[Diagnosis, treatment and follow up of prostata cancer]

Prostate cancer is the most frequent diagnosed malignancy in men with an increasing incidence. In well informed men between the age of 50 and 70 years screening should be offered when requested. Not every newly diagnosed prostate cancer requires immediate treatment. Curative treatment should be offered to men with a minimal life expectancy of 10 years. In men older than 50-75 years, therefore further screening is not necessary due to a lack of a therapeutic consequence. Curative treatment options enclose as the gold standard surgical removal, i.e. open radical prostatectomy with pelvic lymph node dissection, and radio-oncologic treatments, be it percutaneous radiation therapy, brachytherapies or a combination thereof. Palliative treatment options are mainly hormonal treatment (medical or surgical androgen deprivation), local radiation, treatment with bisphosphonates, chemotherapy and surgical desobstruction of the prostate. Regular follow up allows for early detection of recurrences and an active treatment concept.

High-risk clinical stage I nonseminomatous germ cell tumors: the case for chemotherapy

Testis cancer is the most frequent solid malignancy in young men. The majority of patients present with clinical stage I disease and about 50% of them are nonseminomatous germ cell tumors. In this initial stage of disease there is a subgroup of patients at high risk with a likelihood of more than 50% for relapse. Treatment options for these patients include: retroperitoneal lymph node dissection (RPLND), albeit 6-10% of patients will relapse outside the field of RPLND, active surveillance with even higher relapse rates and adjuvant chemotherapy. As most of these patients have the chance to become long-term survivors, avoidance of long-term side effects is of utmost importance. This review provides information on the potential of chemotherapy to achieve a higher chance of cure for patients with high-risk clinical stage I disease than its therapeutic alternatives and addresses toxicity and dose dependency.

Removal of Limited Nodal Disease in Patients Undergoing Radical Prostatectomy: Long-Term Results Confirm a Chance for Cure

Abstract PURPOSE: In 2003 we reported on the outcomes of 88 patients with node positive disease who underwent radical prostatectomy and pelvic lymph node dissection (median 21 nodes) between 1989 and 1999. Patients with limited nodal disease appeared to have a good chance of long-term survival, even without immediate adjuvant therapy (androgen deprivation therapy and/or radiotherapy). In this study we update the followup in these patients and verify the reported projected probability of survival. MATERIALS AND METHODS: The projected 10-year cancer specific survival probability after the initially reported followup of 3.2 years was 60% for these patients with node positive disease. The outcome has been updated after a median followup of 15.6 years. RESULTS: Of the 39 patients with 1 positive node 7 (18%) remained biochemically relapse-free, 11 (28%) showed biochemical relapse only and 21 (54%) experienced clinical progression. Of these 39 patients 22 (57%) never required deferred androgen deprivation therapy and 12 (31%) died of prostate cancer. All patients with 2 (20) or more than 2 (29) positive nodes experienced biochemical relapse and only 5 (10%) of these 49 experienced no clinical progression. Of these 49 patients 39 (80%) received deferred androgen deprivation therapy. CONCLUSIONS: Biochemical relapse is likely in patients with limited nodal disease after radical prostatectomy and pelvic lymph node dissection, but for 47% of patients this does not imply death from prostate cancer. Patients with 1 positive node have a good (75%) 10-year cancer specific survival probability and a 20% chance of remaining biochemical relapse-free even without immediate adjuvant therapy.

Local recurrence after retropubic radical prostatectomy for prostate cancer does not exclusively occur at the anastomotic site

What's known on the subject? and What does the study add? Local recurrence after radical prostatectomy (RP) for clinically organ-confined prostate cancer is largely assumed to occur at the anastomotic site, as reflected in European and North American guidelines for adjuvant and salvage radiotherapy after RP. However, the exact site of local recurrence often remains undetermined. The present study shows that roughly one out of five patients with local recurrence after RP has histologically confirmed tumour deposits at the resection site of the vas deferens, clearly above the anastomotic site. This should be considered when offering ‘blind’ radiotherapy to the anastomotic site in patients with biochemical recurrence alone. Objective To determine the anatomical pattern of local recurrence and the corresponding clinical and pathological variables of patients treated with retropubic radical prostatectomy (RRP). Patients and Methods In all, 41 patients with biopsy confirmed local recurrence after extended pelvic lymph node dissection and RRP performed between January 1992 and December 2009 at a single tertiary referral academic centre were retrospectively studied. The site of local recurrence as assessed on computed tomography or magnetic resonance imaging was reviewed. Two sites were identified: the vesicourethral anastomotic site and the cranial resection margin of the surgical bed, where the vas deferens was transected and clipped. Age and serum prostate-specific antigen (PSA) level at RRP, pathological tumour and nodal stage, Gleason score, tumour location, surgical margin status, age and serum PSA level at the time of local recurrence, and time to diagnosis of local recurrence were assessed for the two sites and compared with the chi-square or Wilcoxon rank sum tests as appropriate. Results Local recurrence occurred at the anastomotic site in 31/41 (76%) patients and at the resection site of the vas deferens in nine of 41 (22%) patients. One patient had distinct lesions at both sites. There was no significant difference in any of the clinical and pathological variables between patients with local recurrence in the former and latter site. Conclusion Most local recurrences after RRP occur exclusively at the anastomotic site. However, 22% of locally recurrent cases had tumour at the resection site of the vas deferens. This should be taken into account when considering adjuvant or salvage radiation therapy.

The impact of pelvic venous pressure on blood loss during open radical cystectomy and urinary diversion: Results from a secondary analysis of a randomized clinical trial

PURPOSE Blood loss and blood substitution are associated with higher morbidity after major abdominal surgery. During major liver resection, low local venous pressure, has been shown to reduce blood loss. Ambiguity persists concerning the impact of local venous pressure on blood loss during open radical cystectomy. We aimed to determine the association between intraoperative blood loss and pelvic venous pressure (PVP) and determine factors affecting PVP. MATERIAL AND METHODS In the frame of a single-center, double-blind, randomized trial, PVP was measured in 82 patients from a norepinephrine/low-volume group and in 81 from a control group with liberal hydration. For this secondary analysis, patients from each arm were stratified into subgroups with PVP <5 mmHg or ≥5 mmHg measured after cystectomy (optimal cut-off value for discrimination of patients with relevant blood loss according to the Youden's index). RESULTS Median blood loss was 800 ml [range: 300-1600] in 55/163 patients (34%) with PVP <5 mmHg and 1200 ml [400-3000] in 108/163 patients (66%) with PVP ≥5 mmHg; (P<0.0001). A PVP <5 mmHg was measured in 42/82 patients (51%) in the norepinephrine/low-volume group and 13/81 (16%) in the control group (P<0.0001). PVP dropped significantly after removal of abdominal packing and abdominal lifting in both groups at all time points (at begin and end of pelvic lymph node dissection, end of cystectomy) (P<0.0001). No correlation between PVP and central venous pressure could be detected. CONCLUSIONS Blood loss was significantly reduced in patients with low PVP. Factors affecting PVP were fluid management and abdominal packing.

Systematic Review and Cumulative Analysis of Oncologic and Functional Outcomes After Robot-assisted Radical Cystectomy

CONTEXT Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. OBJECTIVE To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. EVIDENCE SYNTHESIS The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3-55), with half of the series following an extended template (yield range: 11-55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83-100% in men for daytime continence and 66-76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. CONCLUSIONS Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. PATIENT SUMMARY Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.

Long-term outcome of patients with clinical stage I high-risk nonseminomatous germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and cisplatin chemotherapy

BACKGROUND To report the long-term results of adjuvant treatment with one cycle of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse. PATIENTS AND METHODS In a single-arm, phase II clinical trial, 40 patients with CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin each on days 1-3). Primary end point was the relapse rate. RESULTS Median follow-up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one BEP and died after three additional cycles of BEP chemotherapy. Three patients (7.5%) presented with a contralateral metachronous testicular tumor, and three (7.5%) developed a secondary malignancy. Three patients (7.5%) reported intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%). CONCLUSIONS Adjuvant chemotherapy with one cycle of modified-BEP is a feasible and safe treatment of patients with CS I NSGCT at high risk of relapse. In these patients, it appears to be an alternative to two cycles of BEP and to have a lower relapse rate than retroperitoneal lymph node dissection. If confirmed by other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line treatment option for this group of patients.

Predicting prostate cancer-specific outcome after radical prostatectomy among men with very high-risk cT3b/4 PCa: a multi-institutional outcome study of 266 patients

BACKGROUND The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option. METHODS In a multi-institutional cohort, 266 patients with very high-risk cT3b/4 PCa treated with RP were identified. All patients underwent RP and pelvic lymph-node dissection. Competing-risk analyses assessed 10-year CSM and OCM before and after stratification for age and Charlson comorbidity index (CCI). RESULTS Overall, 34 (13%) patients died from PCa and 73 (28%) from OCM. Ten-year CSM and OCM rates ranged from 5.6% to 12.9% and from 10% to 38%, respectively. OCM was the leading cause of death in all subgroups. Age and comorbidities were the main determinants of OCM. In healthy men, CSM rate did not differ among age groups (10-year CSM rate for ⩽64, 65-69 and ⩾70 years: 16.2%, 11.5% and 17.1%, respectively). Men with a CCI ⩾1 showed a very low risk of CSM irrespective of age (10-year CSM: 5.6-6.1%), whereas the 10-year OCM rates increased with age up to 38% in men ⩾70 years. CONCLUSION Very high-risk cT3b/4 PCa represents a heterogeneous group. We revealed overall low CSM rates despite the highly unfavorable clinical disease. For healthy men, CSM was independent of age, supporting RP even for older men. Conversely, less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment. Outcome after RP as the primary treatment option in cT3b/4 PCa patients is related to age and comorbidity status.

Open radical cystectomy: still the gold standard for muscle invasive bladder cancer

INTRODUCTION Muscle invasive bladder cancer is an unforgiving disease, and if untreated, it leads to death within 2 years of the diagnosis in >85 % of the patients. Long-term oncologic efficacy remains the ultimate standard that all procedures have to be measured by. In the past decades, open radical cystectomy (RC), extended pelvic lymph node dissection (PLND), and urinary diversion have been established as the gold standard. In the last few years, however, growing attention has been set on robotic-assisted radical cystectomy (RARC). RESULTS Even in the very long term, open RC has good oncological results and if an ileal neobladder is performed excellent functional results. Follow-up of patients after open RC exceeds more than a decade which is unsurpassed by any other technique. Its outcomes have been proven to be durable and cost-effective. Least perioperative complications as well as best oncological and functional results can be achieved if open RC and urinary diversion were performed in a high-volume hospital by high-volume surgeons and an experienced team. CONCLUSIONS Despite upcoming new technologies such as RARC, open RC following extended (PLND) remains the gold standard treatment for high-grade muscle invasive bladder cancer.

Standard cystectomy fits all: truth or myth?

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) followed by urinary diversion is the treatment of choice for muscle-invasive bladder cancer (BC) and non-invasive BC refractory to transurethral resection of the bladder (TUR-B) and/or intravesical instillation therapies. Since the morbidity and possible mortality of this surgery are relevant, care must be taken in the preoperative selection of patients for the various organ-sparing procedures (e.g., bladder-sparing, nerve sparing, seminal vesicle sparing) and various types of urinary diversion. The patient’s performance status and comorbidities, along with individual tumor characteristics, determine possible surgical steps during RC. This individualized approach to RC in each patient can maximize oncological safety and minimize avoidable side effects, rendering ‘standard’ cystectomy a surgery of the past.

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy

INTRODUCTION The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

QUALIDADE DE VIDA E ESTRATÉGIAS DE ENFRENTAMENTO DE MULHERES COM E SEM LINFEDEMA APÓS CÂNCER DE MAMA

O linfedema no membro superior é uma complicação inerente ao tratamento de câncer de mama. Caracterizado pelo aumento do volume do membro, leva às limitações físicas e funcionais, e impacto negativo no âmbito psicológico e social. O objetivo deste estudo foi investigar a qualidade de vida e seus domínios, as estratégias de enfrentamento frente ao câncer de mama, e a correlação entre essas variáveis. Este estudo foi realizado em um centro de saúde dedicado às mulheres, por quatro meses. Os instrumentos de avaliação foram: questionário de caracterização geral e específico do câncer de mama, perimetria dos membros superiores; questionários de qualidade de vida da Organização Européia de Pesquisa e Tratamento do Câncer, EORTC QLQ-30 e BR-23; e Inventário de Estratégias de Coping. Foram entrevistadas 82 mulheres, idade média de 57,4 anos (DV12,3), submetidas a tratamento cirúrgico de mama unilateral e esvaziamento axilar, sem metástase. O linfedema apresentou-se em 39,03% (32) e parece não interferir muito na qualidade de vida das mulheres pós-câncer de mama, sendo a função social a mais prejudicada. Sintomas relacionados à quimioterapia e a mama incomodam as mulheres de ambos grupos, porém os sintomas relacionados aos braços foram estatisticamente maiores nas portadoras de linfedema. As estratégias mais utilizadas pelas entrevistadas para enfrentar o câncer foram a reavaliação, resolução de problemas, fuga, suporte social e autocontrole, somente o autocontrole foi estatisticamente maior nas mulheres com linfedema. As estratégias de resolução de problemas, autocontrole e baixo suporte social podem ter colaborado para o desencadeamento do linfedema. Conclui-se que o uso de estratégias ativas e positivas para enfrentar o câncer de mama parece resultar na boa adaptação psicossocial

QUALIDADE DE VIDA E ESTRATÉGIAS DE ENFRENTAMENTO DE MULHERES COM E SEM LINFEDEMA APÓS CÂNCER DE MAMA

O linfedema no membro superior é uma complicação inerente ao tratamento de câncer de mama. Caracterizado pelo aumento do volume do membro, leva às limitações físicas e funcionais, e impacto negativo no âmbito psicológico e social. O objetivo deste estudo foi investigar a qualidade de vida e seus domínios, as estratégias de enfrentamento frente ao câncer de mama, e a correlação entre essas variáveis. Este estudo foi realizado em um centro de saúde dedicado às mulheres, por quatro meses. Os instrumentos de avaliação foram: questionário de caracterização geral e específico do câncer de mama, perimetria dos membros superiores; questionários de qualidade de vida da Organização Européia de Pesquisa e Tratamento do Câncer, EORTC QLQ-30 e BR-23; e Inventário de Estratégias de Coping. Foram entrevistadas 82 mulheres, idade média de 57,4 anos (DV12,3), submetidas a tratamento cirúrgico de mama unilateral e esvaziamento axilar, sem metástase. O linfedema apresentou-se em 39,03% (32) e parece não interferir muito na qualidade de vida das mulheres pós-câncer de mama, sendo a função social a mais prejudicada. Sintomas relacionados à quimioterapia e a mama incomodam as mulheres de ambos grupos, porém os sintomas relacionados aos braços foram estatisticamente maiores nas portadoras de linfedema. As estratégias mais utilizadas pelas entrevistadas para enfrentar o câncer foram a reavaliação, resolução de problemas, fuga, suporte social e autocontrole, somente o autocontrole foi estatisticamente maior nas mulheres com linfedema. As estratégias de resolução de problemas, autocontrole e baixo suporte social podem ter colaborado para o desencadeamento do linfedema. Conclui-se que o uso de estratégias ativas e positivas para enfrentar o câncer de mama parece resultar na boa adaptação psicossocial

Carcinoma da tiróide

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014