Presence Of Signet Ring Cells Research Articles

Identification of prognostic factors for survival in patients with metastatic gastric adenocarcinoma in a Mexican population

Introduction and aimsGastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. Material and methodsPatients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor’s prognostic value for overall survival was determined through univariate and multivariate analyses. ResultsThe study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06 - 1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10-1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53-0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. ConclusionsThe NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making.

Identificación de factores pronósticos para supervivencia en pacientes con adenocarcinoma gástrico metastásico en la población mexicana

Introduction and aimsGastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. Material and methodsPatients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses. ResultsThe study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n=619, 64.7%), followed by intestinal adenocarcinoma (n=293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p<0.001), albumin below 3.5g/dl (HR 1.25, 95% CI 1.06-1.47; p=0.006), and an ECOG performance status of 2 or higher (HR 1.39, 95% CI 1.10-1.76; p=0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, 95% CI 0.53-0.91; p=0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. ConclusionsThe NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma, and be taken into account during therapeutic decision-making.

Primary Endometrial Carcinoma with Signet Ring Cells: A Rare and Unusual Entity

Abstract Introduction/Objective The presence of signet ring cells in an endometrial tumor is suggestive of metastasis, as primary tumors with this morphology are extremely rare. As a result, primary tumors are a diagnosis of exclusion, defined by the presence of signet-ring cells usually associated with mucinous endometrioid carcinoma without clinical or radiographic evidence of metastases from breast, stomach, or colon. Methods/Case Report A 64-year-old woman presented with vaginal bleeding. Ultrasound showed a large, heterogenous uterine mass that was diagnosed as poorly differentiated carcinoma on biopsy. Serum CEA was elevated, and CA-125 was normal. Hysterectomy with salpingo-oophorectomy showed a minor endometrial component of grade 3 endometrioid carcinoma and a predominant component of poorly differentiated carcinoma with signet ring cells. The myoinvasive component consisted of the signet ring cells with pools of acellular mucin. Extensive lymphovascular invasion was noted. Cervix, adnexa, and lymph nodes were free of disease. The signet ring cells were positive for CK7, CK20, and CDX2, and negative for ER and Pax-8. The endometrioid component was positive for ER, Pax-8, and CK7, and negative for CK20 and CDX2. E-cadherin staining was lost in the myoinvasive component of the tumor. Loss of MLH1 and PMS2 nuclear expression was seen, and MLH1 promoter methylation was detected in both components of the tumor. Subsequent colonoscopy and imaging did not reveal any other disease sites. Based on histology, pattern of uterine involvement, and lack of extrauterine disease, a diagnosis of primary poorly-differentiated endometrial adenocarcinoma with signet ring cell features was made. The patient was treated with adjuvant chemotherapy and is currently being followed. Results (if a Case Study enter NA) NA Conclusion We present a rare case of primary signet ring carcinoma of the uterus, a challenging diagnosis made after extensive work-up to rule out metastases. Of the previous 9 reported cases, only one was similar to our tumor with distinct endometrioid and signet ring components. Although these primary endometrial tumors are unified by the presence of signet ring cells, there is considerable immunohistochemical heterogeneity. Some reports suggest the signet ring cells have a Mullerian phenotype, while others, including our case, suggest a gastrointestinal phenotype. In presenting this case, we hope to contribute to this entity’s characterization and bring further awareness that the presence of signet ring cells does not exclude a uterine primary.

Predicting outcomes in esophageal adenocarcinoma following neoadjuvant chemoradiation: Interactions between tumor response and survival

ObjectivesThe prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation. MethodsPatients who underwent esophagectomy for EAC after neoadjuvant CROSS protocol between 2016 and 2020 were evaluated. TRS was grouped according to the modified Ryan score; metabolic response, according to the PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron emission tomography (primary and regional lymph node standardized uptake values [SUVs]) were collected. ResultsThe study population comprised 277 patients. A TRS of 0 (complete response) was identified in 66 patients (23.8%). Seventy-eight patients (28.1%) had TRS 1 (partial response), 97 (35%) had TRS 2 (poor response), and 36 (13%) had TRS 3 (no response). On survival analysis for overall survival (OS), patients with TRS 0 had longer survival compared to those with TRS 1, 2, or 3 (P = .010, P < .001, and P = .005, respectively). On multivariable logistic regression, the presence of signet ring cell features on endoscopic biopsy (odds ratio [OR], 7.54; P = .012) and greater SUV uptake at regional lymph nodes (OR, 1.42; P = .007) were significantly associated with residual tumor at pathology (TRS 1, 2, or 3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (hazard ratio [HR], 1.08; P = .005) was independently associated with decreased OS, whereas pathologic complete response (HR, 0.61; P = .021) was independently associated with higher OS. ConclusionsPatients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.

Prognostic role of the log odds of positive lymph nodes in Western patients with resected gastric cancer: A comparison with the 8th edition of the TNM staging system.

Several alternative lymph node staging systems have recently been described for gastric cancer. The log odds of positive lymph nodes (LODDS) system may be superior to the pN stage (American Joint Committee on Cancer) and lymph node ratio systems in predicting outcomes for patients with gastric cancers, as indicated by some researchers. Most studies, however, have been conducted in Asian countries, and conflicting results have been reported by other investigators. We conducted a retrospective study of all 377 cases of gastric cancer resected at a tertiary hospital in Spain between 2000 and 2019. Clinicopathologic features were collected, LODDS were calculated and categorized into 5 groups (S1-S5), and statistical analysis was performed. The cases included (n = 315) were classified as S1 (25.6%), S2 (18.4%), S3 (21.3%), S4 (20.3%), and S5 (14.4%). The LODDS classification was significantly associated with tumor size, Laurén subtype, presence of signet ring cells, tumor grade, perineural infiltration, lymphovascular invasion, growth pattern, pT, tumor recurrence, and death. Kaplan-Meier analysis based on the LODDS classification demonstrated improved patient stratification compared with the pN stage for both overall survival (OS) and disease-free survival (DFS). Area under the curve values for recurrence and death were superior for the LODDS classification, and this classification was independently related to OS and DFS. In addition, the LODDS classification successfully divided patients without lymph node metastases (pN0) into subgroups with distinct prognoses. For our cohort, the LODDS system showed better prognostic performance than pN stage; it was an independent predictor of OS and DFS, and it provided valuable prognostic information in cases without lymph node metastases. Its prognostic accuracy, however, decreased in cases with fewer than 16 lymph nodes resected.

Primary Signet Ring Cell Mucinous Adenocarcinoma of the Urinary Bladder: A Rare Case Report

Primary ‘signet ring mucinous adenocarcinoma’ is most commonly located in the stomach. The bladder is an uncommon presentation site for the primary location of this tumor. Mucinous signet-ring adenocarcinoma with urinary bladder as the primary origin is uncommon, accounting for fewer than two percent of all upper urinary tract carcinomas. The presence of signet ring cells, which is caused by compression and displaced nucleus of the cell into a crescent placed in the periphery along the cell wall, is a distinguishing feature of signet ring cell carcinoma. These cells are loaded with cytoplasmic mucus-containing vacuoles. Lower than one-third of primary bladder signet ring cell carcinoma cases show this gross morphology showing linitis plastica pattern with subepithelial infiltration without producing an exophytic mass in a pure signet ring cell carcinoma. Because this tumor shares histological features with the adenocarcinomas originating in several other sites, such as the prostate, digestive tract, and reproductive system, immunohistochemistry tests are required to confirm the bladder as the primary origin. Owing to the paucity of the neoplasm and the difficulty in locating the underlying tumor, site identification is frequently prolonged, leaving palliative care as the only choice for roughly half of the patients. This study depicts a rare case report of primary vesicular signet ring cell mucinous adenocarcinoma that considerably invades the pelvis and retroperitoneum's prostate and lymph nodes. This case emphasizes the significant characteristics of bladder mucinous adenocarcinoma, such as the sequence of tumor spread, the propensity for preliminary diagnostic errors, the microscopic pattern, and the significance of immunohistochemistry for defining its primary root from the bladder and selecting the most suitable intervention from the start.

Signet Ring Cell Colorectal and Appendiceal Cancer: A Small Signet Ring Cell Component Is Also Associated with Poor Outcome.

Colorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size. All patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009-2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist. Of the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5-40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6-70), for SRC < 50, 39% (95% CI 24-61); and for non-SRCs, 55% (95% CI 55-60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19-61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25-99). The 5-year recurrence-free survival rates were 51% (95% CI 13-83) for patients with SRC tumours, as compared to 83% (95% CI 77-89) and 81% (95% CI 79-84) for mucinous and non-mucinous adenocarcinoma, respectively. The presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.

OGC P20 Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients undergoing surgical resection for locally advanced oesophageal adenocarcinoma

Abstract Background 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is routinely used for staging of oesophageal cancer and has an emerging role in assessing response to neoadjuvant therapy. Several studies have demonstrated that a reduction in FDG avidity of the primary tumour and loco-regional lymph nodes following neoadjuvant chemotherapy predicts pathological response and survival in this patient group. However, no studies have evaluated the prognostic significance of metabolic parameters with respect to pathological response in lymph nodes. Change in primary tumour maximum standardised uptake value (SUVmax) is the most widely used FDG PET-CT parameter to define metabolic response, with various thresholds described. The most commonly utilised are a 35% reduction in SUVmax (MUNICON), and a 30% reduction in SUVmax (PERCIST). However, there is no consensus regarding the optimal classification; the MUNICON threshold was derived from only 40 patients and PERCIST is not tumour specific. The primary aim of this study was to evaluate the ability of FDG PET-CT to predict pathological response in the primary tumour (pTR) and lymph nodes (pNR) in patients with oesophageal adenocarcinoma undergoing neoadjuvant chemotherapy before surgery. Secondary aims were to assess the prognostic effect of metabolic and pathological response and evaluate the predictive ability of response classifications. Methods Cohort study of 75 patients with locally advanced oesophageal or oesophago-gastric junctional adenocarcinoma who underwent FDG-PET-CT before and after neoadjuvant chemotherapy, prior to surgical resection at Guy's and St Thomas’ NHS Foundation Trust, London, UK, between 2017–2020. SUV metrics related to the primary tumour and loco-regional lymph nodes were derived on pre- and post- treatment FDG PET-CT. pTR and pNR were evaluated using the Mandard classification. Patients with Mandard scores of 1–3 were classified as pathological responders and those with Mandard scores of 4–5 as non-responders. Clinicopathological characteristics were compared using the Chi-squared test. Receiver operator characteristic (ROC) analysis was performed and area under the curve (AUC) calculated to determine optimum SUVmax thresholds for metabolic response in the primary tumour (mTR) and lymph nodes (mNR). Survival curves were created using the Kaplan-Meier method, with subgroups compared using the log-rank test. Survival analysis was performed using Cox proportional hazards regression providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age (continuous), sex (male or female), chemotherapy regimen (ECX or FLOT), cT stage (cT1–2 or cT3–4), cN stage (cN0 or cN+), tumour grade (well / moderately differentiated or poorly differentiated) and presence of signet ring cells (yes or no). Results Mean age was 63 years with the majority male (86.7%). Almost two thirds received FLOT (48/75, 64.0%) with the remainder receiving ECX chemotherapy. There was discordance between pathological response in the primary tumour and lymph nodes in several patients, including 23.1% (6/26) who demonstrated a lymph node response in the absence of a response in the primary tumour. ROC analysis demonstrated an optimum tumour SUVmax decrease of 51.2% for predicting pTR. Using a pragmatic cut-off of 50% this provided better prediction of pTR (AUC 0.714, sensitivity 73.5%, specificity 69.2%, p&amp;lt;0.001) than PERCIST (AUC 0.631, sensitivity 87.8%, specificity 38.5%, p=0.008) and MUNICON (AUC 0.659, sensitivity 85.7%, specificity 46.2%, p=0.003) criteria. ROC analysis demonstrated an optimum nodal SUVmax decrease of 32.6% for predicting pNR or pathological node negativity. Using a pragmatic 30% SUVmax cut-off and excluding metabolically negative nodes, mNR demonstrated high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p=0.010) for predicting pNR. pTR, mTR, pNR and mNR were independent predictive factors for overall survival on adjusted analysis (pTR responder HR 0.10 95% CI 0.03–0.34; mTR responder HR 0.17 95% CI 0.06–0.48; pNR responder HR 0.17 95% CI 0.06–0.54; mNR responder HR 0.13 95% CI 0.02–0.66). Conclusions In this study metabolic response on FDG PET-CT after neoadjuvant chemotherapy was predictive of pathological response in both the primary tumour and lymph node metastases of patients with oesophageal adenocarcinoma. Patients who had a favourable metabolic or pathological response in the primary tumour or lymph nodes had improved survival compared to non-responders. It has been suggested that commonly utilised thresholds of SUVmax are not optimal for response assessment in this patient group. This is supported by the results of the present study which suggest a reduction in SUVmax of 50% in the primary tumour was not only a better predictor of pathologic response, but also tumour recurrence and survival compared with PERCIST and MUNICON criteria. No previous studies have evaluated the ability of FDG PET-CT to predict pathologic nodal response despite recent findings suggesting it is an independent predictor of survival and evidence of a discrepancy, in some patients, who demostrate a nodal response in the absence of a response in the primary tumour. The use of FDG PET-CT in assessing response to neoadjuvant chemotherapy remains an under researched area and further evaluation is needed to establish whether it could be used to tailor individualised treatment strategies.

Trends and Outcomes of Cytoreductive Surgery with HIPEC for Appendiceal Cancer In US

Introduction: Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) has been increasingly being used in the treatment of appendiceal cancers with peritoneal dissemination. Our objective is to describe the trends in HIPEC use and its outcomes at a nationwide level. Methods: Stage IV appendiceal cancer patients who underwent CRC/HIPEC were reviewed from the National Cancer Database (period 2004-2017). Results: A total of 1592 patients were reviewed with steady increase in the number of reported cases over the study period. Mucinous adenocarcinoma was the predominant histology (84.5%), whereas 6% of patients had non-mucinous adenocarcinoma and 9.5% neuroendocrine/goblet cell/mixed histology tumors. The majority of procedures were performed at academic centers (71.8%) and this trend did not change during the study period (p = 0.6). Overtime, there was an increase in margin negative resections (2006: R0: 57.4%, 2017: R0:67.9%; p = 0.006), shorter hospitalizations (2006:14 days, 2017:9 days; p < 0.001), and no difference in the 90-day mortality rates: 2.8%. Survival was optimal for mucinous adenocarcinomas (median OS: mucinous adenocarcinomas:140.4mo vs 41.1mo for non-mucinous adenocarcinomas and 37.3mo for other (p < 0.001). Amongst mucinous adenocarcinomas presence of signet ring cells was associated with poor outcomes (OS: 29.2months vs 141.1mo for non-signet ring cell mucinous adenocarcinomas). Conclusion: The use of CRS/HIPEC has been increasing in the USA and is performed safely. It is being performed mainly at academic centers, with the best outcome for mucin producing tumors except in the presence of signet ring cells. With accumulating experience optimal cytoreductions have increased and hospitalizations have shortened over time.

S3566 Birthing a Baby or Surfacing a Hidden Tumor?

Introduction: Malignancy is a rare finding during pregnancy and if present, often carries poor prognosis. We present to you a case of Krukenberg tumor- a metastatic malignancy of the ovary- in a 29 year old female. Case Description/Methods: A 29-year-old female with no past medical history, presented to the hospital with preterm labor at 30 weeks gestation which lead to low transverse caesarian delivery secondary to recurrent prolonged decelerations and preterm contractions. Patient had an uneventful pregnancy course until this hospitalization. Intraoperatively, a large right sided ovarian mass was discovered. Tissue pathology revealed metastatic poorly differentiated adenocarcinoma. CT scan of the abdomen pelvis was suggestive of right adnexal mass measuring 10 × 14 × 13 cm with increased vascularity, large degree of abdominal pelvic ascites, with few lymph nodes in the upper mesenteric arcade, along with moderate thickening of the gastric wall. Esophagogastroduodenoscopy (EGD) revealed a gastric mass at cardia (Figure a), and tissue pathology was consistent with adenocarcinoma with presence of signet ring cells (Figure b). Additional work up was positive for elevated CA 125 and AFP tumor marker measuring 355 U/ml and 10.8 U/ml, respectively. Subsequent follow up with CT abdomen revealed bilateral ovarian metastasis with large volume ascites. Diagnostic paracentesis was negative for malignant ascites. Clinical course was complicated by recurrent ascites and progressive clinical deterioration. Due to poor performance status, the patient did not undergo any surgical intervention. Patient is currently being managed with palliative chemotherapy and paracentesis for symptomatic relief. Discussion: Krukenberg tumor is a metastatic malignancy of the ovary which is characterized by mucin-rich signet-ring adenocarcinoma that arises primarily from a gastrointestinal site. It accounts for almost 1%–2% of all ovarian tumors. The incidence of gastric cancer in the women of reproductive age group is 0.4%–0.5%, making these tumors extremely rare during pregnancy. Pregnancy symptoms masks the presence of the disease leading to diagnosis at a later stage. Unfortunately, no optimal treatment strategy for these tumors have been identified so far. Chemotherapy as well as radiation therapy does not seem to have any significant role in the prognosis of these patients. Due to metastatic nature and lower rate of resectability, surgery is deferred as it does not offer any increased survival time. The overall prognosis remains poor.Figure 1.: (a) EGD revealing gastric mass at cardia (b) Tissue pathology showing adenocarcinoma with presence of signet ring cells.

Somatic Mutational Landscape in Mexican Patients: CDH1 Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma.

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.

LC3B, mTOR, AMPK Are Molecular Targets for Neoadjuvant Chemotherapy in Gastric Cancers.

Autophagy plays a dual role in oncogenesis processes. On one hand, autophagy enhances the cell resistance to oncogenic factors, and on the other hand, it participates in the tumor progression. The aim of the study was to find the associations between the effectiveness of the FLOT regimen in resectable gastric cancers (GCs) with the key autophagy-related proteins. Materials and Methods: The study included 34 patients with morphologically verified gastric cancer. All patients had FLOT neoadjunvant chemotherapy (NACT) (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed by gastrectomy. The studied tissue material was the non-transformed and tumor tissues obtained during diagnostic video gastroscopy in patients before the start of the combined treatment and after surgical treatment, frozen after collection. The LC3B, mTOR, and AMPK expression was determined by real-time PCR. The content of the LC3B protein was determined by Western blotting analysis. Results: The mRNA level and the content of the LC3B protein were associated with the tumor stage and the presence of signet ring cells. The AMPK mRNA level was increased in patients with the T4N0-2M0 stage by 37.7 and 7.33 times, which was consequently compared with patients with the T2N0M0 and T3N0-1M0 stages. The opposite changes in the mTOR and AMPK in the GCs before anti-cancer therapy were noted. The tumor size and regional lymph node affections were associated with a decrease in the mTOR mRNA level. A decrease in the mTOR expression was accompanied by an increase in the AMPK expression in the GCs. The mTOR expression was reduced in patients with a cancer spreading; in contrast, AMPK grew with the tumor size. There was an increase in the LC3B expression, which can probably determine the response to therapy. An increase in LC3B mRNA before the start of treatment and the protein content in cancers after NACT with a decrease in therapy effectiveness was recorded. There was an increase in the protein level in patients with partial regression and stabilization by 3.65 and 5.78 times, respectively, when compared with patients with complete tumor regression was noted. Conclusions: The anticancer effectiveness in GCS is down to the LC3B, mTOR, and AMPK expression. These were found to be entire molecular targets affecting the cancer progression and metastasis as well as the NACT effectiveness.

62: WHICH GASTRIC CANCER PATIENTS COULD BENEFIT FROM STAGING LAPAROSCOPY? A GIRCG MULTICENTER COHORT STUDY

Abstract Background and aim Staging laparoscopy is an important step of the staging of gastric cancer patients, however, its indication are universally accepted by the different guidelines.This study aimed to define those factors which could help in defining the most appropriate use of staging laparoscopy in a western population. Methods A retrospective cohort study was carried out, including 330 (226 cM- and 104 cM+) gastric cancer patients who had undergone staging laparoscopy between 2010–2020 in seven GIRCG centers. A model including easily-accessible clinical, biochemical and pathological markers was constructed to predict the risk of carcinomatosis. ROC curve and decision curve analyses were used to verify its accuracy and net benefit. Results In the cM- population staging laparoscopy could detect 70 cases who had peritoneal carcinomatosis or positive cytology, for a yield of 31.0%. In cM+ patients staging laparoscopy could exclude carcinomatosis in 15 cases. In cM- patients, intestinal type tumors (0.36, 0.14–0.92; P = 0.035), the presence of signet ring cells (2.58, 1.04–6.33; P = 0.039) and cancers of the upper third (3.36, 1.43–7.92; P = 0.005) were associated with the presence of peritoneal carcinomatosis and/or positive cytology. The ROC curve analysis of the model including the three variables showed an AUC of 0.75 (0.66–0.80, P &amp;lt; 0.001). The decision curve analyses showed that the model had a higher net benefit than the treating all strategy between threshold probabilities of 16 and 50%. Conclusion Staging laparoscopy is a useful tool to address the patient with gastric cancer to the most adequate treatment. In cM- patients the assessment of the location of the tumor, the Lauren’s histotype and the presence of signet ring cells may help in providing additional elements in indicating or not the use of staging laparoscopy.

Serous cavity metastasis: Evaluation of unknown primary.

Malignant effusions can occur in patients with neoplasia. Once a metastatic diagnosis is confirmed, the primary site of origin of malignancy needs to be ascertained. This task can be challenging without a prior history of malignancy. In some patients their effusion may be the initial presentation of an underlying malignancy. Metastases usually present with a dual population of mesothelial and malignant cells. Combining cytomorphologic examination with ancillary testing such as immunocytochemistry can help identify the origin of the foreign malignant cell population. Helpful architectural clues include a single cell pattern, solid cell ball pattern, single file arrangement, papillary formation, psammoma bodies and background mucin. Useful cellular features include the presence of signet ring cells, small cells, pleomorphic and multinucleated giant cells, squamous cells, spindle cells and pigmentation. Rarely, despite an extensive work-up the primary site of origin for a malignant effusion may remain unresolved. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Cytopathologic Diagnosis of Serous Fluids.

Peritoneal metastases from colorectal cancer in the absence of lymph node metastases show a high survival rate despite unfavorable prognostic indicators

BackgroundPatients with colorectal cancer die as a result of metastases to liver, lymph nodes or the peritoneal surfaces. The primary is almost always controlled by colon or rectal cancer resection. MethodsConsecutive patients with isolated metastases to peritoneal surfaces (no lymph node, liver or systemic metastases) were referred to the Washington Cancer Institute from all over the United States and abroad. The study of this particular group of patients was to determine the impact of clinical and histologic features on overall survival. These variables were collected from the primary colorectal cancer resection performed at the referring institute and from the cytoreductive surgery (CRS) performed at the Washington Hospital Center. The data was prospectively accumulated and retrospectively analyzed. ResultsThirty-one consecutive patients had a complete cytoreduction. This restricted cohort of patients was studied in an attempt to eliminate confounding variables. The median age was 47 years (range 19–80). There were 14 (45%) males. The median overall survival following CRS was 67.9 months with a 5-year and 10-year survival of 51.9% and 43.6%, respectively. None of the clinical or histologic features, including peritoneal cancer index (PCI) and presence of signet ring cells, significantly predicted survival except for carbohydrate antigen 19-9 (CA19-9) (p = 0.0033). None of the involved abdominopelvic regions predicted a guarded outcome. ConclusionsIn this restricted group of lymph node negative colorectal PM patients with a complete cytoreduction, a high PCI or the presence of signet ring cells should not exclude patients from CRS and perioperative chemotherapy.

Effect of peri-operative chemotherapy regimen on survival in the treatment of locally advanced oesophago-gastric adenocarcinoma – A comparison of the FLOT and ‘MAGIC’ regimens

BackgroundPeri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates. MethodsCohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas’ Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells. ResultsPatients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50–0.94) and disease-free survival (HR = 0.75, 95% CI 0.58–0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups. ConclusionsPatients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable.

A nomogram for predicting lymph node metastasis in early gastric cancer

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.

Prognosis in primary mucinous ovarian carcinoma: focusing on the five pathological findings indicating metastatic mucinous carcinoma to the ovary.

ObjectivePathological features indicating metastatic mucinous carcinoma to the ovary (MMCO) have been rarely reported in primary mucinous ovarian carcinoma (PMOC). However, little is known about how often they are observed in PMOC and how they relate to patient prognosis. In this study, we investigated the pathological features indicating MMCO in a large cohort of PMOCs and analyzed their association with patient prognosis.MethodsWe reviewed surgically treated PMOC patients diagnosed at the Seoul National University Hospital from 1995 to 2019, according to the updated WHO classification, and investigated the presence of pathological features indicating MMCO.ResultsA total of 144 patients with PMOCs were included. The 5 pathological findings indicating MMCO, including an infiltrative invasive pattern, the absence of benign or borderline components, a smaller tumor size, the presence of signet ring cells and the presence of extracellular mucin were observed in PMOC (21.6%, 43.1%, 20.8%, 4.3% and 12.9%, respectively), and were significantly correlated with poor overall and progression-free survival rates in PMOC. The patient’s prognosis worsened as the extent of the infiltrative invasive pattern increased (p<0.001). In addition, the prognostic power was stronger when the 5 pathological factors were analyzed together (new grouping system) than when analyzed individually (p<0.001) and the new grouping system was identified as an independent prognostic factor regardless of FIGO stage.ConclusionFive pathological findings indicating MMCO in PMOC were significantly associated with poor prognosis in PMOC patients. Also, the new grouping system combining these findings was identified as an independent prognostic factor.

Clinical significance of signet ring cells in surgical esophageal and esophagogastric junction adenocarcinoma: A systematic review and meta-analysis.

BACKGROUNDThe clinical significance of signet ring cells (SRCs) in surgical esophageal and esophagogastric junction adenocarcinoma (EEGJA) remains unclear now.AIMTo explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies.METHODSThe PubMed, Web of Science, and EMBASE electronic databases were searched for the relevant literature up to March 28, 2021. The relative risk (RR) with 95% confidence interval (CI) was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients, and the hazard ratio (HR) with 95%CI was calculated to explore the impact of SRC on the prognosis. All statistical analyses were conducted with STATA 12.0 software.RESULTSA total of ten articles were included, involving 30322 EEGJA patients. The pooled results indicated that the presence of SRCs was significantly associated with tumor location (RR: 0.76, 95%CI: 0.61-0.96, P = 0.022; I2 = 49.4%, P = 0.160) and tumor-node-metastasis stage (RR: 1.30, 95%CI: 1.02-1.65, P = 0.031; I2 = 73.1%, P = 0.002). Meanwhile, the presence of SRCs in surgical EEGJA patients predicted a poor overall survival (HR: 1.36, 95%CI: 1.12-1.65, P = 0.002; I2 = 85.7%, P < 0.001) and disease-specific survival (HR: 1.86, 95%CI: 1.55-2.25, P < 0.001; I2 = 63.1%, P = 0.043). CONCLUSIONThe presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients. However, more high-quality studies are still needed to verify the above findings.

Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer.

A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.