Physician cooperation in outpatient cancer care. An amplified secondary analysis of qualitative interview data.

The importance of outpatient cancer care services is increasing due to the growing number of patients having or having had cancer. However, little is known about cooperation among physicians in outpatient settings. To understand what inter- and multidisciplinary care means in community settings, we conducted an amplified secondary analysis that combined qualitative interview data with 42 general practitioners (GPs), 21 oncologists and 21 urologists that mainly worked in medical practices in Germany. We compared their perspectives on cooperation relationships in cancer care. Our results indicate that all participants regarded cooperation as a prerequisite for good cancer care. Oncologists and urologists mainly reported cooperating for tumour-specific treatment tasks, while GPs' reasoning for cooperation was more patient-centred. While oncologists and urologists reported experiencing reciprocal communication with other physicians, GPs had to gather the information they needed. GPs seldom reported engaging in formal cooperation structures, while for specialists, participation in formal spaces of cooperation, such as tumour boards, facilitated a more frequent and informal discussion of patients, for instance on the phone. Further research should focus on ways to foster GPs' integration in cancer care and evaluate if this can be reached by incorporating GPs in formal cooperation structures such as tumour boards.

Unusually large numbers needed to treat for radical prostatectomy in prostate cancer patients with PSA velocity ≤2 ng/ml/year.

BACKGROUND: The numbers needed to treat (NNT) and the corresponding confidence intervals for patients with prostate cancer and defined annual PSA increases (PSA velocity, PSAV) have not been described previously. AIM: The objective of this study is to assess NNT, numbers needed to treat to harm and corresponding confidence intervals for radical prostatectomy (RP) in patients with prostate cancer defined as a PSAV ≤2 ng/ml/year. METHODS: NNT following RP were estimated in risk groups defined by PSAV using mortality statistics and hazard ratios obtained in a noncontrolled trial. As no suited control group and no appropriate randomized trials were available for doing this calculation and as such trials are unlikely to become available in the near future we have calculated our NNTs as published previously by using relative risk reduction from an earlier randomized trial (RCT) comparing RP with watchful waiting (WW) [Can J Urol 2006;13(suppl 1):48-55]. RESULTS: For preoperative PSAV >2 ng/ml/year, NNT for RP were estimated at 25, whereas for preoperative PSAV ≤2 ng/ml/year, the estimate was 618. The lower 95% confidence limits (NNTBl) were 9 and 126, respectively (treatment with benefit). The implications emerging from these findings are discussed by comparison with published NNT values from other RCTs. The lower 95% confidence limit for preoperative PSAV ≤2 ng/ml/year was found to be large in comparison. CONCLUSION: The NNT estimate obtained here for PSAV >2 ng/ml/year and its lower 95% confidence interval is comparable to values in other studies on prostate cancer for therapies considered to be effective, while the estimated NNT for patients with PSAV ≤2 ng/ml/year is large in comparison. We conclude that the benefits of RP for localized prostate cancer with preoperative PSAV ≤2 ng/ml/year may be considered small. There are several limitations to our findings, the most important of which lies in the fact that while PSAV remains significantly associated with outcomes, the predictive value of PSA measurements is low. While PSAV >2 ng/ml/year clearly indicates a need for surgery, a PSAV ≤2 ng/ml/year should imply further decision making.

Correction to: Patient-Specific Mandibular Reconstruction Plates Increase Accuracy and Long-Term Stability in Immediate Alloplastic Reconstruction of Segmental Mandibular Defects.

[This corrects the article DOI: 10.1007/s12663-019-01323-9.].

Patient-Specific Mandibular Reconstruction Plates Increase Accuracy and Long-Term Stability in Immediate Alloplastic Reconstruction of Segmental Mandibular Defects.

OBJECTIVES: The aim of the current study was to evaluate potential differences in the accuracy of mandibular reconstruction and long-term stability, with respect to different reconstructive procedures. METHODS: In total, 42 patients who had undergone primary segmental mandibular resection with immediate alloplastic reconstruction, with either manually pre-bent or patient-specific mandibular reconstruction plates (PSMRP), were included in this study. Mandibular dimensions, in terms of six clinically relevant distances (capitulum [most lateral points], capitulum [most medial points], incisura [most caudal points], mandibular foramina, coronoid process [most cranial points], dorsal tip of the mandible closest to the gonion point) determined from tomographic images, were compared prior to, and after surgery. RESULTS: Dimensional alterations were significantly more often found when conventionally bent titanium reconstruction plates were used. These occurred in the area of the coronoid process (p = 0.014). Plate fractures were significantly (p = 0.022) more often found within the manually pre-bent group than within the PSMRP group (17%/0%). CONCLUSION: The results suggest that the use of PSMRP may prevent rotation of the proximal mandibular segment, thus avoiding functional impairment. In addition, the use of PSMRP may potentially enhance the long-term stability of alloplastic reconstructions.

Survival after an antiangiogenetic therapy and surgery in a wide spread growing teratoma originating from a testicular mixed malignant germ cell tumor.

Growing teratoma is still an often unsolved problem especially in male with mixed malignant GCTs of the testis or the mediastinum. This specific situation with progressive tumor growth and simultaneous normalization of tumor markers during or after treatment of malignant GCTs with teratomatous elements is judged as a fatal situation if this situation can not be controlled by extensive surgery, as teratoma are not sensible to chemotherapy or irradiation. Here, we report the case history of a 17-year old male patient with a testicular malignant GCT and wide spread lymph node metastases, who developed a rapidly progressive growing teratoma within the lymph node metastases. Within the molecular profile of the tumor we could find a cytogenetic picture typically found in malignant adult GCTs. In view of the bulky abdominal, thoracic and cervical metastases and the uncontrolled tumor progression, the situation was considered incurable. However, following an individual treatment attempt, this patient was treated with a four-agent combination of drugs with antiangiogenetic potential as well as low-dose cyclic chemotherapy. This approach resulted in a sustained disease stabilization followed by extensive surgical resection of the metastases. We therefore would like to highlight this treatment approach in unresectable growing teratoma and would like to stimulate further research and collaboration to come to an optimized treatment suggestion for this group of poor prognostic patients.

[Results of the randomised phase III study of the German Testicular Cancer Study Group. Retroperitoneal lymphadenectomy versus one cycle BEP as adjuvant therapy for non-seminomatous testicular tumours in clinical stage I]. / Ergebnisse der randomisierten Phase-III-Studie der "German Testicular Cancer Study Group". Retroperitoneale Lymphadenektomie vs. 1 Zyklus PEB als adjuvante Therapie beim nichtseminomatösen Hodentumor im klinischen Stadium I.

OBJECTIVE: As 30% of non-seminomas in clinical stage I will progress during active surveillance, alternative adjuvant strategies of 2 cycles of bleomycin, etoposid, cisplatin (BEP) or nerve sparing retroperitoneal lymphadenectomy (RPLND) can be offered. The risk of relapse is reduced to 2% and 10%, respectively. Without prognostic markers and with lowered toxicity it is postulated that only one cycle of BEP could significantly reduce the recurrence rate in comparison to RPLND. MATERIALS AND METHODS: Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n=191) or 1 cycle of BEP (n=191). In accordance with the protocol, 174 patients were treated with 1 cycle of BEP and 173 underwent RPLND. The primary study end-point was a reduction of recurrence from 10% after RPLND to a maximum of 3% after 1 cycle of BEP. RESULTS: After a mean follow-up of 4.7 years, there were 2 and 13 recurrences in the according-to-protocol population with chemotherapy and surgery, respectively. The difference between chemotherapy (1.15%) and surgery (7.5%) was statistically significant (p=0.0033). The tumor-specific survival was 100%. CONCLUSION: This largest randomized trial investigating treatment strategies in clinical stage I non-seminomas (AUO AH 01/94) showed the superiority of one cycle BEP over RPLND. The data obtained represent the basis for a reduced chemotherapy.

[The approach to tumors of the retrocrural mediastinum]. / Zugang zu retrokruralen Tumoren des Mediastinums.

Retrocrural tumors of the lower posterior mediastinum are rare. Most tumors in this region involve lymphatic metastasis of germ cell tumors. Formerly these tumors were resected through a combined thoracoabdominal approach, with division of the diaphragm and effecting an at least partial phrenic paresis. The ventral approach via bilateral subcostal incision with cranial extension avoids this problem and allows a bilateral access to the retrocrural space. From November 1999 to December 2005, using this approach we operated on 12 patients with residual germ cell tumors after chemotherapy. In all cases radical resection was obtained. Intra- or postoperative complications did not occur. All patients are still alive and free of disease.

[Organ-sparing surgery for testicular tumors]. / Organ erhaltende Hodentumorchirurgie.

Benign lesions of the testicles (stromal tumors, dermoid and epidermoid cysts as well as teratomas) are excised with the objective of preserving spermiogenesis and hormone production even though both testicles are present. If palpation, sonography and markers suggest a malignant tumor and the contralateral organ is affected by disease or has been ablated because of previous disease history, then enucleation resection is justified when the preoperative levels of plasma testosterone and LH are within the normal range. Postoperative irradiation of the unavoidable testicular intraepithelial neoplasia (TIN) with 20 Gy ensures the well-documented good results. If a child is desired, irradiation can be postponed with careful monitoring until pregnancy has ensued. Accurate indication and sophisticated technology result in a superiority of enucleation resection in comparison to non-surgical procedures (HIFU, chemotherapy, and irradiation for seminoma).

[Studies on localized low-risk prostate cancer : Do we know enough?] / Studien zum lokal begrenzten Niedrigrisikoprostatakarzinom : Wissen wir genug?

BACKGROUND: Treatment of localized low-risk prostate cancer (PCa) is undergoing a paradigm shift: Invasive treatments such as surgery and radiation therapy are being replaced by defensive strategies such as active surveillance (AS) and watchful waiting (WW). OBJECTIVE: The aim of this work is to evaluate the significance of current studies regarding defensive strategies (AS and WW). METHODS: The best-known AS studies are critically evaluated for their significance in terms of input criteria, follow-up criteria, and statistical significance. RESULTS: The difficulties faced by randomized studies in answering the question of the best treatment for low-risk cancer in two or even more study groups with known low tumor-specific mortality are clearly shown. Some studies fail because of the objective, others-like PIVOT-are underpowered. ProtecT, a renowned randomized, controlled trial (RCT), lists systematic and statistical shortcomings in detail. CONCLUSION: The time and effort required for RCTs to answer the question of which therapy is best for locally limited low-risk cancer is very large because the low specific mortality rate requires a large number of participants and a long study duration. In any case, RCTs create hand-picked cohorts for statistical evaluation that have little to do with care in daily clinical practice. The necessary randomization is also offset by the decision-making of the informed patient. If further studies of low-risk PCa are needed, they will need real-world conditions that an RCT can not provide. To obtain clinically relevant results, we need to rethink things: When planning the study, biometricians and clinicians must understand that the statistical methods used in RCTs are of limited use and they must select a method (e.g. propensity scores) appropriate for health care research.

The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases.

We previously described IQGAP1 as a human protein related to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe. Here we report the identification of a liver-specific human protein that is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N-terminal calponin homology motif which functions as an F-actin binding domain in members of the spectrin, filamin, and fimbrin families. Both IQGAPs also harbor several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and four IQ motifs and have 25% sequence identity with almost the entire S. pombe sar1 RasGAP homolog. As predicted by the presence of IQ motifs, IQGAP2 binds calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the GTPase activity of Ras or its close relatives. Instead, IQGAP2 binds Cdc42 and Racl but not RhoA. This interaction involves the C-terminal half of IQGAP2 and appears to be independent of the nucleotide binding status of the GTPases. Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain, they could play roles in the Cdc42 and Rac1 controlled generation of specific actin structures.

[High-dose chemotherapy and hematopoietic stem cell transplantation in patients with germ cell cancer]. / Hochdosischemotherapie und hämatopoetische Stammzelltransplantation bei Patienten mit Keimzelltumoren.

In cases of germ cell tumors, urologists cooperate with oncologists to determine the best timing for high-dose chemotherapy (HDC). In the primary treatment of patients with"intermediate" and"poor" prognosis, HDC conveys no benefit. These patients are treated with four cycles of cisplatin, etoposide, and bleomycin (BEP). After failure of the standard therapy again four cycles of conventional-dose combination chemotherapy are necessary in good prognosis patients: cisplatin, ifosfamide and either etoposide (VIP or PEI), vinblastine (VeIP) or paclitaxel (TIP). HDC should be considered in patients who fail primary treatment, and who show unfavorable prognostic features prior to salvage treatment.

[Monitoring of NOAC]. / Monitoring von NOAK.

BACKGROUND: Monitoring non-vitamin K antagonist oral anticoagulants (NOAC) is usually not necessary; however, in some patients it may prove beneficial. OBJECTIVES: Patient subgroups who may profit from monitoring were identified, and methods of monitoring (including assessment of which coagulation parameters are affected by NOAC) are described. MATERIALS AND METHODS: We searched the PubMed database for each of the search terms, "NOAC", "DOAC", "rivaroxaban", "dabigatran", and "apixaban", in combination with one of the terms, "monitoring", "measurement", "measuring", or "assessment". The results were compiled and reviewed. RESULTS: Monitoring is most advantageous in emergency cases with severe bleeding where drug activity needs to be assessed. It can also help in deciding for or against lysis therapy after acute stroke in patients taking NOAC. Furthermore, it can also identify compliance problems and help in planning periprocedural management. There are quantitative measurement methods which measure plasma concentrations exactly and qualitative methods which only allow for a rough estimate or a general confirmation of drug activity. Recommended quantitative measurement methods are diluted thrombin time for dabigatran, and anti-factor Xa activity (calibrated) for rivaroxaban and apixaban. CONCLUSIONS: Several patient subgroups may profit from monitoring of NOAC plasma concentration. One should, however, take several issues into consideration before measurements, such as the objective of each individual measurement, possible consequences (e. g., dose adjustment), and which measurement method to pick.

[Diagnostic work-up of bone metastases of genitourinary tumors and their treatment with bisphosphonates. Interdisciplinary consensus conference, Frankfurt, 2006]. / Diagnostik von Knochenmetastasen urologischer Tumoren und deren Behandlung mit Bisphosphonaten. Interdisziplinäre Konsensuskonferenz Frankfurt 2006.

The diagnostic algorithm in cases of suspected bone metastases of genitourinary tumors still starts with a scintigraphic examination. Osseous metastases of hormone-refractory prostate cancer require treatment with zoledronic acid. A potential indication is a hormone-sensitive status. Nephrotoxic substances should not be administered simultaneously. To avoid osteonecrosis of the jaw, prior dental examination, oral hygiene, and if necessary dental reconstruction are recommended. Bisphosphonates can be combined with radiation therapy and chemotherapy; additional administration of calcium and vitamin D is not mandatory. It is recommended that patients with bone metastases of renal cell cancer be treated with bisphosphonates approved for this indication. For urothelial carcinoma and other genitourinary tumors, the available data are not sufficient to give a recommendation.

[Off-label use in oncology: an inexhaustible topic?!]. / Off-Label-Use in der Onkologie: ein Thema ohne Ende?!

In 2002, with its "Off-label verdict", the German Federal Social Court (Bundessozialgericht; BSG) issued a fundamental decision to the effect that in certain circumstances an off-label prescription might be payable by health insurance firms, these circumstances being: severe illness with no prospect of a cure being brought about by any therapy approved for this illness and an evidence-based chance that an off-label treatment could yield a cure. Subsequently, the former German Federal Ministry of Health and Social Security (BMGS) appointed its "expert group on off-label use of treatments". This panel's task was to formulate professional comments and expert recommendations to the Federal Joint Committee (G-BA) on scientific evidence relating to selected medications used for off-label treatment. The group was found not to be sufficiently efficient and was laid down in August 2005. Meanwhile, it has been replaced by other work groups. However, the constant increase in the amount of medical evidence available means that off-label use is a continuing process that cannot easily be regulated by expert committees. It would be preferable for reimbursement for off-label prescriptions to be linked to the qualifications of the attendant physician. One suggestion might be that only specifically authorised physicians with special additional skills be permitted to apply and be reimbursed for off-label prescriptions.

["Second opinion centers". Approach for improving the quality of treatment for testicular tumors]. / "Zweitmeinungszentren". Ansatz zur Verbesserung der Versorgungsqualität bei Hodentumoren.

According to estimations of the German Cancer Research Center in Heidelberg, the management of germ cell tumors in Germany is characterized by a marked difference between the actual mortality and the mortality to be expected with adequate implementation of the therapy standard. Our aim is to reduce the mortality rate by introducing a treatment procedure supported by a second opinion center.

[Interdisciplinary recommendations concerning the therapy for hormone-refractory prostatic carcinoma]. / Interdisziplinäre Therapieempfehlungen zur Behandlung des hormonrefraktären Prostatakarzinoms.

Therapy with Docetaxel for hormone-refractory prostatic carcinoma has for the first time led to an increase in the survival time. Docetaxel has become established as a standard therapy for his indication. Since hormone-refractory prostatic carcinoma is not uniformly defined and is thus for prognosis not a homogeneous entity, the prospects at the start of chemotherapy are uncertain. In the summer of 2005 these questions were addressed in an interdisciplinary consensus conference. It was agreed that the 3-week scheme with 75 mg/m (2) as standard and the indication for symptomatic patients were above question. Opinions differed with regard to the use of chemotherapy in asymptomatic patients. In addition, recommendations for the performance and monitoring of the therapy were formulated.

[TNM-Classification of localized prostate cancer : The clinical T-category does not correspond to the required demands]. / TNM-Klassifikation des lokalisierten Prostatakarzinoms : Die cT-Kategorie entspricht nicht ihren klinischen Erfordernissen.

BACKGROUND: The TNM staging system for localized prostate cancer (PCa) divides tumors based on clinical parameters into a clinical (c)T category and, after radical prostatectomy (RP), a pathological (p)T category. OBJECTIVES: This study examines the extent to which the cT and the pT category correspond to each other and whether the two categories differ in their prediction for organ-confined disease. PATIENTS AND METHODS: Data of 687 RP patients were collected in a prospective, noninterventional, multicenter health service research study for the treatment of localized PCa (HAROW). Group comparisons were performed by analysis of variance and student t­test as well as the chi-squared test or the Fisher exact test. RESULTS: Clinical cT1 category (62.9%) and pathological pT2c category (56.6%) were diagnosed most frequently. The correspondence of cT and pT category was 15% for cT2a , 10.5% for cT2b, and 55% for cT2c. An extraprostatic extension (≥pT3) was observed for the categories cT1 and cT2 in 23.5% and 36.4% (p < 0.001), differences in the subcategories cT2a-c were not significant: cT2a = 28.8%, cT2b = 42.1%, and cT2c = 38.8% (p = 0.194). Tumors with a pathologically extraprostatic extension were not recognized clinically in >50%. CONCLUSIONS: For localized PCa there is low agreement between clinical and pathologic T category, thus, often leading to understaging. An adaptation of the T classification of the TNM system with division into "not palpable" and "palpable" appears sufficient for a prognostic prediction.

[Treatment costs of localized prostate cancer in Germany : Economic results from the HAROW observational study]. / Behandlungskosten des lokal begrenzten Prostatakarzinoms in Deutschland : Ökonomische Ergebnisse der HAROW-Beobachtungsstudie.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men. For medical treatment of PCa, a number of therapies are available. The economic consequences associated with these individual treatment options in routine care in Germany are unclear so far. METHODS: The present analysis was based on the Germany-wide HAROW observational study, which was conducted from 2008-2013. During this study, all participating physicians and involved patients reported and documented individual health care resource consumption. These data were evaluated in monetary terms stratified by treatment regime (hormone therapy, HT; active surveillance, AS; radiotherapy, RT; radical prostatectomy, RP; watchful waiting, WW). RESULTS: Overall, the data of 2672 patients were available for analysis. Based on the observational study design, the included patient groups were heterogeneous in their baseline characteristics. The annual total costs from the societal perspective were the largest for patient undergoing RP (9254 €; 95 % CI 8353-10,154), mainly driven by the costs for the initial hospital stay for surgery. HT, AS, RT, and WW seem to be comparable in terms of direct costs, ranging from 805 € (95 % CI 154-1455) for WW up to 1115 € (95 % CI 826-1405) for RT. The highest indirect costs were observed for patients receiving RT (3928 €; 95 % CI 0-10,675), which can be justified by the frequent incapacity to work in this patient group. CONCLUSION: The treatment of prostate cancer can lead to significant economic follow-up costs which vary greatly depending on the type of treatment. The analysis indicates a need for the implementation of a long-term health economic study in the future, which will be more suitable to show treatment-specific differences in the temporal occurrence of costs.

Morbidity and mortality after surgery for lower urinary tract symptoms: a study of 95 577 cases from a nationwide German health insurance database.

BACKGROUND: Little real-world data is available on the comparison of different methods in surgery for lower urinary tract symptoms due to benign prostatic obstruction in terms of complications. The objective was to evaluate the proportions of TURP, open prostatectomy (OP) and laser-based surgical approaches over time and to analyse the effect of approach on complication rates. METHODS: Using data of the German local healthcare funds (Allgemeine Ortskrankenkassen (AOK)), we identified 95 577 cases with a primary diagnosis of hyperplasia of prostate who received TURP, laser vaporisation (LVP), laser enucleation (LEP) of the prostate or OP between 2008 and 2013. Univariable logistic regression was used to analyse proportions of surgical approach over time, and the effect of surgical method on outcomes was analysed by means of multivariable logistic regression. RESULTS: The proportion of TURP decreased from 83.4% in 2008 to 78.7% in 2013 (P<0.001). Relative to TURP and adjusting for age, co-morbidities, AOK hospital volume, year of surgery and antithrombotic medication, OP had increased mortality (odds ratio (OR) 1.47, P<0.05), transfusions (OR 5.20, P<0.001) and adverse events (OR 2.17, P<0.001), and lower re-interventions for bleeding (OR 0.75, P<0.001) and long-term re-interventions (OR 0.55, P<0.001). LVP carried a lower risk of transfusions (OR 0.57, P<0.001) and re-interventions for bleeding (OR 0.76, P<0.001), but a higher risk of long-term re-interventions (OR 1.43, P<0.001). LEP had increased re-interventions for bleeding (OR 1.35, P<0.01). Complications were also dependent on age and co-morbidity. Limitations include the lack of clinical information and functional results. CONCLUSIONS: OP has the greatest risks of complication despite a low re-intervention rate. LVP demonstrated favourable results for transfusion and bleeding, but increased long-term re-interventions compared with TURP, while LEP showed increased re-interventions for bleeding. Findings support a careful indication and choice of method for surgery for LUTS, taking age and co-morbidities into account.

Alternatively spliced annexin XI transcripts encode proteins that differ near the amino-terminus.

Annexins are a family of structurally related calcium-dependent phospholipid binding proteins. We recently described a new member of this family, bovine annexin XI [1]. Two kinds of cDNAs were identified corresponding to annexin XI mRNA variants A and B, which are generated by alternative splicing of identical primary transcripts. Annexin XI isoforms are predicted to differ at the amino-terminus, suggesting that they may have distinct biological roles.