Surgical resection of lung cancer inhibits mRNA expression of GOT2 gene encoding kynurenine aminotransferase in leukocytes.

INTRODUCTION AND OBJECTIVE: Lung cancer is the most common malignant tumour. More than 80% of all diagnosed cases are non-small cell carcinoma which can be effectively treated by radical resection. Despite significant progress in the field of diagnostic and therapeutic methods, the results of lung cancer treatment are still unsatisfactory. Lung cancer is detected relatively late, which leads to an unfavourable prognosis. Kynurenine aminotransferases are an important element of the kynurenine pathway of tryptophan metabolism, which has recently aroused great interest from the aspect of possible use as a target point of personalized therapies in malignant tumours.The aim of the study was to analyze the expression of the selected gene of kynurenine aminotransferases GOT 2 at the mRNA level in peripheral blood leukocytes of patients with lung cancer. MATERIAL AND METHODS: The mRNA expression of the GOT 2 gene was tested on blood samples from 50 patients treated surgically for non-small cell lung cancer.The control group consisted of 15 healthy individuals.The determination of mRNA expression of the GOT 2 gene was performed using the real-time PCR method.The GAPDH gene was used as the endogenous reference level. RESULTS: The mRNA expression of the GOT2 gene on the 6th day after surgery was statistically significantly lower than before surgery (p = 0,05). In the study group, the average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.192082±0.292174 in woman. This was statistically significantly higher than in men whose average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.004210±0.235065 (p=0.0183). CONCLUSIONS: Surgical resection of lung cancer results in inhibition of GOT2 mRNA expression in leukocytes. Further studies are expected to show whether it may be used as a target point for personalized therapies in lung cancer.

Uniportal video-assisted thoracic surgery lobectomy: a consensus report from the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS).

OBJECTIVES: Our goal was to report the results of the first consensus paper among international experts in uniportal video-assisted thoracoscopic surgery (UniVATS) lobectomy obtained through a Delphi process, the objective of which was to define and standardize the main procedural steps, optimize its indications and perioperative management and identify elements to assist in future training. METHODS: The 40 members of the working group were convened and organized on a voluntary basis by the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS). An e-consensus finding exercise using the Delphi method was applied to require 75% agreement for reaching consensus on each question. Repeated iterations of anonymous voting continued for 3 rounds. RESULTS: Overall, 31 international experts from 18 countries completed all 3 rounds of questionnaires. Although a technical quorum was not achieved, most of the responders agreed that the maximum size of a UniVATS incision should be ≤4 cm. Agreement was reached on many points outlining the currently accepted definition of a UniVATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSIONS: The UVIG Consensus Report stated that UniVATS offers a valid alternative to standard VATS techniques. Only longer follow-up and randomized controlled studies will predict whether UniVATS represents a valid alternative approach to multiport VATS for major lung resections or whether it should be performed only in selected cases and by selected centres. The next step for the ESTS UVIG is the establishment of a UniVATS section inside the ESTS databases.

Anatomical resections are superior to wedge resections for overall survival in patients with Stage 1 typical carcinoids.

OBJECTIVES: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group. METHODS: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates. RESULTS: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.69; P = 0.024). Similar effects of wedge resection are detectable for cause-specific deaths: tumour-related (hazard ratio 2.28, 95% CI 0.86-6.02; P = 0.096) and non-tumour-related (hazard ratio 1.74, 95% CI 0.89-3.40; P = 0.105). CONCLUSIONS: In a large cohort of patients, we were able to demonstrate the superiority of anatomical surgical resection in Stage 1 TCs in terms of OS. This result should therefore be considered for future clinical guidelines for the management of TCs.

Investigation of relationship between precursor of miRNA-944 and its mature form in lung squamous-cell carcinoma - the diagnostic value.

INTRODUCTION: MicroRNA (miRNA) are attractive markers of lung cancer, due to their regulatory role in cell cycle. However, we know more about function of miRNA in cancer development, there is still little known about role of their precursors (primary miRNA; pri-miRNA) in tumorgenesis. In present study we investigated potential role of miRNA-944 and its precursor pri-miRNA-944 in development of squamous-cell lung cancer (SCC) and explored interdependence between miRNA precursor and its mature form. This is a first available literature report analyzing pri-miRNA as a cancer diagnostic marker. MATERIAL AND METHODS: Expression of miRNA-944 and its precursor was analyzed in 58 fresh-frozen tissues of non-small cell lung cancer and corresponding adjacent non-cancerous tissues using qRT-PCR. Expression of pri-miRNA-944 was correlated with TP63 and miRNA-944. Using ROC analysis diagnostic accuracy of studied markers was evaluated. RESULTS: miRNA-944 and its precursor were significantly overexspressed in SCC compared to adenocarcinoma (AC) and non-cancerous tissue. pri-miRNA-944 strongly and positively correlated with TP63 (r = 0.739, p < 0.001) and with mature miRNA-944 expression (r = 0.691, p < 0.001). Also, TP63 expression significantly correlated with mature miRNA (r = 0.785, p < 0.001). Combined analysis of pri-miRNA-944 and mature miRNA-944 allowed to distinguish SCC tissue form AC with sensitivity of 93.3% and specificity of 100% (AUC = 0.978), and SCC from non-cancerous tissue with 92.9% sensitivity and 100% specificity (AUC = 0.992). CONCLUSION: We assumed that pri-miRNA-944 and miRNA-944 may be involved in early squamous-type differentiation of lung tumors. Moreover, analysis of both markers provided high diagnostic accuracy for SCC detection.

The diagnostic role of plasma circulating precursors of miRNA-944 and miRNA-3662 for non-small cell lung cancer detection.

INTRODUCTION: microRNA (miRNA) seem to be most attractive cancer markers due their crucial role in tumor development and possibility of their analysis using liquid biopsy. To date there is little known about role of miRNA precursors (pri-miRNA) in carcinogenesis and their utility as tumor markers. MATERIAL AND METHODS: miRNA-944 and miRNA-3662 precursors as potential non-small cell lung cancer (NSCLC) markers were analyzed in plasma samples of 56 patients in an early stage of NSCLC and 100 healthy individuals. RESULTS: Diagnostic test based on two studied markers for stage I-IIIA of the disease allowed to distinguish NSCLC from healthy individuals with 75.7% sensitivity and 82.3% specificity (AUC=0.898). pri-miRNA-944 distinguished SCC from AC with sensitivity of 78.6% and specificity of 91.7% (AUC=0.771), and pri-miRNA-3662 distinguished AC from SCC with 57.1% sensitivity and 90% specificity (AUC=0.845). CONCLUSION: Circulating pri-miRNA-944 and 3662 can improve non-invasive NSCLC detection of operable stages of SCC and AC. miRNA precursors could be considered as novel potential lung cancer biomarkers.

Analysis of primary-miRNA-3662 and its mature form may improve detection of the lung adenocarcinoma.

INTRODUCTION: Because of the alarming data concerning lung cancer morbidity and mortality, investigation of new molecular markers allowing early cancer detection is desirable. In the present study, we investigated the potential role of miRNA-3662 precursor (pri-miRNA-3662) as potential novel diagnostic marker of lung adenocarcinoma (AC). MATERIALS AND METHODS: Expression of miRNA-3662 and pri-miRNA-3662 was analyzed in 56 fresh-frozen tissues of non-small cell lung cancer and corresponding adjacent non-cancerous tissues using (NCT) qRT-PCR. Using receiver operating curves (ROC) analysis, the diagnostic accuracy of both studied markers for AC detection was assessed. RESULTS: miRNA-3662 and its precursor were significantly overexpressed in AC compared to squamous-cell carcinoma (SCC) and NCT. Combined analysis of pri-miRNA-3662 and mature miRNA-3662 allowed to distinguish AC tissue from SCC with sensitivity of 96% and specificity of 85.7% (AUC = 0.963), and SCC from non-cancerous tissue with 92% sensitivity and 92% specificity (AUC = 0.979). CONCLUSIONS: miRNA-3662 and its precursor are potentially involved in AC development. pri-miRNA seem to be novel interesting group of potential cancer biomarkers, because they demonstrate high diagnostic accuracy for tumor detection.

Impact of beliefs about pain control on perceptions of illness in surgical patients.

OBJECTIVES: Adequacy of pain management in surgical patients is a major contributor to overall treatment outcomes and positive illness perceptions. However, it may be subjectively predetermined by a patient's beliefs about pain control. This study assesses the relationships between beliefs about pain control and perceptions of illness in thoracic surgical patients. MATERIALS AND METHOD: A total of 135 patients (72 women and 63 men; mean age 58.4±14.25y) were enrolled in the questionnaire study based on the Beliefs about Pain Control Questionnaire (BPCQ) by S. Skevington and the Multidimensional Essence of Disease and Illness Scale (MEDIS) by J. Sak. Analyses were conducted with use of the k-means clustering technique and one-way ANOVA. RESULTS: Applied classification revealed 3 different clusters of patients with regard to their beliefs about pain control: 1) weak, undifferentiated pain control; 2) intensified influence of chance pain control; 3) strong undifferentiated pain control. Significant differences in illness perceptions between clusters were disclosed in 3 MEDIS dimensions: self-realization constraints (F=4.70; p=0.01; 1 vs. 3), mental dysfunction (F=3.44, p=0.04; 1 vs. 3) and physical dysfunction (F=3.10, p=0.05; 1 vs 2). Patients in cluster 3 demonstrated a greater feeling of self-realization constraints and mental dysfunction than in cluster 1, whereas patients in cluster 2 perceived physical dysfunction as a greater distress than those in cluster 1. CONCLUSIONS: Beliefs about pain control significantly influence illness perceptions, and thus may affect the results of treatment in surgical patients. Psychological modelling of beliefs about pain control may offer a valuable way to improve overall clinical outcomes.

Multiple recurrences of early-stage, endometrioid-type G2 endometrial cancer with a long-time follow-up: A case study.

The recurrence after a long-time free period of time, in women primarily operated on for early-stage of endometrial cancer (EC), is a unique phenomenon. Currently, we present the case of a 59-year-old woman with multiple recurrences from the moderately-differentiated, stage Ib, endometrioid-type, uterine cancer. All recurrences were pathologically proven to originate from the primary tumor, and the patient expired 12 years after the primary surgery for disseminated neoplasm. We summarize the current data to give a short overview of the role of late recurrences in women operated on for early-stage EC.

Utility of kynurenic acid for non-invasive detection of metastatic spread to lymph nodes in non-small cell lung cancer.

BACKGROUND: Kynurenic acid (KYNA) is a side-stream product of the kynurenine metabolic pathway that plays a controversial role in malignancies either enabling escape of malignant cells from immune surveillance or exerting antiproliferative effect on cancer cells, and is associated with differences in invasiveness related to metastatic spread to lymph nodes in lung cancer. Nodal involvement is a significant negative prognostic factor usually considered a contraindication for primary surgical resection. OBJECTIVE: To assess potential value of circulating KYNA for non-invasive identification of patients with metastatic lymph nodes (N+) in non-small cell lung cancer (NSCLC). METHODS: KYNA level in venous blood serum was determined with use of high performance liquid chromatography (HPLC) in 312 subjects including 230 patients with NSCLC and 32 healthy controls. RESULTS: Circulating KYNA level in NSCLC patients was higher than in controls (93.6±61.9 pmol/ml vs. 31.4±16.6 pmol/ml; p=2.2•10(-15)) and positively correlated with N (R=0.326; p=2•(10-6)) but not with T or M stage (p>0.05). In N+ patients it was higher than in N0 patients (137.7±51.8 pmol/ml vs. 71.9±41.7 pmol/ml; p=4.8•10(-16)). KYNA effectively discriminated N+ from N0 patients at a cut-off value 82.3 pmol/ml with sensitivity 94.7% (95%CI 87.1-98.5%), specificity 80.5% (95%CI 73.4-86.5%), negative predictive value NPV=96.8%, PPV=70.5% and area under the ROC curve AUC=0.900 (95%CI 0.854-0.935; p=0.0001). DISCUSSION AND CONCLUSION: Circulating KYNA level measurement offers reliable non-invasive discrimination between N0 and N+ patients in NSCLC. Robust discriminatory characteristics of KYNA assay predestines it for clinical use as an adjunct facilitating selection of candidates for primary surgical resection.

Prognostic model of survival for typical bronchial carcinoid tumours: analysis of 1109 patients on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours Working Group.

OBJECTIVES: Typical carcinoids (TCs) are uncommon, slow-growing neoplasms, usually with high 5-year survival rates. As these are rare tumours, their management is still based on small clinical observations and no international guidelines exist. Based on the European Society of Thoracic Surgeon Neuroendocrine Tumours Working Group (NET-WG) Database, we evaluated factors that may influence TCs mortality. METHODS: Using the NET-WG database, an analysis on TC survival was performed. Overall survival (OS) was calculated starting from the date of intervention. Predictors of OS were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: gender, age, smoking habit, tumour location, previous malignancy, Eastern Cooperative Oncology Group (ECOG) performance status (PS), pT, pN, TNM stage and tumour vascular invasion. The final model included predictors with P ≤ 0.15 after a backward selection. Missing data in the evaluated predictors were multiple-imputed and combined estimates were obtained from five imputed data sets. RESULTS: For 58 of 1167 TC patients vital status was unavailable and analyses were therefore performed on 1109 patients from 17 institutions worldwide. During a median follow-up of 50 months, 87 patients died, with a 5-year OS rate of 93.7% (95% confidence interval: 91.7-95.3). Backward selection resulted in a prediction model for mortality containing age, gender, previous malignancies, peripheral tumour, TNM stage and ECOG PS. The final model showed a good discrimination ability with a C-statistic equal to 0.836 (bootstrap optimism-corrected 0.806). CONCLUSIONS: We presented and validated a promising prognostic model for TC survival, showing good calibration and discrimination ability. Further analyses are needed and could be focused on an external validation of this model.

Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

BACKGROUND: To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. METHODS: This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. RESULTS: Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). CONCLUSIONS: The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated.

Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group†.

OBJECTIVES: In 2012, the European Society of Thoracic Surgeons (ESTS) created the Lung Neuroendocrine Tumors Working Group (NETs-WG) with the aim to develop scientific knowledge on clinical management of such rare neoplasms. This paper outlines the outcome and prognostic factors of two aggressive NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs). METHODS: Using the ESTS NETs-WG database, we retrospectively collected data on 261 patients in seven institutions in Europe, between 1994 and 2011. We used a Cox regression model to evaluate variables affecting patient survival and disease-free survival. Univariate and multivariate analysis were also carried out. RESULTS: Five-year overall survival rates for ACs and LCNCs were 77 vs 28% (P < 0.001), respectively. We found that for ACs, age (P < 0.001), tumour size (P = 0.015) and sub-lobar surgical resection (P = 0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumours (P = 0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases developed in 93 patients and were statistically more frequent in LCNCs (P = 0.02). CONCLUSIONS: The biological aggressiveness of ACs and LCNCs has been demonstrated with this study. Our aim is to confirm these results with enhanced data collection through the ESTS NETs database.

[Single nucleotide polymorphisms in lung cancer patients and cisplatin treatment]. / Polimorfizm pojedynczych nukleotydów u pacjentów chorych na raka pluca a leczenie cisplatyna.

Lung cancer is a major cause of mortality worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of all cases of lung cancer. Despite efforts to develop and improve early screening methods, the majority of tumors are detected at advanced stages. For over 30 years, cisplatin (CDDP), or any of its analogues, has been used in the treatment of many types of tumors, including lung cancer. The use of platinum-based chemotherapeutics is limited by their toxicity and later on by the development of chemoresistance by tumor cells. The molecular mechanisms of CDDP resistance are not fully resolved. Genetic variants of DNA repair proteins, as well as proteins involved in drug accumulation or detoxification, play a crucial role in determining the cell's response to platinum-based chemotherapy. The identification of selected gene polymorphisms could improve the prognosis of a patient's response to therapy and overall survival. In this review we will focus on the gene polymorphisms involved in CDDP resistance, in particular in lung tumors, and discuss their potential as prognosis and survival markers.

Serum kynurenic acid: possible association with invasiveness of non-small cell lung cancer.

The lung adenocarcinoma is considered more aggressive than other types of non-small cell lung cancer. As metabolites of tryptophan degradation along the kynurenine pathway, including kynurenic acid, have been shown to induce immunosuppression and facilitate escape of tumor cells from immune surveillance, a hypothesis was set up that differences in biological behavior between types of lung cancer may be associated with altered activity of the kynurenine metabolic pathway. The aim of the study was to determine kynurenic acid levels in the serum of patients with bronchial adenocarcinoma for comparison with other types of non-small cell lung cancer. A total of 227 patients with non-small cell lung cancer were enrolled in the study, including 71 with adenocarcinoma and 96 with squamous cell carcinoma. Serum kynurenic acid concentration was determined with use of high performance liquid chromatography and fluorometry. The level of kynurenic acid in the serum of patients with adenocarcinoma was significantly higher than in those with squamous cell lung cancer (107.1 ± 62.8 pmol/ml; 95%CI: 92.4 to 132.3 pmol/ml versus 82.1 ± 47.6 pmol/ml; 95%CI: 78.5 to 91.2 pmol/ml, respectively; p = 0.027). Differences between other histological types of lung cancer were insignificant. We conclude that increased activity of kynurenine metabolic pathway manifested by elevated serum kynurenic acid level may be one of the factors associated with clinically distinct biological behavior of adenocarcinoma, in particular high invasiveness and rapid progression.

Differences in psychological perception of lung cancer between patients, medical staff and medical students.

OBJECTIVES: In clinical practice, medical staff is often unaware that what they think about patient's disease differs much from the perceptions and feelings of the patient. The aim of the study was to analyse the differences in psychological perception of lung cancer between patients treated with combined regimen for lung cancer (n = 30), medical staff (n = 94) and medical students (n = 303). METHODS: A total of 427 persons were enrolled in this questionnaire study using Imagination and Perception of Illness Scale (IPIS) by Sak. The IPIS scale items described: loss of motivation to carry out specific activities (eight items), mental sphere destruction (six items), physical sphere destruction (eight items), pessimism (four items), being a burden to others (three items) and loss of control over the illness (three items). A seven-point scale from '0', meaning the choice of maximum positive feature, to '6', meaning the choice of maximum negative feature, was used. The higher result obtained within a given factor signified the more negative perception of the illness. RESULTS: In all IPIS items, the results among patients were significantly lower than among medical staff or students (P = 0.018 and P = 0.001, respectively). Medical staff and students perceive lung cancer as causing more profound destruction in patient's mental and physical spheres than patients do. CONCLUSIONS: Patients treated for lung cancer with combined regimen perceive their disease more optimistically than what is imagined by medical staff and students, and may underestimate the threat. It may be explained by psychological adaptation of patients to their disease during prolonged treatment. We believe that informing lung cancer patients in detail about their illness should be recommended to enhance self-awareness and doctor-patient cooperation.

Suboptimal perception of illness due to self-realization constraints impairs psychological welfare in surgical patients.

OBJECTIVE: Recognizing patients' psychological problems and understanding their social needs constitute important tasks for medical personnel, because these issues substantially contribute to overall outcome of treatment. People afflicted with surgical diseases need to determine the sense of everyday pursuits and activities and balance it against the therapeutic process. The aim of the study was to assess the relationships between the perception of illness, satisfaction with life and meaning of life among surgical patients. METHODS: A total of 225 patients undergoing surgical treatment in the thoracic surgery department were enrolled in the questionnaire study using Multidimensional Essence of Disease and Illness Scale (MEDIS), Satisfaction With Life Scale (SWLS) and Life Meaningfulness Scale (LMS). Relationships between variables were assessed with Pearson's correlation. RESULTS: The analysis disclosed negative correlations between the perception of the disease in the light of self-realization constraints and the feeling of satisfaction with one's life (R = -0.25; P < 0.01), an affective component of the LMS (R = -0.29; P < 0.001) and the total result of the LMS (R = -0.21; P < 0.01). Similar relationships were observed between the MEDIS dimension describing a disease as a social withdrawal and the total result of the SWLS (R = -0.21; P < 0.05) and the affective component of the LMS (R = -0.23; P < 0.01). CONCLUSIONS: Suboptimal hospitalization-related perception of the disease due to self-realization constraints profoundly impairs psychological welfare of patients and may exert negative impact on the overall outcome of treatment. We believe that surgical patients require early psychological, social and spiritual support to prevent these harmful psycho-social consequences of illness and hospital stay. Preoperative clinical application of presented scales may be useful to select patients who require more psychological attention in providing information about planned surgical treatment and expected outcomes.

Predictive and prognostic value of preoperative symptoms in the surgical treatment of pulmonary aspergilloma.

BACKGROUND: Surgical resection is widely accepted as the treatment of choice for pulmonary aspergilloma (PA). However, the technique involved ranks among the most challenging in thoracic surgery and remains associated with considerable morbidity and mortality. To improve the outcomes, it is essential to establish clear recommendations for optimal timing of surgery and selection of patients. To facilitate this, we analyzed the impact of preoperative clinical factors on the results of treatment. METHODS: Medical records of patients treated surgically for PA between 1979 and 2007 were retrospectively reviewed for clinical variables of potential impact on the surgical outcome with emphasis on preoperative symptoms. RESULTS: Sixty-four patients, including 22 cases of simple aspergilloma and 42 cases of complex aspergilloma were enrolled in the study. Univariable analysis followed by multivariable logistic regression identified weight loss and massive hemoptysis as risk factors for postoperative morbidity [odds ratio (OR) = 8.856, P = 0.006 and OR = 6.9, P = 0.021, respectively]. Ten-year cumulative survival in simple aspergilloma and complex aspergilloma was 88.3% and 70.6%, respectively (P = 0.042). Multivariable analysis by Cox proportional hazard model showed that younger age and lack of massive hemoptysis were independent favorable prognostic factors [hazard ratio (HR) = 1.13, P = 0.0004 and HR = 4.71, P = 0.0319, respectively). CONCLUSION: Massive hemoptysis is an independent unfavorable predictive and prognostic factor in the surgical treatment of PA. We believe that in operable cases, early surgical resection may be recommended even in asymptomatic patients. This strategy may prevent development of life-threatening symptoms and offers a realistic chance of permanent cure with acceptable mortality and morbidity.

Combination chemotherapy for Hodgkin's lymphoma during pregnancy: favorable outcome for mother and child.

The incidence of malignant neoplasms in pregnant women is rising dramatically. The management of such cases poses unusual medical and ethical challenges, particularly in hematological malignancies, when potentially teratogenic chemotherapy is indicated. We report a case of stage IIA nodular sclerosis Hodgkin's lymphoma (HL), diagnosed in a 24-year-old woman at 18 weeks of gestation. Individualized combination chemotherapy according to etoposide-vinblastine-doxorubicin (EVA) regimen was administered, resulting in effective local control of the disease and improvement in the patient's general condition. At the 36th week of pregnancy, the patient delivered a healthy female infant by elective cesarian section. Four weeks later, bleomycin-dacarbazine-doxorubicin-vinblastine (ABVD) chemotherapy was commenced, which provided complete remission after five cycles. Individualized chemotherapy for HL according to EVA regimen during the second and third trimesters of pregnancy, with early cesarian delivery, followed by ABVD regimen, provided a positive outcome both for the mother and her child. This strategy may be considered as an alternative for the treatment of HL in pregnancy, and deserves further clinical assessment.

Surgical treatment of mediastinal parathyroid adenoma: rationale for intraoperative parathyroid hormone monitoring.

BACKGROUND: Recent publications have recommended parathyroidectomy guided solely by preoperative imaging. However, when the parathyroid adenoma is located deep in the mediastinum, the surgeon often encounters difficulties to localize and completely remove all hyperfunctioning parathyroid tissues. Thus, we hypothesized that patients with mediastinal adenoma differ substantially from cervical cases and require a specific strategy. The aim of this study was to evaluate the efficacy of intraoperative serum parathyroid hormone monitoring (ioPTH) used to guide completeness of targeted mediastinal parathyroidectomy. METHODS: In a 10-year period, 33 patients underwent targeted mediastinal parathyroidectomy with ioPTH for primary sporadic hyperparathyroidism. A greater than 50% drop in ioPTH was considered confirming successful resection. If ioPTH failed to decline adequately, the operation was extended to complete cervical exploration. We analyzed the impact of ioPTH on the final surgical outcome. RESULTS: In 26 patients the adenoma was correctly identified and removed at targeted mediastinal parathyroidectomy. In 7 patients lack of adequate ioPTH drop after targeted mediastinal parathyroidectomy triggered continued exploration, providing success at complete cervical exploration in 6 patients. In 1 patient this strategy failed owing to an undiagnosed lesion in the posterior mediastinum. Use of ioPTH decreased the failure rate from a potential 21.2% without ioPTH to 3% in the actual series. CONCLUSIONS: Mediastinal parathyroid adenoma represents a distinct subset of primary hyperparathyroidism and requires a specific diagnostic and therapeutic approach. In these cases ioPTH monitoring is a reliable and effective method to confirm curative resection. It is an important adjunct predictor of postoperative successful outcome, which allows a low failure rate and avoids unnecessary reoperations.