Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a poor 5-year overall survival rate (~10%). The revolution of immunotherapy in clinical oncology has not substantially changed ...clinical outcome for patients with PDAC. Despite outstanding efforts, neither immune checkpoint inhibitors (ICIs) alone, nor in combination with chemotherapy or targeted therapies have shown encouraging results. This failure mirrors the lack of knowledge about the real key players of immune system senescence and the complexity of the tumor microenvironment in PDAC. However, some hope can be derived from PARP-inhibitor combinations, vaccines, and CAR-T-cells therapy. In this review, we comprehensively summarize the latest updates about the use of ICIs in PDAC, focusing on clinical evidence and ongoing studies highlighting explanations for the failure of immunotherapy and possible solutions.
Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, ...liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12-1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00-11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29-13.27) and to any cause (HR = 1.51, 95% CI: 1.18-1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73-337.54). These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is an association between the presence of neuroendocrine neoplasms and incremented risk to develop second primary malignancies. This risk is estimated to be 17%. The most common secondary ...neoplasms were found in the Gastrointestinal and Genitourinary tracts.
A 74-year-old Caucasian patient with melaena came to our observation in June 2015. The Esophago-gastro-duodenoscopy exam found a polypoid formation in the duodenal bulb. Histopathological examination showed a well-differentiated neuroendocrine neoplasm (G1).
During the follow up for the neuroendocrine neoplasm, a CT scan was performed in August 2016 describing infiltration of the right renal sinus and the third proximal ureter segment with heterogeneous enhancement of vascular structure. An US-guided biopsy was conclusive for a Diffuse Large B Cell Lymphoma. In October 2016, a colonoscopy showed a neoplastic lesion at 20 cm from the anal orifice. The Histology exam was positive for an adenocarcinoma with a desmoplastic stroma infiltration.
In November 2016, the patient underwent a left hemicolectomy: the pathologic staging described a G2 adenocarcinoma pT3N1b. In May 2018, the Octreotide scan was negative. In the same month, the patient started a treatment based on 6 cycles of Rituximab, Oxaliplatin, and Capecitabine due to the persistence of lymphomatous disease and hepatic metastases. In July 2018, other 3 cycles of the same treatment were scheduled.
In January 2019, due to an increase in liver metastases' size, it was decided to start a new regimen for the colon cancer with FOLFIRI+Cetuximab. The patient is still in treatment with this regimen in April 2019.
The risk of a second primary tumor is increased among patients older than 70. Therefore, it is necessary to follow them using total body CT scan and endoscopic techniques of gastrointestinal and genitourinary tracts, not only for the evaluation of the neuroendocrine tumor but also for the higher risk to develop other neoplastic diseases.
This article describes the case of a patient with 2 simultaneous malignant diseases: Follicular lymphoma and 'castration sensitive prostate cancer. Patients with multiple cancers are not easy to ...manage and it is difficult to find the appropriate approach and resources to use with them. We focused our attention on how to choose the correct strategy to face 2 different neoplasms and control the adverse reactions related to the corresponding treatments.
We present a case of a 71-year-old man who came to us complaining about an abnormal difficulty in urinating associated with an interrupted flow and excessive urination at night. Clinical examination detected multiple enlarged superior and inferior diaphragmatic lymph nodes.
Prostate biopsy revealed an acinar adenocarcinoma (Gleason 4+3, Grade group 3). Clinical staging by bone scan was negative but computed tomography scan (CT) detected multiple enlarged superior and inferior diaphragmatic, and inguinal lymph nodes. This type of lymph node involvement pattern is unusual for an acinar adenocarcinoma prostate cancer therefore we suspected the simultaneous presence of a lymphatic neoplasm. Fluorodeoxyglucose positron emission tomography scan. The exam showed one of the left inguinal lymph nodes had the highest standardized uptake value (13.0) so a biopsy was taken. The sample analysis confirmed the diagnosis of a follicular non-Hodgkin lymphoma of Grade 3a.
We used a multidisciplinary clinical approach based on Rituximab+CHOP administered every 21 days. Simultaneously, the patient underwent androgen deprivation therapy with triptorelin monthly and bicalutamide administered just during the first month of treatment. When we obtained a complete response for the lymphoma, the patient continued the therapy with Rituximab once every 2 months for the next 2 years. Then we added volumetric modulated arc therapy (VMAT) radiotherapy with simultaneous integrated boost (SIB) to androgen deprivation therapy for the duration of 1 month.
After 1 year and 6 months since the conclusion of therapy for prostate cancer and Follicular lymphoma, patient's conditions are good and he is in complete remission for both diseases. Gut toxicity is reduced with a mean number of 2 to 3 discharges daily and an increased body weight.
The presence of diffuse lymphadenopathy and urinary symptoms in the same patients must induce the suspect of 2 contemporary cancer diseases. Parallel treatments of follicular lymphoma and prostate cancer should consider the increased risk of severe adverse effects related to the treatment and their management. We describe our therapeutic strategy to highlight the importance to balance benefits and disadvantages to get the best possible response and maintain a good quality of life in this complex setting.
Advances in drug treatments for mesothelioma Zucali, Paolo Andrea; De Vincenzo, Fabio; Perrino, Matteo ...
Expert opinion on pharmacotherapy,
05/2022, Letnik:
23, Številka:
8
Journal Article
Recenzirano
The paucity of the therapeutic armamentarium currently available for patients with malignant mesothelioma clearly represents a huge unmet need. Over the last years, based on new advances in ...understanding the biology of mesothelioma, new therapeutic approaches have been investigated.
In this manuscript, the literature data regarding the advances in drug treatment for patients with mesothelioma are critically reviewed, focusing particularly on immunotherapy and targeted therapy.
The latest findings on immunotherapy and targeted therapy are changing the therapeutic armamentarium for mesothelioma. However, mesothelioma comprises genomically different subtypes and the phenotypic diversity combined with the rarity of this disease represents a major criticality in developing new effective therapies. Although the first clinical data are encouraging, the treatment's stratification by molecular characteristics for mesothelioma is only at the beginning. Luckily, the rapid improvement of understanding the biology of mesothelioma is producing new opportunities in discovering new therapeutic targets to test in pre-clinical settings and to transfer in the clinical setting. In this evolving scenario, the future perspectives for mesothelioma patients seem really promising.
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