Methylene blue is a fluorescent dye discovered in 1876 and has since been used in different scientific fields. Only recently has methylene blue been used for intraoperative fluorescent imaging. Here, the authors review the emerging role of methylene blue, not only as a dye used in clinical practice, but also as a fluorophore in a surgical setting. We discuss the promising potential of methylene blue together with the challenges and limitations among specific surgical techniques. A literature review of PubMed and Medline was conducted based on the historical, current and future usage of methylene blue within the field of medicine. We reviewed not only the current usage of methylene blue, but we also tried to grasp its’ function as a fluorophore in five main domains. These domains include the near-infrared imaging visualization of ureters, parathyroid gland identification, pancreatic tumors imaging, detection of breast cancer tumor margins, as well as breast cancer sentinel node biopsy. Methylene blue is used in countless clinical procedures with a relatively low risk for patients. Usage of its fluorescent properties is still at an early stage and more pre-clinical, as well as clinical research, must be performed to fully understand its potentials and limitations.

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3–4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61–0.73), with an acceptable heterogeneity (I² 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.

Gastric cancer is ranked as the fifth most frequently diagnosed type of cancer. Complete resection with adequate lymphadenectomy represents the goal of treatment with curative intent. Quality assurance is a crucial factor in the evaluation of oncological surgical care, and centralization of healthcare in referral hospitals has been proposed in several countries. However, an international agreement about the setting of “high-volume hospitals” as well as “minimum volume standards” has not yet been clearly established. Despite the clear postoperative mortality benefits that have been described for gastric cancer surgery conducted by high-volume surgeons in high-volume hospitals, many authors have highlighted the limitations of a non-composite variable to define the ideal postoperative period. The textbook outcome represents a multidimensional measure assessing the quality of care for cancer patients. Transparent and easily available hospital data will increase patients’ awareness, providing suitable elements for a more informed hospital choice.

Gastric cancer (GC) is the third leading cause of cancer death. Early detection is a key factor to reduce its mortality. We retrospectively collected pre- and postoperative serum samples as well as tumour tissues and adjacent normal tissues from 100 GC patients. Serum samples from non-cancerous patients were served as controls (n = 50). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure levels of over 300 proteins. Alteration of each protein was analysed by univariate analysis. Elastic-net logistic regression was performed to select serum proteins into the diagnostic model. We identified 19 serum proteins (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCP1, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, and ADAMTS-15) that together distinguish GC cases from controls with a diagnostic sensitivity of 93%, specificity of 100%, and area under receiver operating characteristic curve (AUC) of 0·99 (95% CI: 0·98-1). Moreover, the 19-serum protein signature provided an increased diagnostic capacity in patients at TNM I-II stage (sensitivity 89%, specificity 100%, AUC 0·99) and in patients with high microsatellite instability (MSI) (91%, 98%, and 0·99) compared to individual proteins. These promising results will inspire a large-scale independent cohort study to be pursued for validating the proposed protein signature. Based on targeted proteomics and elastic-net logistic regression, we identified a 19-serum protein signature which could contribute to clinical GC diagnosis, especially for patients at early stage and those with high MSI. FUND: This study was supported by a European H2020-Marie Skłodowska-Curie Innovative Training Networks grant (316,929, GastricGlycoExplorer). Funder had no influence on trial design, data evaluation, and interpretation.

An umbrella review was performed to summarize literature data and to investigate benefits and harm of robotic gastrectomy (RG) compared to laparoscopic (LG) approach. To overcome the intrinsic limitations of laparoscopy, the robotic approach is claimed to facilitate lymph-node dissection and complex reconstruction after gastrectomy, to assure oncologic safety also in advanced gastric cancer. A literature search was conducted in PubMed, Cochrane and Embase databases for all meta-analyses published up to December 2019. The search strategy was previously published in a protocol. We selected fourteen meta-analyses comparing outcomes between LG and RG with curative intent in patients with diagnosis of resectable gastric cancer. We highlight that RG has a longer operation time, inferior blood loss, reduction in hospital stay and a more rapid recovery of bowel function. In meta-analyses with statistical significance the number of nodes removed in RG is higher than LG and the distal margin of resection is higher. There is no difference in terms of total complication rate, mortality, morbidity, anastomotic leakage, anastomotic stenosis, intestinal obstruction and in conversion rate to open technique. The safety and efficacy of robotic gastrectomy are not clearly supported by strong evidence, suggesting that the outcomes reported for each surgical technique need to be interpreted with caution, in particular for the meta-analyses in which the heterogeneity is large. Certainly, robotic gastrectomy is associated with shorter time to oral intake, lesser intraoperative bleeding and longer operation time with an acceptable level of evidence. On the other hand, the data regarding other outcomes are insufficient as well as non-significant, from an evidence point of view, to draw any robust conclusion.

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC).