Hodgkin Lymphoma in Children and Adolescents of Northern Greece: 25-Year Results and Long-term Follow-up.

Aim of this study was to evaluate the long-term therapeutic outcome and treatment-related complications in Hodgkin disease. We reviewed the medical records of 93 patients diagnosed with classic Hodgkin lymphoma, treated, and followed-up during the last 25 years. The cohort study included 49 males and 44 females with median age 11.8 years old (range: 3.95 to 17.42 y). The most common subtype was nodular sclerosis in 47/93 (50.5%). B symptoms were present in 15/93 (16.1%). From January 2009 until December 2020, 55 (59%) patients diagnosed with Hodgkin lymphoma were treated according to European Network for Pediatric Hodgkin Lymphoma (EURONET)-PHL-C1 protocol. Concerning outcome, a total of 89/93 patients are alive. Relapse occurred in 7/93. Second malignancies are reported in a total of 5 patients, 3 solid tumors (thyroid cancer, breast cancer, and osteosarcoma), and 2 acute myeloid leukemias. The overall survival and event-free survival for the whole cohort were 95.7% and 83.9%, respectively. Disease-free survival was 92.5%. Although a considerable high fraction of patients with Hodgkin disease can achieve continuous complete remission, they are at a high risk of developing long-term treatment-related complications. High curative rates as well as prevention of late effects can be achieved by implementation of individualized treatment strategies and innovative treatments.

A Time Course of Bevacizumab (Anti-VEGF) Effect on Rat Peritoneum: Relations Between Antiadhesive Action and Fibrin Regulation Enzymes.

BACKGROUND: To investigate the early and late antiadhesive effect and any changes of fibrin matrix regulation enzymes on rat peritoneum, after local administration of bevacizumab. METHODS: Rats were subjected to cecal abrasion. Bevacizumab (5 mg/kg) against placebo was given intraperitoneally. On the 2nd, 14th, and 28th postoperative days adhesions were scored, and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), degree of fibrosis, and angiogenesis were measured in abrased cecum and in intact parietal peritoneum. RESULTS: Bevacizumab significantly reduced adhesions up to 15% on the 2nd, 52.5% on the 14th, and 55% on the 28th postoperative day, and significantly increased tPA concentrations in peritoneum. PAI-1 was decreased, and a significantly higher tPA/PAI-1 ratio along with an increase of MMP-9 was measured at all time points. Fibrosis and angiogenesis were significantly lower on the 14th and 28th postoperative days. CONCLUSIONS: Local bevacizumab administration has a strong early and late antiadhesive action on rat peritoneum, mediated by changes in the tPA/PAI-1 and MMP balance in favor of fibrinolysis up to 28 days after operations.

Aprotinin reduces oxidative stress induced by pneumoperitoneum in rats.

BACKGROUND: Ischemia-reperfusion injury induced by pneumoperitoneum is a well-studied entity, which increases oxidative stress during laparoscopic operations. The reported anti-inflammatory action of aprotinin was measured in a pneumoperitoneum model in rats for the first time in this study. MATERIALS AND METHODS: A total of 60 male Albino Wistar rats were used in our protocol. Prolonged pneumoperitoneum (4 h) was applied, causing splanchnic ischemia and a period of reperfusion with a duration of 60 or 180 min followed. Several cytokines and markers of oxidative stress were measured in liver, small intestine, and lungs to compare the aprotinin group with the control group. Tissue inflammation was also evaluated and compared between groups using a five-scaled histopathologic score. RESULTS: In aprotinin group values of biochemical markers (tumor necrosis factor α, interleukin 6, endothelin 1, C reactive protein, pro-oxidant-antioxidant balance, and carbonyl proteins) were lower in all tissues studied. Statistical significance was greater in liver and lungs (P < 0.05). Histopathologic examination revealed significant difference between control and aprotinin groups in all tissues examined. Aprotinin groups showed mild to moderate lesions, while in control groups severe to very severe inflammation was present. Aprotinin subgroup with prolonged reperfusion period (180 min) showed milder lesions in all tissues than the rest of the groups. CONCLUSIONS: Aprotinin reduced inflammatory response and oxidative stress induced by pneumoperitoneum in liver, small intestine, and lungs.

Upregulation of VEGF expression is associated with accumulation of HIF-1α in the skin of naïve scleroderma patients.

Systemic sclerosis is a disease hallmarked by microangiopathy; the enlargement and leakage of skin capillaries in active stages develops into extensive avascular areas, clinically associated with severe tissue hypoxia and the formation of digital ulcers. Vascular endothelial growth factor (VEGF) is upregulated in all stages of the disease, with little effect on efficient neovascularization. The oxygen-regulated α-subunit of hypoxia-inducible transcription factor-1 (HIF-1α) represents a key mechanism involved in the transcriptional regulation of VEGF. The aim of this study is to investigate expression of the oxygen-regulated α-subunit of HIF-1 and VEGF in naïve scleroderma patients. For this purpose, skin biopsies (dorsal hand surface) from scleroderma patients were analyzed and compared with control skin biopsies. Immunoreactivity for VEGF was enhanced in scleroderma patients, in contrast to restricted positive immunostaining in suprabasal keratinocytes observed in normal skin. In a similar fashion, all skin biopsies from scleroderma patients were strongly HIF-1α reactive, compared with rare immunoreactivity observed in normal skin. The pattern was similar in all stages of scleroderma. These observations for the first time directly connect constitutive hypoxia with VEGF upregulation in scleroderma patients. The sequence of events needs to be precisely mapped, and the pro- and antiangiogenic switches which may interfere with efficient tissue neovascularization identified, in order to provide meaningful therapeutic strategies.

Histological presence of Helicobacter pylori bacteria in the trabeculum and iris of patients with primary open-angle glaucoma.

PURPOSE: To investigate the role of Helicobacter pylori in primary open-angle glaucoma (POAG) pathophysiology by detecting its presence in eye biopsies of POAG patients during trabeculectomy. PATIENTS AND METHODS: Fifty-one consecutive patients who underwent trabeculectomy for POAG not responsive to antiglaucoma therapy, and 35 consecutive anemic controls were examined for H. pylori presence mainly by gastric mucosa histology. In POAG patients, eye biopsies were also obtained and stained for H. pylori presence in situ. RESULTS: Forty-three of 51 (84.3%) POAG patients and 17 of 35 (48.6%) controls were tested H. pylori positive (p = 0.0004). In 5 H. pylori-positive POAG patients, H. pylori bacteria were identified in the trabeculum and iris specimens. CONCLUSION: For the first time, H. pylori bacteria have been detected histologically in eye biopsies of POAG patients.

Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkin's lymphoma.

Apoptosis-related proteins play an important role in lymphoma cell death during chemotherapy. In our study, we investigated the prognostic significance of CD95, BCL2, and P53 expression in extranodal non-Hodgkin's lymphoma (NHL). We examined 71 patients with extranodal NHL [45 diffuse large B-cell lymphomas (DLBCLs) and 26 mucosa-associated lymphoid tissue lymphomas (MALTLs)], 35 male and 36 female, with a median age of 65.8 years. The most common site of origin was the stomach (N = 31). Paraffin-embedded specimens were analyzed immunohistochemically for CD95, BCL2, and P53 expression. Multivariate analysis revealed that in DLBCLs, positive CD95 and negative BCL2 expression were independent prognostic factors for overall survival. We reached the same conclusion for MALTLs, with positive CD95 and negative P53 expression. In DLBCLs, the 5-year overall survival rate was 71.5% for the CD95-positive cases and 35% for the CD95-negative cases (p = 0.004) and the 5-year overall survival was significantly better in BCL2-negative cases (70.8%) when compared to BCL2-positive cases (37%; p = 0.009). In MALTLs, the 5-year overall survival rate for the CD95-positive and CD95-negative groups was 89.5% and 42.9%, respectively (p = 0.004) and the 5-year overall survival rate was 50% for the P53-positive cases and 88.9% for the P53-negative cases (p = 0.016). In conclusion, positive CD95 expression proved to be a good prognostic factor of overall survival in both extranodal DLBCLs and MALTLs. In contrast, positive expression of BCL2 and P53 was found to be unfavorably associated with survival in extranodal DLBCLs and MALTLs, respectively.

Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients.

BACKGROUND: Alzheimer disease (AD) is a progressive, fatal neurodegenerative condition. OBJECTIVE: We tested the hypothesis that eradication of Helicobacter pylori infection (Hp-I) could improve survival in a Greek cohort of AD patients, in a 5-year follow-up. METHOD: Forty-six patients diagnosed with probable AD were enrolled in the analysis. Study population was classified into 3 groups: patients for whom Hp eradication treatment was successful; those for whom eradication of Hp had failed, they refused, and/or were noncompliant with eradication therapy; and those who were Hp negative at baseline. Cox proportional hazards model was built with all-cause mortality as the dichotomous outcome. RESULTS: During the 5-year follow-up [47.19±15.11 mo (range 12 to 60)], overall 21 patients died and 25 patients remained alive. Patients who died were older and exhibited lower mean MMSE score compared with the patients still alive. Successful eradication of Hp-I was associated with a significantly lower mortality risk [HR (95% CI)=0.287 (0.114-0.725), P=0.008]. The results were similar in adjusted and unadjusted models, for age and MMSE at baseline. CONCLUSION: Hp eradication regimen in AD patients is associated with a higher 5-year survival rate.

A case of sebaceous carcinoma arising within a benign ovarian cystic teratoma.

BACKGROUND: Mature cystic teratoma, also known as dermoid cyst, is the most common germ cell tumor of the ovary. Malignant change in a component of a mature ovarian teratoma is rare, occurring in less than 2% of cases, with squamous cell carcinoma corresponding to 80% of such neoplasms. Pure sebaceous carcinoma is exceedingly rare, with only 6 reported cases thus far. CASE REPORT: A 74-year-old woman presented with lower abdominal pain due to a palpable mass in the right abdomen. Abdominal and pelvic ultrasound as well as computed tomography demonstrated a heterogenic tumor of the right ovary. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histological examination of the tumor showed features of a well-differentiated sebaceous carcinoma arising within a mature cystic teratoma. CONCLUSIONS: This is an extremely rare ovarian malignancy of which the clinical behavior and optimal management are not well established. Differential diagnosis with other malignant neoplasms arising in mature cystic teratomas is exceedingly important for treatment and prognosis.

Epstein-Barr virus associated primary intracranial leiomyoma in organ transplant recipient: case report and review of the literature.

INTRODUCTION: A 45 year old female renal transplant recipient presented with headaches of 3 months duration. Clinical and radiological evaluation revealed an approximately 4x4 cm rounded, enhancing mass at the left temporal pole. At surgery, the mass had dural attachment and clinically, radiographically, and macroscopically resembled a meningioma. Histopathological analysis revealed a leiomyoma. Epstein-Barr virus (EBV) DNA was demonstrated within the tumour cell nuclei by the in situ hybridisation technique. DISCUSSION: This is the first documentation of an EBV-associated primary intracranial leiomyoma in an organ transplant recipient and provides additional evidence of a possible relation between EBV infection and development of smooth-muscle tumours (SMT). CONCLUSION: With increasing numbers of individuals being on long-term immuno-suppression, EBV-associated SMTs may be encountered more frequently in the future.

A rare case of malignant triton tumor with pluridirectional differentiation.

An enlarging soft tissue mass was resected from the leg of a young man with neurofibromatosis type 1. Rhabdomyosarcomatous elements admixed with islands of osteoid and chondroid matrix was seen on microscopy. Based on immunohistochemistry, a malignant triton tumor, an uncommon subtype of peripheral nerve sheath tumor with rhabdomyosarcomatous elements, was diagnosed. The important feature of this neoplasm was that it showed pluridirectional differentiation to osteosarcoma and chondrosarcoma. This pathologic finding is rare and seen in only a few cases of all malignant triton tumors.

Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25-29 years to 5.1% for women aged 50-60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25-29) to 76.3% (for women 40-49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

Cardiac tamponade as primary manifestation of angioimmunoblastic T-cell lymphoma (AILT). Coexistence with malignant mesothelioma.

BACKGROUND: Cardiac tamponade (CT) as the primary clinical manifestation of lymphomas is extremely rare. Angioimmunoblastic T-cell lymphoma (AILT) is characterised by systemic disease usually presenting with generalised peripheral lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration. CASE REPORT: We report on a 59-year-old male patient with CT as initial clinical manifestation of AILT. Coexistence with malignant pleural mesothelioma was additionally revealed. Cytologic examination of pericardial fluid presented diffuse lymphoid cells and sporadic malignant mesothelial cells. AILT diagnosis was confirmed by thoracoscopic mediastinal lymph node and bone marrow biopsy. Despite the presence of pleural effusion, the diagnosis of mesothelioma was initially established by cytologic ex-amination of pericardial fluid, due to the patient's critical cardiac condition requiring prompt subxiphoid pericardiocentesis. CONCLUSION: CT as primary clinical manifestation of AILT is very rare. This case reflects the differences in the underlying biology of AILT and consequently the vast spectrum of its clinical presentations. Coexistence of AILT with malignant pleural mesothelioma is also extremely rare.

Clinicopathologically problematic melanocytic tumors: a case-based review.

BACKGROUND: In spite of recent advances in the histopathological and molecular diagnosis of melanocytic neoplasms, a certain proportion of these lesions remain a daunting challenge for both the clinician and the pathologist. OBJECTIVES: To emphasize the importance of close collaboration between clinicians and pathologists in case of problematic melanocytic lesions. PATIENTS: We report and discuss 5 problematic scenarios of melanocytic lesions, including tumoral melanosis, nevoid melanoma, lentiginous melanoma, spitzoid melanoma and BAPoma that may pose diagnostic difficulties in our practice. CONCLUSIONS: Clinico-dermoscopic-pathological correlation, with incorporation of all the available data, in problematic melanocytic skin neoplasms is of paramount importance for accurate diagnosis.