BACKGROUNDClear cell renal cell carcinoma (ccRCC) with pancreatic metastases (PM) is paradoxically associated with prolonged overall survival (OS), but the biological basis for this observation remains unclear.METHODSWe analyzed matched primary and metastatic samples from an international consortium of patients with PM (n = 108) and compared them with a previously characterized ccRCC cohort without PM (n = 273).RESULTSPrimary ccRCC tumors associated with PM were dominated by indolent, angiogenic phenotypes, characterized by low-grade histology and reduced mTORC1 activation (all P < 0.001). Tumors of patients with PM were often PBRM1-deficient (80.4% vs. 54.8%, P < 0.001) and rarely harbored BAP1 loss (3.7% vs. 20.7%, P < 0.001). After metastasis diagnosis, patients with PM had significantly longer median OS compared with those without PM (110 vs. 33 months, HR 0.28 [95% CI, 0.19-0.39], P < 0.001). Survival was further prolonged among patients with PBRM1 loss (143 vs. 64 months, HR 0.41 [95% CI, 0.22-0.81], P = 0.008). Notably, PM lesions were typically low-grade and PBRM1-deficient even when more aggressive and evolved clones were present in primary tumors. Finally, PBRM1 loss was associated with preferential response to angiogenesis inhibitors over immune-oncology therapy, reflected by longer time on treatment (32.1 vs. 9.1 months, HR 0.16 [95% CI, 0.06-0.39], P < 0.001).CONCLUSIONThese findings illustrate selective tropism of indolent, less-evolved, PBRM1-deficient ccRCC clones for pancreatic dissemination. This biological bias likely underlies therapeutic sensitivity and favorable survival, supporting the consideration of PBRM1 status and metastatic tropism in risk stratification and treatment selection.FUNDINGNIH Kidney Cancer SPORE grant (P50CA196516); The Cancer Prevention and Research Institute of Texas (RP220294); Endowment from Jan and Bob Pickens Distinguished Professorship in Medical Science and Brock Fund for Medical Science Chair in Pathology.

Management of rectal bleeding due to various underlying malignant pathologies is a difficult situation, especially in the setting of metastatic disease. Palliative radiation is generally offered to such patients to achieve hemostasis. We report a patient diagnosed with metastatic prostate carcinoma which was infiltrating the rectal mucosa. Fifty-four year old patient, with a case of metastatic prostate carcinoma presented with rectal bleeding. On evaluation, he had a friable growth from the anal verge to 10 cm with severe bleeding. We gave intraluminal high-dose rate brachytherapy using an endoluminal vaginal/rectal cylinder applicator. A dose of 6 Gy, weekly for three weeks was delivered. High-dose-rate brachytherapy was immediately well tolerated. The bleeding stopped completely by day 4 and by day 7 patient was passing yellow stools. Intraluminal high-dose-rate brachytherapy has been proven as an effective palliative treatment in achieving hemostasis from rectal bleeding.

The skin is the largest organ in the human body, and skin cancers are some of the most common malignancies seen across the world. About 80% of all skin cancers are basal cell carcinomas (BCC), 16% are squamous cell cancers (SCC), and 4% are melanomas. In contrast, the most common cancers that arise in a burn scar are squamous cell cancers. The burned area is at risk of constant and chronic irritation due to activities of daily living because the covering lacks hydration and elasticity, as compared to normal skin. Malignant transformation of these areas is accelerated by the prolonged duration of the ulcer, injury, constant irritation, infection, and poor hygiene. There have been anecdotal reports of sarcomas arising in a burn scar, with a total of 21 cases being reported so far in the literature. We present the clinical and pathological details of a 50-year-old lady with a pleomorphic undifferentiated sarcoma arising from a neglected burn scar, who needed palliative surgery to relieve her pain. This case report focuses attention on an unusual presentation of an aggressive tumor in the background of a neglected burn scar and emphasizes the need for early and appropriate management of all non-fatal burn patients.

Adrenocortical tumors are rare tumors in childhood. Virilization is the most common symptom, but about 5.5% of patients may also present with isolated Cushing's syndrome. A girl 15 years and 8 months of age presented with complaints of striae on her legs, acne for 2 weeks, and amenorrhea for 2 months. On physical examination, extensive striae were observed on her legs and abdomen. On hormonal investigation, her adrenocorticotropic hormone level was <5 pg/ml, cortisol was 35.4 µg/dl. Her hypercortisolism raised suspicion of Cushing's syndrome. Adrenal MRI revealed a right adrenal mass approximately 9 cm in diameter. Pleural metastasis was detected and the patient was diagnosed as having stage 4 adrenocortical carcinoma. Despite treatment, she died 9 months after diagnosis. Our case followed an aggressive clinical course and was unique due to the presence of extensive striae without pronounced virilization or Cushingoid symptoms.

The enhanced recovery after surgery (ERAS) pathway is the standard of perioperative care for major surgeries globally. However, integrating it into practice can be challenging, especially given the variety of healthcare systems in low- and middle-income countries. At our hospital, we aimed to establish the ERAS pathway phase-wise for oncosurgeries.

We initiated the ERAS pathway in incremental steps, namely, drafting and team-building, trial run, consolidation, and expansion, with regular auditing and feedback at every stage. Six months after initiation (January to June 2024), we assessed our compliance rates and compared outcomes with historical controls (matched for age, surgical procedure, and ASA classification).

In the oncosurgical patients managed under the ERAS protocol, overall compliance was 70.4%, with maximum compliance for preoperative (77.17%) and least for postoperative elements (54.16%). Compared to matched cohorts, ERAS patients had significantly lower rates of postoperative complications (median ± IQR, 1.00 ± 0.00 versus 1.50 ± 1.00, P = 0.035) and duration of ICU (median ± IQR, 0.00 ± 2.00 versus 2.00 ± 3.00, P = 0.017) and hospital stay (median ± IQR, 7.00 ± 2.00 versus 8.00 ± 4.00, P = 0.035).

Anesthesiologists can champion and build ERAS care pathways in hospitals by assembling a core team and systematically applying ERAS components during each surgical stage.

Berberine (BBR), a bioactive compound from various plants, shows significant therapeutic promise against lung cancer. Research indicates that berberine effectively inhibits cell proliferation in lung cancer cell lines and promotes apoptosis. Its mechanisms of action include inducing apoptosis and inhibiting metastasis-related pathways, showcasing its multifaceted approach to tumor suppression. Berberine also influences important signaling pathways like mitogen-activated protein kinase, phosphoinositide 3-kinase/protein kinase B, and nuclear factor kappa-light-chain-enhancer of activated B cells, thereby boosting its anti-cancer properties. Preclinical animal studies have further demonstrated berberine's effectiveness, especially when combined with conventional chemotherapy, suggesting a synergistic relationship that could enhance treatment efficacy. These promising results have led to ongoing clinical trials exploring berberine's potential as part of lung cancer treatment regimens. However, challenges persist regarding dosage standardization, bioavailability, and the translation of preclinical results into clinical applications. This review highlights the therapeutic mechanisms of berberine, its potential efficacy as a standalone or adjunctive treatment, and the obstacles that must be addressed to leverage its benefits in lung cancer therapy fully. Overcoming these challenges may provide valuable opportunities for improving treatment outcomes, positioning berberine as a key component in future lung cancer therapies. Continued research is essential to better understand its precise mechanisms and enhance its clinical application.

The renin-angiotensin system (RAS), particularly the angiotensin II (AT2)/angiotensin I receptor axis, is implicated in promoting tumorigenesis. However, the causal relationship between angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) use and cancer remains controversial. This study employed a two-sample, two-step Mendelian randomization (MR) approach to investigate whether there is a causal relationship between ACEI/ARB use and various cancers, and if so, the direction and potential mechanism of this association.

Genome-wide association study (GWAS) summary statistics for ACEI/ARB use, 24 site-specific cancers, and potential mediators were obtained from the GWAS Catalog, Integrative Epidemiology Unit (IEU) OpenGWAS project, and FinnGen study. Potential causal effect were primarily estimated using the inverse variance weighted (IVW) method. Sensitivity analyses, including Cochran's Q test, MR-Egger regression, and leave-one-out analysis, were performed to assess the robustness of the findings.

MR analyses demonstrated causal protective effects of genetically proxied ACEI/ARB use on gastric [odds ratio (OR) =0.834, P<0.001], colorectal (OR =0.900, P=0.006), lung (OR =0.928, P=0.02), breast (OR =0.942, P=0.03), and endometrial cancer (OR =0.900, P=0.006). These causal associations remained consistent in validation and sensitivity analyses. Mediation analyses indicated the causal, protective effects were partially mediated by vascular endothelial growth factor A (VEGF-A), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).

This MR study provides robust genetic evidence supporting a causal protective role of ACEI/ARB use in reducing the risk of gastric, colorectal, lung, breast, and endometrial cancers, which is partially mediated by VEGF-A, total cholesterol, triglycerides, LDL-C, and HDL-C.

The global incidence and mortality rates of pancreatic cancer have been on the rise in recent decades. At the same time, pancreatic cancer occupies a leading position among malignant neoplasms, which are often first detected at advanced stages, which significantly worsens the prognosis for patients. In this regard, it is important to create automated systems capable of accurately segmenting and diagnosing pancreatic tumors at an early stage. A diagnostic model based on U-Net is proposed and evaluated, aimed at improving the accuracy of automatic segmentation of medical images for segmentation of the pancreas and identification of malignant changes in computed tomography (CT) images.

The diagnostic model of the algorithm was based on the U-Net architecture, and image texture indices were used as control features. The neural network algorithm was trained using CT data from 310 patients with pancreatic neoplasms. Segmentation datasets from 280 pancreatic cancer studies from an open source, Memorial Sloan Kettering Cancer Center, was used to segment medical images and train the algorithm. Manual segmentation of medical images obtained at Regional Clinical Hospital of the Kaliningrad was performed using specialized three-dimensional (3D) Slicer software: CT images of 30 patients with pancreatic neoplasms. Diagnoses in the patient group were confirmed by morphological diagnostics, including examination of biopsy samples and/or surgical material. Four types of indicators were used to quantify segmentation results: Dice similarity coefficient (DSC), accuracy, sensitivity, and specificity.

The diagnostic model achieved an accuracy of 88% in the classification of pancreatic cancer, and the DSC segmentation accuracy factor was 70%, demonstrating sensitivity of 98% and specificity of 98%. The results obtained emphasize the effectiveness of CT image analysis for the diagnosis of pancreatic malignancies using a neural network algorithm that uses textural features of medical images. In the course of the work, a number of limitations were identified: obtaining false positive results during segmentation, a limited number of medical images and clinical data that may affect the representativeness of the developed diagnostic model. Nevertheless, the results show the prospects for integrating artificial intelligence (AI) technologies into clinical practice, which can significantly improve diagnostic efficiency.

The use of neural network algorithms based on the textural features of medical images has significant potential in the field of clinical decision support systems. Despite certain limitations in the course of work, the using textural features for training neural networks will increase the accuracy of diagnosis of pancreatic malignancies and will play an important role in determining patient management strategies and monitoring the effectiveness of prescribed treatment methods. It is necessary to further study additional textural characteristics, utilize 3D models, and include more clinical data to improve the accuracy of the diagnostic model when differentiating malignant tumors from healthy tissues.

The treatment of multiple myeloma (MM) has revolutionized over the last decade with the advent of CD38-targeting monoclonal antibodies such as daratumumab and isatuximab that were integrated into the therapeutic arsenal of patients with newly diagnosed or with relapsed and/or refractory (R/R) MM. Moreover, the advent of B-cell maturation antigen (BCMA)-targeting therapy continue to improve outcomes in patients with R/R disease. Multiple classes of these agents have been developed such as chimeric antigen receptor (CAR)-T cell therapy and antibody-drug conjugates. Another class of antigen-target therapy was the bispecific antibodies (BsAbs). The class, targeting CD20 and CD3, is now commonly used in patients with R/R B-cell lymphoma. It has also been developed for the treatment of patients with MM with other target antigens such BCMA, G protein-coupled receptor family C group 5 member D (GPRC5D), or Fc receptor-homolog 5 (FcRH5). Four BsAbs-teclistamab, elranatamab, linvoseltamab, and talquetamab-are currently approved by the Food and Drug Administration (FDA) for the management of patients with R/R MM. We review in this paper the most studied BiAbs, their mechanism of action, clinical activity, the mechanism of resistance. We discuss the place of BiAbs in the therapeutic arsenal of MM and the emergence of novel strategies such as combining two classes of BiAbs (for example teclistamab and talquetamab) or novel therapies such as trispecific antibodies to overcome resistance and increase the efficacy of BiAbs.

Biliary tract cancer (BTC) represents a heterogeneous group of malignancies, including intrahepatic, perihilar, and distal cholangiocarcinoma, as well as gallbladder cancer. Surgical resection is the only potential curative treatment for early-stage BTC, though outcomes with surgery alone were poor, with high rates of recurrence. In recent years, studies of adjuvant chemotherapy with capecitabine or S-1 have shown improved survival compared to postoperative observation alone. Ongoing clinical trials are incorporating multiple treatment modalities, including radiotherapy, immunotherapy, and targeted therapy. For instance, building on the success of chemo-immunotherapy in the metastatic setting, trials are testing similar designs as adjuvant treatment. The utility of targeted therapies against genetic alterations like FGFR2, IDH1, KRAS, HER2, and SMAD4 in advanced BTC has also spurred exploration of targeted therapy for early-stage BTCs. Various treatment regimens are now also being tested in the neoadjuvant treatment and perioperative setting. The goal of these treatment strategies is to improve surgical outcomes and identify new modalities to reduce recurrence rates of early-stage BTCs. This review provides an overview of the current management landscape of early-stage BTC, presenting the epidemiology and risk factors, reviewing the current management paradigm, and highlighting emerging therapeutic strategies.