Dose-escalated radiotherapy with PET/CT based treatment planning in combination with induction and concurrent chemotherapy in locally advanced (uT3/T4) squamous cell cancer of the esophagus: mature results of a phase I/II trial.

BACKGROUND: This prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year. METHODS: Eligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1-6, 8-13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals. RESULTS: Between 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48-66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59-100], 53% [34-83], 41% [23-73], and 29% [14-61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40-88], 35% [19-67], and 29% [14-61], corresponding cumulative incidences of loco-regional progressions were 18% [4-39%], 35% [14-58%], and 41% [17-64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%). CONCLUSIONS: Dose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound. Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE ) and authorized to proceed on 2006-09-25.

The value of an additional scrotal suture during orchidopexy.

INTRODUCTION: Undescended testes present in 3-5% of male infants at birth. Orchidopexy is indicated to improve fertility and reduce the risk of testicular tumors. Guidelines recommend orchidopexy as early as six months of age, treatment should be finished within the age of 18 months. So far, no unequivocal proof demonstrated the superiority of one of the different surgical techniques. OBJECTIVE: To evaluate the value of an additional scrotal suture between the tunica albuginea and the dartos fascia during orchidopexy in an outpatient setting. It is yet unclear, whether the suture influences the incidence of secondary cryptorchidism or recurrence. STUDY DESIGN: This is a retrospective cohort study. Between 2010 and 2018 two experienced surgeons performed 561 inguinal orchidopexy-procedures in an open technique (375 boys). In group 1 (2010-2014) they managed 234 IOP (156 boys) without an additional scrotal suture. Since 2014, in group 2 an additional suture has been performed in 327 IOP (219 boys). Statistically, we compared both groups over a period of consecutive 4 years after the model of a life table analysis (Logrank). RESULTS: The numbers of boys with complete follow-up were 118 of 156 in group 1 and 154 of 219 in group 2, demonstrating 7 (5.9%) and 7 (4.5%) recurrences, respectively. There was no statistically significant difference in recurrences between group 1 and group 2 (Logrank-Test, p = 0.97). Orchidopexie failure was detected between 0.9 and 23.1 months after the IOP in group 1 and between 3.2 and 17.7 months in group 2. Mean age in months at the operation in both groups was significantly higher than the recommended 6-18 months in the EAU/AUA-guidelines. Both groups showed similar rates of postoperative complications. DISCUSSION: Orchidopexy is a safe procedure in an outpatient setting. So far there is no evidence that performing an additional scrotal suture decreases the operative failure rate in inguinal standard orchidopexy procedures.

[Results of surgical and radiotherapeutic treatment of adenoid cystic carcinoma of the salivary glands]. / Resultate der operativen und strahlentherapeutischen Behandlung von adenoidzystischen Karzinomen der Speicheldrüsen.

Surgical treatment in patients with rare adenoid cystic carcinoma (ACC) of the salivary glands is considered to be the state of the art. With respect to an additional radiotherapy there are different approaches regarding the type of radiotherapy and timing. In this study the overall survival and recurrence-free survival in 52 individuals with salivary gland ACC who were treated at the University Hospital in Essen and received irradiation with fast neutrons and photons (mixed beam technique) either A) immediately following surgical treatment or B) only after the appearance of local recurrence were compared. Group A (n = 28, first diagnosis, FD September 1991-September 2009) received adjuvant radiotherapy immediately postoperative, group B (n = 24, FD June 1979-November 2001) underwent primarily surgical tumor resection according to the treatment regimen at that time and were irradiated only on the appearance of a local recurrence. In comparison to group B, patients in group A showed a lower recurrence rate and a significantly longer local relapse-free survival. Group B, however, showed a significantly higher overall survival. The frequency of distant metastasis occurred equally in both groups but the onset of distant metastasis was significantly earlier in group A. In general, overall survival was negatively influenced by distant metastasis. The local recurrence rate was very high after primary surgical treatment only. The immediate adjuvant high-linear energy transfer (LET) radiotherapy reduced the local recurrence rates. Irradiation after the appearance of a recurrence had a positive influence on overall survival. Overall, definitive high-LET radiotherapy in the mixed beam technique enabled high local control rates both primarily postoperative and also locoregional recurrences.

Translating the concept of intrinsic subtypes into an oncoplastic cohort of more than 1000 patients - predictors of recurrence and survival.

INTRODUCTION: A paradigm shift in breast cancer was introduced by Sørlie's concept of intrinsic subtypes [1]. We validated this concept - which was originally based on 84 individuals - in a large cohort study of 1035 patients with oncoplastic surgery and analyzed if early and late recurrences are linked to a specific intrinsic tumor subtype or resection margins. MATERIALS AND METHODS: 1035 patients with oncoplastic surgery (2004-2009) were analyzed with regard to treatment characteristics and patterns of early (<5 years) and late recurrence (>5 years) and survival related to the intrinsic subtypes. Data was retrieved from patient's charts, customized patients questionnaires and cancer registries. RESULTS: 944 patients with primary, unilateral breast cancer, median age 58 years, were eligible for analysis. At a median FU of 5.2 years, LRR was 4.0%, 5-year-OS 94.5% and DFS 90.9%. Intrinsic subtypes, but not T-size, nodal-status, resections margins nor histopathology, governed local control and survival. There was no signal for prevelance of unclear margins in any of intrinsic subgroups and no preference of any oncoplastic technique attributed to them. TNBC and Her2 non-luminal breast cancer had highest recurrence and lowest survival rates. Although sentinel involvement (SLN+) was prevailing in the Luminal-B-Her 2 negative subtype at 34.3%, this did not translate into a higher axillary dissection rate. CONCLUSION: This study confirmed the intrinsic subtype concept on a large clinical basis and describes the patterns of early and late recurrence in oncoplastic surgery, concluding that bigger risk may not be overcome by bigger surgery.

Which clinical risk factors determine a pathological urodynamic evaluation in patients with multiple sclerosis? an analysis of 100 prospective cases.

BACKGROUND: Urinary tract symptoms are an underestimated problem in multiple sclerosis (MS). OBJECTIVE: Hundred urodynamics of MS patients have been evaluated prospectively. DESIGN, SETTING AND PARTICIPANTS: In an inpatient rehabilitation, all persons with MS who also suffered from urinary tract symptoms received a voiding diary, post-void sonography and an urodynamic examination according to International Continence-Society-Standard. RESULTS AND LIMITATIONS: Between 10/2009 and 3/2011, 100 patients (79 women; 21 men; mean EDSS, 4.52 ± 2.26) were examined who had primary progressive MS (9×), relapsing-remitting MS (41×), secondary progressive MS (43×) and CIS (1×). The mean duration of MS was 10.26 ± 10.09 years and mean duration of LUTS, 6.9 ± 7.75 years. Urodynamic testing showed normal findings in 22 patients, detrusor overactivity in 7, increased bladder sensation without detrusor overactivity in 21, detrusor-sphincter dyssynergia in 26, detrusor hypocontractility in 12, detrusor acontractility in 4 and unclear diagnosis in 8 patients. Statistically significant risk factors for pathological urodynamic findings were as follows: wheelchair dependency, use of more than one incontinence pad per day and a MS type other than relapsing-remitting. CONCLUSIONS: The urodynamic investigation at hand showed urinary tract dysfunction in 78 of 100 MS patients with lower urinary tract symptoms (LUTS). The long latency between the occurrence of MS and/or the beginning of LUTS and the first neuro-urological evaluation indicates a deficit in treatment. Beyond national guidelines, all MS patients should at regular intervals be questioned about LUTS and receive urodynamic assessment especially according to the presented risk profile.

[Health-related quality of life in children with spina bifida]. / Gesundheitsbezogene Lebensqualität bei Kindern mit Spina bifida.

BACKGROUND: There are no studies on the health-related quality of life (HRQoL) in German children with a myelomeningocele (MMC). This study aims to obtain generalizable epidemiological data on the HRQoL of such children. PATIENTS AND METHODS: KINDL-R questionnaires were filled out and clinical findings on typical MMC disabilities were also documented. Of the 115 families contacted, 70 MMC families responded (response rate 61%). Normative KINDL-R data from a sample of healthy children served as reference. RESULTS: No differences in clinical data were found when comparing responders and non-responders. KINDL total scores as well as scores across all scales were highly concordant for parental reporting and self-reporting. CONCLUSIONS: Despite the fact that children with MMC often suffer from severe physical limitations, their HRQoL is not necessarily lower than that of healthy children.

Outcome at 10 years of severe vesicoureteric reflux managed medically: Report of the International Reflux Study in Children.

OBJECTIVE: To study the progress of vesicoureteric reflux (VUR) grade III or IV in children followed up prospectively over 10 years. STUDY DESIGN: One hundred forty-nine children (33 boys and 116 girls) with VUR were recruited for the International Reflux Study in Children and were treated with a medical regimen and monitored by means of serial cystograms. VUR disappearance was based on negative findings on 2 consecutive cystograms. RESULTS: At 5 years, VUR with dilatation was seen in 72 (48%) children and VUR without dilatation, in 55 (37%); 22 (15%) children had no reflux. At 10 years, VUR with dilatation was seen in 34 (23%) children and VUR without dilatation, in 37 (25%); 78 (52%) children had no reflux. Grade IV VUR persisted in 8 children. Absence of VUR was significantly associated with grade III versus grade IV VUR (P = .007), unilateral versus bilateral reflux (P = .0002), and age > or = 5 years at entry versus age < 5 years (P = .001). Neither sex nor renal scarring at entry individually affected resolution of VUR. Among 43 (29%) children with intermittent VUR, only 6 had reflux with dilatation at 10 years. CONCLUSION: Continuing reduction in the severity of VUR in children receiving careful medical treatment was observed over 10 years. On the basis of negative findings on 2 consecutive cystograms, VUR was absent in half of the children.

Renal growth in children with severe vesicoureteral reflux: 10-year prospective study of medical and surgical treatment: the International Reflux Study in Children (European branch).

PURPOSE: To determine whether medical or surgical treatment better promotes renal growth in children with severe vesicoureteric reflux (VUR) and to examine factors influencing renal growth. MATERIALS AND METHODS: Three hundred two children younger than 11 years with urinary tract infection and grade III or IV VUR were randomly assigned to surgical (n = 149) or medical (n = 153) treatment and were followed up at serial intravenous urography for up to 5 years; 223, for up to 10 years (surgical, n = 110; medical, n = 113). Renal size was measured planimetrically on serial intravenous urograms and was related to the virtual height of L1 through L3 by expressing it as an SD score. RESULTS: There was no significant difference in mean renal growth between patients treated surgically or those treated medically after 5- or 10-year follow-up. Bilateral renal size of 80 surgical and 75 medical patients remained within 1 SD score. In patients entering the study at 2 years of age or younger and in those with grade IV VUR, bilateral VUR, or renal scars, there was a trend toward improved renal growth in those treated medically, but this finding was not statistically significant. When renal scarring or thin parenchyma was unilateral, the affected kidney grew less well, irrespective of treatment. Bilateral renal scarring was usually asymmetrical, with a corresponding effect on renal growth. CONCLUSION: There was no significant difference in renal growth during 10 years between surgical and medical treatment in patients with severe reflux.

The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.

The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced gallbladder smooth muscle contraction are considered both extracellular and intracellular, but the relative need for intracellular calcium especially at low, physiological concentrations is not clear. To better define the calcium sources responsible for guinea-pig gallbladder contractions in vitro, we inhibited calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium-free Krebs' solution. Availability and release of intracellular calcium stores were depleted by strontium substitution and ryanodine. CCK-OP was compared to bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl. Methoxyverapamil, however, had little effect on the time-dependent generation of tension to CCK-OP, but significantly reduced the response to bethanechol and KCl, each at ED50. The duration of the contractile response in the calcium-free Krebs' solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM) significantly attenuated the response to CCK-OP and bethanechol, but not to KCl. Ryanodine significantly reduced contractions induced by CCK-OP but not for bethanechol, both at low dose ED25. These results indicate that contraction of the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires extracellular calcium influx. Further, the initiation and maintenance of contraction by CCK-OP and bethanechol necessitates calcium mobilisation from intracellular stores. CCK-OP may have a greater penchant for these calcium stores, particularly at physiological doses.

[Breast saving cancer surgery. Results of a long-term study (Berlin study, 1963-1982)]. / Die brusterhaltende Karzinomchirurgie. Ergebnisse einer Langzeitbeobachtung (Berliner Studie, 1963-1982).

Between 1963 and 1982, 1,139 patients underwent surgery for unilateral mammary malignoma at the Charlottenburg Gynaecological Clinic of the Free University Berlin. Primary therapy consisted of simple mastectomy in 948 cases and tumourectomy/quadrantectomy with subsequent radiotherapy (40 Gy) in 191 cases. We performed a retrospective analysis of "matched samples" of tumourectomy/quadrantectomy and mastectomy. The observation period of both groups spans a minimum of one year to a maximum of 20 years after primary operation. In pT1- and pT2-tumours the overall survival after tumourectomy/quadrantectomy at 5, 10 and 15 years was no worse than after total breast removal. The results of our long-term follow-up study lead us to conclude that tumourectomy/quadrantectomy and breast irradiation are suitable for primary treatment of mammary cancer.