Hepatic metastases from gastric cancer: A surgical perspective

Management of patients with hepatic metastases as the sole metastatic site at diagnosis of gastric cancer (synchronous setting) or detected during follow-up (metachronous) is controversial. The prevailing attitude in these cases is passive, leading to surgical palliation and, possibly, to chemotherapy. Authors focused this editorial in order to promote a more pragmatic attitude. They stress the importance of recognizing the good candidates to curative surgery of both gastric cancer and hepatic metastases (synchronous setting) or hepatic disease alone (metachronous disease) from those who will not benefit from surgical therapy. In fact, in adequately selected subgroup of patients surgery, especially if integrated in multimodal therapeutic strategies, may achieve unexpected 5-year survival rates, ranging from 10% to 40%. The critical revision of the literature suggests that some simple clinical criteria exist that may be effectively employed in patients selection. These are mainly related to the gastric cancer (factors T, N, G) and to the extent of hepatic involvement (factor H). Upon these criteria it is possible to adequately select about 50% of cases. In the remaining 50% of cases a critical discussion on a case-by-case basis is recommended, considering that among these patients some potential long-survivors exist, that survival is strictly influenced by the ablation of the tumor bulk and by multimodality treatments including chemotherapy and that in expert institutions this kind of surgery is performed with very low mortality and morbidity rates

Probiotics Modulate Intestinal Expression of Nuclear Receptor and Provide Counter-Regulatory Signals to Inflammation-Driven Adipose Tissue Activation

BACKGROUND: Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn's disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR)-α and -γ, pregnane x receptor (PXR), farnesoid x receptor (FXR) and liver x-receptor (LXR) are ligand-activated nuclear receptor that provide counter-regulatory signals to dysregulated immunity and modulates adipose tissue. AIMS: To investigate the expression and function of nuclear receptors in intestinal and adipose tissues in a rodent model of colitis and mesenteric fat from Crohn's patients and to investigate their modulation by probiotics. METHODS: Colitis was induced by TNBS administration. Mice were administered vehicle or VSL#3, daily for 10 days. Abdominal fat explants obtained at surgery from five Crohn's disease patients and five patients with colon cancer were cultured with VSL#3 medium. RESULTS: Probiotic administration attenuated development of signs and symptoms of colitis, reduced colonic expression of TNFα, IL-6 and IFNγ and reserved colonic downregulation of PPARγ, PXR and FXR caused by TNBS. Mesenteric fat depots isolated from TNBS-treated animals had increased expression of inflammatory mediators along with PPARγ, FXR, leptin and adiponectin. These changes were prevented by VSL#3. Creeping fat and mesenteric adipose tissue from Crohn's patients showed a differential expression of PPARγ and FXR with both tissue expressing high levels of leptin. Exposure of these tissues to VSL#3 medium abrogates leptin release. CONCLUSIONS: Mesenteric adipose tissue from rodent colitis and Crohn's disease is metabolically active and shows inflammation-driven regulation of PPARγ, FXR and leptin. Probiotics correct the inflammation-driven metabolic dysfunction

The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

BACKGROUND: GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. AIMS: To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. METHODS: Colitis was induced in wild type and GP-BAR1(-/-) mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. RESULTS: GP-BAR1(-/-) mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. CONCLUSIONS: GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand

A hospital Protocol for decision making in Emergency Admission for Acute Diverticulitis: Initial Results from Small Cohort series

Background and objectives: We present initial results from a small cohort series for a hospital protocol related to the emergency hospitalization decision-making process for acute diverticulitis. We performed a retrospective analysis of 53 patients with acute diverticulitis admitted to the Department of Emergency and Trauma Surgery of the "Azienda Ospedaliero Universiaria-Ospedali Riuniti" in Ancona and to the Department of General and Emergency Surgery of the "Azienda Ospedaliera-Universitaria" in Perugia. Materials and Methods: All patients were evaluated according to hemodynamic status: stable or unstable. Secondly, it was distinguished whether patients were suffering from complicated or uncomplicated forms of diverticulitis. Finally, each patient was assigned to a risk class. In this way, we established a therapeutic/diagnostic process for each group of patients. Results: Non-operative treatment (NonOP) was performed in 16 patients, and it was successful in 69% of cases. This protocol primarily considers the patient's clinical condition and the severity of the disease. It is based on a multidisciplinary approach, in order to implement the most suitable treatment for each patient. In stable patients with uncomplicated diverticulitis or complicated Hinchey grade 1 or 2 diverticulitis, the management is conservative. In all grade 3 and grade 4 forms, patients should undergo urgent surgery. Conclusions: This protocol, which is based on both anatomical damage and the severity of clinical conditions, aims to standardize the choice of the best diagnostic and therapeutic strategy for the patient in order to reduce mortality and morbidity related to this pathology

Can the measurement of amylase in drain after distal pancreatectomy predict post-operative pancreatic fistula?

The most frequent reason for performing a distal pancreatectomy is the presence of cystic or neuroendocrine tumors, in which the distal pancreatic stump is often soft and non fibrotic. This parenchymal consistence represents the main risk factor for post-operative pancreatic fistula. In order to identify the fistula and assessing its severity postoperative monitoring of amylase from intraperitoneal drains is important

A global systematic review and meta-analysis on laparoscopic vs open right hemicolectomy with complete mesocolic excision.

Funder: Università degli Studi di FerraraPURPOSE: The aim of this study was to compare the outcomes of right hemicolectomy with CME performed with laparoscopic and open surgery. METHODS: PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Google Scholar and the ClinicalTrials.gov register were searched. Primary outcome was the overall number of harvested lymph nodes. Secondary outcomes were short and long-term course variables. A meta-analysis was performed to calculate risk ratios. RESULTS: Twenty-one studies were identified with 5038 patients enrolled. The difference in number of harvested lymph nodes was not statistically significant (MD 0.68, - 0.41-1.76, P = 0.22). The only RCT shows a significant advantage in favour of laparoscopy (MD 3.30, 95% CI - 0.20-6.40, P = 0.04). The analysis of CCTs showed an advantage in favour of the laparoscopic group, but the result was not statically significantly (MD - 0.55, 95% CI - 0.57-1.67, P = 0.33). The overall incidence of local recurrence was not different between the groups, while systemic recurrence at 5 years was lower in laparoscopic group. Laparoscopy showed better short-term outcomes including overall complications, lower estimated blood loss, lower wound infections and shorter hospital stay, despite a longer operative time. The rate of anastomotic and chyle leak was similar in the two groups. CONCLUSIONS: Despite the several limitations of this study, we found that the median number of lymph node harvested in the laparoscopic group is not different compared to open surgery. Laparoscopy was associated with a lower incidence of systemic recurrence

Rise and fall of total mesorectal excision with lateral pelvic lymphadenectomy for rectal cancer: an updated systematic review and meta-analysis of 11,366 patients.

Funder: Università degli Studi di FerraraUNLABELLED: The role of lateral lymph node dissection (LLND) during total mesorectal excision (TME) for rectal cancer is still controversial. Many reviews were published on prophylactic LLND in rectal cancer surgery, some biased by heterogeneity of overall associated treatments. The aim of this systematic review and meta-analysis is to perform a timeline analysis of different treatments associated to prophylactic LLND vs no-LLND during TME for rectal cancer. METHODS: A literature search was performed in PubMed, SCOPUS and WOS for publications up to 1 September 2020. We considered RCTs and CCTs comparing oncologic and functional outcomes of TME with or without LLND in patients with rectal cancer. RESULTS: Thirty-four included articles and 29 studies enrolled 11,606 patients. No difference in 5-year local recurrence (in every subgroup analysis including preoperative neoadjuvant chemoradiotherapy), 5-year distant and overall recurrence, 5-year overall survival and 5-year disease-free survival was found between LLND group and non LLND group. The analysis of post-operative functional outcomes reported hindered quality of life (urinary, evacuatory and sexual dysfunction) in LLND patients when compared to non LLND. CONCLUSION: Our publication does not demonstrate that TME with LLND has any oncological advantage when compared to TME alone, showing that with the advent of neoadjuvant therapy, the advantage of LLND is lost. In this review, the most important bias is the heterogeneous characteristics of patients, cancer staging, different neoadjuvant therapy, different radiotherapy techniques and fractionation used in different studies. Higher rate of functional post-operative complications does not support routinely use of LLND

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. Methods Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). Results The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. Conclusion For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients

Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis

Purpose: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. Methods: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. Results: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). Conclusions: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset

Structured and shared CT radiological report of gastric cancer: a consensus proposal by the Italian Research Group for Gastric Cancer (GIRCG) and the Italian Society of Medical and Interventional Radiology (SIRM)

Objectives Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients. Methods Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up). Results In the final round, 23 out of 24 items obtained agreement ( >= 8) and consensus ( 0.05). Conclusions The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making