Factors associated with detection of hereditary diffuse gastric cancer on endoscopy in individuals with germline CDH1 mutations.

BACKGROUND AND AIMS: Individuals with germline pathogenic CDH1 variants have a high risk of hereditary diffuse gastric cancer. The sensitivity of EGD in detecting signet ring cell carcinoma (SRCC) in this population is low. We aimed to identify endoscopic findings and biopsy practices associated with detection of SRCC. METHODS: This retrospective cohort included individuals with a germline pathogenic/likely pathogenic CDH1 variant undergoing at least 1 EGD at Memorial Sloan Kettering Cancer Center between January 1, 2006, and March 25, 2022. The primary outcome was detection of SRCC on EGD. Findings on gastrectomy were also assessed. The study included periods before and after implementation of the Cambridge protocol for endoscopic surveillance, allowing for assessment of a spectrum of biopsy practices. RESULTS: Ninety-eight CDH1 patients underwent at least 1 EGD at our institution. SRCC was detected in 20 (20%) individuals on EGD overall and in 50 (86%) of the 58 patients undergoing gastrectomy. Most SRCC foci were detected in the gastric cardia/fundus (EGD, 50%; gastrectomy, 62%) and body/transition zone (EGD, 60%; gastrectomy, 62%). Biopsy results of gastric pale mucosal areas were associated with detection of SRCC (P < .01). The total number of biopsy samples taken on EGD was associated with increased detection of SRCC (P = .01), with 43% detected when ≥40 samples were taken. CONCLUSIONS: Targeted biopsy sampling of gastric pale mucosal areas and increasing number of biopsy samples taken on EGD were associated with detection of SRCC. SRCC foci were mostly detected in the proximal stomach, supporting updated endoscopic surveillance guidelines. Further studies are needed to refine endoscopic protocols to improve SRCC detection in this high-risk population.

[A Case of Primary Signet Ring Cell Carcinoma of the Urinary Bladder Showing Effectiveness of Chemotherapy with Gemcitabine and Cisplatin].

A 55-year-old female presented to the hospital with a complaint of gross hematuria. Transurethral resection of bladder tumor was performed. The specimens pathologically showed signet ring cells and no urothelial carcinoma components. Magnetic resonance imaging and computed tomographic (CT) scan revealed bladder tumor, cervical metastasis, bilateral ovarian metastasis, and multiple lymph node metastasis. She was diagnosed with a primary signet ring cell carcinoma of the urinary bladder with cT3bN2M1, and was treated with chemotherapy of gemcitabine and cisplatin combination (GC). After 2 cycles of GC, the value of CEA which was elevated to 106 ng/ml before treatment, became negative. CT scan showed that her disease had successfully responded to the chemotherapy, and remained efficacious till the end of 6 cycles. The patient subsequently received 1 cycle of gemcitabine and nedaplatin and 3 cycles of avelumab due to renal insufficiency. Yet, 14 months after diagnosis, cerebellar metastases appeared and the patient died of meningeal carcinomatosis.

CT-based radiomics nomograms for preoperative prediction of diffuse-type and signet ring cell gastric cancer: a multicenter development and validation cohort.

BACKGROUND: The prevalence of diffuse-type gastric cancer (GC), especially signet ring cell carcinoma (SRCC), has shown an upward trend in the past decades. This study aimed to develop computed tomography (CT) based radiomics nomograms to distinguish diffuse-type and SRCC GC preoperatively. METHODS: A total of 693 GC patients from two centers were retrospectively analyzed and divided into training, internal validation and external validation cohorts. Radiomics features were extracted from CT images, and the Lauren radiomics model was established with a support vector machine (SVM) classifier to identify diffuse-type GC. The Lauren radiomics nomogram integrating radiomics features score (Rad-score) and clinicopathological characteristics were developed and evaluated regarding prediction ability. Further, the SRCC radiomics nomogram designed to identify SRCC from diffuse-type GC was developed and evaluated following the same procedures. RESULTS: Multivariate analysis revealed that Rad-scores was significantly associated with diffuse-type GC and SRCC (p < 0.001). The Lauren radiomics nomogram showed promising prediction performance with an area under the curve (AUC) of 0.895 (95%CI, 0.957-0.932), 0.841 (95%CI, 0.781-0.901) and 0.893 (95%CI, 0.831-0.955) in each cohort. The SRCC radiomics nomogram also showed good discrimination, with AUC of 0.905 (95%CI,0.866-0.944), 0.845 (95%CI, 0.775-0.915) and 0.918 (95%CI, 0.842-0.994) in each cohort. The radiomics nomograms showed great model fitness and clinical usefulness by calibration curve and decision curve analysis. CONCLUSION: Our CT-based radiomics nomograms had the ability to identify the diffuse-type and SRCC GC, providing a non-invasive, efficient and preoperative diagnosis method. They may help guide preoperative clinical decision-making and benefit GC patients in the future.

[Late recurrence of gastric cancer diagnosed 10 years after curative gastrectomy: a review of 30 Japanese case reports].

A woman in her 50s was referred to our hospital with intestinal obstruction. Ten years prior, she had been treated for gastric cancer, pathologically confirmed as stage IIIA poorly differentiated adenocarcinoma with signet-ring cell carcinoma. Intraoperatively, a 4-cm hard white tumor was found in the mesoileum and around the ileum. Pathological examination revealed poorly differentiated adenocarcinoma with signet-ring cell carcinoma and infiltration and fibrosis. Late peritoneal recurrence of gastric carcinoma was diagnosed. Recurrence of gastric carcinoma more than 10 years after curative gastrectomy is extremely rare. A review of 30 cases reported in Japan revealed recurrence was more frequent in females (60%) and the mean age was around 50 years at the time of primary surgery. Poorly differentiated adenocarcinoma and/or signet-ring cell carcinoma was the primary gastric cancer in 82% of cases and bone metastasis was the most frequent site of recurrence.

Accuracy of endoscopic size measurements of early gastric signet ring cell carcinoma.

BACKGROUND AND AIMS: Indications for endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) are expanding, but signet ring cell carcinoma (SRC) is still unclear because of its unclear boundaries. The purpose of this study was to compare pathologic size and endoscopic size in SRC-type EGC and to find risk factors associated with tumor size underestimation. METHODS: Medical records of 137 patients diagnosed with SRC-type EGC between January 2009 and December 2016 at our tertiary hospital were reviewed. According to pathologic and endoscopic tumor sizes, they were classified into correct estimation, underestimation, and overestimation groups, and risk factors related to underestimation were analyzed. RESULTS: Among 137 patients with SRC-type EGC, 77 patients (56.2%) had undergone correct estimation, 43 patients (31.4%) had undergone underestimation, and 17 patients (12.4%) had undergone overestimation. Mean pathologic size (SD) was 20.1 (13.8) mm and mean endoscopic size (SD) was 17.9 (10.1) mm, the correlation coefficients were 0.919 (p < 0.001) , and there was no significant difference between the two groups. Multivariate analysis showed that tumor size more than 20 mm (OR 3.419; 95% CI 1.271-9.194; p = 0.015) and atrophy (OR 6.011; 95% CI 2.311-15.633; p = 0.001) were risk factors for tumor size underestimation. CONCLUSION: There was no significant difference in pathologic and endoscopic size in SRC-type EGC. Therefore, ESD may be considered as a therapeutic option if the size of the tumor is less than 20 mm and atrophy is not present in the surrounding mucosa.

Accuracy of whole-body diffusion-weighted MRI (WB-DWI/MRI) in diagnosis, staging and follow-up of gastric cancer, in comparison to CT: a pilot study.

BACKGROUND: Accurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer. METHODS: This retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 T, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard. RESULTS: For overall tumour detection (n = 32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n = 18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/PPV/NPV of 50%/100%/100%/71.4%, and 15.4%/100%/100%/31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumour infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%. CONCLUSIONS: WB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer.

Association of the tumour stroma percentage in the preoperative biopsies with lymph node metastasis in colorectal cancer.

BACKGROUND: Preoperative prediction of lymph node (LN) status is integral to determining the most appropriate treatment strategy for colorectal cancer (CRC). This study aimed to develop and validate a nomogram to predict LN metastasis in CRC preoperatively. METHODS: A total of 530 patients were enrolled and divided into training and validation cohorts. The tumour stroma percentage (TSP) of the preoperative biopsies was assessed. The risk factors for LN metastasis were selected, and a nomogram was constructed subsequently. The performance of the nomogram was assessed by using the AUROC and the calibration curve, and then validated in the validation cohort. RESULTS: High TSP was significantly associated with LN metastasis in both the training and validation cohorts. Computed tomography (CT)-reported T stage, CT-reported LN status, preoperative tumour differentiation, carcinoembryonic antigen, carbohydrate antigen 19-9 and TSP were independent predictors of LN metastasis in CRC. A nomogram incorporating the six predictors was constructed. The nomogram yielded good discrimination and calibration, with an AUROC of 0.846 (95% CI: 0.807-0.886) and 0.809 (95% CI: 0.745-0.872) in the training and validation cohorts, respectively. CONCLUSIONS: Assessment of TSP in the preoperative biopsies provided additional information about the LN status. The nomogram was useful for tailored therapy in CRC preoperatively.

An isolated vaginal metastasis from intestinal signet ring cell carcinoma: a case report and literature review.

BACKGROUND: Isolated vaginal metastases from intestinal signet ring cell carcinoma are extremely rare. There are no reported cases in the domestic or foreign literature. The characteristics of such cases of metastasis remain relatively unknown. As a life-threatening malignant tumor, it is very important to carry out a systemic tumor examination and transvaginal biopsy, even though clinical symptoms are not typical and there is no systemic tumor history. CASE PRESENTATION: We present a case of an isolated vaginal metastasis from intestinal cancer in a 45-year-old female patient. The patient experienced a small amount of irregular vaginal bleeding and difficulty urinating. She had no history of systemic cancer. An early physical examination and transvaginal ultrasound (TVS) showed marked thickening of the entire vaginal wall. Pelvic nuclear magnetic resonance imaging (MRI) and a colposcopic biopsy were used to diagnose her with chronic vaginitis. An analysis of the vaginal wall biopsy showed signet ring cell carcinoma. Colorectal colonoscopy revealed advanced interstitial signet ring cell carcinoma as the primary source of vaginal wall infiltration. We review previous case reports of vaginal metastases from colorectal cancer and discuss the symptoms, pathological type, and outcomes. CONCLUSIONS: We hypothesize that vaginal wall thickening and stiffness accompanied by chronic inflammatory-like changes may be clinical features of a vaginal metastasis of signet ring cell carcinoma of the intestine. We also emphasize that it is very important to perform a systemic tumor examination in a timely manner when a patient has the abovementioned symptoms.

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.

Additive Effect of Magnifying Endoscopy with Narrow-Band Imaging for Diagnosing Mixed-Type Early Gastric Cancers.

BACKGROUND: Pretreatment biopsy may not correctly diagnose mixed-type early gastric cancers. Despite reports on the usefulness of magnifying endoscopy with narrow-band imaging in diagnosing early gastric cancers, no reports exist on differences in magnifying endoscopy with narrow-band imaging findings between differentiated-type-predominant mixed-type and undifferentiated-type-predominant mixed-type early gastric cancers. AIM: This study aimed to clarify differences in magnifying endoscopy with narrow-band imaging findings and investigate the additive effect of combining magnifying endoscopy with narrow-band imaging and biopsy findings for pretreatment histological-type diagnosis. METHODS: Patients undergoing endoscopic submucosal dissection as initial treatment between April 2005 and March 2017 participated in this retrospective study. There were 156 differentiated-type-predominant mixed-type and 36 undifferentiated-type-predominant mixed-type lesions. We extracted the most significant magnifying endoscopy with narrow-band imaging findings of differentiated-type-predominant mixed-type and undifferentiated-type-predominant mixed-type lesions using multivariate analysis and compared the accuracy, sensitivity, and specificity between pretreatment biopsy alone and a combination of biopsy and magnifying endoscopy with narrow-band imaging findings. RESULTS: Significant magnifying endoscopy with narrow-band imaging findings was fine network pattern in differentiated-type-predominant and corkscrew pattern in undifferentiated-type-predominant mixed-type lesions. Accuracy, sensitivity, and specificity were significantly higher with combined biopsy and magnifying endoscopy with narrow-band imaging findings than with pretreatment biopsy alone. CONCLUSIONS: The study results demonstrated the additive effect of magnifying endoscopy with narrow-band imaging with biopsy for diagnosing mixed-type early gastric cancers. This study may be beneficial in routine practice because it indicates a possibility of reducing additional surgery after endoscopic submucosal resection because of incorrect diagnosis of histological type.

Low metabolic activity in primary gastric adenocarcinoma is associated with resistance to chemoradiation and the presence of signet ring cells.

PURPOSES: Preoperative chemoradiation is a potential treatment option for localized gastric adenocarcinoma (GAC). Currently, the response to chemoradiation cannot be predicted. We analyzed the pretreatment maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) on positron emission tomography/computed tomography as potential predictors of the response to chemoradiation. METHODS: We analyzed the SUVmax and TLG data from 59 GAC patients who received preoperative chemoradiation. We used logistic regression models to predict a pathologic complete response (pCR) and Kaplan-Meier curves to determine overall survival among patients with high and low SUVmax or TLG. RESULTS: Twenty-nine patients (49%) had Siewert type III adenocarcinoma and 30 (51%) had tumors located in the lower stomach. Forty-one patients had poorly differentiated GAC, and 26 had signet ring cells. The median SUVmax was 7.3 (0-28.2) and the median TLG was 56.6 (0-1881.5). Patients with signet ring cells had a low pCR rate, as well as a low SUVmax and TLG. In the multivariable logistic regression model, high SUVmax was a predictor of pCR (odds ratio = 11.1, 95% confidence interval = 2.12-50.0, p = 0.004). Overall survival was not associated with the SUVmax (log-rank p = 0.69) or TLG (log-rank p = 0.85) CONCLUSION: A high SUVmax was associated with sensitivity to chemoradiation and pCR in GAC, and signet ring cells seemed to confer resistance.

[Clinicopathological characteristics, diagnosis, and treatment of 29 cases of signet ring cell carcinoma of the rectum and sigmoid colon].

Objective: To investigate the clinicopathological characteristics and the therapeutic effects of signet ring cell carcinoma (SRCC) of rectum and sigmoid colon. Methods: Clinical data and the follow-up information of 29 SRCC patients treated in our tertiary care center from 2008 to 2018 were retrospectively reviewed. The clinicopathological features, diagnostic and therapeutic effects, and the prognostic outcomes were analyzed. Results: Among the 29 patients, 17 were male, 12 were female. The average age was (48.7±14.3) years. Colonoscopy revealed the features of diffuse circumferential thickening of the bowel wall in 20/29 cases (69.0%), while in 9/29 cases (31.0%), endoscopic biopsies showed false negative results. Twenty-five% (4/16) and 17.6% (3/17) lesions were misdiagnosed as the inflammatory changes by endoscopic rectal ultrasonography exam and rectal MRI scan, respectively. Thirteen of the 29 patients received the neoadjuvant chemoradiotherapy (NCRT), 27 patients underwent the radical resection surgeries, and 8 underwent the postoperative radiotherapy. With a median follow-up of 38.5 (3.5-87.0) months, the cumulative 3-years overall survival (OS) rate was 54.0%, and the cumulative 3-years disease-free survival (DFS) rate was 43.0%. The OS rates of patients treated with or without NCRT (non-NCRT) were 46.2% and 69.2%, respectively, without significant difference (P>0.05). The DFS rates of patients treated with or without NCRT were 45.8% and 39.2%, respectively, without significant difference (P>0.05). Parameters including age younger than 40 years and tumor size larger than 5 cm were independent potential risk factors for shortened OS (P<0.05). Conclusions: SRCC of the rectum and sigmoid colon is a rare malignant tumor with special clinical manifestations. It is younger-onset, highly malignant and with very poor prognosis. Therefore, in-depth researches with focus upon the progress of molecular oncology are urgently needed to substantially improve the therapeutic effect of this disease.

Krukenberg Tumor in Association with Ureteral Stenosis Due to Peritoneal Carcinomatosis from Pulmonary Adenocarcinoma: A Case Report.

Krukenberg tumors from pulmonary adenocarcinoma represent an extremely rare situation; only a few cases have been reported. The aim of this paper is to report an unusual such case in which almost complete dysphagia and ureteral stenosis occurred. The 62-year-old patient was initially investigated for dysphagia and weight loss. Computed tomography showed the presence of a thoracic mass compressing the esophagus in association with a few suspect pulmonary and peritoneal nodules, one of them invading the right ureter. A biopsy was performed laparoscopically on the peritoneal nodules. The right adnexa presented an atypical aspect; right adnexectomy was also found. The histopathological and immunohistochemical studies confirmed that the primitive origin was pulmonary adenocarcinoma. Although both peritoneal carcinomatosis and ovarian metastases from pulmonary adenocarcinoma represent a very uncommon situation, this pathology should not be excluded, especially in cases presenting suspect pulmonary lesions.

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.

Risk of lymph node metastasis in undifferentiated-type mucosal gastric carcinoma.

BACKGROUND: Endoscopic resection (ER) has come to be recognized as a standard treatment for early gastric cancer (EGC). While its adoption is expanding, ER remains restricted to cases of EGC without lymph node metastasis for the treatment of local resection. On the other hand, histopathological analyses of surgically resected specimens of EGC have revealed the presence of lymph node (LN) metastasis in some cases of mucosal gastric cancer (MGC) and undifferentiated MGC (UD-MGC) is considered to have higher risk of nodal metastases than differentiated MGC (D-MGC). To evaluate the risk factors for LN metastasis in MGC, we investigated the characteristics of UD-MGC associated with LN metastasis. METHODS: Among all UD-MGC patients who underwent surgery as initial treatment, between January 2000 and March 2016, we reviewed the clinicopathological data, including the preoperative endoscopic findings and histopathological findings in the resected specimens, of the 11 UD-MGC patients who were identified as having lymph node metastasis. Furthermore, in comparison with cases without lymph node metastasis, we examined the possibility of expansion of the indication for local treatment. RESULTS: In most of the cases of UD-MGC with LN metastasis, the lesions were relatively large (> 20 mm in diameter) and of the clearly depressed type with faded color and apparent border, and histopathology revealed a high percentage of cases with lymphatic invasion and a predominance of signet ring cell carcinomas. No cases with LN metastasis without depressed macroscopic type nor signet ring cell carcinoma component existed. A degree of invasion of lamina propria (LP) or muscularis mucosae (MM) had same relation to the risk of LN metastasis. CONCLUSIONS: In this study, none of the cases of undifferentiated-type mucosal cancer (UD-MGC) with LN metastasis satisfied the current adoption criteria for ER. We suggested significant risk factors for LN metastasis in UD-MGC cases as depressed tumor type, presence of a signet ring cell carcinoma component, presence of lymphatic tumor invasion, and a large tumor size. More detailed analyses of the endoscopic and histopathological findings may allow further risk classification for LN metastasis in cases of UD-MGC.

Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality Therapy in Esophageal Adenocarcinoma.

PURPOSE: To develop a nomogram that estimates 1-year recurrence-free survival (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on the basis of 1-year recurrence risk. METHODS: In total, 568 consecutive patients with potentially resectable esophageal adenocarcinoma who underwent CRT were included for analysis, including 373 patients who underwent esophagectomy after CRT (trimodality therapy), and 195 who did not undergo surgery (bimodality therapy). A nomogram for 1-year RFS was created using a Cox regression model. The upper tertile of the nomogram score was used to stratify patients in low-risk and high-risk groups for 1-year recurrence. The 5-year OS was compared between trimodality and bimodality therapy in low-risk and high-risk patients after propensity score matching, respectively. RESULTS: Median follow-up for the entire cohort was 62 months. The 5-year OS in the trimodality and bimodality treatment groups was 56.3% (95% confidence interval [CI] 47.9-64.7) and 36.9% (95% CI 31.4-42.4), respectively. The final nomogram for the prediction of 1-year RFS included male gender, poor histologic grade, signet ring cell adenocarcinoma, cN1, cN2-3, and baseline SUVmax, with accurate calibration and reasonable discrimination (C-statistic: 0.66). Trimodality therapy was associated with improved 5-year OS in low-risk patients (p = 0.003), whereas it showed no significant survival benefit in high-risk patients (p = 0.302). CONCLUSIONS: The proposed nomogram estimates early recurrence risk. The addition of surgery to CRT provides a clear OS benefit in low-risk patients. The OS benefit of surgery in high-risk patients is less pronounced.

Comparative study of endoscopic surveillance in hereditary diffuse gastric cancer according to CDH1 mutation status.

BACKGROUND AND AIMS: Hereditary diffuse gastric cancer (HDGC) accounts for 1% of gastric cancer cases. For patients with a germline CDH1 mutation, risk-reducing gastrectomy is recommended. However, for those delaying surgery or for families with no causative mutation identified, regular endoscopy is advised. This study aimed to determine the yield of signet ring cell carcinoma (SRCC) foci in individuals with a CDH1 pathogenic variant compared with those without and how this varies with successive endoscopies. METHODS: Patients fulfilling HDGC criteria were recruited to a prospective longitudinal cohort study. Endoscopy was performed according to a strict protocol with visual inspection followed by focal lesion and random biopsy sampling to detect foci of SRCC. Survival analysis determined progression to finding of SRCC according to CDH1 mutation status. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and 36-item Short Form Health Survey questionnaires assessed quality of life before surveillance and each endoscopy. RESULTS: Eighty-five individuals fulfilling HDGC criteria underwent 201 endoscopies; 54 (63.5%) tested positive for CDH1 mutation. SRCC yield was 61.1% in CDH1 mutation carriers compared with 9.7% in noncarriers, and mutation-positive patients had a 10-fold risk of SRCC on endoscopy compared with those with no mutation detected (P < .0005). Yield of SRCC decreased substantially with subsequent endoscopies. Surveillance was associated with improved psychological health. CONCLUSIONS: SRCC foci are prevalent in CDH1 mutation carriers and can be detected at endoscopy using a standardized, multiple biopsy sampling protocol. Decreasing yield over time suggests that the frequency of endoscopy might be reduced. For patients with no CDH1 pathogenic variant detected, the cost-to-benefit ratio needs to be assessed in view of the low yield.

Outcomes of screening gastroscopy in first-degree relatives of patients fulfilling hereditary diffuse gastric cancer criteria.

BACKGROUND AND AIMS: The aim of this study was to determine the yield of endoscopic screening in first-degree relatives (FDRs) of CDH1-negative hereditary diffuse-type gastric cancer (HDGC) patients. METHODS: In this retrospective observational cohort study, in 2 expert centers in the Netherlands data were collected on FDRs from families fulfilling the international HDGC criteria that underwent endoscopic screening. Extensive inspection of the stomach was performed by gastroscopy, taking random and/or targeted stomach biopsy specimens to identify diffuse-type gastric cancer. RESULTS: Between 2004 and 2016, 90 persons (40% men; mean age, 48 years) from 40 families were offered endoscopic screening. The mean number of endoscopies per person was 3. The mean follow-up time was 46 months and mean endoscopic interval 20 months. Signet ring cell carcinoma foci restricted to the mucosa (pT1a) were identified in 4 persons (4%) from 1 family, which afterward was diagnosed with a germline CTNNA1 mutation. Advanced poorly cohesive gastric carcinoma was diagnosed in 1 person from another family. Intestinal metaplasia was diagnosed in 38 persons (42%) and low-grade dysplasia in 4 persons (4%). Additionally, in 40 persons (44%) scar tissue was observed in the gastric mucosa, which can hinder the endoscopic detection of small white lesions typical for HDGC. CONCLUSIONS: Endoscopic screening in HDGC families without a pathogenic CDH1 mutation may be reasonable, as we detected signet ring cell carcinomas in 6% of persons screened. However, the criteria and frequency of screening may have to be reconsidered.

Clinical predictors of histologic type of gastric cancer.

BACKGROUND AND AIMS: Gastric cancer is classified into differentiated and undifferentiated types according to the degree of glandular differentiation. Undifferentiated-type early gastric cancer (EGC) carries a higher risk of lymph-node metastasis than differentiated type, and therefore the indication criteria for endoscopic resection differ. This study aimed to clarify the ability of clinical predictors to distinguish between differentiated-type and undifferentiated-type EGCs. METHODS: This was a post hoc study of a multicenter prospective trial carried out in 5 Japanese hospitals, including 343 patients with cT1 EGC of ≥10 mm. According to the protocol, age, sex, and endoscopic findings of cancer (diameter, location, macroscopic type, and invasion depth) were evaluated, and the final diagnosis was confirmed from resected specimens. We evaluated the associations between these clinical factors and the histologic type of cancer and calculated the ability of the factors to diagnose differentiated-type EGC. The diagnostic ability of forceps biopsy was also calculated as a reference. RESULTS: Multivariate analysis identified older age (≥72 years), male sex, larger tumor size (>30 mm), elevated type, and shallower invasion depth (cT1a) as independent significant predictors for differentiated-type EGC, with elevated type showing the highest positive likelihood ratio. The sensitivity, specificity, accuracy, and positive and negative likelihood ratios of elevated type for differentiated-type EGC were 24%, 99%, 38%, 15.7, and 0.77, respectively, compared with 96%, 86%, 95%, 7.0, and 0.04 for forceps biopsy. CONCLUSIONS: Endoscopic elevated type is a significant predictor for differentiated-type EGC and may exclude undifferentiated-type EGC without the need for forceps biopsy.