Clinicopathological Variables Research Articles

Immunohistochemical Expression of Cyclooxygenase-2 in endometrioid carcinoma

Background and objectives: Cyclooxygenase-2 functions as an enzyme which synthesize prostaglandins from Arachidonic acid Cyclooxygenase -2 is one of the important factors in maintaining the endometrium during menstrual cycle. The Aim of this study was to assess expression of Cyclooxygenase-2 in endometrioid carcinoma by immunohistochemistry to explore association between Cyclooxygenase-2 expression and a certain number of clinicopathologic variables. Methods: A retrospective study was carried out for seventy-eight blocks that were preseved in formalin and embedded in paraffin of endometrioid carcinoma were obtained and randomly selected from a private laboratory in Erbil city during October 2020 to October 2022. COX-2 rabbit monoclonal antibody was used to satin slides obtained from endometrioid carcinoma blocks and the expression was scored by multiplying the number of stained cells by the intensity of staining. Results: Cyclooxygenase-2 expressed in 15.4% of cases of study cases. It is down-expressed in high grade endometrioid carcinoma while over-expressed in cases with myometrial invasion ?50%. Regarding other clinicopathological parameters like, lymphovascular invasion, tumor stage and lymphnode status, Cyclooxygenase-2 showing down-expression, there is no existence of notable link between the expression of Cyclooxygenase-2 and clinicopathological parameters, including: Age(p=0.197), Tumor grade(p=0.069), Myometrial invasion(p=0.261), Lympho vascular invasion(p=0.516), Lymph node status(p=1000) and Tumor stage(p=0.872). Conclusion: Cyclooxygenase-2 is expressed in a limited number of endometrioid carcinoma and there is lack of significant association between Cyclooxygenase-2 expression and clinicopathological parameters

Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach.

The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from 10 cases each of GBC and inflammatory lesions, with technical duplicates.Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan-Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real time-polymerase chain reaction (RT-PCR). Out of 5,714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables.Prognostic factors such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival. Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.

Hyperprogressive disease in patients with advanced cancer treated with immune checkpoint inhibitors.

Hyperprogressive disease (HPD) is a new phenomenon developing in the era of immune checkpoint inhibitor (ICI) therapy. HPD is characterized by an unexpected and fast progression in tumor volume and poor survival. There is no standardized definition for HPD and clinicopathological variables associated with HPD are unclear. Herein, we assessed incidence, treatment outcomes and factors predictive of HPD in patients treated with ICIs. We retrospectively analyzed patients with advanced cancer treated with ICI at one academic center between 2014 and 2021. We used the Lo Russo's adopted criteria combined with clinical and radiologic parameters for the definition of HPD. All patients who underwent their first tumor evaluation according to RECIST1.1 were included. Of 155 patients, 147 were eligible for analysis. The median age was 61 and 83% were male. The cancer types were; lung 67.3%, bladder 12.9%, gastric 9.5%, 5, colon 5.4% and renal cell carcinoma 4.8%. 59.9% of patients were treatment-naive and others had one or more lines of chemotherapy. 19 (12.9%) patients had HPD. In patients who had HPD, progression-free survival (PFS) was significantly shorter (1.5 vs 9.8months, (HR 9.56; 95% CI (5.51-16.57), p < 0.001). The median overall survival (OS) was also shorter for HPD patients than non-HPD (3.0 vs 23.1months, respectively, HR 12.03, 95% CI (6.64-21.81), p < 0.001). Gastric cancer, larger sum of target lesion diameters at baseline, liver metastases, higher LDH level and higher neutrophil-lymphocyte ratio (NLR) were significantly associated with HPD. Our findings demonstrated that HPD was a rapid phenomenon with significantly poor survival rates. Several clinicopathological factors and tumor characteristics might indicate HPD.

The prevalence and risk factors associated with zinc deficiency after pancreatic surgery.

To clarify the prevalence, risk factors, and clinical implications associated with zinc deficiency in patients undergoing pancreatic surgery. The serum zinc levels were measured in 329 patients post-pancreatic surgery between January and April 2021. The postoperative serum zinc levels and clinicopathological variables were retrospectively analyzed. The median serum zinc level was 73µg/dL (33-218). Zinc deficiency (zinc level < 60µg/dL) was observed in 52 patients (16%). A total of 329 patients were classified into zinc-deficient (n = 52) and non-deficient (zinc ≥ 60µg/dL, n = 277) groups. A univariate analysis revealed significant differences in sex, postoperative body mass index, serum albumin, total cholesterol, creatinine, aspartate aminotransferase (AST), HbA1c levels, diabetes, surgical procedures, and operative blood loss. According to a multivariate analysis, male sex [odds ratio (OR) 3.70; 95% confidence interval (CI) 1.67-8.20; p = 0.001], postoperative serum albumin levels < 3.9g/dL (OR 6.39; 95% CI 3.30-12.37; p < 0.001), postoperative serum AST ≥ 51 U/L (OR, 4.6; 95% CI 0.07-0.29; p < 0.001), and total pancreatectomy (OR 3.68; 95% CI 1.37-9.85; p = 0.009) were found to be independent predictors of zinc deficiency after pancreatic surgery. Zinc deficiency frequently occurs in patients undergoing pancreatic surgery. Lower postoperative zinc levels could be linked to sex, the serum albumin and AST levels, and surgery type.

Expression Pattern of Estrogen Receptor Alpha and Progesterone Receptor in Gallbladder Carcinoma and Their Association with Clinicopathological Parameters and Overall Survival.

Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival. A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry. The mean age of this study population was 55.47 ± 8.45 with range 28-87years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival. Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.

Effects of fecal microbiota transplantation on clinical outcomes and fecal microbiota of foals with diarrhea.

Diarrhea in foals can be associated with disruption of the intestinal microbiota (dysbiosis). Effective management of intestinal dysbiosis in foals has not been demonstrated. Fecal microbiota transplantation (FMT) in foals with diarrhea influences the intestinal microbiota and improves clinical and clinicopathological outcomes. Twenty-five foals <6 months of age with diarrhea and systemic inflammatory response syndrome at 3 veterinary hospitals. A prospective randomized placebo-controlled cohort study. Foals in the FMT group (n = 19) or control group (n = 9) received FMT or electrolyte solution once daily for 3 days. Fecal samples were obtained on Day 0 (D0), D1, D2, D3, and D7. Within group and between group data analyses were performed for clinical, clinicopathological, and microbiota variables. Treatment had no effect on survival (FMT 79%; control 100%, P = .3) or resolution of diarrhea (FMT 68%; control 55%, P = .4). On D3, the white blood cell count of the FMT group was lower than the control group (D3 FMT group median 6.4 g/L [5-8.3 g/L]; D3 control group median 14.3 g/L [6.7-18.9 g/L] P = .04). Heart rate reduced over time in the FMT group (D0 median 80 bpm [60-150 bpm]; D2 median 70 bpm [52-110 bpm] [P = .005]; and D3 median 64, [54-102 bpm] [P < .001]). Phylum Verrucomicrobiota, genus Akkermansia, and family Prevotellaceae were enriched in the FMT group on D1 (linear discriminate analysis > 4). In foals with diarrhea, FMT appears safe and can be associated with some clinical and microbiota changes suggestive of beneficial effect.

Clinicopathologic Characteristics Influencing Overall Survival of Patients With Early- Versus Average-Onset Colorectal Cancer at a Tertiary Care Center in Indonesia.

There has been a global increase in early-onset colorectal cancer (EOCRC), yet there has been very limited exploration of its impact in Indonesia. This study aimed to determine the clinicopathologic characteristics and the overall survival (OS) of EOCRC compared with those of average-onset colorectal cancer (AOCRC). Medical records were retrospectively reviewed from all patients presenting with colorectal cancer (CRC) at Dr Sardjito General Hospital (Yogyakarta, Indonesia) between 2016 and 2019. Sociodemographic, clinicopathologic, and treatment variables were extracted. t Tests were used to compare characteristics of EOCRC and AOCRC patient groups. The Cox proportional hazards regression model was used to analyze age and other potential prognostic factors. The total population (N = 1,276) comprised EOCRC (n = 149; 11.7%) and AOCRC (n = 1,127; 88.3%) patients. EOCRC patients were more likely to have a higher education level, be single, have out-of-pocket insurance, be underweight, and have signet ring histology (all P values <.05), compared with AOCRC patients. EOCRC and AOCRC groups had a comparable estimated 5-year OS of 34.2% and 36.9%, respectively. In multivariable analyses, performance status (Eastern Cooperative Oncology Group), hemoglobin level, cancer stage, and treatment intention were independent prognostic factors for OS (all P values <.05). To our knowledge, this first major study of EOCRC in Indonesia highlights its role in the overall burden of CRC and its connection with social determinants of health. Patients with EOCRC are more commonly underweight and generally have a higher proportion of signet ring histology than AOCRC, yet OS in both groups is similar. Future research is required to identify risk factors to inform the content and focus of public health education activities, alongside delineating the biology and causes of early and average onset of the disease.

VEGFA gene variants are associated with breast cancer progression.

Angiogenesis is recognized as a hallmark of cancer, and vascular endothelial growth factor (VEGF) is a key regulator of the angiogenic process and is related to cancer progression. Anti-VEGF therapy has been tried but with limited success and without useful stratification for angiogenesis markers. Further, the landscape of VEGF single nucleotide polymorphisms (SNPs) in breast cancer and their clinical relevance is not well studied, and their relation to tissue-based angiogenesis markers has not been explored. Here, we studied a selection of VEGFA SNPs in nontumor lymph nodes from a population-based breast cancer cohort (n = 544), and their relation to clinicopathologic variables, vascular tissue metrics, and breast cancer-specific survival. Two of the SNP candidates (rs833068GA genotype and rs25648CC genotype) showed associations with angiogenesis tissue markers, and the VEGFA rs833068GA genotype was associated with breast cancer-specific survival among ER-negative cases. We also found trends of association between the rs699947CA genotype and large tumor diameter and ER-negative tumors, and between the rs3025039CC genotype and large tumor diameter. Our findings indicate some associations between certain VEGF SNPs, in particular the rs833068GA genotype, and both vascular metrics and patient survival. These findings and their potential implications need to be validated by independent studies.

380. GROWTH CHARACTERISTICS OF ESOPHAGEAL PATIENT DERIVED ORGANOIDS REFLECT CLINICOPATHOLOGIC VARIABLES

Abstract Background Esophageal patient derived organoids (PDOs) are three-dimensional cell culture models derived from esophageal cancer tissue. We have previously shown that PDOs recapitulate the genetic and morphologic characteristics of the primary tumour, and that PDOs may predict patient responses to neoadjuvant regimens and potentially allow personalisation perioperative therapies. Nevertheless, up to 30% of tissue samples fail to establish organoids in vivo, although the reasons for this are unclear. This study interrogates the clinical characteristics of biopsies that establish or fail to establish PDOs. Methods Esophageal adenocarcinomas from locally advanced (LA) or metastatic (M) disease were biopsied at initial endoscopy, following surgical resection, or image-guided biopsy of metastatic disease (n=75 total). Following a standardised protocol, cells were dissociated and seeded for organoid culture. Organoids are considered ‘established’ after passage 4. Samples were discarded if there was obvious contamination (n=9) or if there were no obvious tumour cells (n=6). Clinicopathologic variables for successfully established or unsuccessfully established were compared for both LA and M disease. Statistical analysis was performed to interrogate characteristics associated with successfully establishing organoids. Results There were significant differences between successful and unsuccessful organoids. Organoids were more likely to be established from endoscopic biopsies (p=0.002). Samples pre-treated with neoadjuvant chemoradiation or chemotherapy were less likely to grow (p=0.02). Samples from poorly differentiated tumours were less likely to grow compared with well and moderately differentiated tumours (p=0.05). Tumour stage, lymphovascular invasion, perineural invasion, MSI status and HER-2 status were not associated with growth characteristics. Conclusion Growth characteristics of esophageal adenocarcinoma PDOs correlate with clinicopathologic characteristics. Samples from patients who have undergone chemotherapy or chemoradiation, and poorly differentiated tumours are less likely to establish in vitro models. Understanding the altered in vitro growth patterns is key to translating use of organoids into clinical practice.

798. FEASIBILITY AND EFFICACY OF CISPLATIN, PACLITAXEL AND IMMUNE CHECKPOINT INHIBITORS AS CONVERSION THERAPY FOR LOCOREGIONALLY UNRESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Induction therapy followed by conversion surgery is potentially curative for locoregionally unresectable esophageal squamous cell carcinoma (ESCC). However, the optimal induction treatment strategy is unclear. The study aimed to evaluate the feasibility and efficacy of cisplatin, paclitaxel and immune checkpoint inhibitors as conversion therapy for locoregionally unresectable ESCC. Methods Clinicopathological variables of cT4b ESCC patients who received neoadjuvant chemoimmunotherapy were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. Enhanced computed tomography, ultrasonography and bronchoscopy were routinely used for the diagnosis. The treatment protocol of neoadjuvant chemoimmunotherapy included 2 cycles of immunotherapy plus chemotherapy with the interval of 3 weeks among each cycle. All patients received 2 cycles of Pembrolizumab (200 mg, D1), Sintilimab (200 mg, D1), Tislelizumab (200 mg, D1) or Camrelizumab (200 mg, D1) intravenously. Concurrently all patients received 2 cycles of cisplatin (75 mg/m2 of body-surface area, D1) and paclitaxel (175 mg/m2 body-surface area, D1) intravenously. The perioperative parameters and short-term surgical outcomes were presented (Table). Results Between January 2020 and December 2022, a total of 317 ESCC patients who underwent neoadjuvant chemoimmunotherapy followed by surgery were screened. Twenty cT4b patients with middle or upper thoracic ESCC were finally enrolled in this study. Pretreatment tumor invades the trachea (4, 20%), left main bronchus (16, 80%), and aorta (6, 30%), respectively. All the patients were successfully performed by McKeown minimally invasive esophagectomy except for one patient conversion to thoracotomy. R0 resection was achieved in 15 patients, 4 patients underwent R1 resection and 1 patient underwent R2 resection. Mean operation duration was 290.4 ± 57.5 min. Mean estimated blood loss was 94.4 ± 108.8 ml. Three patients had postoperative pneumonia, two patients had postoperative pleural effusion and one patient had postoperative recurrent laryngeal nerve paralysis. No patient had postoperative anastomotic leak. No postoperative reoperation was needed and there was no perioperative mortality. Mean length of hospital stay was 10.9±1.4 days. 90-day mortality occurred in one patient with postoperative multiple systemic metastasis. Fifteen patients are alive with a median follow up of 18 months. One patient died with regional lymph node recurrence and three patients died with hematogenous dissemination. Conclusion Multimodal treatment strategy combining immunotherapy and chemotherapy may convert unresectable tumors into potentially operable ones, and achieved favorable survival. Longer follow-up and larger sample size are needed to verify our preliminary results.

BioFusionNet: Deep Learning-Based Survival Risk Stratification in ER+ Breast Cancer Through Multifeature and Multimodal Data Fusion.

Breast cancer is a significant health concern affecting millions of women worldwide. Accurate survival risk stratification plays a crucial role in guiding personalised treatment decisions and improving patient outcomes. Here we present BioFusionNet, a deep learning framework that fuses image-derived features with genetic and clinical data to obtain a holistic profile and achieve survival risk stratification of ER+ breast cancer patients. We employ multiple self-supervised feature extractors (DINO and MoCoV3) pretrained on histopathological patches to capture detailed image features. These features are then fused by a variational autoencoder and fed to a self-attention network generating patient-level features. A co-dual-cross-attention mechanism combines the histopathological features with genetic data, enabling the model to capture the interplay between them. Additionally, clinical data is incorporated using a feed-forward network, further enhancing predictive performance and achieving comprehensive multimodal feature integration. Furthermore, we introduce a weighted Cox loss function, specifically designed to handle imbalanced survival data, which is a common challenge. Our model achieves a mean concordance index of 0.77 and a time-dependent area under the curve of 0.84, outperforming state-of-the-art methods. It predicts risk (high versus low) with prognostic significance for overall survival in univariate analysis (HR=2.99, 95% CI: 1.88-4.78, p 0.005), and maintains independent significance in multivariate analysis incorporating standard clinicopathological variables (HR=2.91, 95% CI: 1.80-4.68, p 0.005).

MicroRNA Profiling in Papillary Thyroid Cancer.

Genetic alterations are well known to be related to the pathogenesis and prognosis of papillary thyroid carcinoma (PTC). Some miRNA expression dysregulations have previously been described in the context of cancer development including thyroid carcinoma. In our study, we performed original molecular diagnostics on tissue samples related to our own patients. We aimed to identify all dysregulated miRNAs in potential association with PTC development via sequencing much higher numbers of control-matched PTC tissue samples and analyzing a wider variety of miRNA types than previous studies. We analyzed the expression levels of 2656 different human miRNAs in the context of 236 thyroid tissue samples (118 tumor and control pairs) related to anonymized PTC cases. Also, KEGG pathway enrichment analysis and GO framework analysis were used to establish the links between miRNA dysregulation and certain biological processes, pathways of signaling, molecular functions, and cellular components. A total of 30 significant differential miRNA expressions with at least ±1 log2 fold change were found related to PTC including, e.g., miR-551b, miR-146b, miR-221, miR-222, and miR-375, among others, being highly upregulated, as well as miR-873 and miR-204 being downregulated. In addition, we identified miRNA patterns in vast databases (KEGG and GO) closely similar to that of PTC including, e.g., miRNA patterns of prostate cancer, HTLV infection, HIF-1 signaling, cellular responses to growth factor stimulus and organic substance, and negative regulation of gene expression. We also found 352 potential associations between certain miRNA expressions and states of clinicopathological variables. Our findings-supported by the largest case number of original matched-control PTC-miRNA relation research-suggest a distinct miRNA expression profile in PTC that could contribute to a deeper understanding of the underlying molecular mechanisms promoting the pathogenesis of the disease. Moreover, significant miRNA expression deviations and their signaling pathways in PTC presented in our study may serve as potential biomarkers for PTC diagnosis and prognosis or even therapeutic targets in the future.

Prediction of disease-free survival using strain elastography and diffuse optical tomography in patients with T1 breast cancer: a 10-year follow-up study

BackgroundEarly-stage breast cancer (BC) presents a certain risk of recurrence, leading to variable prognoses and complicating individualized management. Yet, preoperative noninvasive tools for accurate prediction of disease-free survival (DFS) are lacking. This study assessed the potential of strain elastography (SE) and diffuse optical tomography (DOT) for non-invasive preoperative prediction of recurrence in T1 BC and developed a prediction model for estimating the probability of DFS.MethodsA total of 565 eligible patients with T1 invasive BC were enrolled prospectively and followed to investigate the recurrence. The associations between imaging features and DFS were evaluated and a best-prediction model for DFS was developed and validated.ResultsDuring the median follow-up period of 10.8 years, 77 patients (13.6%) developed recurrences. The fully adjusted Cox proportional hazards model showed a significant trend between an increasing strain ratio (SR) (P < 0.001 for trend) and the total hemoglobin concentration (TTHC) (P = 0.001 for trend) and DFS. In the subgroup analysis, an intensified association between SR and DFS was observed among women who were progesterone receptor (PR)-positive, lower Ki-67 expression, HER2 negative, and without adjuvant chemotherapy and without Herceptin treatment (all P < 0.05 for interaction). Significant interactions between TTHC status and the lymphovascular invasion, estrogen receptor (ER) status, PR status, HER2 status, and Herceptin treatment were found for DFS(P < 0.05).The imaging–clinical combined model (TTHC + SR + clinicopathological variables) proved to be the best prediction model (AUC = 0.829, 95% CI = 0.786–0.872) and was identified as a potential risk stratification tool to discriminate the risk probability of recurrence.ConclusionThe combined imaging-clinical model we developed outperformed traditional clinical prognostic indicators, providing a non-invasive, reliable tool for preoperative DFS risk stratification and personalized therapeutic strategies in T1 BC. These findings underscore the importance of integrating advanced imaging techniques into clinical practice and offer support for future research to validate and expand on these predictive methodologies.

Dynamic Assessment of Drain Fluid Amylase Estimates the Risk of CR-POPF Following Pancreatoduodenectomy.

To evaluate whether drain fluid amylase levels on day-1 (DFA1) and day-3 (DFA3) can reliably estimate the risk of clinically relevant-postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) compared to either value alone or in combination with clinicopathologic variables. CR-POPF is a major source of morbidity and mortality following PD. Current drain management algorithms are variable and are mostly dependent on DFA1, while the DFA3 is seldom utilized to guide clinical decision making. Between 2015-2020, patients who underwent PD at two high-volume pancreas centers and had intraoperative drain placement with measurement of DFA1 and DFA3 were retrospectively reviewed. Models to predict CR-POPF were constructed using DFA1, DFA3, fistula risk score (FRS) and other patient or treatment-related parameters. The fittest and more parsimonious model was used to construct a CR-POPF risk calculator. Nine-hundred-twenty-three patients were included in the analysis. The FRS was high in 100(10.9%), intermediate in 524(57.3%), low in 211(23.1%) and negligible in 79(8.6%) patients. The overall rate of CR-POPF was 9.2%. Five logistic regression models were constructed using variables known to be implicated in CR-POPF. A model based solely on DFA1 and DFA3 with a cross-validated area under the curve of 0.846 was selected. A calculator using DFA1 and DFA3 was created based on this model to estimate the risk of CR-POPF. Risk of CR-POPF following pancreatoduodenectomy can be accurately estimated based on measurement of DFA1 and DFA3. Our CR-POPF kinetics calculator can facilitate postoperative risk stratification and guide drain management algorithms.

Lymph node ratio prognosticates overall survival in patients with stage IV colorectal cancer

BackgroundLymph node ratio (LNR) is suggested to address the shortcomings of using only lymph node yield (LNY) or status in colorectal cancer (CRC) prognosis. This study explores how LNR affects survival in patients with metastatic colorectal cancer (mCRC), seeking to provide clearer insights into its application.MethodsThis observational cohort study investigated stage IV patients with CRC (1995–2021) who underwent an upfront resection of their primary tumour at Concord Hospital, Sydney. Clinicopathological data were extracted from a prospective database, and LNR was calculated both continuously and dichotomously (LNR of 0 and LNR > 0). The primary endpoint was overall survival (OS). The associations between LNR and various clinicopathological variables were tested using regression analyses. Kaplan–Meier and Cox regression analyses estimated OS in univariate and multivariate survival models.ResultsA total of 464 patients who underwent a primary CRC resection with clear margins (mean age 68.1 years [SD 13.4]; 58.0% M; colon cancer [n = 339,73.1%]) had AJCC stage IV disease. The median LNR was 0.18 (IQR 0.05–0.42) for colon cancer (CC) resections and 0.21 (IQR 0.09–0.47) for rectal cancer (RC) resections. A total of 84 patients had an LNR = 0 (CC = 66 patients; RC = 18 patients). The 5-year OS for the CC cohort was 10.5% (95% CI 8.7–12.3) and 11.5% (95% CI 8.4–14.6) for RC. Increasing LNR demonstrated a decline in OS in both CC (P < 0.001) and RC (P < 0.001). In patients with non-lymphatic dissemination only (LNR = 0 or N0 status), there was better survival compared with those with lymphatic spread (CC aHR1.50 [1.08–2.07;P = 0.02], RC aHR 2.21 [1.16–4.24;P = 0.02]).ConclusionsLNR is worthy of consideration in patients with mCRC. An LNR of 0 indicates patients have a better prognosis, underscoring the need for adequate lymphadenectomy to facilitate precise mCRC staging.

Relapses in canine leishmaniosis: risk factors identified through mixed-effects logistic regression

BackgroundCanine leishmaniosis (CanL), caused by Leishmania infantum, is an important vector-borne parasitic disease in dogs with implications for human health. Despite advancements, managing CanL remains challenging due to its complexity, especially in chronic, relapsing cases. Mathematical modeling has emerged as a powerful tool in various medical fields, but its application in understanding CanL relapses remains unexplored.MethodsThis retrospective study aimed to investigate risk factors associated with disease relapse in a cohort of dogs naturally infected with L. infantum. Data from 291 repeated measures of 54 dogs meeting the inclusion criteria were included. Two logistic mixed-effects models were created to identify clinicopathological variables associated with an increased risk of clinical relapses requiring a leishmanicidal treatment in CanL. A backward elimination approach was employed, starting with a full model comprising all potential predictors. Variables were iteratively eliminated on the basis of their impact on the model, considering both statistical significance and model complexity. All analyses were conducted using R software, primarily employing the lme4 package, and applying a significance level of 5% (P < 0.05).ResultsThis study identified clinicopathological variables associated with an increased risk of relapses requiring a leishmanicidal treatment. Model 1 revealed that for each 0.1 increase in the albumin/globulin ratio (A/G) ratio, the odds of requiring treatment decreased by 45%. Conversely, for each unit increase in the total clinical score (CS), the odds of requiring treatment increase by 22–30%. Indirect immunofluorescence antibody test (IFAT) was not a significant risk factor in model 1. Model 2, incorporating individual albumin and globulins values, showed that dogs with high IFAT titers, hyper beta-globulinemia, hypoalbuminemia, anemia, and high CS were at increased risk of relapse. Both models demonstrated a good fit and explained a substantial amount of variability in treatment decisions.ConclusionsDogs exhibiting higher CS, dysproteinemia, anemia, and high IFAT titers are at increased risk of requiring leishmanicidal treatment upon clinical relapse in CanL. Regular monitoring and assessment of risk factors prove essential for early detection of relapses and effective intervention in CanL cases. The contrasting findings between the two models highlight the complexity of aspects influencing treatment decisions in this disease and the importance of tailored management strategies to improve outcomes for affected dogs.Graphical

Tissue morphometric measurements do not predict survival following colorectal cancer surgery

BackgroundEx vivo tissue morphometric (TM) measurements have been proposed as a quality marker for colorectal cancer (CRC) surgery. However, their survival associations require clarification. This study aimed to evaluate the feasibility of capturing TM measurements based on ex vivo fresh specimen images and explore the association between these TM measurements and survival outcomes.MethodsA prospective cohort study at Concord Hospital, Sydney was conducted with Stage I to III CRC patients (2009–2019) who underwent an anterior resection (AR) or right hemicolectomy (RH). Using high-resolution digital photographs of fresh CRC specimens, ex vivo tissue morphometric (TM) measurements—resected mesentery area (TM A), distances from high vascular tie to tumour (TM B) and bowel wall (TM C), and bowel length (TM D)—were recorded using Image J. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan–Meier and Cox regression analyses. Linear regression models tested association between TM measurements and lymph node (LN) yield.ResultsOf the 1,425 patients who underwent CRC surgery, TM measurements were performed on 312 patients, with an average age of 69.4 years (SD 12.3), of whom 52.9% were male. The majority had an AR (57.8%). Among AR patients, a 5-year OS rate of 77.4% and a DFS rate of 70.1% were observed, with TM measurements bearing no relationship to survival outcomes. Similarly, RH patients exhibited a 5-year OS rate of 67.2% and a DFS rate of 63.1%, with TM measurements again showing no association with survival. Only TM D (P = 0.02) measurements were associated with the number of LNs examined.ConclusionThis study successfully demonstrates the feasibility of measuring TM measurements on photographs of ex vivo fresh specimens following CRC surgery. The lack of association with survival outcomes questions the utility of TM measurements as a quality metric of CRC surgery.

Impact of obesity on survival outcomes of women with advanced epithelial ovarian cancer in Lagos, Nigeria: a retrospective cohort study.

Epithelial ovarian cancer (EOC) is a major contributor to cancer-related illness and death among women worldwide. Obesity, a prevalent condition in many populations, has been implicated as a risk factor for various malignancies including EOC. This study investigated the impact of obesity on survival outcomes among women with advanced EOC in Lagos, Nigeria. We conducted a retrospective analysis of patient medical records from a major gynaecological cancer unit of a teaching hospital in Lagos, Southwest Nigeria, to examine the relationship between body mass index (BMI) 30 kg/m2 as a measure of obesity, and progression-free (PFS) and overall survival (OS). We used Kaplan-Meier analysis stratified by patients' BMI categories (obese versus non-obese) and compared using the Log Rank test to estimate PFS and OS. The multivariable Cox proportional hazard model was used to estimate hazard ratios (HR) of the associations between the BMI categories and survival outcomes while adjusting for all confounding clinicopathologic variables. Hypothesis tests were conducted using a two-tailed approach with a significance level of 5%. Our study showed no statistically significant association between obesity and PFS (adjusted HR = 0.62, 95% confidence interval = 0.36-1.06, p = 0.282). However, a significant association was observed between obesity with or without ascites and OS (adjusted HR = 3.58, 95% confidence interval 1.28-10.02, p = 0.015). Our findings suggest that obesity negatively impacts OS in patients with EOC, thus highlighting the need to address obesity in the management of EOC by introducing comprehensive, multidisciplinary approaches incorporating weight management and personalized treatment strategies to enhance the prognosis of these patients.

CT Derived Measurement of Body Composition: Observations from a Comparative Analysis of Patients with Colorectal and Lung Cancer

Background CT-derived measures of body composition have been shown to have prognostic value in patients with cancer. However, few studies have compared these observations across tumor types and stages of disease. The aim of the present study was to compare body composition measures between two types of cancers, i.e. colorectal cancer (CRC), which is less inflammatory and patients maintain body composition over a longitudinal study period, whereas lung cancer (LC) is proinflammatory and patients lose more fat and muscle mass using a standard methodology. Methods Clinicopathological characteristics, including those pertaining to nutritional risk/status and systemic inflammation in patients with colorectal cancer (CRC, n = 1047) and lung cancer (LC, n = 662), were compared. The CT image at L3 was used to assess body composition. Comparison of these cohorts was carried out using the chi-square test. Binary logistic regression analysis was performed to assess the impact of clinico-pathological variables on body composition, and scatter plots were used to examine the relationship between body mass index (BMI) and CT-derived measures of body composition. Results According to CT-derived body composition, high subcutaneous (SFI) and visceral fat index (VFI) were common (>70%) in both CRC and LC. Also, low skeletal muscle index (SMI) and density (SMD) were approximately 40–50% and 60–70% in both CRC and LC. Compared with CRC, patients with LC had a higher American Society of Anaesthesia (ASA) (P < 0.001), Malnutrition Universal Screening Tool (MUST) (P < 0.001), modified frailty index (mFI) (P < 0.001), modified Glasgow Prognostic Score (mGPS) (P < 0.001), and neutrophil lymphocyte ratio (NLR) (P < 0.001) scores. On binary logistic regression analysis, MUST, mFI, and NLR were predictors of subcutaneous adiposity (P < 0.05); type of cancer, MUST, and mFI were predictors of visceral obesity (P < 0.001); age, type of cancer, MUST, and mGPS were predictors of low SMI (P < 0.001); and age, type of cancer, mFI, and mGPS were predictors of low SMD (P < 0.05). There was a similar relationship between BMI and other measures of CT-derived body composition across two types of cancers. Conclusion Obesity and low skeletal muscle mass were common in both CRC and LC cohorts despite large differences in comorbidity, nutritional risk, systemic inflammation, and survival, even when normalized for TNM stage. These observations would support the hypothesis that, although prognostic, CT derived body composition analysis primarily reflects patient constitution rather than the effect of tumor stage in patients with cancer. The systemic inflammatory response, as evidenced by mGPS, can be considered as an important therapeutic target and loss of muscle mass in patients with advanced cancer is related to the systemic inflammatory response.

Homotypic cell-in-cell structure as a novel prognostic predictor in non-small cell lung cancer and frequently localized at the invasive front

Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan–Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.