Evaluation of the endoscopic cure criteria in patients undergoing surgery for early gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) prognosis is influenced by the extent of the tumor, lymph node involvement (LNM), and metastasis. Endoscopic resection (ER) or gastrectomy with lymphadenectomy are standard treatments for early GC (EGC). This study evaluated LNM frequency according to eCura categories, clinicopathological characteristics, disease-free (DFS), and overall (OS) survival rates. METHODS: We included EGC patients who underwent curative gastrectomy between 2009 and 2020 from our single-center database. Anatomopathological and clinical reports were reviewed to analyze eCura categories. RESULTS: We included 160 EGC patients who underwent gastrectomy with eCura categories A, B, and C, comprising 26.3%, 13.8%, and 60%, respectively. Baseline clinical characteristics showed no intergroup disparities. LNM incidence for A, B, and C was 4.8%, 18.2%, and 19.8%. When evaluating the criteria for ER and its association with eCura categories, we found that 95.2% of eCura A and 100% of eCura B patients had classic or expanded criteria for ER. On the other hand, 97.9% of eCura C patients were referred to surgical resection. Multivariate analysis demonstrated that lymphatic (OR = 5.57, CI95% = 1.45-21.29, p = 0.012) and perineural (OR = 15.8, CI95% = 1.39-179.88, p = 0.026) invasions were associated with a higher risk of LNM. No significant differences in DFS or OS were found among eCura categories. CONCLUSION: The eCura categories were associated with the occurrence of LNM. In most patients, those with classic and expanded indication criteria for ER were classified as eCura A and B.

Multivisceral resection compared to standard gastrectomy for gastric adenocarcinoma: A propensity score-matching analysis.

BACKGROUND: Multivisceral resection (MVR) in locally advanced gastric cancer (GC) is a morbid procedure. However, the precise impact of removing additional organs remains controversial. This study aimed to compare the outcomes of MVR versus standard gastrectomy (SG) in an unbiased cohort. METHODS: Patients who underwent curative-intent surgery for gastric adenocarcinoma were considered. Those submitted to SG were compared to the ones who received MVR using Propensity Score Matching (PSM) analysis. RESULTS: A total of 685 GC patients were included (621 SG and 64 MVR). Groups were distinct concerning the extent of the gastrectomy, tumor size, pTNM, R0, postoperative complications, and 90-day mortality. After PSM, 57 patients were matched in each group. All variables assigned in the score were well matched. Postoperative complication, 90-day mortality, and overall survival (OS) became similar among groups. Age >65 years old and resection of two or more organs, besides the stomach, were factors associated with 90-day mortality. R1 and not received multimodal therapy were independent prognostic factors for worse OS. CONCLUSIONS: After PSM, the difference in morbidity, mortality, and survival of MVR compared to SG was no longer statistically significant, suggesting that MVR is an acceptable therapeutic strategy to patients with advanced GC.

Preoperative chemotherapy is a better strategy than upfront surgery in cT4 gastric cancer.

BACKGROUND: Chemotherapy (CMT) followed by surgery is recommended by Western countries for advanced gastric cancer (GC). However, cT4 GC usually undergoes upfront surgery, due to symptoms. This study aimed to evaluate if preoperative CMT is a better strategy than upfront surgery in cT4 GC. METHODS: All cT4 GCs who underwent curative gastrectomy were included. Patients were divided according to their initial treatment: upfront surgery (SURG) or CMT + SURG. RESULTS: Among the 226 GC initially staged as cT4, 150 underwent SURG and 76 CMT + SURG. Groups were similar concerning age, comorbidities, American Society of Anesthesiologists, gastrectomy performed, and postoperative complications. The CMT + SURG group had less advanced pTNM. Median overall survival (OS) was 32 and 58.5 months for SURG and CMT + SURG, respectively (p = 0.04). Patients who received perioperative or adjuvant CMT had better OS compared to surgery alone (49.4 vs. 15.9 months, p < 0.001). OS was similar for those receiving preoperative and adjuvant CMT. Non-CMT, pN+, and R1 resection were independent risk factors for worse OS. CONCLUSION: Multimodal treatment associating CMT with surgery, regardless of whether the approach is pre- or postoperative, is essential to improve the survival of cT4 GC. As tolerance to adjuvant treatment is reduced, preoperative CMT is a better strategy than upfront surgery in these patients.

Gastrectomy for elderly gastric cancer patients: A propensity score-matching analysis.

BACKGROUND: Although D2-gastrectomy is the most effective treatment for resectable gastric cancer (GC), it is unclear whether elderly patients have increased risk of morbidity and worse survival. This study aimed to compare the short- and long-term outcomes of older age (OA) patients with those of less advanced age (LAA). METHODS: GC patients undergoing curative gastrectomy were retrospectively analyzed and divided into two groups: OA (>75 years) and LAA (<75 years). Propensity score-matching (PSM) analysis using seven variables was conducted to reduce selection bias. RESULTS: Among 586 patients, 494 (84.3%) were classified as LAA and 92 (15.7%) as OA. OA patients had worse clinical status, higher rates of D1-lymphadenectomy, subtotal gastrectomy, and Lauren type; higher mortality and worse survival. No difference in pathological tumor-node-metastasis (pTNM) stage was observed between groups. Preoperative chemotherapy was performed more frequently in the LAA group. After PSM (92 OA: 92 LAA), all variables included in PSM were matched, and mortality rates and survival became similar between groups. In multivariate analysis, American Society of Anaesthesiologists score III/IV was an independent factor associated with a 90-day mortality after PSM. CONCLUSION: Gastrectomy in elderly GC patients has similar outcomes compared with younger ones. Clinical status and disease stage are more important than the patient's age.

Gastric cancer with microsatellite instability displays increased thymidylate synthase expression.

BACKGROUND: Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. METHODS: We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). RESULTS: Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. CONCLUSION: MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.

Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer.

Objective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune-related score. Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC). Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival. Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.

D2 Lymphadenectomy According to the Arterial Variations in Gastric and Hepatic Irrigation.

BACKGROUND: D2 lymphadenectomy for gastric cancer is technically demanding and requires clearance of the lymph node stations along the main arteries that irrigate the stomach and the liver. As gastric and hepatic irrigation have a different pattern from the classic branching of the celiac trunk in approximately 25% of patients, acquaintance with these variations and knowledge on how to adequately perform the lymphadenectomy in different anatomic settings is of utmost importance for surgeons who manage gastric cancer.1 METHODS: This video demonstrates, step-by-step, how to perform D2 lymphadenectomy in accordance with gastric and hepatic irrigation. Illustrations of the arterial variation correlate with the corresponding computed tomography image and operative management of the lymph node stations. DISCUSSION: D2 lymphadenectomy is the standard of care in advanced gastric cancer.2 It implies clearing the lymph node stations along the celiac trunk, left gastric artery, and common and proper hepatic arteries. However, the celiac trunk and hepatic irrigation are highly variable and surgeons must be aware of how to properly and safely address the lymph node stations in all scenarios. Vessel anatomical variations increase the risk of vascular injuries and its complications, such as bleeding, necrosis, liver function impairment, liver necrosis, and conversion to open surgery.3-5 Additionally, the lymphadenectomy cannot be compromised if a variation is found.6 Preoperative knowledge of the gastric blood supply also shortens the surgical duration.7 CONCLUSIONS: The present video demonstrates how to recognize the most common variations found during D2 gastrectomy, and provides strategies to adequately approach them.

Epstein-Barr Virus Positive Gastric Cancer: A Distinct Subtype Candidate for Immunotherapy.

BACKGROUND: Epstein-Barr virus (EBV) positive gastric cancer (GC) has been described as a distinct molecular subtype of the disease, especially associated with gastric carcinoma with lymphoid stroma (GCLS). The possibility that EBV associated GC (EBVaGC) had better prognosis and may be susceptible to immunotherapy has increased the interest in this subtype. However, immune checkpoint and survival of EBVaGC are still controversial, especially with regard to GCLS and conventional gastric adenocarcinoma (CGA). This study aimed to evaluate the clinicopathological characteristics, immunohistochemical profiles and prognosis of EBVaGC according to the histological type GCLS and CGA. METHODS: we retrospectively evaluated a series of EBVaGC who underwent gastrectomy with D2-lymphadenectomy. Biomarkers and tumor-infiltrating cells were evaluated by immunohistochemistry. PD-L1 was evaluated using a combined positive score (CPS). RESULTS: From a total of 30 EBVaGC, 14 (46.7%) were identified as GCLS and 16 (53.3%) as CGA (9 Intestinal, 6 diffuse, 1 undetermined). There were no significant differences in age, sex, and pTNM between GCLS and CGA. CPS-positivity and high-CD8+ was significantly higher in GCLS compared with CGA (P = 0.007 and P = 0.005, respectively). Diffuse EBVaGC had worse survival than intestinal type (P = 0.020). There was no difference in survival between GCLS and intestinal CGA (P = 0.260). In multivariate analysis, CPS and pN status were related with survival in EBVaGC. CONCLUSIONS: CGLS was associated with a predominance of CD8+ cell infiltration and PD-L1 expression. CPS and lymph node metastasis were independent factors associated with prognosis in EBVaGC. These results suggest that specifically EBV-positive GCLS may be prime candidates for PD-1 directed therapy.

Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. METHODS: All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. RESULTS: Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. CONCLUSION: CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.

Impact of neoadjuvant chemotherapy on surgical and pathological results of gastric cancer patients: A case-control study.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (NACT) followed by radical surgery represents a treatment option for patients with advanced gastric cancer (GC). This case-control study aimed to evaluate the clinicopathological characteristics and surgical outcomes of GC patients who received NACT, and its impact on survival. METHODS: We retrospectively reviewed all patients with GC who underwent gastrectomy. A total of 45 cases with NACT were matched with consecutive 45 patients who underwent upfront gastrectomy for the following characteristics: gender, age, gastrectomy type, lymphadenectomy extent, American Society of Anesthesiologists class, histological type, cT and cN. RESULTS: NACT group had smaller tumors (4.9 vs 6.8 cm P = .006), lower lymphatic invasion rate (40% vs 73.3%, P = .001), lower venous invasion rate (18% vs 46.7%, P = .003) and lower perineural invasion rate (35% vs 77.8%, P < .0001). The ypTNM stage was lower in patients treated with NACT (P < .001). The major postoperative complication (POC) rate was lower in NACT patients (6.7% vs 24.4%, P = .02), as was hospital length of stay (10.8 vs 17 days, P = .005). CONCLUSIONS: NACT allowed nodal and tumor downstaging. In addition, patients who underwent NACT had fewer POC and shorter length of hospital stay.

Multivisceral resection vs standard gastrectomy for gastric adenocarcinoma.

INTRODUCTION: Multivisceral resection (MVR) is potentially curative for selected gastric cancer patients, supposedly at the cost of increased complications. However, current data comparing MVR to standard gastrectomy (SG) is lacking. OBJECTIVES: Compare complications and survival after MVR and SG. METHODS: In a retrospective cohort of 1015 patients with gastric adenocarcinoma, 58 underwent MVR and 466 SG. Groups were compared concerning their characteristics, complications, and survival. RESULTS: One hundred seventy-six patients had postoperative complications. Major complications were more frequent after MVR (P = .002). Surgical mortality was 8.6% and 4.9% for MVR and SG (P = .221). Older age, higher morbidities, and MVR were independent risk factors for major complications. The odds ratio for major complications was 5.89 for MVR with one or two organs and 38.01 for MVR with three or more organs. The pancreas was the most commonly removed organ and pT4b disease were confirmed in 34 (58.6%) of the MVR cases. Disease-free survival (DFS) was lower in MVR patients (51% vs 77.8%; P < .001), being worse according to the number of organs resected. In pN+ patients, DFS was worse after MVR. DFS was equivalent to pT4b and non-pT4b in the MVR group. CONCLUSIONS: Increased morbidity and lower survival are expected for gastric cancer patients undergoing MVR.

Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. METHODS: Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. RESULTS: Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. CONCLUSION: High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.

Risk assessment of lymph node metastases in early gastric adenocarcinoma fulfilling expanded endoscopic resection criteria.

BACKGROUND AND AIMS: Early gastric cancer (EGC) is known to present a low rate of lymph node metastases (LNMs). Gastrectomy with D2 lymphadenectomy is usually curative for EGC. Endoscopic submucosal dissection (ESD) is a well-accepted treatment modality for lesions that meet the classic criteria: those mucosal differentiated adenocarcinoma measuring 20 mm or less, without ulceration. Expanded criteria for ESD have been proposed based on a null LNM rate from large gastrectomy series from Japan. Patients with LNM have been reported in Western centers, heightening the need for validation of expanded criteria. Our aim was to assess the risk of LNM in gastrectomy specimens of patients with EGC who met the expanded criteria for ESD. METHODS: We conducted an evaluation of gastrectomy specimens including LNM staging of patients submitted to gastrectomy for EGC in a 39-year retrospective cohort. RESULTS: A total of 389 surgical specimens were included. From them, 135 fulfilled criteria for endoscopic resection. None of the 31 patients with classic criteria had LNM. From the 104 patients with expanded criteria, 3 had LNM (n = 104 [2.9%], 95% confidence interval, .7%-8.6%), all of them with undifferentiated tumors without ulceration, measuring less than 20 mm. CONCLUSIONS: There is a small risk of LNM in EGC when expanded criteria for ESD are met. Refinement of the expanded criteria for the risk of LNM may be desirable in a Brazilian cohort. Meanwhile, the decision to complement the endoscopic treatment with gastrectomy will have to take into consideration the individual risk of perioperative morbidity and mortality.

Neutrophil-lymphocyte ratio is associated with prognosis in patients who underwent potentially curative resection for gastric cancer.

BACKGROUND AND OBJECTIVES: The role of inflammation in cancer development is a well-known phenomenon that may be represented by the neutrophil-lymphocyte ratio (NLR). The present research intends to determine the impact of NLR on the survival outcome of patients with gastric cancer (GC), and to evaluate its use as a stratification factor for the staging groups. METHODS: Data regarding clinical characteristics, surgery, pathology, and follow-up were retrospectively collected from our single-center prospective database. Blood samples were obtained before surgery. RESULTS: A total of 383 patients (231 males) who underwent gastrectomy with lymphadenectomy were evaluated between 2009 and 2016. NLR established cutoff was 2.44, and patients were divided in NLR ≥2.44 (hNLR) and <2.44 (lNLR). hNLR patients (38.4% of the cases) had lower disease-free survival and overall survival (OS) compared to lNLR patients (P = 0.047 and P = 0.045, respectively). Risk stratification according to NLR value was done in same tumor depth (T4 and

Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. METHODS: We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. RESULTS: EBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P = 0.032), proximal location (P < 0.001), undetermined Lauren type (P < 0.001), poorly differentiated histology (P = 0.043) and severe inflammatory infiltrate (P < 0.001). MSI-tumors were associated to older age (P = 0.002), subtotal gastrectomy (P = 0.004), pN0 (P = 0.024) and earlier TNM stage (P = 0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P < 0.001). MSI was associated to better survival outcomes. CONCLUSION: EBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.

Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy.

OBJECTIVE: Adjuvant chemotherapy with 5-fluorouracil (5-FU) has been widely used in gastric cancer (GC) patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase (TS), and high levels of TS correlate with resistance to treatment with fluoropyrimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. METHODS: We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry (IHC) in tumor cells by tissue microarray (TMA). TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score: negative, low and high. RESULTS: TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age (P=0.007), high neutrophil/lymphocyte ratio (P=0.048), well/moderately differentiated histology (P=0.001), intestinal Lauren type (P<0.001) and absence of perineural invasion (P=0.003). Among 285 patients, 133 stage II/III patients (46.7%) received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival (DFS) in stage III GC patients who received 5-FU-based chemotherapy (P=0.007). Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. CONCLUSIONS: High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.

Probe-based confocal endomicroscopy is accurate for differentiating gastric lesions in patients in a Western center.

OBJECTIVE: Probe-based confocal laser endomicroscopy (pCLE) technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and microvascular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric lesions. METHODS: Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE results. RESULTS: Patients' mean age was 68.3 (range, 42-83) years and six were men. Thirteen suspicious flat or elevated lesions (classified as 0-Is, 0-IIa or 0-IIa + IIc) and seven pre-malignant lesions (atrophy and intestinal metaplasia) were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body (n=10 lesions), the antrum (n=9) and the incisura angularis (n=1). All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% (19/20 lesions). CONCLUSIONS: pCLE is accurate for real time histology of gastric lesions. pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and infection status.

BACKGROUND: Lymphoepithelioma-like gastric carcinoma (LLGC) is a rare subtype of gastric carcinoma (GC) characterized by prominent lymphocytic infiltration. LLGC may be associated with latent Epstein-Barr virus (EBV) infection or microsatellite instability (MSI). This study aims to assess the clinicopathological characteristics, EBV infection, and MSI status in LLGC. METHODS: A retrospective analysis of GC patients submitted to potentially curative resection between 2009 and 2014 was performed. The LLGC subtype specimens were examined for EBV by in situ hybridization and MSI by immunohistochemical analysis. The LLGC profile was analyzed accordingly to clinicopathological parameters. RESULTS: From 255 patients, seven were identified on the pathological report as LLGC. Six cases were EBV-positive and one had MSI, showing loss of MLH1 and PMS2 expression. LLGC was more frequently seen in men, and the mean age was 69 years. When compared to non-LLGC, LLGC cases were larger (∼5.8 cm) poorly differentiated tumors and had lower incidence of lymph node metastasis (P = 0.045). Mean number of lymph nodes dissected in the LLGC group was 39.5, and only one patient had a single positive lymph node. In addition, two patients presented associated lesions. LLGC was not associated with HER-2, chromogranin and synaptophysin positivity or Helicobacter pylori infection. CONCLUSIONS: Distinct pathological aspects and clinical behavior of LLGC reinforce the need for proper recognition of this histological subtype to choose better therapeutic approaches.

Carnoy's solution increases the number of examined lymph nodes following gastrectomy for adenocarcinoma: a randomized trial.

BACKGROUND: Pathological examination of a minimum of 16 lymph nodes is recommended following surgery for gastric adenocarcinoma, despite this a longer survival is expected when 30 or more lymph nodes are examined. Small lymph nodes are difficult to identify, and fat-clearing solutions have been proposed to improve this, but there is no evidence of their clinical benefit. METHODS: Fifty D2 subtotal gastrectomy specimens were randomized for fixation in Carnoy's solution (CS) or 10% neutral buffered formalin (NBF), with subsequent fat dissection. After dissection, the residual fat from the NBF group, instead of being discarded, was immersed in CS and dissected again. Data from 25 D2 subtotal gastrectomies performed before the study were also analyzed. RESULTS: The mean number of examined lymph nodes was 50.4 and 34.8 for CS and NBF, respectively (p < 0.001). Missing lymph nodes were found in all cases from the residual fat group (mean of 16.9), and in eight of them (32%) metastatic lymph nodes were present; this allowed the upstaging of two patients. Lymph nodes in the CS group were smaller than those in the NBF group (p = 0.01). The number of retrieved lymph nodes was similar among the NBF and Retrospective groups (p = 0.802). CONCLUSIONS: Compared with NBF, CS increases lymph node detection following gastrectomy and allows a more accurate pathological staging. No influence of the research protocol on the number of examined lymph nodes was observed.

Imagine a world without cancer.

BACKGROUND: Since the "War on Cancer" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. DISCUSSION: Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient's own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. SUMMARY: Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer.