving CRS-HIPEC, OS was significantly longer than in patients undergoing resection only (median OS 34.1 vs. 17.5 months, adjusted HR 0.44 [0.33-0.66]). Five-year OS was 28.5% for patients having underwent CRS-HIPEC, 11.0% for patients having underwent resection of the primary tumor, 1.2% for patients having underwent palliative treatment, and 0.0% for patients without treatment. CONCLUSIONS: Synchronous ovarian metastases are diagnosed in 4.2% of female colorectal patients presenting with metastatic disease. Risk factors are young age, T4/N+ tumor and histology of signet ring cell carcinoma. Median OS of the entire cohort was 17.5 months, ranging from 3.1 months in patients without treatment to 34.1 months in patients undergoing CRS-HIPEC.

Signet ring cell component in pretreatment biopsy predicts pathological response to preoperative chemoradiotherapy in rectal cancer.

PURPOSE: Neoadjuvant therapy is routinely used in the management of locally advanced rectal cancer. This study aimed to evaluate the predictive value of pathological parameters in tumor response after treatment. METHODS: We reviewed the hematoxylin-eosin slides from pretreatment biopsies of 150 rectal cancer patients who received preoperative chemoradiotherapy (PCRT) at Sun Yat-sen University Cancer Center between May 2013 and June 2016. Pathological and clinical parameters were both studied. The tumor response after chemoradiotherapy was evaluated using the tumor regression grade (TRG). Logistic regression was used to evaluate the relevance between these parameters and tumor response. RESULTS: Complete tumor response (TRG0 and pCR) to PCRT was identified in 40 (26.7%) patients. The pCR rate was 93.33% (14 of 15) in cases with signet ring cell component versus 19.26% (26 of 135) in those without signet ring cell component (p < 0.001). Four cases with signet ring cell component were evaluated as clinical complete response (cCR), all of whom also achieved pCR; in contrast, only 9 of 15 (60%) cCR cases without signet ring cell achieved pCR. CONCLUSION: Our data suggest that the signet ring cell component in pretreatment biopsies may be a potential predictor of tumor response to PCRT in rectal cancer. This suggests patients with clinical complete response are more suitable for a wait-and-watch approach.

Outcomes in Peritoneal Dissemination from Signet Ring Cell Carcinoma of the Appendix Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard treatment for peritoneal dissemination from appendiceal cancer (AC); however, its role in high-grade histopathologic subtypes (high-grade mucinous carcinoma peritonei [HGMCP] and HGMCP with signet ring cells [HGMCP-S]) is controversial due to their aggressive behavior. This study analyzed clinical outcomes of high-grade AC after CRS/HIPEC. METHODS: A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998-2017 was reviewed. Perioperative variables and survival were analyzed. RESULTS: Eighty-six HGMCP and 65 HGMCP-S were identified. HGMCP had more positive tumor markers (TM) (CEA/CA-125/CA-19-9) than HGMCP-S (63% vs 40%, p = 0.005). HGMCP had higher Peritoneal Cancer Index (32 vs 26, p = 0.097) and was less likely to have positive lymph nodes (LN) than HGMCP-S (28% vs 69%, p = < 0.001). Complete cytoreduction was achieved in 84% and 83%, respectively. PFS at 3- and 5-years was 59% and 48% for HGMCP vs 31% and 14% for HGMCP-S. Median PFS was 4.3 and 1.6 years, respectively (p < 0.001). OS at 3- and 5-years was 84% and 64% in HGMCP vs 38% and 25% in HGMCP-S. Median OS was 7.5 and 2.2 years, respectively (p < 0.001). LN negative HGMCP-S had longer median PFS and OS than LN positive HGMCP-S (PFS: 3.4 vs 1.5 years, p = 0.03; OS: 5.6 vs 2.1 months, p = 0.021). CONCLUSIONS: The aggressive histology of HGMCP-S is associated with poor OS, has fewer abnormal TM, and is more likely to have positive LN. However, CRS/HIPEC can achieve a 5-year survival of 25%, which may improve to 51% with negative LN.

Does Primary Tumor Side Matter in Patients with Metastatic Colon Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy?

BACKGROUND: Primary tumor location has been shown to be prognostic of overall survival (OS) in patients with both locally advanced and metastatic colorectal cancer. The impact of sidedness on prognosis has not been evaluated in the setting of peritoneal-only metastases treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective review of prospectively maintained databases of patients with peritoneal surface malignancy undergoing CRS/HIPEC from three high-volume centers was performed. RESULTS: A total of 115 patients with metastatic colon cancer to the peritoneum who underwent CRS/HIPEC with mitomycin C were identified. Fifty-one patients (45%) had left-sided primary tumors, and 64 (55%) had right-sided primary tumors. Patients with right-sided tumors were more likely to be older (median age 56 vs. 49 years, p = 0.007) and to have signet ring cell histology (17% vs. 4%, p = 0.026). Patients with right-sided tumors had median disease-free survival (DFS) and OS of 14 months (95% confidence interval [CI] 10.5-17.5) and 36 months (95% CI 27.4-44.6), respectively, versus 16 months (95% CI 11.0-21.0) and 69 months (95% CI 24.3-113.7) for those patients with left-sided tumors. On multivariate analysis, primary tumor side was an independent predictor of both DFS and OS. CONCLUSIONS: In this study, there was a dramatic, clinically significant difference in OS between patients with right- and left-sided tumors, and primary tumor side was an independent predictor of DFS and OS. Primary tumor side should be considered in patient selection for CRS with or without HIPEC.

Selection and Characteristics of Patients with Peritoneal Dissemination from Appendiceal Cancer with Exceptional/Poor Survival After CRS/HIPEC.

BACKGROUND: Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. METHODS: Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. RESULTS: LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p < 0.001]; 3 vs. 29.5 [p = 0.001]). Fewer LGMCP and HGMCP ExR had abnormal tumor markers (36% vs. 90% [p = 0.003]; 22% vs. 74% [p = 0.003]). More HGMCP and HGMCP-S ExR had CC-0 (vs. CC-1) cytoreductions (84% vs. 50%, p = 0.041; 100% vs. 40%, p = 0.008). CONCLUSIONS: Stratifying patients by recurrence status and follow-up time successfully selects ExR and PoR within each histopathologic subtype. Perioperative characteristics of ExR versus PoR differ across histopathologic subtypes, except for disease burden. Genetic analysis may further elucidate differences and aid in the development of novel targeted therapies.

Natural History of Gastric Cancer: Observational Study of Gastric Cancer Patients Not Treated During Follow-Up.

BACKGROUND: Understanding the natural progression of untreated gastric cancer is critical for determining the disease prognosis as well as treatment options and timing. The aim of this study is to analyze the natural history of gastric cancer. PATIENTS AND METHODS: We included patients with gastric cancer who had not received any treatment and were staged using endoscopy/endoscopic ultrasonography and computed tomography on at least two follow-up visits during intervals of nontreatment. Tumor volumes were also measured in addition to the staging. Survival of each stage at diagnosis was also analyzed. RESULTS: A total of 101 patients were included. The mean follow-up period was 35.1 ± 34.4 months. The gastric cancer doubling time was 11.8 months for T1 and 6.2 months for T4. The progression time from early gastric cancer to advanced gastric cancer was 34 months. It decreased as the stages advanced: from 34 months between tumor-nodes-metastasis stage I and II to 1.8 months between stage III and IV. No variable was identified as a risk factor for cancer progression. The 5-year survival rates of untreated patients were 46.2% in stage I and 0% in stage II, stage III, and stage IV. CONCLUSIONS: The progression and doubling times of gastric cancer shorten as the stages advance. Objective data reported in this study can be a critical factor in determining treatment timing and screening interval.

Adenocarcinoma with mixed subtypes is a rare but aggressive histologic subtype in colorectal cancer.

BACKGROUND: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.

Signet ring cell features with peritoneal carcinomatosis in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are associated with poor overall survival.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective in select patients with peritoneal carcinomatosis (PC). Signet ring cell (SRC) pathology is associated with poor prognosis. The role of CRS/HIPEC in this population is unclear. METHODS: Patients diagnosed with PC due to appendiceal (AC), colorectal (CRC), and gastric cancer (GC) undergoing CRS/HIPEC 2007-2016 were included. RESULTS: A total of 268 patients were referred for CRS/HIPEC. Of the 204 patients who underwent complete CRS/HIPEC, 101 (49.5%) had AC, 85 (41.7%) CRC, and 18 (8.8%) GC. Patients with GC had higher rates of SRC pathology than AC and CRC: 12 (66.7%) vs 16 (15.8%) and 10 (11.7%). The 3-year survival rate after CRS/HIPEC was 5.7% for the SRC group and 66.1% for the non-SRC group (P < 0.001). This was true for both AC and CRC subgroups (P < 0.001 for both). Overall, patients with SRC were more likely to have a peritoneal carcinomatosis index (PCI) score > 15 (P = 0.046). Upon multivariate analysis of the SRC population, PCI > 20 (P = 0.007) and GC (P = 0.008) were found to be independent predictors of poor overall survival. CONCLUSIONS: Performing CRS/HIPEC for PC from gastrointestinal malignancies presenting SRC features is recommended on patients with select diseases of appendiceal and colorectal origins.