Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.

BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment.

Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.

Clinicopathological and prognostic features of Borrmann type IV gastric cancer versus other Borrmann types: A unique role of signet ring cell carcinoma.

Background: Evidence specifically comparing the clinicopathology of Borrmann type IV (B-IV) gastric cancer with that of other Borrmann types is insufficient. Methods: A total of 3130 patients with advanced gastric cancer who underwent gastrectomy from January 2001 to September 2017 were enrolled in the analysis. Logistic regression and survival analysis methodology were used to investigate factors associated with peritoneal metastasis and overall survival (OS). Results: Of the total cohort, 264 (8.43%) patients were B-IV type, 1752 (55.97%) were small-size other Borrmann types, and 1114 (35.59%) were large-size other Borrmann types. Signet ring cell carcinoma (SRC) was more common in B-IV types than in other Borrmann types (33.71% vs 11.42% vs 12.66%, P < 0.001). In B-IV gastric cancers, SRC was significantly associated with peritoneal metastasis (HR = 1.898, 95% CI = 1.112 ~ 3.241, P = 0.019) and poorer OS (HR = 1.492, 95% CI = 1.088 ~ 2.045, P = 0.013) in multivariable analysis. Furthermore, stratified analysis revealed that SRC had worse survival than adenocarcinoma in the B-IV subgroups, with locally advanced stages (stages II ~ III) or negative surgical margins (all P < 0.05). In contrast, SRC failed to be significantly associated with peritoneal metastasis and poor OS in other Borrmann types (all P > 0.05). Conclusion: SRC was more common in B-IV gastric cancer than in other Borrmann types. It was significantly associated with peritoneal metastasis and poorer OS in the B-IV type but not in other Borrmann types. As a unique prognostic factor for B-IV gastric cancer, SRC might help evaluate risk stratification and optimize treatment for this entity, especially for patients with locally advanced stages or R0 resection.

PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study.

Background: The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. Methods: Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. Results: Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. Conclusions: Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.

Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer.

BACKGROUND: The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model. METHODS: We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC. RESULTS: Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC. CONCLUSION: AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.

Recurrence of Gastric Cancer in the Jejunum Close to the Anastomotic Site after Total Gastrectomy.

A 61-year-old man underwent total gastrectomy with esophago-jejunostomy for Borrmann type I gastric cancer. Postoperative intra-abdominal abscess made the patient unable to receive adjuvant chemotherapy. Only 23 weeks after operation, the patient developed melena and anemia, leading to the diagnosis of recurrence in the jejunum close to the anastomotic site. The patient received salvage resection of the recurrence. Pathological study showed that the tumor was composed of atypical cells similar to those of the primary gastric cancer. Normal jejunal mucosa was observed between the esophagus and the recurrent tumor. We judged that exfoliation of the gastric cancer cells caused the recurrence due to both the very short disease-free interval and pathological findings. Surgeons should pay attention to this type of recurrence especially for Borrmann type I gastric cancer. In addition to the adjuvant chemotherapy, gastric irrigation using distilled water during the operation seems to be a feasible measure to prevent this type of recurrence.

Increased Expression of LIPC Is Associated with Aggressive Phenotype of Borrmann Type 4 Gastric Cancer.

PURPOSE: To investigate lipase C hepatic type (LIPC) expression in Borrmann type 4 gastric cancer and its correlation with clinical outcome. The biological roles of LIPC in Borrmann type 4 gastric cancer progression were also investigated. METHODS: We determined LIPC expression in 324 primary gastric cancer tissues and 178 matched adjacent non-tumor tissues by immunohistochemistry. We explored the role of LIPC in Borrmann type 4 gastric cancer cell (OCUM-1) migration, invasion, proliferation, cell cycle, and expression of epithelial-mesenchymal transition-related genes by knocking down LIPC expression. RESULTS: LIPC expression was upregulated in Borrmann type 4 gastric cancer tissues compared with other types of gastric cancer and adjacent non-tumor tissues. High LIPC expression correlated with lymph node metastasis, advanced TNM stage, and poor overall survival in Borrmann type 4 gastric cancer patients. Multivariate analysis demonstrated that high LIPC expression was an independent prognostic factor in patients with Borrmann type 4 gastric cancer. By reducing LIPC expression, OCUM-1 cell invasion and migration were suppressed and Snail and MMP2 expression was downregulated, while E-cadherin expression was upregulated. CONCLUSIONS: High LIPC expression correlates with poor clinical outcome and plays an important role in regulating cell migration and invasion in Borrmann type 4 gastric cancer.

A Transfer Learning Radiomics Nomogram for Preoperative Prediction of Borrmann Type IV Gastric Cancer From Primary Gastric Lymphoma.

OBJECTIVE: This study aims to differentiate preoperative Borrmann type IV gastric cancer (GC) from primary gastric lymphoma (PGL) by transfer learning radiomics nomogram (TLRN) with whole slide images of GC as source domain data. MATERIALS AND METHODS: This study retrospectively enrolled 438 patients with histopathologic diagnoses of Borrmann type IV GC and PGL. They received CT examinations from three hospitals. Quantitative transfer learning features were extracted by the proposed transfer learning radiopathomic network and used to construct transfer learning radiomics signatures (TLRS). A TLRN, which integrates TLRS, clinical factors, and CT subjective findings, was developed by multivariate logistic regression. The diagnostic TLRN performance was assessed by clinical usefulness in the independent validation set. RESULTS: The TLRN was built by TLRS and a high enhanced serosa sign, which showed good agreement by the calibration curve. The TLRN performance was superior to the clinical model and TLRS. Its areas under the curve (AUC) were 0.958 (95% confidence interval [CI], 0.883-0.991), 0.867 (95% CI, 0.794-0.922), and 0.921 (95% CI, 0.860-0.960) in the internal and two external validation cohorts, respectively. Decision curve analysis (DCA) showed that the TLRN was better than any other model. TLRN has potential generalization ability, as shown in the stratification analysis. CONCLUSIONS: The proposed TLRN based on gastric WSIs may help preoperatively differentiate PGL from Borrmann type IV GC.Borrmann type IV gastric cancer, primary gastric lymphoma, transfer learning, whole slide image, deep learning.

Subtotal gastrectomy combined with chemotherapy: An effective therapy for patients with circumscribed Borrmann type IV gastric cancer.

BACKGROUND: Although Borrmann type IV (B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis (PPCM), which is important for selecting an appropriate therapeutic strategy. AIM: To identify factors related to the prognosis and PPCM of B-4 patients. METHODS: A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan-Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SPSS 20.0. RESULTS: Lymph node status, gastrectomy type, and postoperative chemotherapy were independent prognostic factors in 117 circumscribed B-4 patients. Subtotal gastrectomy combined with chemotherapy could significantly improve the long-term survival time. Six patients who were diagnosed with pN0 and received the combination therapy had a 3-year survival rate of 100% and a median survival of 77.7 mo. Even for patients with metastatic lymph nodes (n = 13), the combination therapy also increased the 3-year overall survival rate to 57.1%. In addition, positive lymph node status was the only factor (P = 0.005) correlated with PPCM in certain B-4 patients, and chemotherapy was useful for suppressing PPCM in patients with subtotal gastrectomy but not in those with total gastrectomy. CONCLUSION: Lymph node status is an independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.

Prognostic significance of Borrmann type combined with vessel invasion status in advanced gastric cancer.

BACKGROUND: Borrmann classification (types I-IV) for the detection of advanced gastric cancer has been accepted worldwide, and lymphatic and/or blood vessel invasion (LBVI) status is related to the poor prognosis after gastric cancer. AIM: To evaluate the significance of Borrmann type combined with LBVI status in predicting the prognosis of advanced gastric cancer. METHODS: We retrospectively studied the clinicopathological characteristics and long-term survival data of 2604 patients who were diagnosed with advanced gastric adenocarcinoma at Harbin Medical University Cancer Hospital from January 2009 to December 2013. Categorical variables were evaluated by the Pearson's χ 2 test, the Kaplan-Meier method was used to identify differences in cumulative survival rates, and the Cox proportional hazards model was used for multivariate prognostic analysis. RESULTS: A total of 2604 patients were included in this study. The presence of LVBI [LBVI (+)] and Borrmann type (P = 0.001), tumor location (P < 0.001), tumor size (P < 0.001), histological type (P < 0.001), tumor invasion depth (P < 0.001), number of metastatic lymph nodes (P < 0.001), and surgical method (P < 0.001) were significantly correlated with survival. When analyzing the combination of the Borrmann classification and LBVI status, we found that patients with Borrmann type III disease and LBVI (+) had a similar 5-year survival rate to those with Borrmann IV + LBVI (-) (16.4% vs 13.1%, P = 0.065) and those with Borrmann IV + LBVI (+) (16.4% vs 11.2%, P = 0.112). Subgroup analysis showed that the above results were true for any pT stage and any tumor location. Multivariate Cox regression analysis showed that Borrmann classification (P = 0.023), vascular infiltration (P < 0.001), tumor size (P = 0.012), pT stage (P < 0.001), pN stage (P < 0.001), and extent of radical surgery (P < 0.001) were independent prognostic factors for survival. CONCLUSION: Since patients with Borrmann III disease and LBVI (+) have the same poor prognosis as those with Borrmann IV disease, more attention should be paid to patients with Borrmann III disease and LBVI (+) during diagnosis and treatment, regardless of the pT stage and tumor location, to obtain better survival results.

Prognostic impact of Borrmann classification on advanced gastric cancer: a retrospective cohort from a single institution in western China.

BACKGROUND: Due to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC. METHODS: We retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type. RESULTS: Patients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p < 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p < 0.001) and TNM stage IV (p = 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV. CONCLUSIONS: The clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC.

Borrmann Type IV Gastric Cancer: Focus on the Role of Gastrectomy.

OBJECTIVES: The benefits of curative or palliative gastrectomy for Borrmann type IV (B-IV) gastric cancer remain controversial. This study was conducted to investigate whether or not gastrectomy could benefit prognosis of patients with Borrmann type IV gastric cancer. MATERIAL AND METHODS: A cohort of 469 B-IV gastric cancer patients from January 2001 to September 2017 was retrospectively reviewed. Survival analysis was used to investigate the prognosis of patients with or without gastrectomy. RESULTS: Among this cohort, the average age was 55 years and the median follow-up time was 12 months. One hundred and forty-six (31%) patients underwent curative resection, 187 (40%) patients underwent palliative resection, and the remaining 136 (29%) patients were judged unresectable. During the follow-up, a total of 294 (63%) patients died. Cox multivariate analysis showed that Tumor Node Metastasis (TNM) stage (p = 0.002), grade (p = 0.033), and gastrectomy (p < 0.001) were independent predictors of overall survival. Kaplan-Meier analysis revealed that, no matter in total group or subgroup stratified by tumor stage and grade, overall survival rates at 1 year, 2 years, and 5 years in patients with palliative resection were significantly worse than those in patients with curative resection (all p < 0.05), but significantly better than those in patients with no resection (all p < 0.05). CONCLUSIONS: Curative or palliative gastrectomy could increase the survival rate for B-IV gastric cancer patients. In the absence of alternative effective therapies, surgical resection remains a choice of improved survival or potential cure for B-IV gastric cancer.

Linitis Plastica: a Distinct Type of Gastric Cancer.

BACKGROUND: The prognosis of patients with linitis plastica (LP) gastric cancer is reported to be poor. The purpose of our retrospective study was to characterize the clinicopathologic features and survival outcomes of patients with LP, using a univocal definition. METHODS: We defined LP as gastric cancer that involves more than 1/3 of the gastric wall macroscopically. We reviewed a prospectively maintained institutional database of gastric cancer patients and summarized and compared clinicopathologic factors of patients with and without LP who had undergone gastrectomy. Patients were matched 1:1 using propensity score matching, and their overall survival (OS) rates and durations were compared. Multivariable Cox regression analyses were conducted, using gastrectomy as a time-varying covariate. RESULTS: We identified 740 patients with radiographically non-metastatic gastric cancer, 157 (21.2%) of whom had LP. Most patients with LP had advanced-stage disease (75.8% had stage IV disease, mainly due to peritoneal involvement). Patients with LP had significantly shorter OS durations than did those without LP in the entire cohort (median OS, 14.0 vs. 33.5 months; p value < 0.001) and in the surgical cohort (median OS after gastrectomy, 21.8 vs. 91.0 months; p < 0.001), as well as in the propensity-matched surgical cohort. In the LP cohort, chemotherapy (hazard ratio [HR] = 0.594; p = 0.076), chemoradiation therapy (HR = 0.346; p = 0.001), and gastrectomy (HR = 0.425; p = 0.003) were associated with a longer OS. CONCLUSIONS: LP is a phenotype of gastric cancer that often presents at an advanced stage, with a high rate of peritoneal involvement. The survival durations of patients with LP were poor in our study, even in the surgical cohort. The use of preoperative chemotherapy, chemoradiation therapy, and gastrectomy appeared to be important in carefully selected patients with localized LP.

Clinicopathological Features of Metastatic Gastric Tumors Originating From Breast Cancer: Analysis of Eleven Cases.

BACKGROUND: Metastatic gastric tumor originating from breast cancer (MGTBC) is rare. Endoscopically, gastric cancer (GC)-like lesions and submucosal tumors (SMT) are the features of MGTBC. Their clinicopathological characteristics are currently uncertain. We analyzed the clinicopathological characteristics of 11 patients with MGTBC to better understand the disease progression and thereby improve early detection methods. METHODS: From 2006 to 2016, 11 patients with MGTBC diagnosed by esophagogastroduodenoscopy (EGD) were included. RESULTS: All 11 patients were women, with a median age of 57 years. Histological examination revealed six cases with solid tubular components and five cases with invasive lobular carcinoma components. Melena was the most common symptom; however, asymptomatic cases were also common. Seven and four cases had GC-like lesions and SMTs, respectively. Six of the seven cases had GC-like lesions with peritoneal metastasis, whereas none of the four SMT cases had peritoneal metastasis (P = 0.015). The median overall survival (OS) in all cases was 26 months (range, 1 - 42 months). OS in cases treated with chemotherapy after a diagnosis of gastric metastases was significantly better than that in those treated without chemotherapy (P = 0.047). One patient showed gradual transformation from an SMT-type lesion to a Borrmann type 4-like appearance. CONCLUSIONS: MGTBC is a rare occurrence; however, it should be considered when gastric tumors, especially GC-like lesions in patients with a medical history of breast cancer are found. Patients with breast cancer, especially invasive lobular carcinoma, should undergo screening EGD regularly to detect gastric metastases early and receive chemotherapy to obtain good outcomes.

Prognostic impact and implications of extracapsular lymph node spread in Borrmann type IV gastric cancer.

The purpose of this study was to evaluate the relationship between extracapsular lymph node spread (ECS) and clinicopathology and its influence on the prognosis in patients with Borrmann type IV gastric cancer. Between 2002 and 2014, clinical data were reviewed from 486 patients with Borrmann type IV gastric cancer who underwent curative resection. Of the 486 patients, lymph node metastasis was found in 456. ECS was detected in 213 (46.7%) patients with lymph node metastasis. A positive lymph node with ECS was significantly correlated with the N category, lymphatic/venous invasion, tumor location, and TNM stage. For the whole patients, the mean OS was 34.7 months, and the 5-year OS rate was 15.5%. The 5-year OS rate of node-negative patients was 48%, for node-positive patients without ECS 18.7%, and for node-positive patients with ECS 5.7% (P = 0.000). In a multivariate analysis, adjusted for tumor location, lymphatic/venous invasion, body mass index (BMI), and TNM stages, ECS remained an independent prognostic factor. For patients with the same N category and TNM stage, those with ECS still had a worse survival rate. Recurrent sites were confirmed in 367 patients. The most frequent recurrent site was the peritoneum. There was a significant difference between ECS+ (N = 150) and ECS- (N = 142) patients (P = 0.008). Our results suggested that ECS was an independent prognostic value for Borrmann type IV gastric cancer patients with curative resection and a subgroup indicated a significantly worse long-term survival for patients with the same N or TNM stages. ECS+ was an adverse factor for peritoneal metastasis.

The significance of a nineteenth century definition in the era of genomics: linitis plastica.

BACKGROUND: Linitis plastica due to gastric adenocarcinoma is a condition with a long history, but still lacks a standardized definition and is commonly confused with Borrmann type IV, Lauren diffuse, and signet-cell type gastric cancer. The absence of a clear definition is a problem when investigating its biological characteristics and role as a possible independent factor for prognosis. Nevertheless, the biological behavior for linitis plastica, which is unique, may be valuable in risk stratification and have implications for treatment. A definition of linitis plastica based on molecular or genomic criteria could represent a useful starting point for investigating new targeted therapies. MAIN BODY: This literature review of linitis plastica will focus on the current classifications for gastric cancer, illustrating how the concept of linitis plastica relates to them in most cases and identifying a clear and reproducible definition. Moreover, the review will highlight the diagnostic challenges associated with linitis plastica, its prognostic implications, and the therapeutic options available. Future perspectives for its management are also addressed. CONCLUSION: Linitis plastica is a carcinoma with a scirrhous stroma, involving the submucosal and muscular layers of the stomach even in the absence of mucosal alteration. In most cases, the primary cancer cells are signet-ring cells or scattered cells in the context of a poorly differentiated carcinoma. Diagnosis is challenging. Staging should be thorough, including diagnostic laparoscopy in all cases due to the high incidence of peritoneal involvement. The prognostic significance of linitis plastica is still controversial. Curative-intent surgery, when feasible, should be performed, with a multimodality treatment approach. Cancer-stroma interactions are important features of this disease, and represent attaining potential target for future therapies. Future pathologic assessments of gastric cancer should report the stromal reaction in order to allow better characterization of the tumor.

CT-based radiomics signature for differentiating Borrmann type IV gastric cancer from primary gastric lymphoma.

PURPOSE: To evaluate the value of CT-based radiomics signature for differentiating Borrmann type IV gastric cancer (GC) from primary gastric lymphoma (PGL). MATERIALS AND METHODS: 40 patients with Borrmann type IV GC and 30 patients with PGL were retrospectively recruited. 485 radiomics features were extracted and selected from the portal venous CT images to build a radiomics signature. Subjective CT findings, including gastric wall peristalsis, perigastric fat infiltration, lymphadenopathy below the renal hila and enhancement pattern, were assessed to construct a subjective findings model. The radiomics signature, subjective CT findings, age and gender were integrated into a combined model by multivariate analysis. The diagnostic performance of these three models was assessed with receiver operating characteristics curves (ROC) and were compared using DeLong test. RESULTS: The subjective findings model, the radiomics signature and the combined model showed a diagnostic accuracy of 81.43% (AUC [area under the curve], 0.806; 95% CI [confidence interval]: 0.696-0.917; sensitivity, 63.33%; specificity, 95.00%), 84.29% (AUC, 0.886 [95% CI: 0.809-0.963]; sensitivity, 86.67%; specificity, 82.50%), 87.14% (AUC, 0.903 [95%CI: 0.831-0.975]; sensitivity, 70.00%; specificity, 100%), respectively. There were no significant differences in AUC among these three models (P=0.051-0.422). CONCLUSION: Radiomics analysis has the potential to accurately differentiate Borrmann type IV GC from PGL.

Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer.

The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein-coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin-like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets.

Undiagnosed Borrmann type IV gastric cancer despite repeated endoscopic biopsies and PET-CT examination: A case report.

Borrmann type IV gastric cancer is a particular histological type of carcinoma, which has the characteristic of diffused infiltration that invades the entire stomach, resulting in the thickening and stiffness of the stomach wall. Borrmann type IV gastric cancer is known for the difficulty of detecting tumor cells in endoscopic biopsy specimens. This is crucial in obtaining the pathological results to make a therapeutic decision. The case reported in the present study was highly suspected to be Borrmann type IV gastric cancer according to the clinical manifestations and gastrointestinal barium meal examinations, but demonstrated negative results in multiple endoscopic biopsies and positron emission tomography-computed tomography (PET-CT) examination. The patient was discharged as no affirmative diagnosis was specified. Two weeks after discharge, the patient was administered to another hospital under emergency treatment due to frequent urination. Cystoscopy examination revealed marked thickening of the right bladder wall over a large area. Biopsy specimens were sampled. Pathological consultation suggested a gastrointestinal original of the lesion, which was most likely poorly differentiated gastric adenocarcinoma with neuroendocrine metastasis to the bladder.

Borrmann type IV gastric cancer should be classified as pT4b disease.

BACKGROUND: The impact of macroscopic pathologic features of primary tumor that could be obtained preoperatively on pT classification has not been reported so far. The aim of this study was to investigate the feasibility of incorporation of Borrmann type IV gastric cancer into the pT classification. MATERIALS AND METHODS: Clinicopathologic and prognostic data of 1622 patients with advanced gastric cancer who underwent radical surgery were retrospectively studied. RESULTS: Of 1622 patients, 135 (8.32%) patients were classified as having Borrmann type IV gastric cancer. We first confirmed that Borrmann type IV gastric cancer was one of the independent prognostic factors for patients with advanced gastric cancer who underwent radical surgery. Interestingly, we found that overall survival of patients with Borrmann type IV gastric cancer could be clearly distinguished by pN classification and pathological TNM stage but not by pT classification. Importantly, further analysis demonstrated that the prognosis of Borrmann type IV gastric cancers was homogeneous with that of pT4b cancers but poorer than pT2, pT3, pT4a cancers. Therefore, we proposed a novel pT classification in which pT4b disease was defined as cancers that were Borrmann type IV or those that had invaded adjacent structures. Two-step multivariate analysis demonstrated that the novel pT classification was more suitable for prognostic assessment than the original classification. CONCLUSIONS: Classifying Borrmann type IV gastric cancer as pT4b disease improves pT classification prediction of prognosis in patients with advanced gastric cancer after radical surgery.