Clinical Oncology

[A structured approach to test the clinical benefi t of treatments of advanced cancer]

ALESSANDRO Pastorino, ALBERTO Sobrero

SEPTEMBER 05, 2015

Clinical Oncology - 2015;2(03)

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Clinical Oncology

[Angiogenesis – antiangiogenesis]

PAKU Sándor, SEBESTYÉN Anna, KOPPER László

[Tumor growth requires vascularization to be supplied by oxygen and nutritients. The vascular network could be different between tumors, even during the development of the same tumor (local and systemic spreading), from the occupation of already present vessels to the real angiogenesis (i.e, proliferation of endothelial cells). Moreover, the tumor cells can create channels, mimicking the normal vessels. This spectrum in morphology should be refl ected in the therapeutic response, in the effectiveness of antiangiogens, but the how is unknown. It is sure that acceptable clinical activity can be achieved only with combinations, both with traditional cytotoxic and targeting drugs. The clinical advantage can be hampered by increased toxicity, demanding supportive actions. One of the key decisions is to select the proper therapy considering the patient and the tumor characteristics (today increasingly at molecular level) and predict the response to the therapy. Such (bio)markers are still missing, although intensive research trying the best. Since the main target of antiangiogenic drugs (today and tomorrow) the VEGF/R family, a useful marker is expected from them. The inhibition of angiogenesis is a logical step against the solid tumors and these steps slowly but steadily can improve the patients life-time, as well as their quality of life.]

Clinical Oncology

[Ablation of liver cancer]

DOROS Attila

[Ablative therapies of the malignant liver tumors are used frequently all over the world. It is a very well tolareted minimally invasive treatment, followed by a short observation period. Patients might be sent home within 24 hours. Nowadays, there is suffi cient data supporting its effectiveness in the treatment of early primary liver cancer, equalling the results of surgical resection. The situation is different in liver metastasis, especially from coloectal cancer. In these cases ablative techniques have a supporting role, limiting their action on the multimorbid patients and small non-resectable tumors. These facts and trends - worldwide and in Hungary - are discussed, focusing on effectiveness, places in therapeutic protocols and domestic diffi culties.]

Clinical Oncology

[Up-to-date treatment of head and neck cancers]

PACZONA Róbert, CSENKI Melinda, HIDEGHÉTY Katalin

[The head and neck squamous cell cancer is often detected at an advanced stage, resulting in dismal prognosis despite the relevant developments of the oncotherapy in the last decades. The introduction of new techniques, new drugs and combinations though improves the survival for certain subgroups of patients, meanwhile the organ-function preservation and side effects reduction approaches lead to improved quality of life. The preventive-supportive care prior and during the therapy (dental care, nutrition, toxicity management) and the complex rehabilitation has paramount importance. MRI and 18FDG PET-CT and the advanced methods of molecular pathology became part of the diagnostic work up. The selection of the therapy based on the tumor characteristics, HPV detection, on the patient’s condition and wishes, as well as on multi-disciplinary team decision based on the available technical options. Early stage tumors can be successfully treated either by surgery alone or by radiation therapy. For locally advanced cases concomittant chemo-radiotherapy stays in the axis of the complex management using advanced radiation technique (IGRT-adaptive- IMRT) with cisplatin (or if contraindicated with cetuximab), which could be complemented by induction chemotherapy and/or surgery. Several new approaches are currently being tested in clinical studies after establishment of cisplatine-cetuximab treatment for recurrent/metastatic tumors. In the future, detection of molecular processes and driver mutations could result in development of more effective targeted anti-tumor agents, and individual molecular tumor profi le guided therapy, including the various forms and combinations with emerging immunotherapy.]

Clinical Oncology

[Treatment of testicular germ cell tumors – an up-date]

BAKI Márta

[The frequency of germ cell tumors is about 1% of all male cancers. The incidence increases in developed countries. The prevalence is the highest among the young males. The histologic type, extent of disease and therapy is based on international guidelines. The surgery, radio- and chemotherapy can achieve cure in the germ cell cancer patients. Regarding the late toxicity, the minimal invasive tumors are suggested to keep on the wait and see policy. The complex therapy of poor risk groups reached more than 80% permanent remission rate. The chemotherapy is based on cisplatin, but in second and third line therapy paclitaxel, gemcitabin and oxaliplatin is widely used. After the cure of germ cell cancer patients the careful follow up is mandatory.]

Clinical Oncology

[Mucositis - prevention and therapy]

NAGY Zsuzsanna, VALTINYI Dorottya

[Side-effects are critical challenges in cancer therapy. These complications can threaten the quality of life, sometimes the life itself. One of the most frequent side effects is mucositis, the damage of mucosa, either in the oral cavity (oral mucositis, OM), or in the gastrointestinal tract (gastrointestinal mucositis, GIM). Prevention is a key action for the effi cient supportation. Recognition of OM is relative easy, but of GIM is rather diffi cult. The risk factors could come from the patients and/or can be caused by the therapy. The successful management of mucositis mostly depends on the cooperation of the patient, which is highly infl uenced by the success of care (e.g. decreasing the level of pain). In general, mucositis (especially oral mucositis) a well managable disease, burt more informations are required to increase the quality of prevention and therapy. Such expectation could be realized by specifi c and sensitive biomarkers, however, they are still missing]

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Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

Creutzfeldt-Jakob Disease: A single center experience and systemic analysis of cases in Turkey

USLU Ilgen Ferda, ELIF Gökçal, GÜRSOY Esra Azize, KOLUKISA Mehmet, YILDIZ Babacan Gulsen

We aimed to analyze the clinical, laboratory and neuroimaging findings in patients with sporadic Creutzfeldt-Jakob disease (CJD) in a single center as well as to review other published cases in Turkey. Between January 1st, 2014 and June 31st, 2017, all CJD cases were evaluated based on clinical findings, differential diagnosis, the previous misdiagnosis, electroencephalography (EEG), cerebrospinal fluid and cranial magnetic resonance imaging (MRI) findings in our center. All published cases in Turkey between 2005-2018 were also reviewed. In a total of 13 patients, progressive cognitive decline was the most common presenting symptom. Two patients had a diagnosis of Heidenhain variant, 1 patient had a diagnosis of Oppenheimer-Brownell variant. Seven patients (53.3%) had been misdiagnosed with depression, vascular dementia, normal pressure hydrocephalus or encephalitis. Eleven patients (87%) had typical MRI findings but only 5 of these were present at baseline. Asymmetrical high signal abnormalities on MRI were observed in 4 patients. Five patients (45.4%) had periodic spike wave complexes on EEG, all appeared during the follow-up. There were 74 published cases in Turkey bet­ween 2005 and 2018, with various clinical presentations. CJD has a variety of clinical features in our patient series as well as in cases reported in Turkey. Although progressive cognitive decline is the most common presenting symptom, unusual manifestations in early stages of the disease might cause misdiagnosis. Variant forms should be kept in mind in patients with isolated visual or cerebellar symptoms. MRI and EEG should be repeated during follow-up period if the clinical suspicion still exists.

Clinical Neuroscience

Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery

ONDER Burcu, KELES Yavuz Betul

After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose – The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.