Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real-world study.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.

Impact of endobiliary radiofrequency ablation on survival of patients with unresectable cholangiocarcinoma: a narrative review.

Cholangiocarcinoma (CCA) is a rare cancer originating from the biliary epithelium and accounts for about 3% of all gastrointestinal malignancies. Unfortunately, the majority of patients are not eligible for surgical resection at the time of diagnosis, because of the locally advanced stage or metastatic disease. The overall survival time of unresectable CCA is generally less than 1 year, despite current chemotherapy regimens. Biliary drainage is often required as a palliative treatment for patients with unresectable CCA. Recurrent jaundice and cholangitis tend to occur because of reobstruction of the biliary stents. This not only jeopardizes the efficacy of chemotherapy, but also causes significant morbidity and mortality. Effective control of tumor growth is crucial for prolonging stent patency and consequently patient survival. Recently, endobiliary radiofrequency ablation (ERFA) has been experimented as a treatment modality to reduce tumor mass, and delay tumor growth, extending stent patency. Ablation is accomplished by means of high-frequency alternating current which is released from the active electrode of an endobiliary probe placed in a biliary stricture. It has been shown that tumor necrosis releases intracellular particles which are highly immunogenic and activate antigen-presenting cells, enhancing local immunity directed against the tumor. This immunogenic response could potentially enhance tumor suppression and be responsible for improved survival of patients with unresectable CCA who undergo ERFA. Several studies have demonstrated that ERFA is associated with an increased median survival of approximately 6 months in patients with unresectable CCA. Furthermore, recent data support the hypothesis that ERFA could ameliorate the efficacy of chemotherapy administered to patients with unresectable CCA, without increasing the risk of complications. This narrative review discusses the results of the studies published in recent years and focuses on the impact that ERFA could have on overall survival of patients with unresectable cholangiocarcinoma.

Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives.

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as "oligometastatic disease" (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.

Cone beam computed tomography (CBCT) guidance is helpful in reducing dose exposure to pediatric patients undergoing radiofrequency ablation of osteoid osteoma.

PURPOSE: To assess efficacy and safety of cone beam computed tomography (CBCT) in the radiofrequency ablation (RFA) of osteoid osteoma (OO) in children and adolescents, and to compare technical success, clinical success, radiation dose and procedure duration time of CBCT guidance to conventional computed tomography (CT) guidance. MATERIALS AND METHODS: Between 2015 and 2019, 53 consecutive percutaneous RFA were performed on pediatric patients with CBCT or conventional CT guidance, respectively, in 24 and 29 children and adolescents with 24-month follow-up. Dose area product (DAP) and dose length product (DLP) were recorded, respectively, for CBCT and conventional CT and converted to effective doses (ED). RESULTS: CBCT and conventional CT groups were similar in terms of patient age and weight, tumor size and tumor location. Technical success was achieved in all cases. Primary clinical success was 91.67% (22/24) for the CBCT group and 89.66% (26/29) for the conventional CT group. Mean DAP was 64.75Gycm2 (range 6.0-266.7). Mean DLP was 972.62mGycm (range 337-2344). ED was significantly lower in the CBCT group compared to the conventional CT group (0.34 mSv vs. 5.53 mSv, p = 0.0119). Procedure duration time was not significantly longer in the CBCT group (102.25 min vs. 92.34 min, p = 0.065). No major complication was registered. Minor complications were observed in 4 patients (2 in CBCT; 2 in conventional CT). CONCLUSIONS: Compared to conventional CT guidance, CBCT guidance for percutaneous OO ablation shows similar technical and clinical success rates, with reduced radiation dose and equivalent procedure duration time. This technique helps sparing dose exposure to pediatric patients.

The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer.

Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor. PIK3CA is the main significant mutated gene after PTEN alterations. Overall, over 90% of endometrioid tumors have activating PI3K molecular alterations that suggests its critical role in the EC pathogenesis. Thus, the dysregulation of PI3K pathway represents an attractive target in EC treatment. Herein, we report a radiological and clinically meaningful response to a selective PIK3 inhibitor in a patient with extensively pre-treated advanced endometrioid EC harboring a somatic activating PIK3CA hotspot mutation. These evidences provide the rational for translational strategies of the PI3K inhibition and could support the clinical usefulness of PIK3CA genotyping in advanced EC. To our knowledge, this is the first clinical case of PIK3CA-mutated EC successfully treated with alpelisib.

Recovery of a broken PICC migrated in cardiac chambersan endovascular approach.

Complications related to the placement of a peripherally inserted central catheter are a common phenomenon and they can lead to acute complications which must be treated in an emergency regime. The aim of this study was to describe cases in their most practical and technical aspect, especially in complicated conditions. This was a descriptive case report of a 64 years old female patient who presented with a fractured peripherally inserted central catheter, migrated into the right heart chambers and inferior vena cava, and how the team arranged for its recovery by endovascular technique, in a frail patient who could not undergo to open surgery.The procedure was completed without any complications. The use of the endovascular technique allows a recovery of the foreign body in a short time, essential for a life-saving procedure; the interventional radiological approach allows less invasiveness in fragile patients and shorter hospitalization times.

Application of a personal Santini technique in the resolution of a complex celiac trunk aneurysm - endovascular treatment.

Aim Vascular pathologies have been already explored for the most of their aspects. It is a group of pathologies with unclear ethology and with an evolution in time not easy to forecast. Treatment guidelines are conflicting. The aim of this study was to describe cases in their most practical and technical aspect, especially in complicated conditions. Methods This was a descriptive case report of a patient with a hepatic artery aneurysm complicated by a dissection leading up to the splenic artery, and how the team had invented a planned treatment for the patient using a minimally invasive approach. The experience was born with the intention of showing how the endovascular approach is at least as safe as the traditional one despite the complexity of our case. Results The procedure was completed without any complications. After a stay in long day surgery, the patient returned home. Conclusion Using a minimally invasive technique allows to reduce the patient's post-operative suffering and the economic burden on the health system.

Acute epiploic appendagitis: ultrasound and computed tomography findings of a rare case of acute abdominal pain and the role of other imaging techniques.

PURPOSE: Acute epiploic appendagitis (EA) is a relatively rare, benign and local inflammatory disease involving the epiploic appendices. Unlike its mimics, EA is generally a self-limiting inflammatory disease and can be treated conservatively. CASE PRESENTATION: A 33-year-old Caucasian man presented to our emergency department with a sever and sharp left iliac fossa pain. He underwent abdominal X-ray, ultrasound (US) and computed tomography (CT) evaluations. CONCLUSION: We illustrate US and CT findings to increase the radiologists' awareness of this condition and to avoid diagnostic delay and unnecessary use of antibiotics, hospitalization and surgery.

Randomised Clinical Trial: Calorie Restriction Regimen with Tomato Juice Supplementation Ameliorates Oxidative Stress and Preserves a Proper Immune Surveillance Modulating Mitochondrial Bioenergetics of T-Lymphocytes in Obese Children Affected by Non-Alcoholic Fatty Liver Disease (NAFLD).

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

A rare case of hydrometrocolpos from persistent urogenital sinus in patient affected by adrenogenital syndrome.

Persistent urogenital sinus (PUGS) is a congenital pathological condition characterized by an abnormal communication between the urethra and vagina, which has an estimated incidence of 0.6/10,000 female births. It could be the only known malformation or part of a syndrome. PUGS is commonly shown by a pelvic mass, related to a distended bladder, hydrometrocolpos which is due to an obstruction leading to the dilation of the vagina and uterus (i.e., imperforate hymen, transverse vaginal septum or atresia, and PUGS) or both. We present a case of female patient with classical congenital adrenal hyperplasia, diagnosed on the 7th day of life, with ambiguous genitalia, untreated surgically only with hormone therapy by parental decision. The patient, at the age of 5 years and 5 months, came to our observation for a pelvic ultrasound, which revealed retrovesical neoformation with anechoic content and regular walls. We performed the ultrasound examination that showed the dilation of the cervix and the vaginal canal with anechoic finely corpuscolated content in the declining portion, compatible with hydrometrocolpos from probable persistence of the urogenital sinus. The voiding cystourethrography (VCUG) confirmed the ultrasound diagnosis, with evidence of urogenital sinus. In conclusion, ultrasound is the first diagnostic tool, but need to be completed by other technical procedures, which VCUG or magnetic resonance imaging to observe the site of fusion of the urinary and genital tract.