DaPeCa-1: diagnostic accuracy of sentinel lymph node biopsy in 222 patients with penile cancer at four tertiary referral centres - a national study from Denmark.

OBJECTIVES: To estimate the diagnostic accuracy of sentinel lymph node biopsy (SNB) in patients with penile cancer and assess SNB complications in a national multicentre setting. PATIENTS AND METHODS: Retrospectively data were collected from records in four university centres by one medical doctor covering all SNBs performed in Denmark between 1 January 2000 and 31 December 2010. Patients had either impalpable lymph nodes (LNs) in one or both groins, or had a palpable inguinal mass from which aspiration cytology failed to reveal malignancy. Patients were injected with nanocolloid technetium and had a scintigram recorded before the SNB. The primary endpoint was LN recurrence on follow-up. The secondary endpoint was complications after SNB. Diagnostic accuracy was computed. RESULTS: In all, 409 groins in 222 patients were examined by SNB. The median (interquartile range) follow-up of patients who survived was 6.6 (5-10) years. Of 343 negative groins, eight were false negatives. The sensitivity was 89.2% (95% confidence interval 79.8-95.2%) per groin. Interestingly, four of 67 T1G1 patients had a positive SNB. In all, 28 of 222 (13%) patients had complications of Clavien-Dindo grade I-IIIa. CONCLUSION: Penile cancer SNB with a close follow-up stages LN involvement reliably and has few complications in a national multicentre setting. Inguinal LN dissection was avoided in 76% of patients.

Preoperative blood pressure targets and effect on hemodynamics in pheochromocytoma and paraganglioma.

Patients with pheochromocytoma and paraganglioma (PPGL) are treated with α-adrenoceptor antagonists to improve peroperative hemodynamics. However, preoperative blood pressure targets differ between institutions. We retrospectively compared per- and postoperative hemodynamics in 30 patients with PPGL that were pretreated with phenoxybenzamine aiming at different blood pressure targets at two separate endocrine departments. All patients were subsequently undergoing laparoscopic surgery at Department of Urology, Herlev University hospital. Fourteen patients were treated targeting to symptomatic and significant orthostatic hypotension and 16 patients to a seated blood pressure below 130/80 mmHg. As a control group, we included 34 patients undergoing laparoscopic adrenalectomy for other reasons. The group titrated to orthostatic hypotension required a higher dose of phenoxybenzamine to achieve the blood pressure target. This group had less intraoperative systolic and diastolic blood pressure fluctuation (Mann-Whitney U test; P < 0.05) and less periods with heart rate above 100 b.p.m. (Mann-Whitney U test; P = 0.04) as compared to the group with a preoperative blood pressure target below 130/80 mmHg. Peroperative use of intravenous fluids were similar between the two groups, but postoperatively more intravenous fluids were administered in the group with a target of ortostatism. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. We conclude that phenoxybenzamine pretreatment targeting ortostatic hypotension may improve peroperative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.

Should we use laparoscopic adrenalectomy for metastases? Scandinavian multicenter study.

INTRODUCTION: Laparoscopic adrenalectomy for metastases is considered controversial. Multicenter retrospective study was performed to gain new knowledge in this issue. MATERIALS AND METHODS: From January 1997 till November 2008, 41 adrenalectomies were performed during follow-up of the patients operated for malignant tumors. The median age was 64 (52-77) years. Metastases were confirmed in 31/41 cases. Metastatic lesions were further studied and to define factors influencing on survival, patients were divided to sub-groups of metachronous/synchronous, tumor origin and tumor size. RESULTS: The median operative time was 104 (50-230) min, the median blood loss was 100 (0-500) ml. One procedure (3.2%) was converted. There were 3 (10.7%) intraoperative and 2 (7.4%) postoperative complications. The median tumor size was 6 (1.5-16) cm. Pathohistological analysis revealed 12 colorectal, 9 renal cell carcinoma, 5 lung carcinoma, 4 melanoma, and 1 hepatocellular metastases. The resection margin was not free in one case (3.7%). The median hospital stay was 2 (1-21) days. The median length of survival was 29 +/- 2.1 months for all patients. CONCLUSION: Laparoscopic adrenalectomy for metastases is feasible regardless of their sizes. However these procedures should be performed by highly skilled laparoscopic surgeon in a fully equipped operating room and with a coordinated operation team.

Robotic versus laparoscopic urological surgery: incidence of reoperation and complications.

Objective: To report the introduction of minimum invasive surgery in Denmark with focus on the reoperation and complication rates. Materials and methods: Data were prospectively collected at the national UroLap database. The database was established in 2003 in Denmark to register all laparoscopic urological procedures as well as their peri- and post-operative outcomes. In the period from 2009-2014, 10,843 patients were registered with the database, of which 10,546 (97%) had a complete Clavien-Dindo score within the first 30 postoperative days. Results: The mean age of patients was 60.5 years (S.D. = 16.2), and 415 patients (4%) were under the age of 17 years. The male-to-female ratio was 4:1. At the end of 2010, 25% of surgeries used the robotic technique, but the frequency of robotic surgeries increased to 56% in 2014. No complications were reported in 74.6% of the urological procedures. The mortality rate was reported at only 0.27% of all patients. Patients who underwent a urological procedure performed by consultant urologists had a lower rate of complication compared to procedures performed by trainees (p = 0.03) but not staff doctors (p = 0.9). There were no significant differences in complication rates between staff doctors and trainee (p = 0.2). Conclusion: Robotic and laparoscopic urological procedures are associated with low serious complication rates. Postoperative complications were more common among surgeries performed by trainees. The robotic approach is associated with a shorter L.O.S. compared to the laparoscopic approach and linked to lower reoperation rates.

Use of venous-thrombotic-embolic prophylaxis in patients undergoing surgery for renal tumors: a questionnaire survey in the Nordic countries (The NORENCA-2 study).

PURPOSE: To examine the variation in venous thromboembolism prophylactic treatment (VTEP) among renal cancer patients undergoing surgery. MATERIALS AND METHODS: An Internet-based questionnaire on renal tumor management before and after surgery was mailed to all Nordic departments of urology. The questions focused on the use of VTEP and were subdivided into different surgical modalities. RESULTS: Questionnaires were mailed to 91 institutions (response rate 53%). None of the centers used VTEP before surgery, unless the patient had a vena caval tumor thrombus. Overall, the VTEP utilized during hospitalization for patients undergoing renal surgery included early mobilization (45%), compression stockings (52%) and low-molecular-weight heparin (89%). In patients undergoing open radical Nx, 80% of institutions used VTEP during their hospitalization (23% compression stockings and 94% low-molecular-weight heparin). After leaving the hospital, the proportion and type of VTEP received varied considerably across institutions. The most common interval, used in 60% of the institutions, was for a period of 4 weeks. The restriction to the Nordic countries was a limitation and, therefore, may not reflect the practice patterns elsewhere. It is a survey study and, therefore, cannot measure the behaviors of those institutions that did not participate. CONCLUSION: We found variation in the type and duration of VTEP use for each type of local intervention for renal cancer. These widely disparate variations in care strongly argue for the establishment of national and international guidelines regarding VTEP in renal surgery.

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy.

In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCL) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared with those generated from metastatic melanoma. Immune recognition of autologous TCLs or fresh tumor digests was observed in CD8+ TILs from 82% of patients (18/22). Cytotoxicity assays confirmed the tumoricidal capacity of RCC-TILs. The overall expansion capacity of RCC-TILs was similar to MM-TILs. However, the magnitude, polyfunctionality, and ability to expand in classical expansion protocols of CD8+ T-cell responses was lower compared with MM-TILs. The RCC-TILs that did react to the tumor were functional, and antigen presentation and processing of RCC tumors was similar to MM-TILs. Direct recognition of tumors with cytokine-induced overexpression of human leukocyte antigen class II was observed from CD4+ T cells (6/12; 50%). Thus, TILs from primary RCC specimens could be isolated, expanded, and could recognize tumors. However, immune responses of expanded CD8+ RCC-TILs were typically weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select, enrich, and expand tumor-reactive polyfunctional T cells may be critical in developing effective ACT with TILs for RCC. In summary, TILs isolated from primary RCC specimens could recognize tumors. However, their immune responses were weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select and expand polyfunctional T cells may improve cell therapy for RCC. Cancer Immunol Res; 6(2); 222-35. ©2018 AACR.

Contemporary treatment of renal tumors: a questionnaire survey in the Nordic countries (the NORENCA-I study).

OBJECTIVE: The five Nordic countries comprise 25 million people, and have similar treatment traditions and healthcare systems. To take advantage of these similarities, a collaborative group (Nordic Renal Cancer Group, NORENCA) was founded in 2015. MATERIALS AND METHODS: A questionnaire of 17 questions on renal tumor management and surgical education was designed and sent to 91 institutions performing renal tumor surgery in 2015. The response rate was 68% (62 hospitals), including 28 academic, 25 central and nine district hospitals. Hospital volume was defined as low (LVH: < 20 operations), intermediate (IVH: 20-49 operations), high (HVH: 50-99) and very high (VHVH: ≥ 100). Descriptive statistics were performed. RESULTS: Fifteen centers were LVH, 16 IVH, 21 HVH and 10 VHVH. Of all 3828 kidney tumor treatments, 55% were radical nephrectomies (RNs), 37% partial nephrectomies (PNs) and 8% thermoablations. For RN and PN, the percentages of open, laparoscopic and robotic approaches were 47%, 40%, 13% and 47%, 20%, 33%, respectively. The mean complication rate (Clavien-Dindo 3-5) was 4.9%, and 30 day mortality (TDM) was 0.5%. The median length of hospital stay was 4 days. Training with a simulator, black box or animal laboratory was possible in 48%, 74% and 21% of institutions, respectively. CONCLUSIONS: Despite some differences between countries, the data suggest an overall general common Nordic treatment attitude for renal tumors. Furthermore, the data demonstrate high adherence to international standards, with a high proportion of PN and acceptable rates for major complications and TDM.

The database of the Danish Renal Cancer Group.

AIM OF THE DATABASE: The main purpose of the database of the Danish Renal Cancer Group (DaRenCaData) is to improve the quality of renal cancer treatment in Denmark and secondarily to conduct observational research. STUDY POPULATION: DaRenCaData includes all Danish patients with a first-time diagnosis of renal cancer in the Danish National Pathology Registry since August 1, 2010. MAIN VARIABLES: DaRenCaData holds data on demographic characteristics, treatments, and pathology collected through linkage to central registries and online registration of a few clinical key variables. Eight quality indicators have been selected for monitoring treatment quality and outcome after renal cancer. DESCRIPTIVE DATA: The incidence of renal cancer in Denmark has increased from 12.7 per 100,000 population-years in 2010-2011 to 15.9 per 100,000 population-years in 2014-2015. A total of 3,977 Danish patients with renal cancer have been enrolled in the database in the period August 1, 2010-July 31, 2015. The completeness of data registration has increased substantially since the first years of the database. A tendency toward smaller and less advanced tumors, less invasive surgery, and a shorter hospital stay was observed, while the postoperative morbidity and mortality remained stable. Concurrently, the 1-year survival has improved and was 84.1% in 2014-2015. CONCLUSION: DaRenCaData provides valuable information on quality of and outcome after renal cancer treatment. Efforts to improve collection and registration of data are ongoing.

Implementation of a multidisciplinary robotic centre in a high-volume university hospital.

INTRODUCTION: We describe the initiation of a multidisciplinary centre for robotic surgery including the implementation of robotic-assisted procedures as standard procedure for the majority of cancer operations in urology, gynaecology and gastrointestinal surgery. METHODS: All robotic procedures performed from 2008 to 2013 were included. The information gathered included body mass index, the American Society of Anesthesiologists' physical status classification value (ASA), age, sex, time and type of surgery, duration of procedure, conversion to open surgery, length and type of anaesthesia, re-operations, length of hospital stay and 30-day mortality. RESULTS: The implementation strategy was to start with one specialty at a time, passing on experience from one specialty to the next. The surgical strategy was to begin with standard procedures for which international experience was available and subsequently perform more complex procedures, ending up with robotic-assisted procedures as the standard for most cancer surgery procedures. A total of 2,473 procedures were performed. The operative time was reduced over the period for the main procedures of all three specialties. For prostatectomies, hysterectomies and colectomies, conversion to open surgery occurred in 1.2, 3.8 and 7.7%; the risk of re-operation was 0.2, 2.3 and 7.3%; and, finally, the 30-day mortality was 0.1, 0 and 1%, respectively. CONCLUSION: The implementation was possible as a stepwise introduction across three specialties with low conversion and re-operation rates and a low mortality. A high-volume centre for robotic surgery was developed and patients with malignant diagnoses were offered robotic-assisted surgery within the framework of multidisciplinary cooperation. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency R. No.: 2007-58-0015.

Prostate cancer: 1.5 T endo-coil dynamic contrast-enhanced MRI and MR spectroscopy--correlation with prostate biopsy and prostatectomy histopathological data.

PURPOSE: To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data. MATERIALS AND METHODS: 43 patients, scheduled for radical prostatectomy, underwent prostate MR examination. Prostate cancer was identified by transrectal ultrasonographically (TRUS) guided sextant biopsy. MR examination was performed at 1.5 T with an endorectal MR coil. Cancer localisation was performed on sextant-basis--for comparison between TRUS biopsy, MR techniques and histopathological findings on prostatectomy specimens. RESULTS: Prostate cancer was identified in all 43 patients by combination of the three MR techniques. The detection of prostate cancer on sextant-basis showed sensitivity and specificity: 50% and 91% for TRUS, 72% and 55% for T2WI, 49% and 69% for DCEMRI, and 46% and 78% for CSI. CONCLUSION: T2WI, DCEMRI and CSI in combination can identify prostate cancer. Further development of MR technologies for these MR methods is necessary to improve the detection of the prostate cancer.

Malignant pheochromocytomas and paragangliomas - the importance of a multidisciplinary approach.

Approximately 10% of the pheochromocytomas and 20% of the paragangliomas are malignant with poor survival. As the biological behaviour of these tumours cannot be predicted with certainty from pathology the diagnosis of malignancy is difficult. Genetic testing is gaining impact as mutations in the tumour suppressor gene Von Hippel-Lindau and the mitochondrial succinate dehydrogenase enzyme complex subunit B (SDHB) are associated with malignancy. Excess release of catecholamines is characteristic for pheochromocytomas. High levels of chromogranin A, that is co-stored and co-secreted with catecholamines, may indicate tumour mass and malignancy and can be used to monitor response and relapse. The secretory and non-secretory tumours can be visualised with functional (specific and non-specific) imaging as SPECT and PET using ¹²³I-MIBG, somatostatin analogues, ¹8F-DOPA, and ¹8F-FDG. These modalities are recommended in patients with extra-adrenal and suspected metastatic/malignant disease, in case of distorted post-operative anatomy, and when suspected recurrence. The sensitivities of ¹²³I-MIBG scintigraphy or ¹8F-DOPA PET are relatively low in SDHB mutated tumours, but high using ¹8F-FDG. Specific PET imaging with somatostatin analogues generally has high sensitivity in malignant disease. There are no curative therapeutic options for malignant, metastatic pheochromocytomas/paragangliomas, wherefore consolidation of quality of life is essential. Adjuvant radionuclide treatment with beta-emitting isotopes coupled to MIBG or somatostatin analogues have shown response in approximately 30%. Chemotherapy is restricted to patients not accessible for surgery and resistant to radionuclide therapy. Novel targeted therapies, which mainly through a cytostatic effect interfere with specific targeted molecules needed for carcinogenesis and tumour growth show encouraging results.

[The penis was gone. A case report on penile cancer]. / Penis var vaek. En kasuistik om cancer penis.

Penile cancer is a rare disease. Patients develop symptoms early in the course of the disease for which reason late stages are seldom in western countries. The present case report describes a 64-year-old man with complete erosion of the penis, leaving an ulcer measuring 10 by 15 cm. The case report discusses incidence, symptoms, aetiology and different modalities of treatment and their correlation with survival.

[Adrenalectomy in Denmark 2002-2006]. / Adrenalektomi i Danmark 2002-2006.

INTRODUCTION: Laparoscopic adrenalectomy is replacing open adrenalectomy. The advantages are reduced mortality and morbidity, and shorter postoperative hospitalisation. The organization and short-term outcomes of adrenalectomy in Denmark are largely unknown. MATERIAL AND METHODS: Extraction, review, and analysis of data from the National Patient Register and discharge notes from 2002-2006. RESULTS: A total of 297 adrenalectomies, of which 161 were laparoscopic, were identified. Discharge notes were reviewed in 221 of these cases (2002-2005). All except three were performed in a university hospital setting. The laparoscopic to open conversion rate was 7.6%, mortality 1%, and complication rates for open/laparoscopic adrenalectomy 25%/16%. The mean postoperative hospital stays on surgical/urological wards were 6.0/2.9 days for open and laparoscopic procedures, respectively. CONCLUSION: In Denmark, the share of adrenalectomies performed laparoscopically is growing, currently reaching about 65%. Laparoscopic adrenalectomies are only performed at departments with a high frequency of laparoscopic surgery and specialized endocrinological and anaesthesiological support. For educational and research purposes, adrenalectomy should be performed at an even smaller number of departments. Postoperative hospital stay and mortality are at par with internationally reported levels, but the conversion rate of laparoscopic adrenalectomies should be reduced.

[Laparoscopic donor nephrectomy at the Herlev University Hospital, Denmark]. / Erfaringer med laparoskopisk donornefrektomi på Herlev Hospital.

INTRODUCTION: The purpose of this investigation was to evaluate the morbidity and convalescence of donors after laparoscopic nephrectomy. Transperitoneal laparoscopy was initiated at Herlev University Hospital in November 2002. MATERIALS AND METHODS: All 24 records from patients who underwent laparoscopic donor nephrectomy were reviewed. Demographic data and perioperative data were collected. RESULTS: Median operation time was 162 min. Estimated blood loss was 200 ml and warm ischemia time 5 min. Postoperative side effects were nausea/vomiting (nine patients) and shoulder pain (two patients). Most serious complication was bleeding, leading to laparotomy the day of surgery in one patient. Other complications were ileus due to herniation of small intestine in porthole 1/24, wound infection 3/24, vaso-vagal episode 1/24, bronchospasms with CO2-retention 1/24, pneumonia 1/24. Length of stay was three days. Return to activities of daily life after 3-4 weeks. Typical analgesics were ketorolac and paracetamol. No laparoscopic procedures were converted to open surgery. There was no mortality. One year graft survival is 96%. CONCLUSION: Transperitoneal laparoscopic donor nephrectomy can be performed safely without serious complications. It is a good alternative to the conventional open approach. No laparoscopic procedures were converted to open nephrectomy. These results are similar to experiences from large centres.