Current trends in the management of Gastro-oEsophageal cancers: Updates to the ESSO core curriculum (ESSO-ETC-UGI-WG initiative).

Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges.

Hepatic cancer is widely regarded as the leading cause of cancer-related mortality worldwide. Despite recent advances in treatment options, the prognosis of liver cancer remains poor. Therefore, there is an urgent need to develop more representative in vitro models of liver cancer for pathophysiology and drug screening studies. Fortunately, an exciting new development for generating liver models in recent years has been the advent of organoid technology. Organoid models hold huge potential as an in vitro research tool because they can recapitulate the spatial architecture of primary liver cancers and maintain the molecular and functional variations of the native tissue counterparts during long-term culture in vitro. This review provides a comprehensive overview and discussion of the establishment and application of liver organoid models in vitro. Bioengineering strategies used to construct organoid models are also discussed. In addition, the clinical potential and other relevant applications of liver organoid models in different functional states are explored. In the end, this review discusses current limitations and future prospects to encourage further development.

Evaluation of indocyanine green tracheobronchial fluorescence (ICG-TBF) via nebulization during minimally invasive esophagectomy.

Surgical manipulation of the tracheobronchial complex is a contributing factor in pulmonary morbidity of esophagectomy. Accurate dissection between membranous trachea and bronchi with esophagus is essential. This study tests the feasibility of delivering indocyanine green (ICG) in an aerosol form to achieve tracheobronchial fluorescence (ICG-TBF). Patients with esophageal and esophagogastric junction carcinoma (N = 37) undergoing minimally invasive esophagectomy (McKeown type) were included. ICG was aerosolized by nebulization in supine position before thoracoscopy. ICG-TBF was observed with real-time fluorescence-enabled camera. Intra- and postoperative complications related to ICG were the primary focus. ICG-TBF was identified in 94.6% (35/37) of patients with median time to fluorescence identification of 15 minutes (range 1-43). There were no airway injuries in the study. The ICU median stay was 2 (range 2-21) days. No intra- or postoperative complications attributable to ICG were observed. Grade 3 or 4 pulmonary complications were seen in total 8.1% patients. No 90-day postoperative mortality was seen. ICG delivered in aerosol form was found to be safe and effective in achieving ICG-TBF. It aided in accurate dissection of esophagus from the tracheobronchial complex. Further studies on effect of ICG-TBF in decreasing pulmonary complications of esophagectomy are needed.

Current status of indocyanine green fluorescent angiography in assessing perfusion of gastric conduit and oesophago-gastric anastomosis.

Anastomotic leak (AL) remains a significant complication after esophagectomy. Indocyanine green fluorescent angiography (ICG-FA) is a promising and safe technique for assessing gastric conduit (GC) perfusion intraoperatively. It provides detailed visualization of tissue perfusion and has demonstrated usefulness in oesophageal surgery. GC perfusion analysis by ICG-FA is crucial in constructing the conduit and selecting the anastomotic site and enables surgeons to make necessary adjustments during surgery to potentially reduce ALs. However, anastomotic integrity involves multiple factors, and ICG-FA must be combined with optimization of patient and procedural factors to decrease AL rates. This review summarizes ICG-FA's current applications in assessing esophago-gastric anastomosis perfusion, including qualitative and quantitative analysis and different imaging systems. It also explores how fluorescent imaging could decrease ALs and aid clinicians in utilizing ICG-FA to improve esophagectomy outcomes.

Impact of fluorescent thoracic duct lymphography via intranodal approach in minimal access esophageal cancer surgery.

PURPOSE: Chyle leak resulting from thoracic duct (TD) injury poses significant morbidity and mortality challenges. We assessed the feasibility of using near-infrared (NIR) indocyanine green (ICG) imaging for intraoperative fluorescence TD lymphography during minimal access esophagectomy (MAE) in a semiprone position with inguinal nodal injection of ICG dye. METHODS: Ninety-nine patients with esophageal or gastroesophageal junctional cancer undergoing MAE received inguinal node injections of 2.5 mg ICG dye (total 5 mg) under sonographic guidance during anesthesia induction. Stryker's 1688 AIM HD system was used in 76 cases, Karl Storz OPAL 1 S in 20, and in three cases the Karl Storz Rubina. RESULTS: In 93 patients (94%), the TD was clearly delineated along its entire length; it was not visualized in 6 patients (6%). Fluorescence guidance facilitated TD ligation in 16 cases, while 3 cases required clipping of duct tributaries for oncological considerations. Twenty-eight patients exhibited minor duct variations. Fluorescence was sustained throughout surgery (median observation time 60 min post-injection; range 30-330). No patient experienced any chyle leak within 30 days post-surgery and no adverse reactions to ICG was evident. CONCLUSIONS: Intraoperative fluorescence TD lymphography using ICG during MAE in a semiprone position with inguinal nodal injection proved safe, feasible, and effective, allowing clear visualization of the TD in almost all cases. This approach aids safe ligation and reduces chyle leak risk. It offers real-time imaging of TD anatomy and variations, providing valuable feedback to surgeons for managing TD injuries during MAE procedures and represents an excellent educational tool.

Dissecting the genetic heterogeneity of gastric cancer.

BACKGROUND: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. METHODS: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. FINDINGS: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. INTERPRETATION: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. FUNDING: German Research Foundation (DFG).

Current Trends in Volume and Surgical Outcomes in Gastric Cancer.

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.

Heat shock protein 90 (HSP90) inhibitors in gastrointestinal cancer: where do we currently stand?-A systematic review.

PURPOSE: Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. METHODS: We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. RESULTS: Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. CONCLUSION: It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.

Current standards of surgical management of gastric cancer: an appraisal.

PURPOSE: Gastric cancer (GC) is the fifth most common malignancy worldwide and portends a grim prognosis due to a lack of appreciable improvement in 5-year survival. We aimed to analyze the available literature and summarize the current standards of surgical care for curative and palliative intent treatment of GC. METHODS: We conducted a systematic search on the PubMed database for studies on the management of GC. RESULTS: Endoscopic resection is an acceptable treatment option for T1a tumors. The role of optimal resection margin for GC remains unclear. D2 lymph node dissection remains the standard of care with splenectomy needed selectively for splenic hilum involvement. A distal pancreatic resection should be avoided. The advantage of bursectomy and omentectomy in GC surgery is not clear. Multi-visceral resection may be considered for locally advanced GC in carefully selected patients. Minimally invasive approaches are non-inferior to open surgery. Surgery should be abandoned prior even in metastatic GC within the frame of multimodal therapy approach. CONCLUSION: Various trials have conclusively shown improved patient outcomes when well-established surgical standards are followed.

Current Cannabidiol Safety: A Review.

BACKGROUND: Marijuana, also known as cannabis, is the second most widely used illegal psychoactive substance smoked worldwide after tobacco, mainly due to the psychoactive effects induced by D-9-tetrahydrocannabinol (9-THC). Cannabidiol (CBD) is extracted from cannabis and may be used as an anti-inflammatory agent. Some patents on cannabidiol are discussed in this review. The cannabinoid is a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC); and is available in several administration modes, most known as CBD oil. OBJECTIVES: This study aims to provide an enhanced review of cannabidiol properties used in treating inflammation. This review also emphasises the current safety profile of cannabidiol. METHODS: Cannabis is also called Marijuana. It is the second most commonly used illegal psychoactive substance in the universe after tobacco. D-9-tetrahydrocannabinol (9-THC) present in cannabis produces psychoactive effects. Cannabidiol (CBD) extracted from cannabis is used for antiinflammatory purposes. Cannabis smoking causes various types of cancer, such as lung, tongue, and jaw. The current review took literature from Google Scholar, PubMed, and Google Patents. Many clinical investigations are included in this review. RESULT: After analysing the literature on cannabis, it has been suggested that although cannabis is banned in some countries, it may be included in the treatment and mitigation of some diseases and symptoms like pain management, epilepsy, cancer, and anxiety disorder. Mild side effects were frequently observed in cannabis medications, which included infertility in females, liver damage, etc. Conclusion: Cannabis contains chemical compounds such as the cannabinoids delta-9- tetrahydrocannabinol (THC), a psychoactive substance, and non-psychoactive cannabidiol (CBD). Cannabidiol has been confirmed as an efficient treatment of epilepsy in several clinical trials, with one pure CBD product named Epidiolex. It is also used in treating anxiety and acne, as a pain reliever, and has anti-inflammatory properties.

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Inferior Mesenteric Artery Ligation Level in Rectal Cancer Surgery beyond Conventions: A Review.

Within the intricate field of rectal cancer surgery, the contentious debate over the optimal level of ligation of the inferior mesenteric artery (IMA) persists as an ongoing discussion, influencing surgical approaches and patient outcomes. This narrative review incorporates historical perspectives, technical considerations, and functional as well as oncological outcomes, addressing key questions related to anastomotic leakage risks, genitourinary function, and oncological concerns, providing a more critical understanding of the well-known inconclusive evidence. Beyond the dichotomy of high versus low tie, it navigates the complexities of colorectal cancer surgery with a fresh perspective, posing a transformative question: "Is low tie ligation truly reproducible?" Considering a multidimensional approach that enhances patient outcomes by integrating the surgeon, patient, technique, and technology, instead of a rigid and categorical statement, we argued that a balanced response to this challenging question may require compromise.

Therapeutic Effect of Regional Chemotherapy in Diffuse Metastatic Cholangiocarcinoma.

BACKGROUND: Current therapeutic options in diffuse metastatic cholangiocarcinoma (CCC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) using arterial infusion (AI), hypoxic stop-flow abdominal perfusion (HAP), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 36 patients with metastatic perihilar and intrahepatic CCC. METHODS: Ten patients had previously undergone a liver resection and in 14 patients the previous systemic chemotherapy (sCTx) approach had failed. A total of 189 RegCTx cycles (90 AI, 74 UAP, 13 HAP and 12 ITP) were applied using cisplatin alone or with Adriamycin and Mitomycin C. A minimum of three cycles were applied in 75% of the study population. The response was evaluated using RECIST criteria with MediasStat 28.5.14. Mortality, morbidity and survival analysis were performed using a prospective follow-up database and SPSS-28.0. RESULTS: No procedure related mortality occurred. The overall morbidity was 56% and dominated by lymph fistulas at the inguinal access site. No grade III or IV haematological complication occurred. The overall response rate was 38% partial response, 41% stable and 21% progressive disease. Median overall survival was 23 months (95%CI 16.3-29.7). The RegCTx specific survival was 12 months (95%CI 6.5-17.5) in completely therapy naive patients but also in patients who had failed a sCTx attempt previously. CONCLUSION: RegCTx is feasible, safe and superior to the current proposed therapeutic options in metastatic CCC. The role of RegCTx should be determined in a larger cohort of diffuse metastatic CCC patients but also at early stages especially in initially not resectable but potentially resectable patients.

Regional Chemotherapy Is a Valuable Second-Line Approach in Metastatic Esophageal Cancer after Failure to First-Line Palliative Treatment.

BACKGROUND: Therapeutic options in metastatic esophageal cancer (EC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) approach in diffuse metastatic EC using arterial infusion (AI), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 14 patients (N = 8 adenocarcinoma (AC) and N = 6 squamous cell carcinoma (SQCC)) after failure to first-line palliative treatment. METHODS: All patients had previously failed first-line palliative treatment attempt with systemic chemotherapy (sCTx). In total 51 RegCTx cycles (12 AI, 3 UAP and 36 ITP) were applied using cisplatin, Adriamycin and Mitomycin C. The outcome was evaluated using RECIST criteria with MediasStat 28.5.14 and SPSS-28.0. RESULTS: No grade III or IV hematological complications occurred. The overall response rate was 41% partial response, 27% stable and 32% progressive disease. Median overall survival (OS) was 38 months (95%CI 10.1-65.9). The OS was better in SQCC with 51 months The RegCTx specific survival was 13 months (95%CI 2.9-23.1) in the entire cohort and 25 months in SQCC patients. CONCLUSION: RegCTx is a valuable safe approach and superior to the current proposed therapeutic options in metastatic EC after failure to first-line therapy.

Sporadic nonfunctional pancreatic neuroendocrine tumors: Risk of lymph node metastases and aggressiveness according to tumor size: A multicenter international study.

BACKGROUND: Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. METHODS: Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. RESULTS: Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. CONCLUSION: In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS).

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

Management and follow-up of gallbladder polyps: updated joint guidelines between the ESGAR, EAES, EFISDS and ESGE.

MAIN RECOMMENDATIONS: 1. Primary investigation of polypoid lesions of the gallbladder should be with abdominal ultrasound. Routine use of other imaging modalities is not recommended presently, but further research is needed. In centres with appropriate expertise and resources, alternative imaging modalities (such as contrast-enhanced and endoscopic ultrasound) may be useful to aid decision-making in difficult cases. Strong recommendation, low-moderate quality evidence. 2. Cholecystectomy is recommended in patients with polypoid lesions of the gallbladder measuring 10 mm or more, providing the patient is fit for, and accepts, surgery. Multidisciplinary discussion may be employed to assess perceived individual risk of malignancy. Strong recommendation, low-quality evidence. 3. Cholecystectomy is suggested for patients with a polypoid lesion and symptoms potentially attributable to the gallbladder if no alternative cause for the patient's symptoms is demonstrated and the patient is fit for, and accepts, surgery. The patient should be counselled regarding the benefit of cholecystectomy versus the risk of persistent symptoms. Strong recommendation, low-quality evidence. 4. If the patient has a 6-9 mm polypoid lesion of the gallbladder and one or more risk factors for malignancy, cholecystectomy is recommended if the patient is fit for, and accepts, surgery. These risk factors are as follows: age more than 60 years, history of primary sclerosing cholangitis (PSC), Asian ethnicity, sessile polypoid lesion (including focal gallbladder wall thickening > 4 mm). Strong recommendation, low-moderate quality evidence. 5. If the patient has either no risk factors for malignancy and a gallbladder polypoid lesion of 6-9 mm, or risk factors for malignancy and a gallbladder polypoid lesion 5 mm or less, follow-up ultrasound of the gallbladder is recommended at 6 months, 1 year and 2 years. Follow-up should be discontinued after 2 years in the absence of growth. Moderate strength recommendation, moderate-quality evidence. 6. If the patient has no risk factors for malignancy, and a gallbladder polypoid lesion of 5 mm or less, follow-up is not required. Strong recommendation, moderate-quality evidence. 7. If during follow-up the gallbladder polypoid lesion grows to 10 mm, then cholecystectomy is advised. If the polypoid lesion grows by 2 mm or more within the 2-year follow-up period, then the current size of the polypoid lesion should be considered along with patient risk factors. Multidisciplinary discussion may be employed to decide whether continuation of monitoring, or cholecystectomy, is necessary. Moderate strength recommendation, moderate-quality evidence. 8. If during follow-up the gallbladder polypoid lesion disappears, then monitoring can be discontinued. Strong recommendation, moderate-quality evidence. SOURCE AND SCOPE: These guidelines are an update of the 2017 recommendations developed between the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery-European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE). A targeted literature search was performed to discover recent evidence concerning the management and follow-up of gallbladder polyps. The changes within these updated guidelines were formulated after consideration of the latest evidence by a group of international experts. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. KEY POINT: • These recommendations update the 2017 European guidelines regarding the management and follow-up of gallbladder polyps.

Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer.

Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted.

Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk.

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, p = 3.03 × 10-6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.