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.

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.

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.

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.

Expression of the activation markers Blimp1, Foxp1 and pStat3 in extranodal diffuse large B-cell lymphomas.

Different studies have suggested that the expression of biomarkers related to lymphoid cell activation may provide information on the behavior of DLBCL. Most studies have concentrated on nodal or a mixture of nodal and extranodal lymphomas. The differential expression and potential clinical impact of these markers in a homogeneous group of extranodal DLBCLs are not well defined. In this study, we investigated the expression of three activation markers, Blimp1, Foxp1 and pStat3, in a cohort of 35 extranodal DLBCLs homogeneously treated with R-CHOP. Immunohistochemical stains were evaluated using an immunoreactivity score on representative paraffin sections. Blimp1 was positive in 55% (19/35), Foxp1 in 60% (21/35), and pStat3 in 69% (24/35) of our cases. We did not observe any statistical differences in the expression of these markers in GCB and non-GCB tumors or in gastrointestinal and non-gastrointestinal tumors. Blimp1 expression was negatively correlated with overall survival (OS) (p=0.001) in the whole series and in the non-GCB group (Muris algorithm) (p=0.002). Foxp1 positivity and pStat3 positivity had no impact on the outcome of the patients in the global cohort, but they were associated with a better survival in the non-GCB subgroup (p=0.033, p=0.044 respectively). Multivariate analysis showed that Blimp1 expression but not COO was an independent negative prognostic factor for OS (HR=17.5, 95%, CI=2.2-141.1, p=0.007). Our results suggest that these markers are differentially expressed and have different impacts on outcome in extranodal DLBCLs compared to nodal tumors, emphasizing the need to evaluate separately these and probably other markers in these subsets of tumors.

Potential use of pericardial cTnI, Mg2+ and Ca2+ in the forensic investigation of seawater drowning in Greece: An initial assessment.

The investigation of drowning constitutes one of the biggest problems in forensic practice. Elevated cardiac troponin I (cTnI) levels in biological fluids have been associated with myocardial damage, whereas increased Mg2+ and Ca2+ levels were found in cases of seawater drowning. The aim of this study was to examine the diagnostic utility of postmortem determination of cTnI, Mg2+ and Ca2+ in the pericardial fluid, in differentiating between cases of seawater drowning related to myocardial injury and those brought about by other causes. This study included 76 cases selected during a 2-year period from medicolegal autopsies. The cases were divided into three groups, according to the cause of death established based on macroscopic and microscopic evidence. The groups were: 1) seawater drowning (n=23), 2) seawater drowning with histological evidence of myocardial infarction (n=28), and 3) myocardial infarction unrelated to drowning (n=25). cTnI was determined with an enzyme immunoassay; Mg2+ and Ca2+ with standard colorimetric assays. Pericardial cTnI levels were significantly lower in group 1 compared to groups 2 and 3. In contrast, pericardial Mg2+ and Ca2+ levels were both significantly higher in groups 1 and 2 compared to group 3. Our results suggest that the postmortem determination of pericardial cTnI levels may be useful in detecting previous myocardial damage as a contributory factor in death from seawater drowning and provide independent confirmation of the usefulness of pericardial Mg2+ and Ca2+ levels for differentiating between seawater drowning and fatal acute myocardial injury unrelated to the former.

A clinicopathological study of atypical leiomyomas: Benign variant leiomyoma or smooth-muscle tumor of uncertain malignant potential.

Atypical leiomyomas are histopathologically recognized by moderate to severe pleomorphic atypical tumor cells showing low mitotic counts without coagulative tumor cell necrosis. The histopathological features and clinical behavior of these tumors are unclear. The surgical management of these lesions includes myomectomy and hysterectomy. The current study presents 5 cases of women with atypical leiomyomas that were managed surgically. The clinicopathological characteristics of the patients and recurrences were analyzed. The median age of the patients was 43 years old. While 3 out of 5 patients were treated by hysterectomy (with or without salpingo-oophorectomy), the remaining 2 patients were treated by myomectomy. The median mitotic index was 3 mitotic figures/10 high-power fields. The post-operative course of all patients was uneventful, and there was no evidence of local or distant recurrence in a median follow-up time of 72 months. The treatment of choice for atypical leiomyomas is hysterectomy. However, myomectomy may be an option for fertility sparing cases. A thorough consultation with regard to the uncertain behavior of such tumors and a rigorous follow-up must be offered in such patients.

Relationship between Helicobacter pylori infection and multiple sclerosis.

BACKGROUND: Recent data indicate the presence of immunomodulating properties of Helicobacter pylori (Hp) (Hp Sydney Strain-1 antigen) in an experimental model of multiple sclerosis (MS), and there are limited contradictory epidemiologic data regarding Hp serology in MS patients. METHODS: The aim of this prospective, comparative study was to validate the incidence of active Hp infection by histology and the endoscopic abnormalities, in 44 patients with relapsing-remitting MS and 20 anemic controls. RESULTS: The overall prevalence of histologically confirmed active Hp infection in 44 MS patients was 86.4% vs. 50% in 20 matched anemic control participants (P=0.002, odds ratio 6.33, 95%CI 1.85-21.64). Concomitant diseases of autoimmune origin including hypothyroidism and ulcerative colitis were exclusively present in MS patients. Moreover, a trend of increased presence of pathological endoscopic findings such as hiatus hernia, Barrett's esophagus and duodenal ulcer disease was observed in MS patients compared with controls; Barrett's esophagus and duodenal ulcers were exclusively observed in MS patients. Likewise, Hp (+) MS patients showed exclusive presence of hiatus hernia, esophagitis and duodenal ulcer disease compared with Hp (-) MS patients. CONCLUSION: Hp infection appears to be more frequent in MS patients. If confirmed, this might indicate either a common factor that causes susceptibilities to both MS and Hp infection or that Hp might be a causal factor for developing MS. If a causal link between Hp infection and MS is confirmed in the future, this may have a major impact on the pathophysiology and management of MS.

Primary gallbladder small lymphocytic lymphoma as a rare postcholecystectomy finding.

Introduction. Primary lymphoma of the gallbladder is an extremely rare entity with approximately 50 cases reported so far. In many of these cases the presenting symptoms were mimicking symptomatic gallstone disease and the diagnosis was made postoperatively, especially when the preoperative imaging results were far from suspicious for malignant disease. Patients and Methods. We report a case of primary lymphoma of the gallbladder in an 85-year-old man with gallstone disease, who was admitted for elective cholecystectomy 2 months after an episode of acute cholecystitis and pancreatitis. Histological evaluation of the specimen revealed a small lymphocytic lymphoma of the gallbladder. This type of primary gallbladder lymphoma has not been previously reported. Discussion. The most common primary lymphomas of the gallbladder are MALT lymphomas and diffuse large B-cell lymphomas, although a variety of other histological types have been reported. The association of these lesions with chronic inflammation is the most convincing theory for their pathogenesis. For lesions confined to the gallbladder, cholecystectomy is considered to be sufficient, while supplementary chemotherapy significantly improves prognosis in more advanced disease.

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.