Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Sunday, March 6, 2022

Prognostic Value of the Regional Lymph Node Station in Pancreatoduodenectomy for Ampullary Carcinoma

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In Vivo. 2022 Mar-Apr;36(2):973-978. doi: 10.21873/invivo.12789.

ABSTRACT

BACKGROUND/AIM: The optimal extent of lymph node dissection for ampullary carcinoma is controversial. The aim of this study was to investigate the efficacy of lymph node dissection for ampullary carcinoma.

PATIENTS AND METHODS: Between 2000 and 2020, a total of 75 patients undergoing radical resection for ampullary carcinoma were included. The efficacy index (EI) was calculated by multiplication of the frequency of lymph node metastasis (LNM) at the station and the 5-year survival rate of patients with metastasis at the station.

RESULTS: Out of 75 patients, 14 had LNM. The EI for the peri-pancreatic head (station 13 and 17) and superior mesenteric artery (station 14) lymph node were 4.4 and 3.5, respectively. Whereas the peri-gastric (station 5 and 6), common hepatic artery (station 8), and liver hilum (station 12) lymph node stations had zero EI. Alt hough the number of patients with the station 16 dissected was small (9%), the para-aortic (station 16) lymph nodes had the highest EI of 14.3 despite being distant lymph nodes.

CONCLUSION: We identified the distribution of LNM and survival benefit of lymph node dissection for ampullary carcinoma. Our results suggest that the optimal extent of lymph node dissection for ampullary carcinoma could be reconsidered.

PMID:35241558 | DOI:10.21873/invivo.12789

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Investigation of the Mechanism of Impaired Skin Barrier Function in Dogs With Malignant Tumors

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In Vivo. 2022 Mar-Apr;36(2):743-752. doi: 10.21873/invivo.12761.

ABSTRACT

BACKGROUND/AIM: No study has investigated skin barrier dysfunction with systemic diseases in veterinary medicine. We investigated the mechanism of disturbed skin barrier function in dogs with internal diseases.

MATERIALS AND METHODS: Healthy controls and dogs with systemic diseases were enrolled in three different disease groups: malignant tumor, hyperadrenocorticism and kidney disease. Transepidermal water loss (TEWL), serum levels of five selective pro-inflammatory cytokines and claudin-1, and complete blood count were measured.

RESULTS: TEWL was significantly increased in the malignant tumor group while serum claudin-1 concentrations were significantly lower compared to controls. Tumor necrosis factor-α was also significantly increased in the cancer group. In addition, the malignant tumor group showed significantly higher monocyte chemotactic prot ein-1 after chemotherapy, but lower interleukin-6 levels, compared to dogs with no chemotherapy.

CONCLUSION: Skin barrier function was decreased in dogs with malignant tumors compared to dogs with other systemic diseases by oxidative stress and a reduction in tight junction proteins.

PMID:35241530 | DOI:10.21873/invivo.12761

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Tremella fuciformis Inhibits Melanogenesis in B16F10 Cells and Promotes Migration of Human Fibroblasts and Keratinocytes

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In Vivo. 2022 Mar-Apr;36(2):713-722. doi: 10.21873/invivo.12757.

ABSTRACT

BACKGROUND/AIM: Natural skin whiteners have been investigated for centuries. The development of preparations that safely achieve whitening of hyper-pigmented skin lesions is a challenge for the cosmetics industry. Furthermore, promoting rapid wound healing and minimizing inflammation in injured skin are key to prevent from abnormal pigmentation in scar tissue. Natural products, including the fungus Tremella fuciformis (TF), are attracting attention as potential sources of lead compounds for these applications.

MATERIALS AND METHODS: We investigated the in vitro effects of TF on melanogenesis in murine B16F10 cells. Melanin and tyrosinase levels were measured after treatment with TF. Wound healing in human keratinocytes (HaCaT) and fibroblasts (Detroit 551) was also determined via cell migration assay prior to TF exposure.

RESULTS: TF significantly dec reased melanin content and tyrosinase expression in a concentration-dependent manner in B16F10 cells. Furthermore, TF promoted wound healing in human HaCaT keratinocytes and Detroit 551 fibroblasts.

CONCLUSION: TF proved effectively on inhibiting melanogenesis and promoting wound healing in vitro, demonstrating its potential as a novel skin-whitening agent. However, further clinical studies of safety and efficacy are required.

PMID:35241526 | DOI:10.21873/invivo.12757

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The Role of Programmed Cell Death Receptor 1 in Lung Cancer

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In Vivo. 2022 Mar-Apr;36(2):1007-1012. doi: 10.21873/invivo.12794.

ABSTRACT

BACKGROUND/AIM: Lung cancer is the most common cancer worldwide. Cancer immunotherapy is the activation of the immune system against cancer. The latest method of immunotherapy involves immune checkpoint inhibitors. Increased levels of programmed death ligand 1 (PD-L1) expression were observed on non-small-cell lung cancer. The association between PD-L1 expression and clinicopathological characteristics in lung cancer is still unclear.

PATIENTS AND METHODS: This is a cross-sectional, observational study that evaluated a sample of 41 lung cancer patients diagnosed between March 2019 and December 2020. PD-L1 tumor expression is described as a percentage.

RESULTS: Patients were diagnosed with non-microcellular lung cancer and aged 37 to 87 years. Most patients were diagnosed with adenocarcinoma. According to the analysis, the average age of patients wit h negative PD-L1 tumors was 65.6 years, and of those with positive PD-L1 tumors was 63.6 years. The average value of the tumor proportion score for males was 26.97%, and for females 25.55%.

CONCLUSION: No correlation was found between PD-L1 tumor expression and the age and sex of patients.

PMID:35241563 | DOI:10.21873/invivo.12794

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Cisplatin Versus Carboplatin and Paclitaxel in Radiochemotherapy for Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

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In Vivo. 2022 Mar-Apr;36(2):821-832. doi: 10.21873/invivo.12769.

ABSTRACT

BACKGROUND/AIM: The implementation of a platinum-containing regimen is recommended for definitive and adjuvant therapy of patients with locally advanced head and neck tumour. We compared the conditions for the use of cisplatin or carboplatin/paclitaxel or for changing between these two regimens on a clinic-specific basis.

PATIENTS AND METHODS: We evaluated 150 patients with advanced head and neck squamous cell carcinoma who received simultaneous radiochemotherapy at our institution between 2012 and 2017. Chemotherapy with weekly doses of cisplatin (40 mg/m2, group 1) or, in cases of impaired renal and/or cardiac function, with weekly doses of carboplatin AUC2 and paclitaxel (45 mg/m2, group 2), was performed as a first-choice therapy. If toxicities occurred in group 1, treatment was switched to the carboplatin/paclitaxel regimen (group 3). Patient- and therapy-related parameters, toxicity and survival data were compared across groups.

RESULTS: We examined 99, 30, and 21 patients in each group who received at least 1 course of chemotherapy. Group 3 patients switched from cisplatin to carboplatin/paclitaxel after a median of 3 courses due to nephrotoxicity (95.2%). The target of at least 5 chemotherapy courses was most frequently achieved by patients in group 1 (69.7%), followed by group 3 (61.9%) and then group 2 (40.0%). Multivariate analysis revealed that patients who switched groups were more likely to be over 60 years old (p=0.021), undergo definitive radiochemotherapy (p=0.049) and develop higher nephrotoxicity (p=0.036) than group 1 patients. Outcomes did not differ between groups.

CONCLUSION: When cisplatin application is contraindicated due to renal- or cardiotoxicity, carboplatin/paclitaxel is an appropriate option.

PMID:35241538 | DOI:10.21873/invivo.12769

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Background Parenchymal Enhancement in Contrast-enhanced Spectral Mammography: A Retrospective Analysis and a Pictorial Review of Clinical Cases

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In Vivo. 2022 Mar-Apr;36(2):853-858. doi: 10.21873/invivo.12773.

ABSTRACT

BACKGROUND/AIM: Despite the popularity of contrast enhanced spectral mammography (CESM), univocal classification of the background parenchymal enhancement (BPE), a bilateral enhancement of the normal breast parenchyma after contrast administration, is lacking. The present study aimed to evaluate the application of BPE Breast Imaging Reporting and Data System Magnetic Resonance (BI-RADS-MR) score for the CESM BPE. Moreover, a pictorial review of four different cases with CESM is provided.

PATIENTS AND METHODS: A single-center, retrospective study from a prospectively maintained database of all women undergoing digital mammography (DM) and CESM in our institution between 2016 and 2019. DM and CESM were classified by two experienced radiologists.

RESULTS: No statistically significant difference between DM breast density and BPE CESM classification was fo und. Agreement between readers ranged from substantial to almost perfect.

CONCLUSION: BIRADS-RM score for the CESM BPE represents a handy option for radiologists with high inter-reader and DM agreement.

PMID:35241542 | DOI:10.21873/invivo.12773

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Recurrent Metastatic Parotid Acinic Cell Carcinoma Responsive to Pembrolizumab

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In Vivo. 2022 Mar-Apr;36(2):1047-1051. doi: 10.21873/invivo.12801.

ABSTRACT

BACKGROUND: No clear chemotherapy regimen for recurrent or metastatic parotid cancer exists. We describe our experience with pembrolizumab to treat recurrent or metastatic parotid cancer.

CASE REPORT: A 73-year-old woman with swelling in the lower part of the right ear for 10 years before surgery was diagnosed with right parotid cancer, underwent total right parotidectomy, and reported recurrence. She requested treatment due to diminished quality of life caused by neurological symptoms. Tissue was collected from the recurrent lesion and its combined positive score was >20; pembrolizumab was started 9 years postoperatively.

RESULTS: To date, the patient has received 14 cycles of pembrolizumab. Evaluation by computed tomography showed a partial response to treatment. The only immune-related adverse event was grade 1 pneumonia in both lungs.

C ONCLUSION: Significant response to pembrolizumab in recurrent or metastatic parotid cancer is rarely reported, making this a remarkable case. We plan to continue pembrolizumab administration.

PMID:35241570 | DOI:10.21873/invivo.12801

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Sequential Loss of Mandibular Permanent Incisors in Noonan Syndrome

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In Vivo. 2022 Mar-Apr;36(2):1021-1029. doi: 10.21873/invivo.12797.

ABSTRACT

BACKGROUND: Noonan syndrome (NS) is a multigenic disorder with a highly variable phenotype. Cardiac disorders and a predisposition to neoplasm often require early medical attention. Central giant central lesions (CGCLs) of the jaws are part of the phenotype.

CASE REPORT: In a patient with genetically confirmed NS and multiple teeth loss presumably caused by CGCL, careful review of the medical history and radiographic findings made it probable that the cause of tooth loss was cervical root resorption (CRR) of the teeth following long-term orthodontic therapy.

CONCLUSION: CRR is a rare dental disease of unknown origin. However, association with prior orthodontic therapy is well documented. In NS, mandibular lesions can occur which, at first glance, might lead the examiner to assume that it is a CGCL, but on closer analysis, obviously are of non-tumoro us origin and should be assessed as coincidental. The report adds relevant information to orthodontic treatment of NS patients.

PMID:35241566 | DOI:10.21873/invivo.12797

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The Geriatric Nutritional Risk Index Predicts Tolerability of Lenvatinib in Patients With Hepatocellular Carcinoma

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In Vivo. 2022 Mar-Apr;36(2):865-873. doi: 10.21873/invivo.12775.

ABSTRACT

BACKGROUND/AIM: We aimed to investigate the association between The Geriatric Nutritional Risk Index (GNRI) and the tolerability of lenvatinib in patients with hepatocellular carcinoma (HCC).

PATIENTS AND METHODS: We retrospectively evaluated 61 HCC patients treated with lenvatinib and compared those with low GNRI (≤98, n=26) to those with high GNRI (>98, n=35).

RESULTS: The discontinuation of lenvatinib due to adverse events was more frequent in the low GNRI group (46.2%) than in the high GNRI group (17.1%) (p=0.014). Multivariate analysis revealed that low GNRI (p=0.014), hypothyroidism (model 1 p=0.021, model 2 p=0.013), and advanced age (p=0.026) were independently associated with the discontinuation of lenvatinib. The progression-free survival in the low GNRI group was significantly shorter than that in the high GNRI group (p=0.047).

C ONCLUSION: The GNRI might be independently associated with the tolerability of lenvatinib in patients with HCC.

PMID:35241544 | DOI:10.21873/invivo.12775

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Predictive Value of Circulating Tumor Cells in Prognosis of Stage III/IV Colorectal Cancer After Oxaliplatin-based First-line Chemotherapy

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In Vivo. 2022 Mar-Apr;36(2):806-813. doi: 10.21873/invivo.12767.

ABSTRACT

BACKGROUND/AIM: Insufficient data exist to support the concept of the circulating tumor cell (CTC) level as a prognostic factor for platinum-based first-line chemotherapy. This study investigated the impact of CTCs on the prognosis of patients with advanced colorectal cancer (CRC) after receiving platinum-based chemotherapy. Analyses were carried out of clinicopathological features and molecular phenotypes to clarify independent risk factors for a high CTC count.

PATIENTS AND METHODS: Patients diagnosed with stage III/IV CRC (n=76) were included in the study. The blood samples of patients were evaluated for CTCs using the CellRich™ platform system. Immunohistochemistry (Ias used to analyze epithelial-mesenchymal transition-associated biomarkers E-cadherin and vimentin. Univariate and logistic regression analyses were then conducted to analyze the risk fac tors for CTC expression. Additionally, the influence of oxaliplatin on disease-free survival after first-line chemotherapy or during chemotherapy was analyzed through a 2-year follow-up.

RESULTS: Patients in the CTC+ group experienced shorter DFS after receiving oxaliplatin first-line chemotherapy than patients in the CTC- group (p<0.01). In addition, univariate analysis revealed that the tumor M-stage, tumor location, RAS mutation, high expression of vimentin, and deletion of E-cadherin expression were correlated with a high CTC count. Multivariate analysis suggested that the presence of RAS gene mutations and high vimentin expression were independent risk factors for high CTC loads (p<0.01).

CONCLUSION: CTC positivity can indicate the efficacy of first-line chemotherapy with oxaliplatin in stage III/IV colorectal cancer. This may be linked to tumor epithelial-mesenchymal transition in patients with CTCs. Moreover, RAS gene mutation and high expression of vimentin were identified as independent risk factors for a high CTC count.

PMID:35241536 | DOI:10.21873/invivo.12767

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Optimization of Culture Conditions for the Generation of Canine CD20-CAR-T Cells for Adoptive Immunotherapy

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In Vivo. 2022 Mar-Apr;36(2):764-772. doi: 10.21873/invivo.12763.

ABSTRACT

BACKGROUND/AIM: Chimeric antigen receptor (CAR) T cell therapy targeting CD20 has the potential to become a promising novel treatment for canine B cell lymphoid malignancy. However, the optimal approach for producing potent CAR-T cells with favorable phenotype for dogs remains unknown. In this study, we assessed several culture conditions and their effects on the phenotypic characteristics of CD20-CAR-T cells.

MATERIALS AND METHODS: Canine CAR-T cells were generated by incubating with several mitogens in the presence or absence of Akt inhibitor. Gene transduction efficiency and phenotypic characteristics were determined by flow cytometry.

RESULTS: Comparison of several kinds of mitogens revealed that stimulation with phytohemagglutinin has high transduction efficacy, whereas stimulation with concanavalin A was superior in memory T cell formation. Akt inhibition at the initial stage of CAR-T production tended to enhance transduction efficiency and memory T cell formation.

CONCLUSION: This study provides a significant insight into the understanding of the ex vivo expansion of canine T cells in adoptive immunotherapy.

PMID:35241532 | DOI:10.21873/invivo.12763

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