Advances in Cancer Therapy from Research to Clinical Practice—Surgical, Molecular or Systemic Management of Cancer

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 57804

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Department of Surgical Specialities, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
Interests: urology; cancer
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Department of Medical Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
Interests: cancerogenesis; chemotherapy; miR
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Dear Colleagues,

Cancer remains one of the most challenging diseases from epidemiologic, clinical and therapeutic perspectives. The rhythm of changes in various aspects of the oncological disease, the molecular characterization of new subtypes of classical primary-type tumors, new pathways in cancerogenesis and new classes of therapeutical agents makes it very difficult to follow all relevant findings in this research field. Most significantly, what remains are the personal clinical observations and experiences of each of us. We all know very well of the level of trust required in these things, but we remain doctors who treat real-life patients, not those selected for a clinical trial.

We invite you to participate in this Special Issue of Medicina, in order to facilitate the presentation of your research or institutional experience of treating cancer patients. Your clinical experience and research ideas represent a very precious tool for each of every one of us.

Prof. Dr. Nicolae Crisan
Prof. Dr. Călin Căinap
Guest Editors

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Keywords

  • cancer
  • systemic therapy
  • surgery
  • molecular
  • research

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Published Papers (22 papers)

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Editorial

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4 pages, 243 KiB  
Editorial
Advances in Cancer Therapy from Research to Clinical Practice—Surgical, Molecular or Systemic Management of Cancer
by Calin Cainap and Nicolae Crisan
Medicina 2023, 59(7), 1309; https://doi.org/10.3390/medicina59071309 - 14 Jul 2023
Viewed by 1196
Abstract
Cancer represents one of the most important general health problems of our day [...] Full article

Research

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11 pages, 1577 KiB  
Article
BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
by Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin and Ahrong Kim
Medicina 2023, 59(6), 1085; https://doi.org/10.3390/medicina59061085 - 4 Jun 2023
Cited by 3 | Viewed by 2064
Abstract
Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected [...] Read more.
Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected primary NSCLC who were enrolled from January 2015 to December 2017. The authors obtained formalin-fixed paraffin-embedded (FFPE) tissue blocks and performed peptide nucleic acid (PNA)-clamping polymerase chain reaction (PCR) for detecting BRAF V600, real-time PCR for detecting BRAF V600E, and immunohistochemical analyses using the mutation-specific Ventana VE1 monoclonal antibody. For positive cases in any methods mentioned above, direct Sanger sequencing was additionally performed. Results: The PNA-clamping method revealed the BRAF V600 mutation in 5 (1.3%) of the 378 patients. Among these five patients, real-time PCR, direct Sanger sequencing detected BRAF V600E mutations in three (0.8%) patients. Thus, two cases showed differences in their PNA-clamping and the others. Direct Sanger sequencing of PNA-clamping PCR product was performed for two cases showing negative results on direct Sanger sequencing; both contained BRAF mutations other than V600E. All patients harboring BRAF mutations had adenocarcinomas, and all patients with V600E mutation exhibited minor micropapillary components. Conclusions: Despite the low incidence of the BRAF mutation among Korean patients with NSCLC, lung adenocarcinoma patients with micropapillary components should be prioritized in terms of BRAF mutation testing. Immunohistochemical staining using Ventana VE1 antibody may serve as a screening examination for BRAF V600E. Full article
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11 pages, 1529 KiB  
Article
Associations between Body Mass Index and Prostate Cancer: The Impact on Progression-Free Survival
by Dorel Popovici, Cristian Stanisav, Marius Pricop, Radu Dragomir, Sorin Saftescu and Daniel Ciurescu
Medicina 2023, 59(2), 289; https://doi.org/10.3390/medicina59020289 - 2 Feb 2023
Cited by 8 | Viewed by 3065
Abstract
Background and objectives: This study aimed to evaluate the impact of body mass index on PCa outcomes in our institution and also to find if there are statistically significant differences between the variables. Materials and Methods: A retrospective chart review was performed to [...] Read more.
Background and objectives: This study aimed to evaluate the impact of body mass index on PCa outcomes in our institution and also to find if there are statistically significant differences between the variables. Materials and Methods: A retrospective chart review was performed to extract information about all male patients with prostate cancer between 1 February 2015, and 25 October 2022, and with information about age, weight, height, follow-up, and PSA. We identified a group of 728 patients, of which a total of 219 patients resulted after the inclusion and exclusion criteria were applied. The primary endpoint was progression-free survival, which was defined as the length of time that the patient lives with the disease, but no relapses occur, and this group included 105 patients. In this case, 114 patients had a biological, local or metastatic relapse and were included in the progression group. Results: Our study suggests that prostate cancer incidence rises with age (72 ± 7.81 years) in men with a normal BMI, but the diagnostic age tends to drop in those with higher BMIs, i.e., overweight, and obese in the age range of 69.47 ± 6.31 years, respectively, 69.1 ± 7.51 years. A statistically significant difference was observed in the progression group of de novo metastases versus the absent metastases group at diagnostic (p = 0.04). The progression group with metastases present (n = 70) at diagnostic had a shorter time to progression, compared to the absent metastases group (n = 44), 18.04 ± 11.37 months, respectively, 23.95 ± 16.39 months. Also, PSA levels tend to diminish with increasing BMI classification, but no statistically significant difference was observed. Conclusions: The median diagnostic age decreases with increasing BMI category. Overweight and obese patients are more likely to have an advanced or metastatic prostate cancer at diagnosis. The progression group with metastatic disease at diagnostic had a shorter time to progression, compared to the absent metastases group. Regarding prostate serum antigen, the levels tend to become lower in the higher BMI groups, possibly leading to a late diagnosis. Full article
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14 pages, 1351 KiB  
Article
Elevated Preoperative NMPR Predicts an Unfavorable Chance of Survival in Resectable Esophageal Squamous Cell Carcinoma
by Meng-Ying Peng, Zhi-Gang Zuo, Feng-Jun Cao, Yuan-Dong Yu, Xiao-Jun Cai and Guo-Xing Wan
Medicina 2022, 58(12), 1808; https://doi.org/10.3390/medicina58121808 - 8 Dec 2022
Cited by 1 | Viewed by 1556
Abstract
Background and objectives: Combined peripheral neutrophil–platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil–platelet indexes in operable esophageal squamous cell carcinoma (ESCC) [...] Read more.
Background and objectives: Combined peripheral neutrophil–platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil–platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil–meanplateletvolume–platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy. Full article
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12 pages, 1637 KiB  
Article
Characterization of Microscopic Multicellular Foci in Grossly Normal Renal Parenchyma of Von Hippel-Lindau Kidney
by Nayef S. Al-Gharaibeh, Sharon B. Shively and Alexander O. Vortmeyer
Medicina 2022, 58(12), 1725; https://doi.org/10.3390/medicina58121725 - 24 Nov 2022
Cited by 2 | Viewed by 1644
Abstract
Background and Objectives: This study aims to describe the earliest renal lesions in patients with von Hippel-Lindau (VHL) disease, especially the multicellular microscopic pathologic events, to get information into the genesis of renal neoplasms in this condition. Materials and Methods: Multicellular [...] Read more.
Background and Objectives: This study aims to describe the earliest renal lesions in patients with von Hippel-Lindau (VHL) disease, especially the multicellular microscopic pathologic events, to get information into the genesis of renal neoplasms in this condition. Materials and Methods: Multicellular events were identified, and 3dimensional reconstruction was performed in grossly normal kidney parenchyma from VHL disease patients by using H&E-stained slides previously prepared. Results: The lesions were measured and the volume of clusters was calculated. Immunohistochemistry was performed for downstream HIF-target protein carbonic anhydrase 9 (CAIX) as well as CD34 for assessment of angiogenesis. We divided lesions into four types according to lesion height/size. The number of lesions was markedly decreased from lesion 1 (smallest) to lesion 2, then from lesions 2 to 3, and again from lesion 3 to 4. Distribution was highly consistent in the four cases, and the same decrement pattern was seen in all blocks studied. The volumes of clusters were measured and divided into three categories according to their volume. The most frequent pathologic event in VHL kidneys was category 1 (smallest volume), then category 2, and then category 3. Conclusion: We demonstrate that tracking histologic and morphologic changes in 3 dimensions of multicellular microscopic pathologic events enabled us to confirm a protracted sequence of events from smaller to larger cellular amplification events in VHL kidney. Full article
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13 pages, 2073 KiB  
Article
Multiparametric MRI Features of Breast Cancer Molecular Subtypes
by Madalina Szep, Roxana Pintican, Bianca Boca, Andra Perja, Magdalena Duma, Diana Feier, Bogdan Fetica, Dan Eniu, Sorin Marian Dudea and Angelica Chiorean
Medicina 2022, 58(12), 1716; https://doi.org/10.3390/medicina58121716 - 23 Nov 2022
Cited by 10 | Viewed by 2448
Abstract
Background and Objectives: Breast cancer (BC) molecular subtypes have unique incidence, survival and response to therapy. There are five BC subtypes described by immunohistochemistry: luminal A, luminal B HER2 positive and HER2 negative, triple negative (TNBC) and HER2-enriched. Multiparametric breast MRI (magnetic [...] Read more.
Background and Objectives: Breast cancer (BC) molecular subtypes have unique incidence, survival and response to therapy. There are five BC subtypes described by immunohistochemistry: luminal A, luminal B HER2 positive and HER2 negative, triple negative (TNBC) and HER2-enriched. Multiparametric breast MRI (magnetic resonance imaging) provides morphological and functional characteristics of breast tumours and is nowadays recommended in the preoperative setting. Aim: To evaluate the multiparametric MRI features (T2-WI, ADC values and DCE) of breast tumours along with breast density and background parenchymal enhancement (BPE) features among different BC molecular subtypes. Materials and Methods: This was a retrospective study which included 344 patients. All underwent multiparametric breast MRI (T2WI, ADC and DCE sequences) and features were extracted according to the latest BIRADS lexicon. The inter-reader agreement was assessed using the intraclass coefficient (ICC) between the ROI of ADC obtained from the two breast imagers (experienced and moderately experienced). Results: The study population was divided as follows: 89 (26%) with luminal A, 39 (11.5%) luminal B HER2 positive, 168 (48.5%) luminal B HER2 negative, 41 (12%) triple negative (TNBC) and 7 (2%) with HER2 enriched. Luminal A tumours were associated with special histology type, smallest tumour size and persistent kinetic curve (all p-values < 0.05). Luminal B HER2 negative tumours were associated with lowest ADC value (0.77 × 10−3 mm2/s2), which predicts the BC molecular subtype with an accuracy of 0.583. TNBC were associated with asymmetric and moderate/marked BPE, round/oval masses with circumscribed margins and rim enhancement (all p-values < 0.05). HER2 enriched BC were associated with the largest tumour size (mean 37.28 mm, p-value = 0.02). Conclusions: BC molecular subtypes can be associated with T2WI, ADC and DCE MRI features. ADC can help predict the luminal B HER2 negative cases. Full article
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11 pages, 1252 KiB  
Article
Development and Preliminary Characterization of Polyester-Urethane Microparticles Used in Curcumin Drug Delivery System for Oropharyngeal Cancer
by Alexandru Chioreanu, Ion Cristian Mot, Delia Ioana Horhat, Nicolae Constantin Balica, Cristian Andrei Sarau, Raluca Morar, Eugenia Maria Domuta, Catalin Dumitru, Rodica Anamaria Negrean, Bogdan Andrei Bumbu, Madhavi Ravulapalli, Satish Alambaram, Raja Akshay and Marius Pricop
Medicina 2022, 58(11), 1689; https://doi.org/10.3390/medicina58111689 - 21 Nov 2022
Cited by 5 | Viewed by 2633
Abstract
Background and Objectives: Curcumin (Cc) as an active substance is known for its anti-inflammatory, anticoagulant, antioxidant, and anti-carcinogenic effects, together with its role in cholesterol regulation, and its use in different gastrointestinal derangements. On the other hand, curcumin can be used for [...] Read more.
Background and Objectives: Curcumin (Cc) as an active substance is known for its anti-inflammatory, anticoagulant, antioxidant, and anti-carcinogenic effects, together with its role in cholesterol regulation, and its use in different gastrointestinal derangements. On the other hand, curcumin can be used for its properties as an inactive substance, with Cc particles being more often tested in pharmaceutical formulations for drug delivery, with promising safety records and kinetics. The aim of this research was to obtain and characterize polyurethane microparticles that can be used as a carrier with a controlled Cc release. Materials and Methods: The in vitro samples were characterized by the Zetasizer procedure, and UV–Vis spectroscopy, while the in-vivo measurements on human subjects were performed by non-invasive skin assays (trans-epidermal water loss, erythema, and skin hydration). A total of 16 patients with oropharyngeal cancer stages II and III in equal proportions were recruited for participation. Results: The experimental values of sample characteristics using the Zetasizer identified a mean structural size of 215 nm in the polyester-urethane preparate (PU), compared to 271 nm in the curcumin-based PU. Although the size was statistically significantly different, the IPDI and Zeta potential did not differ significantly (22.91 mV vs. 23.74 mV). The average age during the study period was 57.6 years for patients in the PU group, respectively, and 55.1 years in those who received the curcumin preparations. The majority of oropharyngeal cancers were of HPV-related etiology. There were no significant side effects; 75.0% of patients in the PU group reporting no side effects, compared to 87.5% in the Cc group. The 48 h TEWL measurement at the end of the experiment found a statistically significant difference between the PU and the Cc group (2.2 g/h/m2 vs. 2.6 g/h/m2). The erythema assessment showed a starting measurement point for both research groups with a 5.1-unit difference. After 48 h, the difference between PU and PU_Cc was just 1.7 units (p-value = 0.576). The overall difference compared to the reference group with sodium lauryl sulfate (SLS) was statistically significant at a 95% significance level. Conclusions: Our findings indicate the obtaining of almost homogeneous particles with a medium tendency to form agglomerations, with a good capacity of encapsulation (around 60%), a medium release rate, and a non-irritative potential. Therefore, this polyester-urethane with Cc microparticles can be tested in other clinical evaluations. Full article
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15 pages, 1403 KiB  
Article
The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy
by Lorena Alexandra Lisencu, Andrei Roman, Simona Visan, Eduard-Alexandru Bonci, Andrei Pașca, Emilia Grigorescu, Elena Mustea, Andrei Cismaru, Alexandru Irimie, Cosmin Lisencu, Loredana Balacescu, Ovidiu Balacescu and Oana Tudoran
Medicina 2022, 58(10), 1494; https://doi.org/10.3390/medicina58101494 - 20 Oct 2022
Cited by 4 | Viewed by 2324
Abstract
Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting [...] Read more.
Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the association of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. Material and methods: Sixty female patients diagnosed with invasive breast cancer at The Oncology Institute “Ion Chiricuță”, Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database was used as an independent external validation cohort. Results: miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller–Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller–Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Conclusions: Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response. Full article
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14 pages, 2638 KiB  
Article
PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
by Andreas-Evangelos Makrantonakis, Eleni Zografos, Maria Gazouli, Konstantinos Dimitrakakis, Konstantinos G. Toutouzas, Constantinos G. Zografos, Despoina Kalapanida, Andriani Tsiakou, George Samelis and Flora Zagouri
Medicina 2022, 58(10), 1399; https://doi.org/10.3390/medicina58101399 - 6 Oct 2022
Cited by 4 | Viewed by 2118
Abstract
Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A [...] Read more.
Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan–Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan–Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival. Full article
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13 pages, 1489 KiB  
Article
Hepatic Arterial Infusion Chemotherapy with Oxaliplatin Plus Raltitrexed as an Alternative Option in Advanced Hepatocellular Carcinoma Patients with Failure of, or Unsuitability for, Transarterial Chemoembolization
by Yanfang Wu, Susu Zheng, Zhenzhen Zhang, Guobin Chen, Xiaochun Chen, Tanghui Zheng, Xinkun Guo, Hong Chen, Meixia Wang, Xiaoying Xie and Boheng Zhang
Medicina 2022, 58(10), 1343; https://doi.org/10.3390/medicina58101343 - 24 Sep 2022
Cited by 3 | Viewed by 2539
Abstract
Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. [...] Read more.
Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. Materials and Methods: From July 2020 to November 2021, a total of 35 HCC patients were enrolled and received HAIC with oxaliplatin plus raltitrexed. The overall survival (OS) and time to progression (TTP) were primary and secondary endpoints, respectively. The tumor response was assessed by the modified response evaluation criteria in solid tumors (mRECIST), and the adverse events were investigated using the common terminology criteria for adverse events version 5.0 (CTCAE 5.0). Results: The median OS and TTP were 10 months (95% confidence interval (CI): 5.5–14.6) and 3.5 months (95% CI: 2.3–4.7), respectively. By means of multivariate analysis, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was found to be an independent prognostic factor for better survival. No patients experienced toxicity-related death. Thrombocytopenia, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) elevation were the most common toxicities. No grade 3 or higher adverse events related to HAICROX were observed. Conclusion: HAICROX showed valuable efficacy and tolerable toxicity in advanced HCC patients who progressed on TACE or were ineligible for TACE. HAICROX is a promising treatment for advanced-stage HCC patients with TACE failure or ineligibility. Full article
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11 pages, 6869 KiB  
Article
Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice
by Danilo D. Obradović, Nataša M. Milić, Nenad Miladinović, Lana McClements and Dejan M. Oprić
Medicina 2022, 58(10), 1330; https://doi.org/10.3390/medicina58101330 - 22 Sep 2022
Cited by 4 | Viewed by 2206
Abstract
Background and Objectives: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously [...] Read more.
Background and Objectives: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously been shown in studies with breast and ovarian cancer. The role of FKBPL in angiogenesis, growth, and carcinogenesis of endometrioid endometrial carcinoma (EEC) is still largely unknown. The aim of this study was to examine the expression of FKBPL in EEC and benign endometrial hyperplasia (BEH) and its correlation with the expression of vascular endothelial factor-A (VEGF-A) and estrogen receptor alpha (ERα). Materials and Methods: Specimens from 89 patients with EEC and 40 patients with BEH, as well as histological, clinical, and demographic data, were obtained from the Clinical Hospital Centre Zemun, Belgrade, Serbia over a 10-year period (2010–2020). Immunohistochemical staining of the tissue was performed for FKBPL, VEGF-A, and ERα. Slides were analyzed blind by two pathologists, who measured the intensity of FKBPL and VEGF-A expression and used the Allred score to determine the level of ERα expression. Results: Immunohistochemical analysis showed moderate to high intensity of FKBPL expression in 97.5% (n = 39) of samples of BEH, and low or no expression in 93.3% (n = 83) of cases of EEC. FKBPL staining showed a high positive predictive value (98.8%) and a high negative predictive value for malignant diagnosis (86.7%). The difference in FKBPL expression between EEC and BEH was statistically significant (p < 0.001), showing a decrease in intensity and loss of expression in malignant tissues of the endometrium. FKBPL expression was positively correlated with ERα expression (intensity, percentage and high Allred score values) and negatively correlated with the expression of VEGF-A (p < 0.05 for all). Conclusions: FKBPL protein expression demonstrated a significant decrease in FKBPL in EEC in comparison to BEH tissue, with a high predictive value for malignancy. FKBPL might be emerging as a significant protein with antiangiogenic and antineoplastic effects, showing great promise for the diagnostic and therapeutic applications of its therapeutic derivatives in gynecological oncology. Full article
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8 pages, 1001 KiB  
Article
Absolute and Functional Iron Deficiency in Colon Cancer: A Cohort Study
by Vlad Făgărășan, David Andraș, Giorgiana Amarinei, Radu Ioan Seicean, Vasile Virgil Bințințan, George Calin Dindelegan and Calin Ioan Căinap
Medicina 2022, 58(9), 1202; https://doi.org/10.3390/medicina58091202 - 1 Sep 2022
Cited by 4 | Viewed by 2489
Abstract
Background and Objectives: Iron is an essential micronutrient for many biological functions and has been found to be intimately linked to cancer biology. Although the effects of increased dietary iron consumption in the development of CRC have been previously investigated in several [...] Read more.
Background and Objectives: Iron is an essential micronutrient for many biological functions and has been found to be intimately linked to cancer biology. Although the effects of increased dietary iron consumption in the development of CRC have been previously investigated in several cohort studies, the available evidence on the involvement of iron deficiency in this process is relatively scarce. Previously published papers did not analyze specific outcomes, such as the presence of biologically aggressive histopathological characteristics, that are associated with the subtypes of iron deficiency. The purpose of this study was to investigate the connection between the development of colorectal cancer and the presence of functional iron deficiency (FID), which is defined as insufficient biological availability of iron in the presence of adequate storage reserves, or absolute iron deficiency (AID), which is defined as severely depleted iron storage levels. Materials and Methods: Our paper represents a single center registry-based cohort study. Iron levels were routinely evaluated upon diagnosis of CRC and the collected data were coupled with patient- and tumor-specific data (2018–2022). Spearman’s correlation coefficient and the chi-squared test were used to analyze the association. Results: Out of 129 patients, 75 (58.13%) were anemic. AID was identified in 26.35% of cases and FID was encountered in 51.16% of cases. A statistically significant association between FID and lymphatic invasion was encountered. An analysis of the correlation demonstrated a significant association between anemia and right-sided tumor location. Conclusions: Functional iron deficiency seems to be independently associated with lymphatic invasion. Although a statistically significant correlation with the T or N stage was not demonstrated, the analysis suggested a potential positive relationship between the presence of FID and more aggressive tumor characteristics. Full article
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12 pages, 825 KiB  
Article
Recurrence Outcome in Hepatocellular Carcinoma within Milan Criteria Undergoing Microwave Ablation with or without Transarterial Chemoembolization
by Guobin Chen, Hong Chen, Xing Huang, Sisi Cheng, Susu Zheng, Yanfang Wu, Tanghui Zheng, Xiaochun Chen, Xinkun Guo, Zhenzhen Zhang, Xiaoying Xie and Boheng Zhang
Medicina 2022, 58(8), 1016; https://doi.org/10.3390/medicina58081016 - 29 Jul 2022
Cited by 1 | Viewed by 2313
Abstract
Background and Objectives: The recurrence outcome in patients who underwent microwave ablation (MWA) with or without transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) within Milan criteria remains unclear. The aim of this retrospective study was to identify the predictive factors of recurrence [...] Read more.
Background and Objectives: The recurrence outcome in patients who underwent microwave ablation (MWA) with or without transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) within Milan criteria remains unclear. The aim of this retrospective study was to identify the predictive factors of recurrence in these patients. Materials and Methods: From May 2018 to April 2021, 66 patients with HCC within Milan criteria were enrolled. Local tumor progression (LTP) and recurrence-free survival (RFS) were evaluated. Univariate and multivariate analyses were used to evaluate the risk factors of recurrence. The propensity score analysis was conducted to reduce potential confounding bias. Results: During the median follow-up of 25.07 months (95% confidence interval [CI], 21.85, 28.28), the median time to LTP and RFS were 20.10 (95%CI, 14.67, 25.53) and 13.03 (95%CI, 6.36, 19.70) months. No group difference (MWA vs. MWA + TACE) was found in 1-year cumulative LTP (p = 0.575) and RFS (p = 0.515), but meaningful significant differences were found in two-year recurrence (LTP, p = 0.007 and RFS, p = 0.037). Univariate and multivariate analyses revealed that treatment received before ablation was an independent risk factor of LTP (hazard ratio [HR] 4.37, 95%CI, 1.44, 13.32) and RFS (HR 3.41, 95%CI, 1.49, 7.81). Conclusions: The LTP and RFS in the MWA group were similar to that in the MWA combined with TACE. For HCC within Milan criteria, both groups preferentially selected MWA. More endeavor and rigorous surveillance should be taken to relapse prevention, in patients who have received previous treatment. Full article
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10 pages, 2447 KiB  
Article
Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma—A Histopathological Study
by Miguel A. Ortega, Oscar Fraile-Martinez, Cielo García-Montero, Sandra Borja-Vergel, Diego Torres-Carranza, Leonel Pekarek, Coral Bravo Arribas, Juan A. De León-Luis, Cristina Sánchez-Rojo, Miguel Angel Alvarez-Mon, Natalio García-Honduvilla, Julia Buján, Santiago Coca, Melchor Alvarez-Mon, Miguel A. Saez and Luis G. Guijarro
Medicina 2022, 58(6), 722; https://doi.org/10.3390/medicina58060722 - 28 May 2022
Cited by 2 | Viewed by 2456
Abstract
Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer [...] Read more.
Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients. Full article
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Review

Jump to: Editorial, Research, Other

20 pages, 1008 KiB  
Review
Ovarian Cancer—Insights into Platinum Resistance and Overcoming It
by Andrei Havasi, Simona Sorana Cainap, Ana Teodora Havasi and Calin Cainap
Medicina 2023, 59(3), 544; https://doi.org/10.3390/medicina59030544 - 10 Mar 2023
Cited by 22 | Viewed by 6825
Abstract
Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor [...] Read more.
Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells’ resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients’ poor prognosis, discussing current strategies, novel combinations, and therapeutic agents. Full article
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17 pages, 1147 KiB  
Review
What Is Different in Acute Hematologic Malignancy-Associated ARDS? An Overview of the Literature
by Mihail Cotorogea-Simion, Bogdan Pavel, Sebastian Isac, Teodora Telecan, Irina-Mihaela Matache, Anca Bobirca, Florin-Teodor Bobirca, Razvan Rababoc and Gabriela Droc
Medicina 2022, 58(9), 1215; https://doi.org/10.3390/medicina58091215 - 3 Sep 2022
Cited by 5 | Viewed by 4583
Abstract
Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The [...] Read more.
Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy. Full article
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17 pages, 657 KiB  
Review
Association of Parathyroid and Differentiated Thyroid Carcinomas: A Narrative Up-To-Date Review of the Literature
by Razvan Simescu, Miana Pop, Andra Piciu, Valentin Muntean and Doina Piciu
Medicina 2022, 58(9), 1184; https://doi.org/10.3390/medicina58091184 - 30 Aug 2022
Cited by 2 | Viewed by 2315
Abstract
Aim: Parathyroid carcinoma (PC) is a rare endocrine malignancy that represents 0.005% of all malignant tumors. Associated PC and differentiated thyroid carcinoma (DTC) is an exceptionally rare condition, and the preoperative diagnostics and proper treatment are challenging. Almost all PCs and the majority [...] Read more.
Aim: Parathyroid carcinoma (PC) is a rare endocrine malignancy that represents 0.005% of all malignant tumors. Associated PC and differentiated thyroid carcinoma (DTC) is an exceptionally rare condition, and the preoperative diagnostics and proper treatment are challenging. Almost all PCs and the majority of DTCs are diagnosed postoperatively, making correct surgical treatment questionable. Specific guidelines for parathyroid and thyroid carcinomas association treatment are lacking. The purposes of our study were to identify the association between parathyroid and thyroid carcinomas, to analyze the available published data, and to evaluate the possible relationship between preoperative diagnostic and surgical decision-making, and outcome-related issues. Material and methods: We performed a literature review of several databases from the earliest records to March 2022, using controlled vocabulary and keywords to search for records on the topic of PC and WDTC pathological association. The reference lists from the initially identified articles were analyzed to obtain more references. Results: We identified 25 cases of PC and DTC association, 14 more than the latest review from 2021. The mean age of patients was 55, with a female to male ratio of about 3:1. Exposure to external radiation was identified in only one patient, although it is considered a risk factor the development of both PC and DTC. The preoperative suspicion of PC was stated by the authors in only 25% of cases, but suspicion based on clinical, laboratory, ultrasound (US), and fine needle aspiration (FNA) criteria could have been justified in more than 50% of them. With neck ultrasound, 40% of patients presented suspicious features both for PC and thyroid carcinoma. Intra-operatory descriptions of the lesions revealed the highest suspicion (83.3%) of PC, but en bloc resection was recommended and probably performed in only about 50% of the cases. Histopathological examinations of the thyroid revealed different forms of papillary thyroid carcinoma (PTC) in most cases. Postoperative normocalcemia was achieved in 72% of patients, but follow-up data was missing in about 25% of cases. Conclusion: Associated PC and DTC is an exceptionally rare condition, and the preoperative diagnostic and treatment of the patients is a challenge. However, in most cases pre- and intraoperative suspicious features are present for identification by a highly specialized multidisciplinary endocrine team, who can thus perform the optimal treatment to achieve curability. Full article
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Other

8 pages, 2971 KiB  
Case Report
A Rare Co-Occurrence of Maffucci Syndrome and Astrocytoma with IDH1 R132H Mutation: A Case Report
by Nurali Ashirov, Iroda Mammadinova, Aidos Moldabekov, Berik Zhetpisbaev, Daniyar Teltayev, Nurzhan Ryskeldiyev and Serik Akshulakov
Medicina 2023, 59(6), 1056; https://doi.org/10.3390/medicina59061056 - 31 May 2023
Cited by 2 | Viewed by 2094
Abstract
Background: Maffucci syndrome is a rare genetic disorder associated with the development of multiple enchondromas and soft tissue cavernous hemangiomas, as well as an increased risk of malignant tumors. Case Description: Here we report a case of Maffucci syndrome in a [...] Read more.
Background: Maffucci syndrome is a rare genetic disorder associated with the development of multiple enchondromas and soft tissue cavernous hemangiomas, as well as an increased risk of malignant tumors. Case Description: Here we report a case of Maffucci syndrome in a patient who presented with a giant left frontal lobe tumor. Molecular genetic analysis of the tumor revealed an isocitrate dehydrogenase (IDH) mutation p.R132H (c.395C>A) mutation in the IDH1 gene and a heterozygous duplication of the CDKN2A genes. Conclusions: The presence of an IDH1 mutation is notable because this mutation is frequently seen in glial tumors and other neoplasms, and its co-occurrence with Maffucci syndrome may represent a novel risk factor for the development of gliomas. This case underscores the importance of genetic testing in patients with Maffucci syndrome who present with central nervous system tumors, as well as the need for further research to understand the relationship between IDH1 mutations and the development of gliomas in this population. Full article
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7 pages, 2152 KiB  
Case Report
Melanoma: BRAFi Rechallenge
by Christoforos S. Kosmidis, Konstantina Papadopoulou, Chrysi Maria Mystakidou, Evanthia Papadopoulou, Stylianos Mantalovas, Nikolaos Varsamis, Charilaos Koulouris, Vasiliki Theodorou, Konstantinos Papadopoulos, Christina Sevva, Petrina Miltiadous, Savvas Petanidis, Eleni Georgakoudi, Eleni Papadopoulou and Sofia Baka
Medicina 2023, 59(5), 975; https://doi.org/10.3390/medicina59050975 - 18 May 2023
Cited by 1 | Viewed by 1822
Abstract
Melanoma is the most aggressive type of skin cancer. Half of melanoma cases are characterized by the mutation BRAF V600. The case presented concerns a 41-year-old patient with locally advanced melanoma, being positive in mutation BRAF V600. The patient underwent surgery and received [...] Read more.
Melanoma is the most aggressive type of skin cancer. Half of melanoma cases are characterized by the mutation BRAF V600. The case presented concerns a 41-year-old patient with locally advanced melanoma, being positive in mutation BRAF V600. The patient underwent surgery and received additional targeted therapy as part of a clinical study. In subsequent disease progression, immunotherapy was used. When the disease progressed again while the patient was in a good performance status, targeted therapy was administered again, and a good response was noted, making the patient reach a statistically significant overall survival, exceeding four years. Targeted therapy has proven to be an important tool in the treatment of melanoma. The use of BRAFi targeted therapy does not exclude the option of readministration at subsequent disease progression (BRAFi rechallenge). Preclinical models suggest that the resistance mechanism of cancer cells to BRAFi therapy bends, as these cell clones lose their evolutionary advantage after stopping BRAFi. Cell clones sensitive to BRAFi may then outcompete, making the treatment effective again. Therapeutical dilemmas in the management of patients with locally advanced melanoma that progresses to metastatic cancer are discussed. Full article
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11 pages, 335 KiB  
Systematic Review
A Systematic Review Investigating the Difference between 1 Cycle versus 2 Cycles of Adjuvant Chemotherapy in Stage I Testicular Germ Cell Cancers
by Emanuiela Florentina Rohozneanu, Ciprian Deac and Călin Ioan Căinap
Medicina 2023, 59(5), 916; https://doi.org/10.3390/medicina59050916 - 10 May 2023
Cited by 1 | Viewed by 2454
Abstract
Standard care for stage I testicular germ cell cancers (seminomatous—STC or non-seminomatous—NSTC) is orchiectomy followed by active surveillance, 1 or 2 cycles of adjuvant chemotherapy, surgery or radiotherapy. The decision on the adjuvant therapeutic approach is guided by the associated risk factors of [...] Read more.
Standard care for stage I testicular germ cell cancers (seminomatous—STC or non-seminomatous—NSTC) is orchiectomy followed by active surveillance, 1 or 2 cycles of adjuvant chemotherapy, surgery or radiotherapy. The decision on the adjuvant therapeutic approach is guided by the associated risk factors of the patient and the potential related toxicity of the treatment. Currently, there is no consensus regarding the optimal number of adjuvant chemotherapy cycles. Although in terms of overall survival, there is no proven inconsistency regarding the number of cycles of adjuvant chemotherapy, and the rate of relapse may vary. Full article
13 pages, 30989 KiB  
Case Report
Adrenal Gland Primary Neuroblastoma in an Adult Patient: A Case Report and Literature Review
by Teodora Telecan, Iulia Andras, Maria Raluca Bungardean, Diana Muntean, Claudia Militaru, Ion Perciuleac, Andrei Maga and Nicolae Crisan
Medicina 2023, 59(1), 33; https://doi.org/10.3390/medicina59010033 - 23 Dec 2022
Cited by 3 | Viewed by 2217
Abstract
Neuroblastoma (NB) is an undifferentiated malignant tumor of the sympathetic ganglia, occurring in children under 5 years of age. However, it is a rare histology in adult patients, occurring once per every 10 million patients per year. We present the case of a [...] Read more.
Neuroblastoma (NB) is an undifferentiated malignant tumor of the sympathetic ganglia, occurring in children under 5 years of age. However, it is a rare histology in adult patients, occurring once per every 10 million patients per year. We present the case of a 68-year-old male patient presented to our department for right lumbar pain, asthenia, loss of weight and altered general status. The contrast-enhanced abdominal computer tomography revealed bilateral adrenal tumoral masses of 149 mm and 82 mm on the right and left sides, respectively, with invasion of the surrounding organs. The patient underwent right 3D laparoscopic adrenalectomy and right radical nephrectomy. The pathological result concluded that the excised tumor was a neuroblastoma of the adrenal gland. The patient followed adjuvant oncological treatment; however, due to disease progression, he passed away 22 months after the surgery. To our knowledge, less than 100 cases of adrenal NB in adult patients have been published, the eldest case being diagnosed at 75 years of age; meanwhile, the largest reported tumor measured 200 mm, and was excised through open surgery. Minimally invasive techniques have been limited so far to smaller, organ-confined diseases, thus making the present case the largest adrenal NB removed entirely laparoscopically. Neuroblastoma in the adult population is a rare finding, with worse prognosis compared to pediatric patients. The available literature does not provide enough data for standardized, multimodal management, as the patients are treated following adapted pediatric protocols, thus reinforcing the need for international, multidisciplinary boards for rare tumors. Full article
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13 pages, 2259 KiB  
Case Report
Insights on Lipomatosis after Platinum-Based Chemotherapy Use in Pediatric Oncology: A Case Report
by Estera Boeriu, Alexandra Georgiana Boc, Alexandra Borda, Rodica Anamaria Negrean, Bogdan Feciche, Amalia Iulia Boeriu, Florin George Horhat, Ion Cristian Mot, Ioana Delia Horhat, Madhavi Ravulapalli, Omar Sabuni, Abduljabar Adi, Adnan Anjary and Smaranda Teodora Arghirescu
Medicina 2022, 58(12), 1715; https://doi.org/10.3390/medicina58121715 - 23 Nov 2022
Cited by 5 | Viewed by 2475
Abstract
Agents of platinum-based chemotherapy, such as cisplatin or carboplatin, are used in the treatment of a wide range of malignancies that affect children, such as brain tumors, osteosarcoma, neuroblastoma, hepatoblastoma, and germ cell tumors (GCTs). The Cyclophosphamide Equivalent Dose (CED) calculator for reproductive [...] Read more.
Agents of platinum-based chemotherapy, such as cisplatin or carboplatin, are used in the treatment of a wide range of malignancies that affect children, such as brain tumors, osteosarcoma, neuroblastoma, hepatoblastoma, and germ cell tumors (GCTs). The Cyclophosphamide Equivalent Dose (CED) calculator for reproductive risk does not take platinum-based chemotherapy into account, despite the fact that it accounts for the majority of chemotherapy medications that are typically administered for pediatric GCTs. As a result, exposure to platinum-based drugs throughout infancy can have predictable long-term effects such as infertility, as well as other rare encounters such as lipoma formation and lipomatosis. Lipomas are the most prevalent benign soft tissue tumor subtype. They may be either solitary entities or engaged in multiple lipomatosis, which may have a familial origin or be an acquired disorder. Chemotherapy is a possible cause of lipomatosis. Chemotherapy based on cisplatin has been linked to a variety of long-term consequences, including kidney damage, neurotoxicity, and pulmonary toxicity, and may even create secondary cancers. However, lipoma development is known to occur in fewer than 1 in 100 individuals, and only a few examples of multiple cutaneous lipomatosis triggered by this therapy have been documented. Here we present a very rare case of lipomatosis in a pediatric patient with GCT under cisplatin therapy, which might be the third report of this kind affecting children. Full article
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