Liver transplantation in patient with Berardinelli-Seip syndrome: A literature review and case report.

BACKGROUND: Berardinelli-Seip syndrome is an infrequently seen and potentially fatal genetic disorder characterized by the absence of adipose tissue. Herein, we report a first-in-literature liver transplant done on a 7-year-old girl because of liver cirrhosis caused by the Berardinelli-Seip syndrome. CASE REPORT: Physical examination showed prominent subdermal fat tissue loss and mild muscle hypertrophy, giving her a slim appearance, hirsutism, thick hair, a large head in contrast to the body, low anterior hairline, icterus, prominent facial contours, prominent mandibula, loss of buccal fat, low set ears, and large limbs. After the diagnosis, she admitted to our clinic because of variceal esophageal bleeding and increasing liver enzymes. Transplantation decision was made and orthothopic liver transplantation done by the surgery team. DISCUSSION: Common causes of death in Berardinelli-Seip syndrome patients are infections and liver cirrhosis. The mean age of the patients was 27.1 at the time of death. There is no any established cure for congenital lipodystrophies so far. However, some symptomatic treatment methods are found to be helpful. The main point of the case report to be discussed is the liver transplantation done by our surgical team. There are no examples of any transplantation in Berardinelli-Seip syndrome patients, but several reports can be found of patients with kidney or liver failure. CONCLUSION: Berardinelli-Seip syndrome is a rare disorder with no cure but a chance of improving lifestyle and life expectancy. The transplantation option should be considered in young patients after a multidisciplinary review.

Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study.

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p=0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

CIRCULATING THYROID-STIMULATING HORMONE RECEPTOR MESSENGER RNA AS A MARKER OF TUMOR AGGRESSIVENESS IN PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA.

BACKGROUND: We have previously shown that thyroid-stimulating hormone receptor messenger RNA (TSHR mRNA) is detectable in the peripheral blood of patients with papillary thyroid microcarcinoma (PTmC). The aim of this study was to analyze the utility of TSHR mRNA status as a marker of tumor aggressiveness in patients with PTmC. METHODS: Preoperative TSHR mRNA values were obtained in 152 patients who underwent thyroidectomy and were found to have PTmC on final pathology. Clinical parameters were analyzed from an institutional review board-approved database using χ(2) and t tests. RESULTS: Preoperatively, TSHR mRNA was detected in the peripheral blood in 46% of patients, which was less than that for macroscopic papillary thyroid carcinoma (PTC) (80%) but higher than for benign thyroid disease (18%) (P<.001). The focus of cancer was larger in the TSHR mRNA-positive group compared to the negative group (0.41 vs. 0.30 cm, respectively, P = .015). The prevalence of tall-cell variant was higher in the TSHR mRNA positive group. The rates of lymph node (LN) metastasis (16% vs. 10%), multifocality (46% vs. 49%), and extra-thyroidal extension (10% vs. 5%) were similar between the TSHR mRNA-positive and-negative groups, respectively. In patients 45 years or older, rate of LN metastasis was higher in those who were TSHR mRNA positive (10%) versus negative (2%) (P = .039). TSHR mRNA positivity predicted a higher likelihood of radioactive iodine treatment (36% vs. 17%, P = .009) postoperatively. CONCLUSION: This study shows that TSHR mRNA, which is a marker of circulating thyroid cancer cells, is detectable in about half of patients with PTmC. The positivity of this marker predicts a higher likelihood of LN involvement in patients with PTmC who are 45 years or older.

Global Burden of Disease: Digestive Disease Alarm in South Caucasus.

Digestive disease-caused death rates are significantly high in the South Caucasus region. The latest Global Burden of Disease (GBD) data are a subject of discussion and should lead to serious steps to be taken. Azerbaijan, Armenia, and Georgia are three countries in the region with similar cultures but different roots. The problem seems to affect every country in the region with slightly different rates. It is crucial to start investigations into the detailed cause and to take serious steps in order to prevent digestive disease-caused deaths in the region. This letter aims to arouse awareness of the problem in the region.

A Rare Case of Symptomatic Ciliated Hepatic Foregut Cyst in a 17-Year-Old Female.

A ciliated hepatic foregut cyst (CHFC) is a very uncommon cystic hepatic lesion that arises from an embryonic remnant of the foregut epithelium. CHFC is predominantly asymptomatic and is found incidentally. However, it can show various clinical presentations such as pain and weight loss. We present the case of a 17-year-old female who came to our hospital with complaints of right subcostal pain and abdominal discomfort and was diagnosed with CHFC by biopsy. Successful laparoscopic resection was performed due to the possibility of malignant transformation. Even though the majority of the patients are asymptomatic and cysts are commonly found incidentally, when the lesion has concerning features, they may need follow-up or resection due to rare reported cases of malignant transformation.

Metastasis to the stomach: a systematic review.

Background: This study reviews the literature on gastric metastases (GM) in terms of diagnosis, treatment, and outcomes. The goal of this study was to provide clinicians with a reliable and beneficial source to understand gastric metastases arising from various primary tumors and to present the growing literature in an easily accessible form. Methods: Articles published in English language from implementation of MEDLINE and Cochrane databases until May 2022 were considered for the systematic review. Articles other than English language, letters to the editor, posters, and clinical images were excluded. Hematogenous and lymphogenic metastases were included whereas direct tumoral invasion and seeding were excluded. Articles and abstracts were analyzed and last selection was done after cross-referencing and by use of defined eligibility criteria. Results: In total 1,521 publications were identified and 170 articles were finally included totaling 186 patients with GM. The median age of patients was 62 years. Gynecologic cancer was the most common cancer type causing GM (67 patients), followed by lung cancer (33 patients), renal cancer (20 patients), and melanoma (19 patients). One of the main treatment methods performed for metastasis was resection surgery (n=62), sometimes combined with chemotherapy (ChT) or immunotherapy. ChT was the other most used treatment method (n=78). Also, immunotherapy was amongst the most preferred treatment options after surgery and ChT (n=10). Conclusions: As 172 case reports were screened in the systematic review from different journals, heterogeneity was inevitable. Some articles missed important information such as complete follow-up or clinical information. Moreover, since all of the included articles were case reports quality assessment could not be performed. Among 172 case reports reviewed, resection surgery was performed the most and was sometimes combined with ChT and immunotherapy. Further research about what type of treatment has the best outcomes for patients with gastric metastases is needed.

Evaluation of toxic effects of chemotherapy in lung malignancies on cerebral white matter using diffusion tensor imaging.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of morbidity and mortality. Carboplatin and cisplatin based regimens are used in the treatment of NSCLC. The aim of the study was to find out whether there is a difference in white matter (WM) changes between two platinum-based chemotherapy agents using diffusion tensor imaging (DTI). PATIENTS AND METHODS: 25 patients who received chemotherapy for NSCLC and 27 age-matched healthy controls were enrolled in the study. Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD) values of the study population were measured from 11 regions of interest in pre-chemotherapy and post-chemotherapy MRI data. RESULTS: Cisplatin group showed a significant decrease in the FA of the inferior longitudinal fasciculus (P = 0.028). Carboplatin group showed a significant FA decrease and RD increase in the forceps minor (P = 0.022 and P = 0.011, respectively), and a significant reduction in AD and increase in MD in frontal white matter (WM) (P = 0.008 and P = 0.029, respectively). In comparison of post chemotherapy DTI values of the two groups, carboplatin group showed lower FA, and higher MD and RD values than cisplatin group in parieto-occipital WM (P = 0.034, P = 0.034, P = 0.029, respectively). CONCLUSIONS: The findings of the study suggest that subtle effects of chemotherapy detectable with DTI may emerge after the treatment. In addition, carboplatin regimen may have more impact on WM than cisplatin regimen.

Successful retreatment with erlotinib after erlotinib-related interstitial lung disease.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors are effectively being used in the treatment of non-small cell lung cancer. Although most of their adverse effects are mild to moderate, they occasionally can cause life-threatening interstitial lung disease. We aimed to present a case of lung adenocarcinoma successfully re-treated with erlotinib after recovery with effective treatment of erlotinib-induced interstitial lung disease. CASE DESCRIPTION: A 54-year-old nonsmoking woman was diagnosed with metastatic adenocarcinoma of the lung. After progression with first-line chemotherapy, erlotinib 150 mg daily was initiated. On the 45th day of erlotinib treatment, interstitial lung disease occurred and erlotinib was discontinued. Clinical improvement was achieved with dexamethasone treatment and erlotinib was re-initiated. Ten weeks after re-initiation of erlotinib, 100 mg daily partial response was observed. CONCLUSIONS: Incidence of interstitial lung disease is higher in men, smokers, and patients with pulmonary fibrosis. Interstitial lung disease radiologically causes ground-glass opacity and consolidation. The physician should quickly evaluate new respiratory symptoms in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors, discontinue the epidermal growth factor receptor tyrosine kinase inhibitor treatment, and initiate corticosteroids if clinical diagnosis is interstitial lung disease.

Primitive Neuroectodermal Tumor of the Testis.

A 21-year male presenting with left testicular mass and retroperitoneal lymphadenopathy underwent radical orchiectomy; and his pathological examination showed a mixed germ cell tumor composed of primitive neuroectodermal tumor mixed with mature teratoma. Six cycles of IE (ifosfamide, etoposide) and VAC (vincristine, doxorubicin, cyclophosphamide) chemotherapy were given after sperm preservation. He then underwent retroperitoneal lymph node dissection (RPLND). No tumor was detected in the removed lymph nodes, and all lymph nodes were reported as showing reactive changes. Key Words: Chemotherapy, Primitive neuroectodermal tumor, Surgery, Teratom, Testis.

Diffusion Tensor Imaging of Brain Metastases in Patients with Breast Cancer According to Molecular Subtypes.

BACKGROUND AND PURPOSE: Recent studies have shown that diffusion tensor imaging (DTI) parameters are used to follow the patients with breast cancer and correlate well as a prognostic parameter of breast cancer. However, as far as we know, there is no data to compare the DTI features of breast cancer brain metastases according to molecular subtypes in the literature. Our aim is to evaluate whether there are any differences in DTI parameters of brain metastases in patients with breast cancer according to molecular subtypes. METHODS: Twenty-seven patients with breast cancer and 82 metastatic brain lesions were included. We classified subjects into three subgroups according to their hormone expression; Group 0, triple- negative (n; 6, 19 lesions), group 1, HER2-positive (n;16, 54 lesions) and group 2, hormone-- positive group (n; 5, 9 lesions). The apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values in DTI were measured and compared between three groups. RESULTS: ADC, AD and RD values of group 2 were significantly lower compared to group 0. No significant differences were found in FA, ADC, AD and RD values between the group 0 and 1 and the group 1 and 2. CONCLUSION: Metastasis of aggressive triple-negative breast cancer showed higher ADC values compared to the less aggressive hormone-positive group. Higher ADC values in brain metastases of breast cancer may indicate a poor prognosis, so DTI findings could play a role in planning appropriate treatment.

Is lymph node dissection necessary for staging while undergoing nephrectomy in patients with renal cell carcinoma?

OBJECTIVE: The essential treatment for patients with renal cell carcinoma is nephrectomy. As no lymph node dissection (LND) could be performed in the majority of these patients, healthy staging could not be carried out. In this study, we investigated the impact of LND during nephrectomy on patient survival. METHODS: A total of 181 patients-58 (32%) were female and 123 (68%) were male-were included in the study. Median follow-up period was 48 months. The patients were separated into 4 groups according to their stage during diagnosis; group 1 (T1-3N0M0), group 2 (T1-3NXM0), group 3 (T1-3N1M0), and group 4 (T1-4N0/XM1). The disease-free survival of nonmetastatic patients and the overall survival of all groups were calculated. RESULTS: Mean age was 58.4 ± 12.0 years. Median survival for Group 1 could not be reached. Median survival was 89 months in Group 2, 50 months in Group 3, and 39 months in Group 4 (P <0.001). There was no statistically significant difference between the N1 and M1 groups (P = 0.297). For the NX patient group without LND, median survival was 89 months, which is worse than the N0 group and better than the N1 group (P = 0.002). CONCLUSIONS: Our study presumes that the patients without LND are not staged sufficiently, NX patients have worse survival rates when compared with N0 patients, node-positive patients have poor survival rates as do the metastatic patients, and it should be defined as TNM stage4.

The Utility and Efficiency of Diffusion Tensor Imaging Values to Determine Epidermal Growth Factor Receptor Gene Mutation Status in Brain Metastasis from Lung Adenocarcinoma; A Preliminary Study.

BACKGROUND: This study aims to investigate the existence of any Diffusion Tensor Imaging (DTI) value differences in Brain Metastases (BM) due to lung adenocarcinoma based on the Epidermal Growth Factor Receptor (EGFR) gene mutation status. MATERIAL AND METHODS: 17 patients with 32 solid intracranial metastatic lesions from lung adenocarcinoma were included prospectively. Patients were divided according to the EGFR mutation status as EGFR (+) (group 1, n:8) and EGFR wild type (group 2, n:9). The Fractional Anisotropy (FA), apparent diffusion coefficient (ADC), normalized ADC (nADC), Axial Diffusivity (AD), and Radial Diffusivity (RD) values were measured from the solid component of the metastatic lesions and nADC values were calculated. DTI values were compared between group 1 and group 2. The receiver-operating characteristic analysis was used to obtain cut-off values for the parameters presenting a statistical difference between the EGFR gene mutation-positive and wild type group. RESULTS: There were statistically significant differences in measured ADC, nADC, AD, and RD values between group 1 and group 2. The ADC, nADC, AD, and RD values were significantly lower in group 1. There was no significant difference in FA values between the two groups. Analysis by the ROC curve method revealed a cut-off value of ≤721 x 10-6 mm2/s for ADC (Sensitivity= 72.7, Specificity=85.7); ≤0.820 for nADC (Sensitivity=72.7, Specificity=90.5), ≤ 886 for AD (Sensitivity=81.8, Specificity=81.0), and ≤588 for RD (Sensitivity=63.6, Specificity=90.5) in differentiating EGFR mutation (+) group from wild type group. CONCLUSION: A combination of the decreased ADC, nADC, AD, and RD values in BM due to lung adenocarcinoma can be important for predicting the EGFR gene mutation status. DTI features of the brain metastases from lung adenocarcinoma may be utilized to provide insight into the EGFR mutation status and guide the clinicians for the initiation of targeted therapy.

Usefulness of serum M30 and M65 levels to predict response to neoadjuvant chemotherapy in patients with breast cancer.

OBJECTIVE: M30 and M65 levels reflect tumor cell activity in patients with epithelial cancer. Cytokeratin 18 is one of the cell skeletal elements. M30 is a apoptotic marker of cytokeratin 18. M65 levels are both an apoptosis and a necrosis marker. The aim of our study was to determine the predictive value of M30 and M65 levels in neoadjuvant treatment of breast cancer. MATERIALS AND METHODS: In this prospective study, 41 patients with breast cancer who underwent neoadjuvant chemotherapy were included. Following 4 cycles of chemotherapy with anthracycline containing regimen, patients received paclitaxel treatment for 12 weeks. Blood was collected from the patients before chemotherapy and on day 21, after the 2nd, 4th, and 8th cycles. M30 and M65 levels were measured with the ELISA method. RESULTS: While there was an increase in M30 and M65 levels at the 4th cycle (P < 0.05), levels were decreased after the 8th cycle. In addition, there was no significant relationship among M30, M65 levels, and prognostic factors such as ER, PR, c-Erb-2, Ki-67, pathologic-T, pathologic-N, and chemotherapy responses. CONCLUSION: M30 and M65 levels are not of predictive values of response to breast cancer patients receiving neoadjuvant chemotherapy. Nevertheless, M30 and M65 levels increased when patients kept receiving anthracycline containing chemotherapy.

Role of Urotensin-2 in 5-Fluorouracil-Related Arterial Vasoconstriction in Cancer Patients.

BACKGROUND: The aim of this study was to identify the possible relationship of 5-fluorouracil (5-FU)-related arterial vasoconstriction with urotensin-2 (UT-2), which has a high potential as an endogenic vasoconstrictor. METHODS: We assigned the patients to 1 of 3 groups. Patients in group 1 received a bolus of 5-FU, those in group 2 a continuous infusion (CI) of 5-FU, and those in group 3 no 5-FU, which was also a control group. Pre- and post-treatment UT-2 levels and brachial arterial diameters were measured and recorded in all patients. RESULTS: 132 patients were included in the study. Pre- and post-treatment brachial artery diameters were similar in all groups: in group 1 (3.28 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.740), in group 2 (3.57 ± 0.47 vs. 3.46 ± 0.45 mm, p = 0.441) and in the control group (3.51 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.818). Pre- and post-treatment UT-2 levels were significantly different in each group: in group 1 (39.5 ± 30.9 vs. 56.7 ± 27.1 ng/ml, p = 0.0001), in group 2 (37.7 ± 33.7 vs. 62.5 ± 37.7 ng/ml, p = 0.0001) and in the control group (52.9 ± 40.2 vs. 60.8 ± 40.7 ng/ml, p = 0.006). CONCLUSION: Our findings suggest that UT-2 has a high potential as a vasoconstrictor agent in our bodies and its level increases through a bolus or CI 5-FU. Increased UT-2 levels are likely to play a role in 5-FU-related cardiac toxicity pathogenesis.

Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda III-V thyroid cytology.

BACKGROUND: The aim of this study was to analyze the usefulness of thyrotropin receptor messenger RNA (TSHR-mRNA) combined with neck ultrasonography (US) in the management of thyroid nodules with Bethesda III-V cytology. METHODS: Cytology slides of patients with a preoperative fine needle aspiration (FNA) and TSHR-mRNA who underwent thyroidectomy between 2002 and 2011 were recategorized based on the Bethesda classification. Results of thyroid FNA, TSHR-mRNA, and US were compared with the final pathology. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: There were 12 patients with Bethesda III, 112 with Bethesda IV, and 58 with Bethesda V cytology. The sensitivity of TSHR-mRNA in predicting cancer was 33%, 65%, and 79 %, and specificity was 67%, 66%, and 71%, for Bethesda III, IV, and V categories, respectively. For the same categories, the PPV of TSHR-mRNA was 25%, 33%, and 79%, respectively; whereas the NPV was 75%, 88%, and 71%, respectively. The addition of neck US to TSHR-mRNA increased the NPV to 100% for Bethesda III, and 86%, for Bethesda IV, and 82% for Bethesda V disease. CONCLUSION: This study documents the potential usefulness of TSHR-mRNA for thyroid nodules with Bethesda III-V FNA categories. TSHR-mRNA may be used to exclude Bethesda IV disease. A large sample analysis is needed to determine its accuracy for Bethesda category III nodules.

The utility of peripheral thyrotropin receptor mRNA in the management of differentiated thyroid cancer.

BACKGROUND: Our aim was to analyze the utility of peripheral thyrotropin receptor (TSHR) messenger RNA (mRNA) in predicting and detecting the recurrence of differentiated thyroid cancer. METHODS: Peripheral blood TSHR-mRNA was obtained in 103 patients before and after total thyroidectomy. An analysis was performed to correlate peripheral blood TSHR-mRNA concentration with oncologic outcomes. RESULTS: Tumor types were papillary (n = 92), follicular (n = 9) and Hürthle cell (n = 2) cancer. Preoperative TSHR-mRNA was ≥1.02 ng/µg in 85% (88/103). On follow-up (median 48 months), 10 patients (10 %) developed recurrence. Recurrence rate in patients with a preoperative TSHR-mRNA ≥ 1.02 ng/µg was 11% versus 0% in those with a lesser concentration. TSHR-mRNA correctly diagnosed 7 (70%) of 10 recurrences. Of 19 patients with positive thyroglobulin (Tg) antibodies, TSHR-mRNA confirmed disease-free status in 12 (63%) and recurrence in 1 (5%). For Tg, TSHR-mRNA and whole-body radioactive iodine scan, sensitivity was 70%, 70%, and 75%; specificity 94%, 76%, 97%; PPV 54%, 24%, and 67%; and NPV 97%, 96%, and 98%, respectively, in detecting recurrent disease. CONCLUSION: This study shows that patients with preoperative TSHR-mRNA ≥1.02 ng/µg may be at a greater risk for recurrence compared with those with a lesser concentration. In the presence of Tg antibodies, TSHR-mRNA accurately predicted disease status in 68% of patients. Its overall performance in detecting recurrence was similar to Tg and whole-body radioactive iodine scan, albeit with lower specificity and PPV.