Signet Ring Cell Histology Research Articles

The prognostic value of signet ring cell histology in stage I/II colon cancer-a population-based, propensity score-matched analysis.

Previous research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer. Stage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods. Eighty-eight thousand nine hundred fifty-eight stage I-II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, p < 0.001; CSS, p < 0.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82-1.12%) p = 0.616; CSS: HR, 1.01 (95% CI, 0.79-1.28%) p = 0.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82-1.14%) p = 0.669 and CSS: HR: 1.09 (95% CI: 0.84-1.40%) p = 0.529), a survival disadvantage was found for signet ring cell histology. This is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.

The impact of American Indian and Alaska Native ethnicity on the presentation and surgical treatment of gastric cancer: An NCDB analysis from 2004-2014.

13 Background: American Indian/Alaska Natives (AI/ANs) with gastric adenocarcinoma (GC) have an incidence and mortality nearly double that of matched Non-Hispanic Whites (NHW) in historical data sets. However, the impact of AI/AN ethnicity on disease presentation and treatment is underrepresented in gastric cancer epidemiologic studies and has not been evaluated in a contemporary population. Methods: The National Cancer Data Base (NCDB) was queried from 2004-2014 to identify patients with gastric cancer who identify as AI/AN or NHW. Patient demographics, tumor characteristics, and treatment details, including surgical quality metrics, were compared using Chi-square and Student's t-tests. Results: There were 22,286 NHW and 115 AI/AN GC patients with complete staging information. Compared to NHW, AI/ANs were younger (age ≤65) at diagnosis (p &lt; 0.001), which translated to a younger median age at death (NHW:70 years, AI/ANs:60 years, p &lt; 0.001). AI/ANs more often lived over 100 miles from their treatment facility (p &lt; 0.001) in non-metropolitan cities (p &lt; 0.001). Stage distribution was not different for the AI/AN population when compared to the NHW population: 37% vs. 35% Stage I; 33% vs. 37% Stage II; 10% vs. 11% Stage III; and 19% vs. 16% Stage IV (p = NS). However, AI/ANs had a higher rate of signet ring cell histology and linitis plastica (26% vs. 15%, p = 0.002) compared to NHWs. More AI/AN patients compared to NHW patients had delays over eight weeks to initiation of treatment, 19% vs. 11% (p = 0.008). There were no statistically significant differences for surgical quality metrics, including type of surgery, rate of ≥15 lymph nodes retrieved, margin positivity, or 30-day mortality (p = NS). Conclusions: Both biological and social disparities are evident for AI/ANs with gastric cancer. AI/ANs develop and die from gastric cancer at younger ages compared to NHWs and present with higher rates of aggressive histology. They also travel longer distances for treatment and experience greater treatment delays. These features may partly underlie the higher mortality rates previously described.

Lymphovascular invasion and lymph node metastasis rates in papillary adenocarcinoma of the stomach: implications for endoscopic resection.

Current Japanese gastric cancer treatment guidelines recommend the same endoscopic resection criteria for papillary early gastric cancer (EGC) and well-differentiated (WD) or moderately differentiated (MD) EGC. To evaluate the appropriateness of this recommendation, we compared the clinicopathological characteristics of papillary EGC with those of WD, MD, poorly differentiated (PD), and signet ring cell (SRC) EGC. A total of 6710 patients who underwent radical gastrectomy for EGC were included. Clinicopathological characteristics of papillary EGC were retrospectively reviewed and compared with those in other EGC subtypes. Papillary EGC accounted for 1.9% (130/6710) of total cases. Patients with papillary EGC were older and showed a male predominance compared to patients with PD or SRC EGC. Papillary EGCs showed significantly higher submucosal and lymphovascular invasion rates than WD or MD EGC or PD or SRC EGC. However, the LN metastasis rate of papillary EGC was comparable to or lower than that in other EGC subtypes. LN metastasis rates in mucosal cancers were 1.5%, 1.1%, and 4.0%, and those in submucosal cancers were 9.4%, 11.9%, and 17.6% for papillary EGC, WD or MD EGC, and PD or SRC EGC, respectively. In multivariate analysis, lymphatic invasion and PD or SRC histology were the strongest risk factors for LN metastasis. Among 63 papillary EGC that met the curative endoscopic resection criteria, no case showed LN metastasis. Endoscopic resection can be indicated for papillary EGC according to current guidelines. Given a considerable lymphovascular invasion rate, careful histological evaluation is required after endoscopic resection for papillary EGC.

PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer.

BackgroundTrastuzumab is an active agent against human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). This study aimed to characterize resistance to trastuzumab-based front-line chemotherapy in HER2+ GC patients and to establish factors predictive of this resistance.ResultsAmong 129 HER2+ GC patients, 25% displayed rapid disease progression within 4 months from initiation of therapy. These patients showed a higher rate of signet ring cell histology, bone metastasis, poor performance status, frequent loss of PTEN expression, and low HER2 amplification index compared with patients who were progression-free for at least 4 months. In contrast, there was no significant difference in the frequency of the PIK3R1 variant. Multivariate analyses confirmed two independent molecular predictors for trastuzumab resistance: loss of PTEN expression and low HER2 amplification index (<5). Patients with one or both molecular predictors at diagnosis exhibited worse progression-free and overall survival compared to those without risk factors (p < 0.001 and p = 0.001, respectively).ConclusionIn HER2+ GC patients, loss of PTEN expression and low HER2 AI correlated with resistance to trastuzumab-based therapy and dismal prognosis. Since patients harboring these molecular predictors are unlikely to respond to trastuzumab-based therapy, other novel therapeutic targets needed to be considered.MethodsHER2+ GC patients who were treated with trastuzumab in combination with either 5-fluorouracil/cisplatin or capecitabine/cisplatin were enrolled. Clinicopathologic features and molecular alterations of HER2, phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1), and phosphatase and tensin homolog (PTEN) were correlated with treatment outcome. Factors predictive of resistance were also explored.

A Road Less Traveled: A Case of Spinal Metastasis In Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is a relatively infrequent neoplasm in the United States. Common sites of metastasis include liver, peritoneum, and ovaries. Metastasis to bone is exceedingly rare with an overall incidence of ˜1% in all cases of GAC. We present an unusual case of a patient diagnosed with GAC with metastasis to the spine and lungs. A 41-year-old male presented to the emergency department with pleuritic chest and upper back pain for a month. Physical exam revealed increased respiratory rate and spinal tenderness. Laboratory data was unremarkable except for an elevated alkaline phosphatase (ALP) level. A CT scan of the chest showed reticulonodular opacities in the right apex, right upper lobe and adenopathy in mediastinum and hila, as well as a compression fracture in the second thoracic vertebrate (T2) with possible lytic lesions. MRI thoracic spine revealed pathological compression fractures of T2 and T3 with abnormal bone marrow signal with heterogeneous enhancement with perivertebral soft tissue thickening and enhancement. Pulmonology was consulted and an endobronchial ultrasound was performed which demonstrated morphological features of a metastatic adenocarcinoma. Interventional radiology performed a biopsy of the paravertebral mass which revealed metastatic adenocarcinoma likely from gastric origin. An esophagogastroduodenoscopy was performed which demonstrated a 2.5 x1 cm clean based ulcer with heaped up margins in the antrum, and an erythematous and edematous area in the in the bulb and descending duodenum concerning for tumor infiltration. Biopsies from the gastric ulcer demonstrated poorly differentiated adenocarcinoma with signet ring cell features. The patient was started on palliative radiation treatments and further management is pending formal multidisciplinary tumor board. Bone metastasis is relatively uncommon is patients with GAC. Patients with bone metastasis on initial presentation tend to be younger, have signet ring cell histology, pleural metastasis, and elevated serum ALP. Our patient had all these characteristics. Previous reports have demonstrated a correlation between serum ALP elevation and bony metastasis in GAC. While our patient presented with a pathological fracture, patients with GAC and elevated serum ALP levels should be investigated for bone metastasis, to prevent complications including pain and fracture, as well as helping to guide therapy.Figure. 2: 5 x1 cm clean based ulcer with heaped up margins in the antrum.Figure: Biopsy from paravertebral mass: CDX2 positive indicating more likely gastric in origin.Figure: Biopsy from paravertebral mass: CK7 negative indicating less likely lung in origin.

External Validation of the Prognostic Nomogram (COMPASS) for Patients with Peritoneal Carcinomatosis of Colorectal Cancer.

To optimize outcome, selection of patients for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critical. Recently, Simkens et al.7 evaluated the peritoneal surface disease severity score (PSDSS) and suggested a new prognostic nomogram, the colorectal peritoneal metastases prognostic surgical score (COMPASS) based on age, peritoneal carcinomatosis index score, locoregional lymph node status, and signet ring cell histology. This COMPASS nomogram had better discriminative ability according to the Harrell c-index than PSDSS (c=0.72 vs. 0.62). This study aimed to validate the COMPASS nomogram externally. Data were retrieved from a prospectively maintained database, and all patients who underwent surgery between May 2005 and May 2016 were included in the study. For each patient, the PSDSS and COMPASS were calculated and then divided into subgroups. The discriminative ability of both scores for overall survival were quantified using Harrell c indices. A total of 153 patients underwent CRS+HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. The median overall survival (OS) was 46months, and the mean PSDSS was 7.8±3.7. When the PSDSS was divided into subgroups, the c index was 0.67. The mean COMPASS was 55.5±25.6. When the patients were divided into four groups according to cutpoints of Simkens et al.7 a c index of 0.72 was obtained, showing its significant superiority over the discriminative ability of the PSDSS (p=0.016). External validation of the COMPASS confirms its moderate to good discriminative ability and its superiority over the PSDSS. Nevertheless, discrimination with the COMPASS score remains suboptimal, and further research on prognostic variables is essential for optimal patient selection.

Predictive factors for lymph node metastasis in early gastric cancer with signet ring cell histology: a meta-analysis.

Less invasive surgery is widely used in the treatment of early gastric cancer; however, no definite guidelines exist regarding indications for less invasive surgery to treat early gastric cancer with signet ring cell histology. The aim of this study was to identify risk factors for lymph node metastasis (LNM) in early signet ring cell carcinoma (SRC). An extensive search of PubMed, Embase and the Cochrane library was performed for pertinent articles involving early SRC and LNM. Eligible data (gender, depth of invasion, lymphovascular invasion, size, ulceration, macroscopic type and location) were extracted from the included studies and systematically reviewed via a meta-analysis. Review Manager version 5.3 was used to perform the data processing. The Newcastle-Ottawa Scale was utilized to evaluate the quality of the included articles. Fourteen studies were included in the final analysis. After meta-analysis, female gender, submucosal invasion, lymphovascular invasion and size >20 mm were associated with LNM in early SRC. Four variables were identified as risk factors for LNM in early SRC. The significance of the results of the present study should be further confirmed in more early SRC patients for future clinical use.

Patient selection for cytoreductive surgery and HIPEC for the treatment of peritoneal metastases from colorectal cancer.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a viable option for selected patients with peritoneal metastases (PM) from colorectal origin, resulting in long-term survival and even cure in some cases. However, adequate patient selection for this treatment is currently one of the major challenges. The aim of this review is to provide a comprehensive overview of clinically relevant factors associated with overall survival. This may help to guide clinicians through the complex interplay of patient, tumor, and treatment characteristics to adequately select patients who benefit the most from this extensive surgical treatment. First, basic principles of colorectal PM and the CRS and HIPEC treatment will be discussed. According to available literature, especially extent of peritoneal disease, completeness of cytoreduction, and signet ring cell histology have great influence on the outcome after CRS and HIPEC. Other factors that seem to have a negative prognostic value are the presence of liver metastases and the absence of treatment with neo-adjuvant systemic therapy. Prognostic models combining the above-mentioned factors, such as the Colorectal Peritoneal Metastases Prognostic Surgical Score nomogram, may provide clinically relevant tools to use in everyday practice.

Ovarian Metastases of Colorectal Origin: Treatment Patterns and Factors Affecting Outcomes.

The purpose of this study is to evaluate the patterns of treatment and factors affecting outcomes in ovarian metastases of colorectal origins treated at our institution and to assess the response of ovarian metastases to chemotherapy. Survival in R0 and R+ resections and patients receiving only chemotherapy is also analyzed. This is a retrospective study of 25 patients registered between January 2012 and December 2015. Patient's age, disease status, mode of presentation, disease spread, mode of treatment, response to chemotherapy, completeness of resection, histology, and outcomes were considered as variables for analysis. There were 21 synchronous presentations and 4 metachronous presentations. In synchronous presentations, only 2 had extra-abdominal disease. Of these patients, 15 underwent surgeries of various extents. The remaining 6 patients were treated with chemotherarpy initially. Only one of them could come up to surgery later. In R0 resections, disease recurred between 1 and 9months (median 3.5months). The recurrence was in peritoneum and ovaries. In operated cases, 12 of 15 patients received chemotherapy and 9 patients progressed on first line chemotherapy. In all 4 metachronous patients, the disease was in the peritoneum. No one underwent surgery for the recurrence due to the extensive nature of the disease. All received chemotherapy. Sixty-six percent ovarian metastases showed progression on chemotherapy. There was no significant difference in the median survival between patients treated with surgery plus chemotherapy (23months) vs. those treated with chemotherapy alone (28months). Age and presence of disease at other sites did not affect the outcomes. Non-signetring cell histologies showed better outcomes compared to signet ring cell histology (p=0.02). Synchronous presentation, R0 resections, and responsive disease showed better survival, however it was clinically not significant. Treatment of ovarian metastases of colorectal origins is varied but has consistently poor outcome. Non-signet histology was the only prognostic factor which showed better outcome. Survival was not different between patients treated with surgery+chemotherapy and chemotherapy alone but majority of ovarian metastases progressed on chemotherapy. Considering the poor response to chemotherapy and peritoneum being the most common site of disease, both in primary and recurrent setting, R0 resection should always be attempted after selecting the correct patients using PETscan, laparoscopy and standard exploratory protocols. Treatment should be tailored upon patient's status and disease burden with an aim to do complete cytoreduction whenever possible. CRS+HIPEC (cytoreductive surgery + hyperthermic intraperitoneal chemotherapy) can be considered on case to case basis as even R0 resections tend to recur.

Is surgical resection beneficial in recurrent or metastatic gastric cancer?

4043 Background: Although chemotherapy is currently established as a standard treatment in recurrent or metastatic gastric cancer, the role of palliative surgical resection is still controversial. We investigated the survival benefit of surgical resection in patients (pts) with recurrent or metastatic gastric cancer who received systemic chemotherapy. Methods: A retrospective review was conducted on 698 pts who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 391) gastric cancer. Overall survival (OS) of pts who underwent surgical resection followed by chemotherapy was compared to that of pts who received chemotherapy alone. Results: Among 140 pts (primary metastatic: 97, recurrent: 43) with surgical resection, gastrectomy, metastasectomy, and gastrectomy with metastasectomy were performed in 83 (primary metastatic: 81), 44, and 13 pts, respectively. Higher surgical resection rate was observed in pts with young age ( &lt; 70) (p = 0.010), ECOG PS 0 or 1 (p = 0.010), primary metastatic (p &lt; 0.0001), absence of liver metastasis (p = 0.002), and signet ring cell histology (p = 0.002). The median OS of pts who underwent surgical resection before chemotherapy was significantly longer than that of pts who received chemotherapy alone (19 vs. 9 months, p &lt;0.0001). The OS benefit of surgical resection was consistent across subgroups in terms of baseline characteristics including age, ECOG PS, disease status (primary metastatic vs. recurrent), peritoneal metastasis, and first-line chemotherapy regimen (single vs. combination). In multivariate analysis, surgical resection was independently associated with favorable OS (hazard ratio = 0.41, p &lt; 0.0001) along with ≥second-line chemotherapy (p &lt; 0.0001), whereas ECOG PS 2 or 3 (p = 0.013), signet ring cell histology (p &lt; 0.0001), and peritoneal metastasis (p = 0.046) were independent prognostic factors of poor OS. Conclusions: The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer pts may result in favorable outcome, although large scale phase III trials are essential to establish this treatment approach as a standard practice.

Is third-line chemotherapy routine practice in recurrent or metastatic gastric cancer?

e15558 Background: Patients (pts) with recurrent or metastatic gastric cancer eventually experience disease progression during or after completion of first-line chemotherapy. Second-line therapy is generally recommended in the current guidelines. Although third-line therapy is often performed in daily practice in some countries, there are few reports about the benefit of third-line therapy. Methods: A retrospective review was conducted on 683 pts who underwent at least first-line palliative chemotherapy for recurrent (n = 297) or primary metastatic (n = 386) gastric cancer. Clinicopathological characteristics and overall survival (OS) were analyzed according to the lines of chemotherapy as well as for all study pts. Results: One hundred and forty-nine pts (21.8%) underwent third- or further-line therapy. Third- or further-line therapy was more frequently performed in pts with young age ( &lt; 70) (p &lt; 0.0001), ECOG PS 0 or 1 (p &lt; 0.0001) at the initiation of first-line therapy, first-line combination regimen (p = 0.006), and palliative surgical resection before first-line therapy (p = 0.029). The median follow-up duration was 62 months (24-151 months) for the survivors. The median OS for pts after first- and third-line therapy was 10 and 6 months, respectively. The median OS of pts who received third-line therapy was significantly longer than that of pts who received second- or lesser-line therapy (18 vs. 8 months, p &lt; 0.0001). Multivariate analysis revealed that third- or further-line therapy was independently associated with favorable OS (hazard ratio = 0.56, p &lt; 0.0001) along with surgical resection (p &lt; 0.0001) and first-line combination regimen (p = 0.008), whereas signet ring cell histology (p = 0.002) and peritoneal metastasis (p = 0.027) were independent prognostic factors of poor OS. Conclusions: This study suggests that recurrent or metastatic gastric cancer pts may benefit from third-line chemotherapy, although careful selection is essential.

Signet ring cell colorectal cancer: Genomic insights into a rare subpopulation of colorectal adenocarcinoma.

606 Background: Colorectal signet ring cell carcinoma (SRCC) has been shown to be associated with advanced tumor stage at presentation and worse outcomes. Due to the rarity of this subtype, 1% of all colorectal adenocarcinoma (CRC), little is known about its molecular characteristics. We aimed to characterize the molecular alterations of this subgroup. Methods: Metastatic CRC (mCRC) patients (pts) with signet ring cell (SC) histology who had tumors evaluated with next generation sequencing between February 2009 and November 2015 were reviewed. SC mCRC were classified into 2 groups; SRCC (&gt;50% of signet cells) and adenocarcinoma (AC) with SC component. Genomic alterations, microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) status noted in SC mCRC were compared to non-SC mCRC pts from the Assessment of Targeted Therapies Against Colorectal Cancer program at MD Anderson Cancer Center using Pearson’s χ 2 test. Results: A total of 665 mCRC pts were included in this study. 93 pts (14%) had SC histology of which 30 (32.3%) pts were SRCC. The Table below shows key cancer genes mutation frequencies. Conclusions: Colorectal SRCC has distinct molecular features compared with non-SC and AC with SC component CRC. The frequencies of KRAS, PIK3CA and APC mutations were lower than the frequencies reported in non-SC CRC. SRCC was not associated with MSI-H or CIMP-H tumor in this study. Further studies on identification of activated pathways underlying this worse prognosis and potential therapeutic targets are required. [Table: see text]

Abstract IA06: Colorectal cancer in inflammatory bowel disease

Abstract IA06: Colorectal cancer in inflammatory bowel disease

593P - Prognostic value of signet ring cell histology for survival in stage I and II colon cancer patients: a population-based, propensity score matched analysis

593P - Prognostic value of signet ring cell histology for survival in stage I and II colon cancer patients: a population-based, propensity score matched analysis

Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer.

Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion.

The characteristics and prognostic value of signet ring cell histology in gastric cancer: A retrospective cohort study of 2199 consecutive patients.

Although signet ring cell cancer (SRCC) has long been regarded as an adverse prognostic factor of gastric cancer, the findings of existing studies on this issue are inconsistent. We conducted a retrospective cohort study of 2199 consecutive patients with gastric cancer treated in a tertiary cancer hospital in Beijing, China, 1994 to 2013. The characteristics of SRCC and non-SRCC were compared. The prognostic effects of SRCC and other important clinicopathological factors on overall survival were evaluated by both univariate and multivariate Cox regression analyses and expressed as hazard ratio (HR) with 95% confidence interval (CI). SRCC accounted for 16.1% of gastric cancer, increasing from 6% to 20% over the last 2 decades, and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. SRCC (HR: 1.387, 95% CI: 1.177-1.634), stage (HR: 1.752, 95% CI: 1.458-2.106), surgery (palliative resection: HR: 0.712, 95% CI: 0.590-0.859; curative resection: HR: 0.490, 95% CI: 0.380-0.633), performance status (HR: 1.849, 95% CI: 1.553-2.201), and age (HR: 1.070, 95% CI: 1.001-1.143) were independent prognostic factors for gastric cancer, whereas time period of diagnosis, sex, and tumor location were not statistically significantly associated with overall survival. Subgroup analyses showed that the prognostic value of SRCC did not vary much with age, sex, performance status, stage, and surgery and chemotherapy status. As compared with non-SRCC, SRCC accounted for increasingly more of gastric cancer and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. It was an independent prognostic factor associated with worse survival in gastric cancer.

Clinicopathological Parameters in Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Metastases: A Meta-analysis.

To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC. Peritoneal metastases (PMs) originating from colorectal cancer are treated with CRS and HIPEC. Despite increasing survival, high morbidity and mortality warrant selection of patients with optimal benefit from this treatment. Many studies report a number of variables to be associated with survival after CRS and HIPEC, but no definitive analysis has been made to validate various markers. In concordance with PRISMA guidelines, we performed a literature search encompassing 4110 articles to select 50 articles that reported the influence of 1 or more clinicopathological variables on overall survival after CRS and HIPEC. In absence of RCTs, 25 cohort studies could be used to perform a meta-analysis on 10 prognostic variables. We determined that concurrent liver metastasis, lymph node metastasis, Eastern Cooperative Oncology Group score, tumor differentiation, and signet ring cell histology are all negative prognostic variables on overall survival after CRS and HIPEC. Conversely, sex and location of primary could not be validated as prognostic markers. More research is required to make definitive conclusions about neoadjuvant chemotherapy, onset of PMs, and mucinous histology. Current clinical practice, which selects patients based on extraperitoneal metastasis, lymph node stage, performance status, and tumor histology, is validated by our pooled analysis. Our data merit further research into neoadjuvant chemotherapy in the setting of CRS and HIPEC for PMs.

The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation

Background: Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. Methods: We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or <pathCR in the resected specimens. Results: Most patients were men (60%), had stage cIII LGAC (50%), and received chemotherapy before chemoradiation (93%). Most had G3 tumors (78%) and SRC (58%). Presence of SRC was associated with a lower rate of pathCR (11 vs. 36%, p = 0.004), and the association remained significant even with a low percentage of SRC (1-10%; p = 0.014). The higher the fraction of SRC, the lower was the probability of pathCR (p = 0.03). G3 and SRC led to a shorter overall survival (OS) (p = 0.046 and p = 0.038, respectively). yp stage independently prognosticated OS and recurrence-free survival (p < 0.001). Conclusion: Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted.

Development of a Prognostic Nomogram for Patients with Peritoneally Metastasized Colorectal Cancer Treated with Cytoreductive Surgery and HIPEC.

With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), long-term survival can be achieved in selected patients with colorectal peritoneal metastases (PM). Patient selection and outcome may be improved significantly with a tool that adequately predicts survival in these patients. This study was designed to validate the peritoneal surface disease severity score (PSDSS) in patients with colorectal PM treated with CRS+HIPEC. If performance of the PSDSS was suboptimal (c<0.7), we aimed to develop a new prognostic model. Patients were included if they had colorectal PM and underwent CRS+HIPEC with intended complete cytoreduction in a Dutch tertiary hospital between 2007 and 2015. Statistical analyses were performed with R-software. A total of 200 patients underwent CRS+HIPEC. External validation of the PSDSS showed a Harrell's c statistic of 0.62. After analysis, four parameters appeared prognostically relevant factors for overall survival: age, PCIscore, locoregional lymph node status, and signet ring cell histology. The weighted relevance of these parameters was turned into a prognostic nomogram that we termed colorectal peritoneal metastases prognostic surgical score (COMPASS). The COMPASS differentiated well and showed a Harrell's c statistic of 0.72 with a calibration plot showing good agreement. This study externally validated the PSDSS and developed a new prognostic score, the COMPASS. This pre-cytoreduction nomogram was more accurate than PSDSS in predicting survival of patients undergoing CRS+HIPEC. It can be used as tool to assist in the decision about continuing cytoreduction and HIPEC and can provide valuable information in the follow-up period after CRS+HIPEC.

Clinicopathological features and outcomes in patients undergoing radical resection for early gastric cancer with signet ring cell histology

The signet ring cell histology is regarded as an independent predictor of poor prognosis in advanced gastric adenocarcinomas, but its biologic behavior in early gastric cancer remains highly controversial. Our objective was to compare the clinicopathological features and outcomes in patients undergoing curative resection between SRCs and non-SRCs histologic types of early gastric cancer. Clinicopathologic features and the overall survival rates of 334 patients with early gastric cancer undergoing D2 curative resection from January 1994 to December 2008 were retrospectively reviewed and compared according to the histologic type. Clinicopathologic features were comparable between two groups, except age, ulcer findings and the presence of lymph node metastasis. The incidence of recurrence for SRCs group was significantly lower than that for non-SRCs group (10.4% vs. 19.6%; P<0.05). The overall 5-year survival rate was 88.6% in all cases. The overall survival rate of patients in SRCs group was significantly better than that of patients in non-SRCs group (5-year survival, 93.9% vs. 85.8%; P=0.027). Multivariable analysis revealed that SRCs subtype, lymphovascular invasion, and lymph node metastasis were independent prognostic factors. Our analysis revealed that the biological behavior of SRCs was different from other undifferentiated cancer histologic subtypes in early stage. Early gastric cancer with signet ring cell histology had low incidence of lymph node metastasis and a relatively favorable prognosis.