Textbook Outcome in Colorectal Surgery for Cancer: An Italian Version.

Background/Objectives: The textbook outcome (TO) is a composite tool introduced to uniform surgical units and regulate surgical quality and outcomes. A patient is considered TO only if all predetermined items are met. In colorectal surgery, TO represents a new tool that can achieve important results given the prevalence of colorectal cancers. However, at present, there is a lack of uniformity in the TO's definition. This study utilized the Delphi process to define an Italian version of the TO in colorectal cancer. Methods: The survey consisted of two rounds of online questionnaires submitted to an expert panel in colorectal oncological surgery, renowned academic surgeons, who had attended multiple scientific conferences and who were authors of papers on this specific topic. Five main topics with 26 questions were investigated through an online modified Delphi method. Items with almost 75% agreement achieved consensus. Results: Twenty-eight Italian experts were selected and participated in the two rounds. The Italian version of the textbook outcome in colorectal surgery was defined as the presence of 90-day postoperative survival, negative margins and at least 12 lymph nodes, a minimally invasive approach, ostomy fashioning if preoperatively planned, postoperative complication < Clavien-Dindo 3b, at least 10 ERAS items, no readmission, proper CHT and RT regimens, complete colonoscopy after or before surgery and Tumor Board Evaluation. Conclusions: The textbook outcome in colorectal cancer patients is a quality instrument providing a complete overview of the care of such patients, from diagnosis to treatment. We hereby propose an Italian version of the TO with outcomes chosen by an expert panel.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in the Management of Colorectal Cancer with Peritoneal Metastasis: A Single-Center Cohort Study.

Multimodal treatment in peritoneal metastases (PM) from colorectal neoplasms may improve overall survival (OS). In this study, we reported our experience in using cytoreductive surgery (CRS) combined with intraperitoneal chemohyperthermia (HIPEC) for the treatment of peritoneal metastases (PM) from colorectal neoplasms. The first aim was to evaluate the overall survival of these patients. Furthermore, using the results of the Prodige 7 Trial and incorporating them with the entropy balance statistical tool, we generated a pseudopopulation on which to test the use of CRS alone. We performed a retrospective analysis based on a prospective database of all 55 patients treated with CRS + HIPEC between March 2004 and January 2023. The median OS was 47 months, with 1-, 3- and 5-year survival rates of 90.8%, 58.7% and 42.7%, respectively. There was no significant difference in the data in the pseudogroup generated with entropy balance. This finding confirms the critical role of complete cytoreduction in achieving the best OS for patients with PM. PCI > 6 seems to be the most important prognostic factor influencing OS. At present, CRS + HIPEC seems to be the therapeutic strategy that guarantees the best results in terms of OS for patients with relatively low PCI and in whom a CCS ≤ 1 can be achieved.

Genomic events stratifying prognosis of early gastric cancer.

BACKGROUND: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. METHODS: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. RESULTS: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). CONCLUSIONS: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.

The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

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.

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, distant tumor recurrence remains a concern, prompting the exploration of total neoadjuvant therapy (TNT) as a comprehensive treatment strategy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Nonoperative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving complete clinical response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for the assessment of treatment response. This review synthesizes current evidence on TNT, ICIs, NOM, and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series.

INTRODUCTION: The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. MATERIALS AND METHODS: We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. RESULTS: Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p < 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p < 0.001). CONCLUSIONS: Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival.

A Systematic Review of Varying Definitions and the Clinical Significance of Fredet's Fascia in the Era of Complete Mesocolic Excision.

BACKGROUND: Fredet's fascia represents a crucial landmark for vascular surgical anatomy, especially in minimally invasive complete mesocolic excision (CME) for right-sided colon adenocarcinoma. Fredet's fascia allows access to the gastrocolic trunk of Henle (GCTH), the most critical step in both open and minimally invasive right-sided CME techniques. Despite this, a recent workshop of expert surgeons on the standardization of the laparoscopic right hemicolectomy with CME did not recognize or include the term of Fredet's fascia or area. Hence, we undertook a systematic review of articles that include the terms "Fredet's fascia or area", or synonyms thereof, with special emphasis on the types of articles published, the nationality, and the relevance of this area to surgical treatments. METHODS: We conducted a systematic review up to 15 July 2022 on PubMed, WOS, SCOPUS, and Google Scholar. RESULTS: The results of the study revealed that the term "Fredet's fascia" is poorly used in the English language medical literature. In addition, the study found controversial and conflicting data among authors regarding the definition of "Fredet's fascia" and its topographical limits. CONCLUSIONS: Knowledge of Fredet's fascia's surgical relevance is essential for colorectal surgeons to avoid accidental injuries to the superior mesenteric vascular pedicle during minimally invasive right hemicolectomies with CME. In order to avoid confusion and clarify this fascia for future use, we suggest moving beyond the use of the eponymous term by using a "descriptive term" instead, based on the fascia's anatomic structure. Fredet's fascia could, therefore, be more appropriately renamed "sub-mesocolic pre-duodenopancreatic fascia".

Robotic versus laparoscopic left colectomy: a propensity score matched analysis from a bi-centric experience.

The advantages of using the robotic platform may not be clearly evident in left colectomies, where the surgeon operates in an "open field" and does not routinely require intraoperative suturing. Current evidences are based on limited cohorts reporting conflicting outcomes regarding robotic left colectomies (RLC). The aim of this study is to report a bi-centric experience with robotic left colectomy in order to help in defining the role of the robotic approach for these procedures. This is a bi-centric propensity score matched study including patients who underwent RLC or laparoscopic left colectomy (LLC) between January 1, 2012 and May 1, 2022. RLC patients were matched to LLC patients in a 1:1 ratio. Main outcomes were conversion to open surgery and 30-day morbidity. In total, 300 patients were included. Of 143 (47.7%) RLC patients, 119 could be matched. After matching, conversion rate (4.2 vs. 7.6%, p = 0.265), 30-day morbidity (16.1 vs. 13.7%, p = 0.736), Clavien-Dindo grade ≥ 3 complications (2.4 vs 3.2%, p = 0.572), transfusions (0.8 vs. 4.0%, p = 0.219), and 30-day mortality (0.8 vs 0.8%, p = 1.000) were comparable for RLC and LLC, respectively. Median operative time was longer for RLC (296 min 260-340 vs. 245, 195-296, p < 0.0001). Early oral feeding, time to first flatus, and hospital stay were similar between groups. RLC has safety parameters as well as conversion to open surgery comparable with standard laparoscopy. Operative time is longer with the robotic approach.

Advantages of laparoscopic distal pancreatectomy: Systematic review and meta-analysis of randomized and matched studies.

BACKGROUND: We sought to provide a meta-analysis and credibility assessment of available randomized controlled trials and propensity score matched studies when assessing early and oncologic outcomes of laparoscopic distal pancreatectomy compared with open distal pancreatectomy. METHODS: The MEDLINE, Scopus, Web of Science, and Cochrane databases were searched for pertinent literature up to June 2022. Random-effect meta-analyses were applied. Trial sequential analysis was applied to verify whether results were true- or false-positive or -negative findings. RESULTS: Thirteen studies were identified (2 randomized controlled trials and 11 propensity score matched studies). The early outcomes were assessed on 12 studies, including 4,346 patients. In this population, laparoscopic distal pancreatectomy decreased postoperative stay (mean difference = 1.8 days; P = .001) and estimated blood loss (mean difference = 148 mL; P = .001), and trial sequential analysis confirmed these as true-positive findings. Laparoscopic distal pancreatectomy and open distal pancreatectomy had similar operating times (P = .165), and trial sequential analysis confirmed this as a true-negative finding. Major morbidity, mortality, and readmission were similar, but results were inconclusive by trial sequential analysis. Oncologic outcomes were assessed on 5 studies, including 2,430 patients. In this population, laparoscopic distal pancreatectomy showed higher R0 resection rate (OR = 1.46; P = .001) and shorter time to adjuvant therapy (mean difference 4.0 days P = .003). A survival benefit was observed at 1 year after laparoscopic distal pancreatectomy (OR = 1.45; P = .001), which was not confirmed at 3 years (P = .650). CONCLUSION: Laparoscopic distal pancreatectomy is superior to open distal pancreatectomy for most of the early outcomes analyzed. The operating time was equalized as a result of the learning curve. Results from patients with pancreatic cancer suggest at least an oncologic noninferiority of laparoscopic distal pancreatectomy compared with open distal pancreatectomy.

Fluorescence Cholangiography Using Indocyanine Green Improves the Identification of Biliary Structures During Laparoscopic Cholecystectomy.

BACKGROUND: This cross-sectional survey aimed to determine whether fluorescence cholangiography using indocyanine green (ICG-FC) can improve the detection of the cystic duct and the main bile duct during laparoscopic cholecystectomy (LC). METHODS: The survey was distributed to 214 surgeons (residents/faculties) in 2021. The confidence in the identification of the cystic duct and of the main bile duct was elicited on a 10-point Likert scale before/after the use of ICG-FC. This was repeated for three LCs ranging from a procedure deemed easy to a LC for acute cholecystitis. RESULTS: There were 149 responses. ICG-FC increased the responders' confidence in identifying the cystic duct, raising the median value from 6 (IQR, 5-8) with white light up to 9 (IQR, 9-10) with ICG-FC (paired p < 0.001). This increase was even more evident when identifying the main bile duct, where the median confidence value increased from 5 (IQR, 4-7) with white light to 9 (IQR, 8-10) with the use of ICG-FC (p < 0.001). ICG-FC significantly increased the detection of residents of the main bile duct in case of intermediate difficulty LCs and in LCs for acute cholecystitis. CONCLUSIONS: The results support that the use of near-infrared imaging can ameliorate detection of biliary structures, especially of the main bile duct and this was particularly true for young surgeons and in more complex situations.

Frail patients dropping out of neoadjuvant treatment: what should we do?

Perioperative oncological treatment is currently the gold standard approach in Europe for Advanced Gastric Cancer patients. Unfortunately, patients dropping out due to worsening conditions has been frequently observed, but these data are seldomly considered and reported. To analyze frequency and propose solutions to support these patients, we reconsidered our results from the GASTRODOC randomized trial performed by [blinded for reviewers] and GIRCG on 91 patients. Thirty-four patients (37.4%) suspended chemotherapy and five (5.4%) did not reach surgery. Ten patients (11%) presented unacceptable toxicity related to gastrointestinal symptoms, six ended the treatment for investigator decision and six for progression, five patients withdrew their consent, five patients were excluded because of surgical complications and long hospitalization, and two patients died. Even though not significant, survival rates for patients who interrupted treatment in the whole trial were lower (5-year OS completed 64.6 vs. interrupted 41.8 p 0.07). Promptness in giving patient support for gastrointestinal symptoms, careful evaluation of anemia and patient nutritional status, and psychological programs from the beginning of the oncologic treatment may improve the final results.

Consequences of the COVID-19 pandemic on the diagnosis and treatment of gastric cancer in referral centers in Italy.

BACKGROUND: The coronavirus pandemic had a major impact in Italy. The Italian health system's re-organization to face the emergency may have led to significant consequences especially in the diagnosis and treatment of malignancies. This study aimed to assess the impact of the pandemic in the diagnosis and treatment of gastric cancer in nine Gruppo Italiano RIcerca Cancro Gastrico (GIRCG) centers. METHODS: All patients assessed for gastric adenocarcinoma at nine GIRCG centers between January 2019 and November 2020 were included. Patients were grouped according to the date of "patient 1's" diagnosis in Italy: preCOVID versus COVID. Clinico-pathological and outcome differences between the two groups were analyzed. RESULTS: A total of 632 patients were included in the analysis (205 in the COVID group). The cT4 weighted ratios were higher in 2020 from April to September, with the greatest differences in May, August and September. The cM+ weighted ratio was significantly higher in July 2020. The mean number of gastrectomies had the greatest reduction in March and May 2020 compared with 2019. The median times from diagnosis to chemotherapy, to complete diagnostic work-up or to operation were longer in 2019. The median time from the end of chemotherapy to surgery was 17 days longer in the preCOVID group. CONCLUSIONS: A greater number of advanced or metastatic cases were diagnosed after the spread of SARS-CoV-2 infection, especially after the "full lockdown" periods. During the pandemic, once gastric cancer patients were referred to one of the centers, a shorter time to complete the diagnostic work-up or to address them to the best treatment option was required.

Implementation of a patient blood management in an Italian City Hospital: is it effective in reducing the use of red blood cells?

To evaluate the effect of patient blood management (PBM) since its introduction, we analyzed the need for transfusion and the outcomes in patients undergoing abdominal surgery for different types of tumor pre- and post-PBM. Patients undergoing elective gastric, liver, pancreatic, and colorectal surgery between 2017 and 2020 were included. The implementation of the PBM program was completed on May 1, 2018. The patients were grouped as follows: those who underwent surgery before the implementation of the program (pre-PBM) versus after the implementation (post-PBM). A total of 1302 patients were included in the analysis (445 pre-PBM vs. 857 post-PBM). The number of transfused patients per year decreased significantly after the introduction of PBM. A strong tendency for a decreased incidence of transfusion was evident in gastric and pancreatic surgery and a similar decrease was statistically significant in liver surgery. With regard to gastric surgery, a single-unit transfusion scheme was used more frequently in the post-PBM group (7.7% vs. 55% after PBM; p = 0.049); this was similar in liver surgery (17.6% vs. 58.3% after PBM; p = 0.04). Within the subgroup of patients undergoing liver surgery, a significant reduction in the use of blood transfusion (20.5% vs. 6.7%; p = 0.002) and a decrease in the Hb trigger for transfusion (8.5, 8.2-9.5 vs. 8.2, 7.7-8.4 g/dl; p = 0.039) was reported after the PBM introduction. After the implementation of a PBM protocol, a significant reduction in the number of patients receiving blood transfusion was demonstrated, with a strong tendency to minimize the use of blood products for most types of oncologic surgery.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

Oligometastatic Gastric Cancer: Clinical Data from the Meta-Gastro Prospective Register of the Italian Research Group on Gastric Cancer.

BACKGROUND: Interest in the field of metastatic gastric cancer has grown in recent years, and the identification of oligometastatic patients plays a critical role as it consents to their inclusion in multimodal treatment strategies, which include systemic therapy but also surgery with curative intent. To collect sound clinical data on this subject, The Italian Research Group on Gastric Cancer developed a prospective multicentric observational register of metastatic gastric cancer patients called META-GASTRO. METHODS: Data on 383 patients in Meta-Gastro were mined to help our understanding of oligometastatic, according to its double definition: quantitative/anatomical and dynamic. RESULTS: the quantitative/anatomical definition applies to single-site metastases independently from the metastatic site (p < 0.001) to peritoneal metastases with PCI ≤ 12 (p = 0.009), to 1 or 2 hepatic metastases (p = 0.024) and nodal metastases in station 16 (p = 0.002). The dynamic definition applies to a percentage of cases variable according to the metastatic site: 8%, 13.5 and 23.8% for hepatic, lymphatic and peritoneal sites, respectively. In all cases, the OS of patients benefitting from conversion therapy was similar to those of cases deemed operable at diagnosis and operated after neoadjuvant chemotherapy. CONCLUSIONS: META-GASTRO supports the two-fold definition of oligometastatic gastric cancer: the quantitative/anatomical one, which accounts for 30% of our population, and the dynamic one, observed in 16% of our cases.

Hyperthermic intraperitoneal chemotherapy and colorectal cancer: From physiology to surgery.

The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) used in colorectal cancer (CRC). We focus on principal biological aspects of CRC, hyperthermia effects, and surgical procedures. We searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment (CRS + HIPEC) against local and advanced CRC. In the literature, from several studies, it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall survival. Despite these studies, there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with CRC. Even if the concept is still not very clear and shared, after a careful evaluation of the published data, and after some technical and pathophysiological descriptions, we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced (pT4) CRC with peritoneal metastases.

Laparoscopic Cholecystectomy in Acute Cholecystitis: Refining the Best Surgical Timing Through Network Meta-Analysis of Randomized Trials.

BACKGROUND: Acute cholecystitis (AC) is largely diffused among population worldwide. Laparoscopic cholecystectomy is the treatment of choice. Current evidence suggests a clinical benefit of early cholecystectomy. The aim of the present study was to evaluate the different "timing" ("early" vs. "delayed" cholecystectomy), through the application of network meta-analyses, to define the most adequate interval associated with the best outcomes. MATERIALS AND METHODS: A network meta-analysis of randomized controlled trials was conducted. RESULTS: Early cholecystectomy ≤72 hours from symptoms reduced conversion rate in comparison to: cholecystectomy ≤7 days from symptoms ( P =0.044), delayed cholecystectomy within 1 to 5 weeks from first admission ( P =0.010) and 6 to 12 weeks from symptoms resolutions ( P =0.009). Delaying cholecystectomy to 6 to 12 weeks reduces operating time in respect to early cholecystectomy ≤72 hours from symptoms ( P =0.001), within 24 hours from admission ( P =0.001), ≤72 hours from admission ( P =0.001) and ≤7 days from symptoms ( P =0.001). Cholecystectomy ≤24 hours from admission was the best strategy to reduce total in-hospital stay, whereas delaying cholecystectomy to 6 to 12 weeks was the worst strategy. The same applied when cholecystectomy was performed ≤72 hours from symptoms in respect to both delayed strategies ( P =0.001 for both comparisons) or when it was performed ≤72 hours from admission ( P =0.001 for both comparisons). Cholecystectomy ≤72 hours from symptoms onset was the best strategy to reduce postoperative complications, the worst was represented by delayed cholecystectomy at 1 to 5 weeks from first admission. CONCLUSION: AC should be operated as soon as possible. AC surgical management should be considered in a dynamic time conception to optimize clinical, organizational, and economical outcomes.

Development and Multicenter Validation of a Novel Immune-Inflammation-Based Nomogram to Predict Survival in Western Resectable Gastric and Gastroesophageal Junction Adenocarcinoma (GEA): The NOMOGAST.

Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation cohort (VC) of patients undergoing radical surgery for c/uT2-T4 and/or node-positive GEA were retrieved, and potentially interesting variables were collected. Cox proportional hazards in univariate and multivariate regressions were used to assess the effects of the prognostic factors on OS. A graphical nomogram was constructed using R software's package Regression Modeling Strategies (ver. 5.0-1). The performance of the prognostic model was evaluated and validated. Results. The TC and VC consisted of 185 and 151 patients. ECOG:PS > 0 (p < 0.001), angioinvasion (p < 0.001), log (Neutrophil/Lymphocyte ratio) (p < 0.001), and nodal status (p = 0.016) were independent prognostic values in the TC. They were used for the construction of a nomogram estimating 3- and 5-year OS. The discriminatory ability of the model was evaluated with the c-Harrell index. A 3-tier scoring system was developed through a linear predictor grouped by 25 and 75 percentiles, strengthening the model's good discrimination (p < 0.001). A calibration plot demonstrated a concordance between the predicted and actual survival in the TC and VC. A decision curve analysis was plotted that depicted the nomogram's clinical utility. Conclusions. We externally validated a prognostic nomogram to predict OS in a joint independent cohort of resectable GEA; the NOMOGAST could represent a valuable tool in assisting decision-making. This tool incorporates readily available and inexpensive patient and disease characteristics as well as immune-inflammatory determinants. It is accurate, generalizable, and clinically effectivex.