Do Spirituality and Faith Make a Difference? Report from the Southern European Psycho-Oncology Study Group

OBJECTIVE: In the last decade, some attention has been given to spirituality and faith and their role in cancer patients' coping. Few data are available about spirituality among cancer patients in Southern European countries, which have a big tradition of spirituality, namely, the Catholic religion. As part of a more general investigation (Southern European Psycho-Oncology Study--SEPOS), the aim of this study was to examine the effect of spirituality in molding psychosocial implications in Southern European cancer patients. METHOD: A convenience sample of 323 outpatients with a diagnosis of cancer between 6 to 18 months, a good performance status (Karnofsky Performance Status > 80), and no cognitive deficits or central nervous system (CNS) involvement by disease were approached in university and affiliated cancer centers in Italy, Spain, Portugal, and Switzerland (Italian speaking area). Each patient was evaluated for spirituality (Visual Analog Scale 0-10), psychological morbidity (Hospital Anxiety and Depression Scale--HADS), coping strategies (Mini-Mental Adjustment to Cancer--Mini-MAC) and concerns about illness (Cancer Worries Inventory--CWI). RESULTS. The majority of patients (79.3%) referred to being supported by their spirituality/faith throughout their illness. Significant differences were found between the spirituality and non-spirituality groups (p ≤ 0.01) in terms of education, coping styles, and psychological morbidity. Spirituality was significantly correlated with fighting spirit (r = -0.27), fatalism (r = 0.50), and avoidance (r = 0.23) coping styles and negatively correlated with education (r = -0.25), depression (r = -0.22) and HAD total (r = -0.17). SIGNIFICANCE OF RESULTS: Spirituality is frequent among Southern European cancer patients with lower education and seems to play some protective role towards psychological morbidity, specifically depression. Further studies should examine this trend in Southern European cancer patients.

Laparoscopic Assisted Vaginal Hysterectomy Versus Vaginal Hysterectomy

Introduction: Hysterectomy is the commonest gynecologic operation, performed for malignant and benign conditions. There are many approaches to hysterectomy for benign disease. Studies comparing the techniques have showed that vaginal hysterectomy has benefits in terms of reduced hospital stay, faster recovery and less operating time. Objective: The purpose of this study is to compare the surgical and immediate postoperative outcomes of Laparoscopic Assisted Vaginal Hysterectomy (LAVH) with those of Vaginal Hysterectomy (VH). Methods: Retrospective descriptive study, comparing two groups of women who underwent LAVH or VH in our department during a 24 months period, from January 2009 to December 2010. The two groups were compared regarding age, vaginal deliveries, previous abdominal surgery, uterine and adnexal pathology, intra-operative and post-operative complications, uterus weight, blood loss and number of days until discharge. Results: In our study 42 LAVH and 99 VH were included, with a patient mean age of 47 and 59, respectively. The most frequent indication for hysterectomy was fibroids (80%) for LAVH and POP(58.6%) for HV. In LAVH group 47.6% of patients had previous abdominal surgery, vs 28.2% in VH group. The medium operative time was 167 minutes for LAVH vs 99 minutes for HV. The intra-operative complications were one case (2%) of accidental incision of rectum in LAVH, and one bladder incision in the VH (1%). There were 3 conversions to laparotomy for difficult technique (7%) in LAVH group. There were no significant post-operative complications for LAVH. In VH group there were 2 cases of haemoperitoneum (2%) and 1 case requiring blood transfusion (1%). The mean time for discharge was 4.23 days for LAVH and 4.46 days for VH. Conclusions: In our study, the main advantage for VH was the reduced operative time. In terms of time to discharge there was no difference between the 2 groups. The main intra-operative complication of LAVH was the risk of conversion to laparotomy, but post-operatively this procedure had fewer complications than VH. In conclusion, LAVH is a safe option for women requiring hysterectomy in cases where VH is anticipated to be technically difficult.

Recurrence After Operative Management of Intrahepatic Cholangiocarcinoma

INTRODUCTION: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC. METHODS: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. RESULTS: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. CONCLUSION: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.

Ambulatory Hysteroscopy Results Post-Menopause: Comparative Study Between Patients With and Without Metrorrhagia

Our objective was to compare the results of ambulatory hysteroscopy in postmenopausal women with and without uterine bleeding. A retrospective descriptive study was carried out on 236 women who were at least 2 years into the menopause, who were not undergoing hormone treatment and who had had abnormal pelvic ultrasound results. Of these women, 150 were asymptomatic and 86 reported haemorrhage. Diagnostic and operative outpatient hysteroscopy was performed between January 2002 and December 2003. There was no difference between the two groups regarding age of patients, age of menopause and presence of at least one of the risk factors for endometrial carcinoma evaluated, although obesity was more frequent in the symptomatic group. Abnormal ultrasound results for these women corresponded in the majority of cases to intracavitary disease, and the absence of organic endometrial pathology was 9.3% vs 11.3% in each group. The more frequent pathology was benign endometrial polyps (64% in bleeding patients and 84.7% in asymptomatic ones). Endometrial carcinoma was diagnosed in 23.3% of women with metrorrhagia and in 1.3% of asymptomatic women. We diagnosed 2.6% of malignancy inside polyps. Hysteroscopy results were confirmed by histology in 90.3% of cases. See and treat in one session was achieved in 91% of benign endometrial polyps. Ambulatory hysteroscopy has high sensitivity and specificity for intracavitary pathology and high tolerability and safety. See and treat in one session can be achieved in the majority of lesions with indication for excision. These results make us advise our menopausal patients with abnormal uterine bleeding to undergo diagnostic hysteroscopy complemented with biopsy.

Métodos Preditivos de Metastização Ganglionar Adicional em Cancro da Mama com Gânglio Sentinela Positivo

Objectivos As recomendações para a realização de linfadenectomia axilar nos doentes com cancro da mama em estádio precoce e sujeitas a biópsia de gânglio sentinela com presença de macrometástase foram recentemente actualizadas, baseadas nos últimos estudos publicados (Z0011 e IBCSG 23-01). Mantém-se, no entanto, alguma controvérsia na decisão de não realização de cirurgia radical axilar nos doentes com gânglio sentinela positivo. Têm sido desenvolvidos métodos preditivos de metastização ganglionar adicional. Um dos mais conhecidos, desenvolvido no Memorial Sloan-Kettering Cancer Center (MSKCC), recorre a variáveis do tumor e características do gânglio sentinela. Mais recentemente com a utilização de métodos moleculares (como o One Step Nucleic Acid - OSNA) para estudo do gânglio sentinela tem sido avaliada a capacidade preditiva da quantidade total de cópias mRNA da citoqueratina 19. Pretende-se estudar na nossa amostra a capacidade preditiva do nomograma do MSKCC e da carga tumoral total. Propõe-se ainda avaliar o número de macrometástases encontradas na biópsia de gânglio sentinela e sua relação na metastização ganglionar adicional. Material e métodos Avaliação retrospectiva de 819 doentes com cancro da mama (Tis – T2) submetidos a biópsia de gânglio sentinela no Centro Hospitalar de Lisboa Central durante o período de 1 de Janeiro de 2005 e 31 de Dezembro de 2013. Foram identificados 123 doentes com gânglio sentinela positivo que realizaram linfadenectomia axilar imediata. A análise do gânglio sentinela foi executada por métodos histológicos em 78 doentes e por método molecular (OSNA) em 45 doentes. Os dois grupos foram estudados separadamente, tendo sido no primeiro aplicado o nomograma do MSKCC e no segundo obtida a carga tumoral total. Utilizou-se o modelo de regressão logística para analisar o poder preditivo e discriminativo destes dois métodos. Adicionalmente, para avaliar a potencial importância do número de macrometástases na metastização ganglionar adicional, foi ajustado um novo modelo de regressão logística considerando esta variável e a carga tumoral total. Ambos os métodos foram também avaliados através da área sob a curva ROC (AUC) e do teste de Hosmer-Lemeshow, respectivamente. O nível de significância adoptado foi α = 0.05. O estudo estatístico foi realizado com recurso ao SPSS. Resultados No grupo em que foi aplicado o nomograma do MSKCC obteve-se uma AUC=0.67 (I.C. 95% = 0.55 – 0.79), e no grupo em que foi avaliada a carga tumoral total uma AUC=0.78 (I.C. 95% = 0.64 – 0.91). Os poderes preditivos de ambos foram, respectivamente, p=0.15 e p=0.46. Constatou-se que o desempenho do modelo resultante da junção da carga tumoral total com o número de macrometástases encontradas no estudo do gânglio sentinela foi bastante satisfatório (AUC=0.87, I.C 95% = 0.76 – 0.98, poder preditivo p=0.33). Conclusão Foi validado externamente o modelo do MSKCC para a amostra em estudo, apresentando uma menor acuidade discriminativa em relação ao estudo original (AUC=0.67 versus AUC=0.75). Por outro lado, após verificação da homogeneidade de ambos os grupos no que diz respeito a todas as variáveis de interesse, conclui-se que a carga tumoral total aparenta uma maior acuidade preditiva e discriminativa na metastização ganglionar adicional que o nomograma do MSKCC. Quando desenvolvido um modelo agregando a carga tumoral total avaliada por OSNA e o número de macrometástases no gânglio sentinela, obteve-se uma capacidade discriminativa ainda superior. A carga tumoral total avaliada por OSNA, ou esta incluída num modelo conjunto com o número de macrometástases obtidas no estudo do gânglio sentinela, poderão representar importantes ferramentas preditivas. Serão no entanto necessários estudos adicionais com amostras superiores para consolidar estes resultados. Bibliografia 1. 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Multicenter validation of two nomograms to predict non-sentinel node involvement in breast cancer. Clin Transl Oncol. Fevereiro de 2013;15(2):117–23. 5. Banerjee SM, Michalopoulos NV, Williams NR, Davidson T, El Sheikh S, McDermott N, et al. Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: experience from a London teaching hospital. Breast. Agosto de 2014;23(4):378–84. 6. Peg V, Espinosa-Bravo M, Vieites B, Vilardell F, Antúnez JR, de Salas MS, et al. Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients. Breast Cancer Res Treat. Maio de 2013;139(1):87–93. 7. Tiernan JP, Verghese ET, Nair A, Pathak S, Kim B, White J, et al. Systematic review and meta-analysis of cytokeratin 19-based one-step nucleic acid amplification versus histopathology for sentinel lymph node assessment in breast cancer. Br J Surg. Março de 2014;101(4):298–306. 8. Heilmann T, Mathiak M, Hofmann J, Mundhenke C, van Mackelenbergh M, Alkatout I, et al. Intra-operative use of one-step nucleic acid amplification (OSNA) for detection of the tumor load of sentinel lymph nodes in breast cancer patients. J Cancer Res Clin Oncol. Outubro de 2013;139(10):1649–55. 9. Chaudhry A, Williams S, Cook J, Jenkins M, Sohail M, Calder C, et al. The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making. Eur J Surg Oncol. Fevereiro de 2014;40(2):150–7.

Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological Group

BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Infections After Liver Transplantation: A Retrospective, Single-Center Study

Objective. To access the incidence of infectious problems after liver transplantation (LT). Design. A retrospective, single-center study. Materials and Methods. Patients undergoing LT from January 2008 to December 2011 were considered. Exclusion criterion was death occurring in the first 48 hours after LT. We determined the site of infection and the bacterial isolates and collected and compared recipient’s variables, graft variables, surgical data, post-LT clinical data. Results. Of the 492 patients who underwent LT and the 463 considered for this study, 190 (Group 1, 41%) developed at least 1 infection, with 298 infections detected. Of these, 189 microorganisms were isolated, 81 (51%) gram-positive bacteria (most frequently Staphylococcus spp). Biliary infections were more frequent (mean time of 160.4 167.7 days after LT); from 3 months after LT, gram-negative bacteria were observed (57%). Patients with infections after LT presented lower aminotransferase levels, but higher requirements in blood transfusions, intraoperative vasopressors, hemodialysis, and hospital stay. Operative and cold ischemia times were similar. Conclusion. We found a 41% incidence of all infections in a 2-year follow-up after LT. Gram-positive bacteria were more frequent isolated; however, negative bacteria were commonly isolated later. Clinical data after LT were more relevant for the development of infections. Donors’ variables should be considered in future analyses.

Intravenous Busulfan for Autologous Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia: a Survey of 952 Patients on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.