Squid male alternative reproductive tactics are determined by birth date.

Alternative reproductive tactics (ARTs) are discontinuous phenotypes associated with reproduction, observed in males of many species. Typically, large males adopt a tactic of competing with rivals for mating, while small males adopt a tactic of stealing fertilization opportunities from the large males. The 'birth date hypothesis', proposing that the date of birth influences the determination of each male's reproductive tactic, has been tested only in teleost fish to date. Here, the birth date hypothesis was tested in ARTs of Japanese spear squid Heterololigo bleekeri (consort/sneaker) by analysing statolith growth increments. The birth date significantly differed between consorts (early-hatched) and sneakers (late-hatched). However, no differences were detected in growth history up to 100 days from hatching. Most immature males caught during the reproductive season were larger than sneakers, and their hatch date was similar to that of consorts, suggesting that these immature males had already been following a life-history pathway as a consort. These results indicate that ARTs of H. bleekeri are determined based on their hatch date in early life. This study firstly suggests that the birth date hypothesis applies to aquatic invertebrates, suggesting that the mechanism by which birth date determines the individual phenotype is a phenomenon more common than previously believed.

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumors.

BACKGROUND: Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41 ± 0.367 months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. CONCLUSION: This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8 months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

Superior Mesenteric Artery First Approach for Minimally Invasive Pancreaticoduodenectomy: A Step-By-Step Surgical Technique Video.

INTRODUCTION: In the past decade, minimally invasive pancreaticoduodenectomy has been gaining interest. However, minimally invasive pancreaticoduodenectomy remains technically challenging and is associated with a steep learning curve. Additionally, the operating surgeon should be cognizant of replicating the same oncological steps as observed in the typical open approach. In view of this, there exist various maneuvers that are designed to achieve negative margins and a safer mesopancreatic dissection. One of these techniques is the superior mesenteric artery first approach, which is garnering interest among pancreatic surgeons. MATERIAL AND METHODS: According to existing literature, there are several superior mesenteric artery dissections approaches. We describes 5 different minimally invasive approaches. RESULTS: This multimedia manuscript provide, for the first time in literature, a comprehensive step-by-step overview of the superior mesenteric artery first approach for minimally invasive pancreaticoduodenectomy by a team of expert surgeons from various international institutions. CONCLUSIONS: Through the tips and indications presented in this article, we aim to guide the choice of this approach according to tumor location, type of minimally invasive approach and the operating surgeon's experience and increase familiarity with such a complex procedure.

A systematic review and meta-analysis of total endovascular versus hybrid repair for the treatment of thoracoabdominal aortic aneurysms.

OBJECTIVE: Although open repair has been the traditional mainstay therapy for thoracoabdominal aortic aneurysms (TAAAs), it remains a surgical challenge. Recently, hybrid repair (HR) and total endovascular repair (TEVR) have emerged as viable alternatives in treating TAAAs. Thus, we aimed to compare the primary outcomes of in-hospital/30-day mortality, as well as secondary outcomes of postoperative complications including spinal cord ischemia, bowel ischemia, long-term dialysis, myocardial infarction and lower limb ischemia for HR vs TEVR for the treatment of TAAAs. We postulated that TEVR was associated with lower in-hospital and 30-day mortality and postoperative complication rates as compared with HR. METHODS: Four scientific databases were searched from inception to November 18, 2021. Meta-analyses were performed for the primary and secondary outcomes. This study was conducted in adherence to the PRISMA guidelines. RESULTS: The search yielded 3312 articles. After a two-stage selection process, five articles were included for final analysis. The in-hospital/30-day mortality rate for TEVR was significantly lower compared with HR (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.20-0.36; P < .00001). TEVR was also associated with reduced bowel ischemia (OR, 0.22; 95% CI, 0.14 -0.35; P < .00001) and long-term dialysis (OR, 0.22; 95% CI, 0.16-0.29; P < .00001). There was, however, no difference in the incidence of spinal cord ischemia (OR, 1.26; 95% CI, 0.74-2.14; P = .39), stroke (OR, 0.65; 95% CI, 0.10-4.20; P = .65), myocardial infarction (OR, 0.60; 95% CI, 0.17-2.05; P = .41), and lower limb ischemia (OR, 0.67; 95% CI, 0.29-1.55; P = .35). Most study outcomes had low heterogeneity. Findings were also robust to sensitivity analysis. CONCLUSIONS: Compared with the HR, TEVR of TAAAs were associated with lower in-hospital and 30-day mortality, bowel ischemia, and long-term dialysis.

Vitamin D supplementation for irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a prevalent and complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Observational studies have suggested a relationship between serum vitamin D levels and IBS symptoms. This systematic review and meta-analysis aimed to investigate the clinical effects of vitamin D supplementation on IBS symptom severity and quality of life (QoL) measures. METHODS: Medline, Embase, Scopus, Web of Science, and The Cochrane Library databases were systematically searched. Data abstraction and quality assessment were conducted by four authors independently, and discrepancies were resolved through consensus from the senior author. Continuous data were pooled with standardized mean difference (SMD) using the DerSimonian and Laird's random-effects model. Sensitivity analysis by risk of bias and potentially "predatory" publication were performed as well. RESULTS: A total of 685 patients across eight studies were included in the meta-analysis. Vitamin D supplementation significantly improved IBS symptom severity scale scores, with a SMD of -0.77 (95% confidence interval [CI] -1.47 to -0.07, P = 0.04, I2  = 91%). Improvements in IBS-QoL scores were also observed, albeit not statistically significant (SMD 0.54; 95% CI -0.34 to 1.41, P = 0.15, I2  = 87%). However, small sample sizes, a relatively young study population, limited ethnicities, and varied vitamin D dosing strategies across the studies were notable limitations. CONCLUSIONS: Vitamin D supplementation could be part of our clinical armamentarium when managing IBS patients due to the potential efficacy and good safety profile. Further randomized, controlled trials are required to confirm the therapeutic effects.

Surgery for liver metastases from primary melanoma: a systematic review and meta-analysis.

BACKGROUND: Historically , liver metastases due to melanoma have been associated with dismal prognosis. Moreover, the actual survival benefit from the treatment of melanoma liver metastases is still controversial. Hence, this study aims to evaluate the difference in surgical versus non-surgical options for melanoma liver metastases. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to July 17, 2022. Studies were included if they compared outcomes between surgical and non-surgical treatment for patients with liver metastases from resectable melanoma. Meta-analyses were performed for the outcomes of 1-year, 2-year, 3-year and 5-year OS. Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. To account for possible moderators that might contribute to statistical heterogeneity, univariate meta-regression with mixed-effects models and subgroup analyses were conducted for the outcome of 2-year OS. RESULTS: The search yielded 6610 articles; 13 studies were included in our analysis. Meta-analyses showed that survival outcomes were in favour of patients undergoing surgery as compared to non-surgery: 1-year OS (HR = 0.29, 95%CI 0.19-0.44, p < 0.00001), 2-year OS (HR = 0.19, 95%CI 0.09-0.38, p < 0.00001), 3-year OS (HR = 0.07, 95%CI 0.03-0.19, p < 0.00001) and 5-year OS (HR = 0.07, 95%CI 0.02-0.22, p < 0.00001). All included studies were of high quality. There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. Subgroup analyses and univariate meta-regression revealed neoadjuvant therapy and age as statistically significant subgroup and moderator respectively. CONCLUSIONS: This study suggests that surgical treatment of melanoma liver metastases could offer better OS outcomes compared with non-surgical treatment.

A scoping review of qualitative studies on pre-hospital analgesia administration and practice.

BACKGROUND: Pain is an exceedingly common complaint in the pre-hospital setting. Despite advancements in organizational protocols and guidelines, many emergency medical services (EMS) systems still fail to provide optimal pain management. This scoping review thus aimed to map the body of qualitative literature pertaining to factors influencing pre-hospital analgesia administration and practice in order to clarify concepts and understanding as well as to identify any knowledge gaps. METHODS: The review protocol was guided by the framework outlined by Arksey and O'Malley and ensuing recommendations made by Levac and colleagues. Five databases were searched from inception till October 26, 2021, namely MEDLINE, EMBASE, CINAHL, The Cochrane Library, and Scopus. The search strategy was developed in consultation with a medical information specialist. A total of 5848 records were screened by abstract and title by four independent researchers. 199 records were included for full text review. From these, 15 articles were eligible for thematic analysis based on pre-defined inclusion criteria. RESULTS: Included studies found that practitioner, patient, and environmental factors influenced the administration and practice of pre-hospital analgesia. Key barriers included the difficulty in assessing pain, poor inter-professional relationship, knowledge deficits, stress and anxiety, and miscellaneous factors, such as concerns over drug-seeking behaviours. Some possible solutions were proposed, and pre-hospital EMS systems and healthcare institutions could consider bridging some of these gaps. There was a notable paucity of Asian studies, and a variety of EMS settings with different protocols and workflows were examined, hence systemic factors including guidelines and legislations cannot and should not be generalized across every healthcare system. CONCLUSION: The factors influencing pre-hospital analgesia administration and practice remain incompletely understood. Existing tools and practice guidelines were also inadequate. This scoping review provided an overarching perspective of the extant literature, highlighting some of the significant barriers, enablers, and areas for further research.

Lobar versus Sublobar Resection in the Elderly for Early Lung Cancer: A Meta-Analysis.

OBJECTIVES: We performed a systematic review and meta-analysis of outcomes of lobectomy versus sublobar resection in elderly patients (≥65) with stage 1 nonsmall cell lung carcinoma (NSCLC). METHODS: We searched for relevant articles using a set of inclusion and exclusion criteria. Meta-analytic techniques were applied. RESULTS: Twelve studies (n = 5834) were chosen. Our results indicate that in the elderly, lobectomy for stage 1 NSCLC confers a survival advantage over sublobar resection. Lobectomy patients had a lower risk of death within 5 years and lower odds of local cancer recurrence. Our results show that lobectomy had a better 5-year cancer-specific survival and 5-year disease-free survival that trended toward significance. The sublobar resection group showed better 30-day operative mortality that trended toward significance. Subgroup analysis of stage 1A cancer demonstrated no difference in 5-year overall survival rates. However, for stage 1B tumors 5-year overall survival favored lobectomy. CONCLUSION: Lobectomy for stage 1 NSCLC in elderly patients is superior to sublobar resection in terms of survival and cancer recurrence and should be afforded where possible. For stage 1A tumors, sublobar resection is noninferior and may be considered. Further randomized controlled trials in this topic is required.

Evaluation of the usefulness of protocol-based pharmacist-facilitated laboratory monitoring to ensure the safety of immune checkpoint inhibitors in patients with lung cancer.

WHAT IS KNOWN AND OBJECTIVE: Immune checkpoint inhibitors can cause immune-related adverse events (irAEs). Improved monitoring systems for irAEs, which include laboratory tests by a qualified multidisciplinary team, might prevent patients from irAE-associated events. Kobe City Medical Center General Hospital developed protocol-based pharmacist-facilitated laboratory tests named protocol-based pharmacotherapy management (PBPM) to aid the administration of immunotherapy to patients with lung cancer. The protocol defines the laboratory test items and times at which they should be performed. It requires pharmacists to check laboratory orders initiated by physicians and enter additional test items if the orders are incomplete. We evaluated the efficacy of PBPM in irAE monitoring and compared it with those of conventional care systems. METHODS: From January 2016 to March 2018, 114 patients with lung cancer received immunotherapy, which was managed by conventional care (conventional group). From April to September 2018, 62 patients were managed by PBPM (PBPM group), among those 28 patients were transited from conventional group to PBPM group. Data on whether the laboratory tests were conducted or omitted were collected retrospectively for the conventional group and prospectively for the PBPM group. RESULTS: Within the conventional group, 4604 (87.6%) out of the 5253 laboratory test items were ordered by physicians. Of the remaining 649 test items, 224 (4.3%) items were added by physicians based on recommendations by pharmacists. However, of the 1581 (86.6%, from among 1826) test items that were previously ordered by physicians, only 231 (12.7%) test items were added by pharmacists. The execution rate was found to be significantly higher in the PBPM group (99.2% vs 91.9%, P < .001). WHAT IS NEW AND CONCLUSION: PBPM-based pharmacist-facilitated laboratory monitoring systems provided higher executing rate of laboratory order to monitor irAEs during immunotherapy.

Intramucosal colorectal carcinoma with lymphovascular invasion: clinicopathological characteristics of nine cases.

AIMS: Recent studies have provided the concept of invasive intramucosal colorectal carcinoma (CRC), and a case of intramucosal CRC with lymphatic invasion has been reported; however, the characteristics of such cases and the risk of lymph node metastasis have never been investigated. Therefore, we aimed to assess the pathological characteristics of intramucosal CRCs with lymphovascular invasion as well as the possibility of lymph node metastasis as an indication for additional surgery. METHODS AND RESULTS: To delineate the histological features of intramucosal CRCs with lymphovascular invasion, we analysed several histological features and compared their incidence among nine such cases, as well as 20 other cases of intramucosal CRCs without lymphovascular invasion. High-grade tumour budding and a pattern of 'eosinophilic cytoplasm and round nuclei with inflammatory reaction (ERI)' were morphological characteristics of intramucosal CRCs with lymphovascular invasion, compared with those without lymphovascular invasion (both P < 0.05). Among the seven lymph node-dissected cases of intramucosal CRCs with lymphovascular invasion, none showed lymph node metastasis. CONCLUSIONS: In intramucosal CRCs with lymphovascular invasion, high-grade tumour budding and the 'ERI' pattern are morphological characteristics that are distinct from those of non-invasive CRC, which is synonymous with high-grade dysplasia. Further studies using a larger number of cases by focusing on the above-mentioned histological pattern are expected to clarify the potential of lymph node metastasis of such cases.

Assessment of exposure risk of irinotecan and its active metabolite, SN-38, through perspiration during chemotherapy.

BACKGROUND: Irinotecan (CPT-11) is the key drug used in chemotherapy for many malignant tumors. CPT-11 has cholinergic activity and induces perspiration during intravenous administration. In this study, concentrations of CPT-11 and its active metabolite, SN-38, released during perspiration were measured and risk of exposure of these drugs was assessed. METHOD: Beads of sweat were collected using a dropper from four patients undergoing a chemotherapy regimen involving intravenous administration of CPT-11. The concentrations of CPT-11 and SN-38 in sweat were measured using liquid chromatography tandem mass spectrometry. RESULT: Chemotherapy regimens were capecitabine and irinotecan plus bevacizumab (n = 1), CPT-11 monotherapy (n = 1), and oxaliplatin-irinotecan-leucovorin-5-fluorouracil (n = 2). Uridine diphosphate-glucuronosyltransferase 1A1 phenotypes were *6 homo-type (n = 1), *6 hetero-type (n = 1), and wild type (n = 2). CPT-11 dose was 292.3 ± 75.5 mg/body weight (mean ± standard deviation). CPT-11 was detected in sweat secreted by all the four patients, and its mean (±standard deviation) concentration was 252.6 (±111.9) ng/ml. SN-38 was detected in only one of the patients who received oxaliplatin-irinotecan-leucovorin-5-fluorouracil treatment and who had the wild-type uridine diphosphate-glucuronosyltransferase 1A1 phenotype at a concentration of 74.37 ng/ml. CONCLUSION: CPT-11 and SN-38 are detected in sweat released during intravenous CPT-11 administration. Beads of sweat or linen clothes that absorb the sweat might be the source of CPT-11 and SN-38 exposure.

L-type amino acid transporter 1 expression in esophageal carcinogenesis according to WHO and Japanese classifications of intraepithelial neoplasia.

L-type amino acid transporter 1 (LAT1) has an essential role in cell proliferation especially in neoplasms. Although immunohistochemical expression of LAT1 has been investigated in invasive esophageal carcinoma, its expression in intraepithelial neoplasia (IEN) has not been reported. Further, classification of esophageal IEN is currently different between the World Health Organization (WHO) and Japanese criteria. Therefore, in this study, immunohistochemical expressions of LAT1 along with Ki-67 were analyzed in 66 esophageal samples of endoscopic submucosal dissection. Extension of cells positive for either marker within the epithelium, along with LAT1 intensity at the base of the epithelium, was evaluated. The results among early IENs, progressed IENs, and invasive carcinoma based on both WHO and Japanese criteria were compared. It was demonstrated that Ki-67+ cells extended toward the superficial layer in IENs, which was more pronounced in progressed compared with early IENs based on both WHO and Japanese criteria. Although similar results were obtained for LAT1+ cells, LAT1+ cell extended more in invasive carcinoma than in progressed IENs according to the WHO criteria. Further, LAT1 intensity was different between early and progressed IENs based on the Japanese criteria alone. Thus, use of LAT1 immunohistochemistry and Japanese classification may be more meaningful to characterize esophageal carcinogenesis.

[Comparison of garenoxacin and levofloxacin for the prophylaxis of febrile neutropenia].

Placebo-controlled randomized trials have demonstrated that prophylactic levofloxacin (LVFX) significantly reduced the incidence of febrile neutropenia (FN) in patients receiving chemotherapy for advanced solid tumors. Garenoxacin (GRNX) has been reported to be more effective than LVFX against gram-positive bacteria especially Streptococcus pneumoniae. Against this background we conducted a study to compare the efficacy and safety of GRNX with that of LVFX for the prophylaxis of FN. We retrospectively analyzed 127 patients at high risk for FN who were administered GRNX or LVFX for the prophylaxis of FN that occurred during chemotherapy for advanced solid tumors. Our primary outcome of interest was the incidence of febrile episodes. Secondary outcomes included evidence of bacterial infection and infection focus when febrile episodes were observed; adverse drug reactions and mortality were also evaluated. Febrile episodes were observed in 2 patients administered GRNX and 7 patients administered LVFX (p=0.044). Definitive pathogenic bacteria and infection focus could not be identified in any patient with febrile episodes and all cases of fever resolved simultaneously with the recovery from neutropenia. We observed 4 cases of rashes and 3 cases of liver dysfunction in the GRNX group and 2 cases of rashes and 2 cases of liver dysfunctions were observed in the LVFX group(not statistically significant in both the groups). No severe adverse effects or deaths were associated with either of these drugs. These results suggest that GRNX is useful for the prophylaxis of FN.

Surgery for liver metastases from primary breast cancer: A reconstructed individual patient data meta-analysis.

BACKGROUND: Currently, the outcomes of standard-of-care palliative treatment for BCLM remain poor. Recent literature has shown promising results of hepatic resection, however, not all studies concur. Given the lack of standardized international guidelines in this field, the aim of this study is to provide gold-standard evidence for breast cancer liver metastases (BCLM) through a reconstructed individual patient data meta-analysis approach. METHODS: Four databases were searched for articles comparing surgical and non-surgical treatment for BCLM. One-stage meta-analysis was performed using patient-level survival data reconstructed from Kaplan-Meier curves with plot digitizer software. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. RESULTS: Four propensity-score matched (PSM) studies involving 205 surgical and 291 non-surgical patients for BCLM were included. There was a significant difference between both groups for overall survival (OS) (Hazard Ratio [HR] = 0.40, 95%CI 0.32-0.51). Sensitivity analyses for hormone receptor status of breast cancer (HR = 0.41, 95%CI 0.31-0.55) and type of resection performed (HR = 0.45, 95%CI 0.33-0.61) yielded HRs in favor of surgery. CONCLUSIONS: This meta-analysis concludes that surgery offers superior OS outcomes, compared to non-surgery, in a select group of patients. Future randomized controlled trials and PSM studies are warranted, using this study as a point of reference for similar parameters.

A systematic review and meta-analysis of mediastinoscopy-assisted transhiatal esophagectomy (MATHE).

BACKGROUND: Transhiatal esophagectomy (THE) avoids thoracotomy but sacrifices mediastinal lymphadenectomy. Mediastinoscopy-assisted transhiatal esophagectomy (MATHE) allows for visualisation and en-bloc dissection of mediastinal lymph nodes while retaining the benefits of THE. However, given its novel inception, there is a paucity of literature. This study aimed to conduct the first meta-analysis to explore the efficacy of MATHE and clarify its role in the future of esophagectomy. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to May 1, 2023. Studies were included if they reported outcomes for patients with esophageal cancer who underwent MATHE. Meta-analyses of proportions and pooled means were performed for the outcomes of intraoperative blood loss, lymph node (LN) harvest, mean hospital length of stay (LOS), mean operative time, R0 resection, conversion rates, 30-day mortality rate, 5-year OS, and surgical complications (anastomotic leak, cardiovascular [CVS] and pulmonary complications, chyle leak and recurrent laryngeal nerve palsy [RLN]). Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 223 articles; 28 studies and 1128 patients were included in our analysis. Meta-analyses of proportions yielded proportion rates: 30-day mortality (0 %, 95 %CI 0-0), 5-year OS (60.5 %, 95 %CI 47.6-72.7), R0 resection (100 %, 95 %CI 99.3-100), conversion rate (0.1 %, 95 %CI 0-1.2). Among surgical complications, RLN palsy (14.6 %, 95 %CI 9.5-20.4) were most observed, followed by pulmonary complications (11.3 %, 95 %CI 7-16.2), anastomotic leak (9.7 %, 95 %CI 6.8-12.8), CVS complications (2.3 %, 95 %CI 0.9-4.1) and chyle leak (0.02 %, 95 %CI 0-0.8). Meta-analysis of pooled means yielded means: LN harvest (18.6, 95 %CI 14.3-22.9), intraoperative blood loss (247.1 ml, 95 %CI 173.6-320.6), hospital LOS (18.1 days, 95 %CI 14.4-21.8), and operative time (301.5 min, 95 %CI 238.4-364.6). There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. CONCLUSION: MATHE is associated with encouraging post-operative mortality and complication rates, while allowing for radical mediastinal lymphadenectomy with reasonable lymph node harvest.

Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model-a Western European multicenter study.

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child-Pugh B7 score (HR 4.29; 95% CI 1.74-10.55; p = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07-3.54; p = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38-4.67; p = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85-2.90; p = 0.015), and Clavien-Dindo Grade 3 or more (HR 2.73; 95% CI 1.44-5.18; p = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34-3.44; p = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25-3.32; p = 0.004), MVI (HR 1.81; 95% CI 1.19-2.75; p = 0.005), satellite nodules (HR 1.63; 95% CI 1.09-2.45; p = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19-5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

A machine learning predictive model for recurrence of resected distal cholangiocarcinoma: Development and validation of predictive model using artificial intelligence.

INTRODUCTION: Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA. MATERIAL AND METHODS: This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm. RESULTS: Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/. CONCLUSIONS: This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.