Ventral hernia repair: an increasing burden affecting abdominal core health.

PURPOSE: To estimate the annual volume and cost of ventral hernia repair (VHR) performed in the United States. METHODS: A retrospective cohort study was performed using the National Inpatient Sample (NIS) and the Nationwide Ambulatory Surgery Sample (NASS) for 2016-2019. Patients over the age of 18 who underwent open (OVHR) or minimally invasive ventral hernia repair (MISVHR) were identified. NIS procedural costs were estimated using cost-to-charge ratios; NASS costs were estimated using the NIS cost-to-charge ratios stratified by payer status. Costs were adjusted for inflation to 2021 dollars using US Bureau of Labor Statistics Consumer Price Index. RESULTS: On average 610,998 VHRs were performed per year. Most were outpatient (67.3% per year), and open (70.7%). MIS procedures increased from 25.8% to 32.8% of all VHRs. Inpatient OVHR had significantly higher associated cost than MISVHR [$35,511 (34,100-36,921) vs. $21,165 (19,664-22,665 in 2019]. Outpatient MISVHR was more expensive than OVHR [$11,558 (11,174-11,942 MIS vs. $6807 (6620-6994) OVHR in 2019]. The estimated cost of an inpatient MISVHR remained similar between 2016 and 2019, from $20,076 (13,374-20,777) to $21,165 (19,664-22,665) and increased slightly from $9975 (9639-10,312) to $11,558 (11,174-11,942) in the outpatient setting. The estimated cost of an inpatient OVHR increased from $31,383 (30,338-32,428) to $35,511 (34,100-36,921), while outpatient costs increased from $6018 (5860-6175) to $6807 (6620-6994). VHR costs decreased slightly over the study period to a mean cost of $9.7 billion dollars in 2019. CONCLUSION: Compared to 2006 national data, VHRs in the United States have almost doubled to 611,000 per year with an estimated annual cost of $9.7 billion. A 1% decrease in VHR achieved through recurrence reduction or hernia prophylaxis could save the US healthcare system at least $139.9 million annually.

Primary thoracoabdominal hernias.

BACKGROUND: Primary thoracoabdominal hernias involve the triad of an intercostal hernia, abdominal wall hernia, and diaphragmatic hernia. We report a case series of this rare entity and describe the evolution and outcomes. METHODS: We completed a retrospective analysis of thoracoabdominal hernia repairs performed January 2010-April 2019 at Prisma Health-Upstate and Carolinas Medical Center. This includes all patients with spontaneous defects, excluding incisional hernias or those resulting from external trauma. RESULTS: Of 16 patients with thoracoabdominal hernias, 15 patients developed hernias after forceful coughing and one patient developed a hernia after strenuous physical activity. Seven patients required at least one additional intervention; two for recurrence; two for recurrence of original intercostal repairs done elsewhere; two for wound complications; and one had a missed abdominal wall component. CONCLUSIONS: Primary thoracoabdominal hernias require a high index of suspicion. Durable repair involves complex reconstruction of the thoracoabdominal wall including the diaphragm, intercostal space, rib fracture fixation, and mesh reinforcement of the abdominal wall with permanent fixation constructs.

The impact of preoperative anxiety, depression, and chronic pain on outcomes in abdominal wall reconstruction.

PURPOSE: An association of anxiety with surgical outcomes has been suggested, including with open ventral hernia repair (OVHR). This study examines the interaction of multiple comorbidities, including anxiety, depression, chronic pain, and hernia characteristics with outcomes after OVHR. METHODS: Patients with anxiety were identified in an existing, prospectively collected, data set of OVHR with preoperative work-up including CT scans (2007-2018). A patient with a diagnosis or prescription for anxiolytics, anti-depressants, or narcotics was considered to have anxiety, depression, or chronic pain, respectively. Hernia characteristics were analyzed using 3D volumetric software. Univariate and multivariate analyses were performed to assess for the impact of anxiety on surgical outcomes. RESULTS: A total of 1178 OVHRs were identified. The diagnosis of anxiety (23.9%) was associated with female gender (29.1% females vs. 16.9% males, p = 0.002), depression (56.7 vs. 18.8%, p < 0.0001), preoperative chronic pain (43.6 vs. 26.9%, p < 0.0001), COPD, arrhythmia, history of MRSA, and sleep apnea (p ≤ 0.05 all values). Patients with anxiety had larger hernia volume and defect size, and were more likely to undergo component separation, with higher rates of wound complication and intervention for pain (p ≤ 0.05 all values). After multivariate analysis controlling for multiple potentially confounding factors, the comorbidities of anxiety, depression, and preoperative chronic pain were not found to be significantly associated with adverse outcomes. CONCLUSIONS: The diagnosis of anxiety is associated with preoperative comorbidity, surgical complexity, and adverse outcomes after OVHR. However, when comorbidities are controlled for, the diagnosis of anxiety, depression or preoperative pain does not independently predict adverse outcomes. In this context, anxiety may be considered a marker of patient comorbidity in a complex patient population.

MELD-Na score associated with postoperative complications in hernia repair in non-cirrhotic patients.

PURPOSE: In patients with cirrhosis, the Model for End-Stage Liver Disease Sodium (MELD-Na) score is a validated predictor of outcomes after transplant and non-transplant surgical procedures. This study investigates the association of MELD-Na score with complications following elective ventral hernia repair in non-cirrhotic patients. METHODS: The ACS NSQIP database was queried (2005-2016) for all elective laparoscopic and open ventral hernia procedures in patients without ascites or esophageal varices. Postoperative outcomes were compared by MELD-Na score using Chi-square tests. Multivariate logistic regression was used to control for potentially confounding variables. RESULTS: A total of 48,955 elective hernia repairs were identified; 68.7% were open repairs. The overall complication rate (Clavien-Dindo ≥ 1) was 14.3%, with a wound complication rate of 5.5%, and major complication rate (Clavien-Dindo ≥ 3) of 4.3%. A preoperative MELD-Na score ≥ 10 was present in 29.4%. Incremental increases in MELD-Na score (10-14, 15-19, and ≥ 20) were associated with increased overall complications (OR 1.25, CI 1.31-1.37; OR 1.53, CI 1.30-1.80; OR 1.70, CI 1.24-2.31, respectively), major complications (OR 1.42, CI 1.20-1.69; OR 1.85, CI 1.43-2.39; OR 2.13, CI 1.35-3.38, respectively), 30-day mortality (OR 1.58, CI 1.05-2.37; OR 2.34, CI 1.39-3.96; OR 3.16, CI 1.37-7.28, respectively), and return to the operating room (OR 1.19, CI 1.01-1.41; OR 1.38, CI 1.05-1.81; OR 1.78, CI 1.10-2.90, respectively). CONCLUSION: MELD-Na score is independently associated with postoperative complications in ventral hernia repair. As an objective and simple predictive model, it may be useful in preoperative risk calculations for complex patients.

A new AQP1 null allele identified in a Gypsy woman who developed an anti-CO3 during her first pregnancy.

BACKGROUND AND OBJECTIVES: The Colton blood group antigens are carried by the AQP1 water channel. AQP1(-/-) individuals, also known as Colton-null since they express no Colton antigens, do not suffer any apparent clinical consequence but may develop a clinically significant alloantibody (anti-CO3) induced by transfusion or pregnancy. Identification and transfusion support of Colton-null patients are highly challenging, not only due to the extreme rarity of this phenotype, the lack of appropriate reagents in most laboratories, as well as the possibility of confusing it with the recently described CO:-1,-2,3,-4 phenotype where AQP1 is present. This study investigated a new Colton-null case and evaluated three commercially available anti-AQP1s to identify Colton-null red blood cell samples. METHODS: The Colton-null phenotype was investigated by standard serological techniques, AQP1 sequencing, immunoblot and flow cytometry analyses. RESULTS: We identified and characterized the Colton-null phenotype in a Gypsy woman who developed an anti-CO3 during her first pregnancy. After developing a simple and robust method to sequence AQP1, we showed that she was apparently homozygous for a new AQP1 null allele, AQP1 601delG, whose product is not expressed in her red blood cells. We also established the Colton specificity of three commercially available anti-AQP1s in immunoblot and/or flow cytometry analyses. CONCLUSION: This Gypsy woman represents the sixth Colton-null case characterized at the serological, genetic and biochemical levels. The validation here of new reagents and methods should facilitate the identification of Colton-null individuals.

Do soft skills predict surgical performance?: a single-center randomized controlled trial evaluating predictors of skill acquisition in virtual reality laparoscopy.

BACKGROUND: Virtual reality (VR) training in minimal invasive surgery (MIS) is feasible in surgical residency and beneficial for the performance of MIS by surgical trainees. Research on stress-coping of surgical trainees indicates the additional impact of soft skills on VR performance in the surgical curriculum. The aim of this study was to evaluate the impact of structured VR training and soft skills on VR performance of trainees. METHOD: The study was designed as a single-center randomized controlled trial. Fifty first-year surgical residents with limited experience in MIS ("camera navigation" in laparoscopic cholecystectomy only) were randomized for either 3 months of VR training or no training. Basic VR performance and defined soft skills (self-efficacy, stress-coping, and motivation) were assessed prior to randomization using basic modules of the VR simulator LapSim(®) and standardized psychological questionnaires. Three months after randomization VR performance was reassessed. Outcome measurement was based on the results derived from the most complex of the basic VR modules ("diathermy cutting") as the primary end point. A correlation analysis of the VR end-point performance and the psychological scores was done in both groups. RESULTS: Structured VR training enhanced VR performance of surgical trainees. An additional correlation to high motivational states (P < 0.05) was found. Low levels of self-efficacy and negative stress-coping were related to poor VR performance in the untrained control group (P < 0.05). This correlation was absent in the trained intervention group (P > 0.05). CONCLUSION: Low self-efficacy and negative stress-coping strategies seem to predict poor VR performance. However, structured training along with high motivational states is likely to balance out this impairment.

Differentiation between thyroidal and ectopic calcitonin secretion in patients with coincidental thyroid nodules and pancreatic tumors - a report of two cases.

Although elevated blood levels of calcitonin are considered highly indicative for the presence of medullary thyroid carcinomas, they may be observed in patients with chronic kidney disease or in consequence of ectopic calcitonin production. We report two patients who presented with excessively elevated calcitonin levels. Diagnostic work-up revealed a single thyroid nodule and a pancreatic tumor with ectopic calcitonin secretion in both of them. On the basis of these case reports, the diagnostic work flow and management in case of clearly elevated calcitonin levels are described and discussed.

The impact of parathyroid gland autotransplantation during bilateral thyroid surgery for Graves' disease on postoperative hypocalcaemia.

OBJECTIVE: The aim of this study was to compare the rate of hypocalcaemia after bilateral thyroid resection for Graves' Disease in patients with and without parathyroid gland autotransplantation (PTAT). PATIENTS AND METHODS: A total of 153 patients following thyroid surgery for Graves' disease were studied. Patients were divided into three groups. Subgroup I comprised of 129 patients without PTAT, Subgroup II comprised of 19 patients with PTAT of one parathyroid gland and Subgroup III comprised of 6 patients with PTAT of two parathyroid glands. Association between PTAT and postoperative hypocalcaemia (PH) after thyroidectomy was investigated. RESULTS: There were 27/128 (21.1%) patients with transient and 10/128 (7.8%) patients with permanent hypocalcemia within Subgroup I. Among Subgroup II 4/19 (21.1%) patients developed transient and no patient developed permanent hypocalcaemia, while in Subgroup III 2/6 (33.3 %) patients developed transient hypocalcaemia which became persistent. Thus, the frequency of permanent postthyroidectomy hypocalcaemia (PH) was significantly higher in the Subgroup III with PTAT of two parathyroid glands when compared to the Subgroup I without PTAT (p=0.032) and Subgroup II with PTAT of only one parathyroid glands (p=0.012). CONCLUSION: PTAT of one parathyroid gland is an effective procedure to reduce the incidence of permanent hypoparathyroidism after bilateral surgery for Graves disease. Transient hypoparathyroidism was not influenced by PTAT.

[Introduction of a critical incident reporting system in a surgical university clinic. What can be achieved in a short term?]. / Einführung eines Critical Incident Reporting System in einer chirurgischen Universitätsklinik: Was kann kurzfristig erreicht werden?

BACKGROUND AND OBJECTIVE: "Critical incident reporting systems" (CIRS) are voluntary systems which, within the framework of risk management, provide pointers to the type and origin of critical incidents (including "errors"). The interest in introducing a CIRS is great, but whether it can fulfill its promises remains to be clarified. The aim of this study was to answer the question of whether an CIRS in a structured form would be acceptable to staff and whether it would be suitable for introducing targeted measures for achieving improvements. METHODS: The introduction of a CIRS in the Department of Visceral, Thoracic and Vascular Surgery proceeded according to the recommendations of the Action Alliance for Patients' Safety (Aktionsbündnis für Patientensicherheit e.V.). RESULTS: During a period of 13 months we received a total of 96 reports, 29.3% from various levels of carers/nurses, while 35.4% were from doctors. 40.6% of the incidents had been observed by the reporting person, in 38.5% of cases the reporting person had been involved in the incident and in 12.5% this person had helped in dealing with the incident. 38.5% of the reported critical incidents occurred between 06.00 and 12.00, while 34.4% occurred between 12:00 and 18:00 o/c. In 32.3% of cases the estimated duration of dealing with the incident was under four hours and between four and eight hours in 26%. During the first year of this study 12 actions were started and continued in consequence of an analysis of the reported critical incidents. CONCLUSION: After one year of the study it was found that a CIRS can be reliably introduced into a surgical department in accordance with the recommendations of the Action Alliane for Patients' Safety. When introduced correctly CIRS provides valuable information, which will lead to risk reduction in surgery.

Graft-dependent renal hyperparathyroidism despite successful kidney transplantation.

INTRODUCTION: Only a few reports can be found on the recurrence or persistence of hyperparathyroidism after total parathyroidectomy and autotransplantation (PTX + AT) following kidney transplantation (KTX). The objective of the present study was to assess the frequency and pathophysiological mechanisms responsible for the development of graft-dependent renal hyperparathyroidism (rHPT) after KTX. PATIENTS AND METHODS: Between 1986 and 2006, 69 patients underwent surgery for rHPT after KTX at our institution. Patients with reoperations at the parathyroid autograft (AT) were identified. Kidney graft function (KGF) was assessed by the glomerular filtration rate (GFR). Representative parts of the parathyroid gland chosen for autotransplantation during the initial parathyroidectomy and of the excised AT at reoperation were reanalyzed according to the morphologic pattern and the proliferative index. RESULTS: Eight of the 69 patients underwent reoperation of the AT. All patients had undergone initial PTX + AT before KTX. The GFR before parathyroid reoperation was 66.6 +/- 9.6 ml/min per1.73 m(2) (mean +/- SEM). Histopathological re-examination revealed nodular hyperplasia in the parathyroid tissue for autotransplantation and in the excised parathyroid autografts. The Ki67 index was increased in the glands chosen for autotransplantation prior to KTX, but was overall low in the excised autografts. DISCUSSION: Although not reported in the literature to date, tertiary hyperparathyroidism (tHPT) may arise from parathyroid autografts even in patients with a good KGF. In these cases, graft-dependent tHPT represents the inability of autonomous, nodular parathyroid tissue to regress despite the recovery of renal function. Non-nodular tissue should be selected for parathyroid autotransplantation to decrease the incidence of graft-dependent recurrent rHPT.

Technical complications in organ procurement.

It is of crucial importance that harvested organs are not discarded because of lesions inflicted during the procurement operation. From January 2005 to January 2006, a total of 395 organs were procured: 266 kidneys, 102 livers, and 27 pancreas. Two kidneys were lost due to vascular lesions, and 1 liver could not be transplanted because of a severe parenchymal injury (0.75% total organ losses). In 33 of 198 cases (16.7%) despite lesions to renal vessels or to the ureter, the kidneys were transplanted after back-table repair procedures. Vascular lesions were observed in 10% of the evaluated livers (8 of 102) and in 3 of 18 pancreatic grafts. In the literature, a total organ loss of 0.75% because of technical problems demonstrates a high standard of visceral organ procurement in our region. Hence, reparable vascular and ureteral lesions in 10% to 16.4% indicated the need for better surgical training and standardization in procurement techniques. We believe that double-checking both the organ and quality reports and giving immediate feedback to the procurement surgeons in cases of technical problems are effective ways to perform quality control. It must be our goal to increase the response rate of the quality forms.

[Instituting a surgical skills lab at a training hospital]. / Einrichtung eines chirurgischen Trainingslabors an einer Ausbildungsklinik.

The improvement of surgical skills of trainees in Germany often occurs solely in the operating room. In recent years, several countries have established surgical skills labs as an essential part of surgical education, with the goal of improving and refining surgical skills before clinical application. Several years ago, training units were established by the industry wherein the curricula focused on products of the respective company. Selected training courses are still offered in a few clinics. Presently, laboratories which train the surgical skills of novices in an individually adapted form are lacking. A surgical skills lab with a comprehensive curriculum of training courses was introduced at the University Hospital of Marburg in 2005. The present article describes the development and introduction of such facilities. The authors are convinced that surgical skills labs will become increasingly important in German surgical education for improving patient safety in the operating room.

[A virtual reality simulator for objective assessment of surgeons' laparoscopic skill]. / Laparoskopiesimulator Abbildung der manuellen Geschicklichkeit in der laparoskopischen Chirurgie.

BACKGROUND: The aim of this study was to validate computed virtual reality simulation as a tool to assess laparoscopic skills and to establish whether the simulator allows differentiating between surgeons with different laparoscopic experience. METHODS: 27 physicians at the surgical department of the University of Marburg, Germany, with different experience in laparoscopic surgery were divided into three groups: experienced (group I), intermediate (group II), and novices (group III). Following a brief introduction to the virtual reality simulator (LapSim), each participant performed twice a training program consisting of seven tasks (examinations I and II). RESULTS: Comparison of experienced surgeons with less experienced laparoscopic physicians showed a significant (P<0.05) superiority of group I at examinations I and II in most exercises. The groups' difference was more obvious in examination II, since the technique was new for all participants during examination I. Tasks of low complexity in virtual reality such as camera navigation, which are performed by young, not yet responsible surgeons in real surgery, did not show significantly different results between the three groups. CONCLUSION: Differences in laparoscopic experience can be visualised with a virtual reality simulator, and thus a simulator is helpful for assessing surgeons' laparoscopic skills.

Medical and surgical treatment for secondary and tertiary hyperparathyroidism.

Prevention and treatment of secondary hyperparathyroidism (SHPT) in patients on chronic maintenance hemodialysis and of tertiary hyperparathyroidism (THPT) in patients after kidney transplantation is a challenge for the nephrologist and for the surgeon. Indication and results of medical and surgical therapy for SHPT and THPT have remained under discussion during the last decades. This review resumes the current medical and surgical strategies for patients with SHPT and THPT.

Low-dose-rate ionizing irradiation for inhibition of secondary cataract formation.

INTRODUCTION: Secondary cataract formation limits visual function after cataract surgery. Various experimental methods utilizing the pharmacologic inhibition of lens epithelial cell proliferation have been proposed. However, diffusion into the anterior chamber may lead to damage of corneal endothelial cells. This study evaluated the inhibition of lens epithelial cell proliferation with a capsular bag ring, labeled with a beta-emitting radioisotope. METHODS AND MATERIALS: In vitro studies using rabbit lens epithelial cells were performed to investigate the dose-dependent effect of irradiation. Based on these results, P-32-labeled PMMA rings were implanted into the capsular bag of NZW rabbits in vivo after phacoemulsification. Animals were examined for development of posterior capsule opacification over a period of 12 weeks following surgery. Radiation damage to the surrounding ocular tissue was subsequently analyzed in histologic sections using TUNEL assay and proliferation marker. RESULTS: Irradiation of lens epithelial cells in vitro with >5 Gy resulted in a dose-dependent decrease in the number of cells. BrdU testing demonstrated a near complete inhibition of cell proliferation. In vivo, implantation of P-32-labeled PMMA rings led to inhibition of epithelial cell proliferation and secondary cataract formation but was not able to fully inhibit aberrant differentiation of some remaining cells. Histologic examination showed no evidence of radiation damage of the ciliary body or the corneal endothelium. CONCLUSIONS: Low-dose beta irradiation exhibits the potential for inhibition of lens epithelial cell proliferation both in vitro and in vivo. Further investigation of various nuclides and their radiation profiles is needed to optimize the prevention of posterior capsule opacification due to epithelial cell proliferation.

Double-blind, randomised, placebo-controlled, dose-finding study of oral ibandronate in patients with metastatic bone disease.

BACKGROUND: Bisphosphonates are an important component of the treatment of metastatic bone disease but more potent, oral formulations are required to improve the effectiveness and convenience of treatment. An oral formulation of the new bisphosphonate, ibandronate (BM 21.0955) has recently been developed. PATIENTS AND METHODS: One hundred ten patients with bone metastases (77 breast, 16, prostate, 3 myeloma, 14 others) were recruited from a single institution to this double blind placebo-controlled evaluation of four oral dose levels (5, 10, 20 and 50 mg) of ibandronate. No changes in systemic anti-cancer treatment were allowed in the month before commencing treatment or during the study period. After an initial four-week tolerability phase, patients could continue on treatment for a further three months without unblinding; patients initially allocated to placebo received ibandronate 50 mg. The primary endpoint was urinary calcium excretion (UCCR). Bone resorption was also assessed by measurement of pyridinoline (Pyr), deoxypyridinoline (Dpd), and the N-terminal (NTX) and C-terminal (Crosslaps) portions of the collagen crosslinking molecules. RESULTS: Two patients did not receive any trial medication thus, 108 patients were evaluable for safety. Ninety-two patients were evaluable for efficacy. A dose dependent reduction was observed in both UCCR and collagen crosslink excretion. At the 50 mg dose level, the percentage reductions from baseline in UCCR, Pyr, Dpd, Crosslaps and NTX were 71%, 28%, 39%, 80% and 74% respectively. One or more gastrointestinal (GI) adverse events occurring in the first month of treatment were reported by six (30%), seven (33%), nine (39%), nine (41%) and eleven (50%) patients at the placebo, 5, 10, 20 and 50 mg dose levels respectively. One patient (20 mg dose) developed radiographically confirmed oesophageal ulceration. GI tolerability may have been adversely affected by concomitant administration of non-steroidal anti-inflammatory agents. Nine (8%) patients stopped treatment within the first month due to GI intolerability but these patients were evenly distributed across the five treatment groups. There was no difference in non-GI adverse events between groups. CONCLUSIONS: Oral ibandronate has potent effects on the rate of bone resorption at doses which are generally well tolerated. Further development is appropriate to evaluate the effects of long-term administration in the prevention of metastatic bone disease and the management of established skeletal metastases.

On the production of radioactive stents.

In the last few years, radioactive stents has been proved to inhibit neointima formation. This paper describes the actual status of producing such radioactive stents. After a short discussion of the different radioisotopes suitable for radioactive stents, potential production methods are discussed. The ion beam implantation of P-32 applied at the Karlsruhe Research Centre shall be described in more detail.

Biochemical markers as surrogates in clinical trials in patients with metastatic bone disease and osteoporosis.

Biochemical markers of bone turnover have been employed in phase II dose-finding trials to determine the therapeutic window of the highly potent bisphosphonate ibandronate. For intravenous dose finding in metastatic bone disease 158 patients with breast cancer were treated by single bolus injection of up to 3.0 mg and by single infusion of 4 and 6 mg of ibandronate. In the oral double-blind dose-finding trial, 108 patients received up to 50 mg of ibandronate or placebo once daily for 28 days. For dose-finding in osteoporosis 126 postmenopausal women with osteoporosis were treated in a double-blind trial by four injections of up to 2.0 mg of ibandronate or placebo every 3 months. In the phase II dose-finding trial, 180 postmenopausal women with osteoporosis received up to 5 mg of ibandronate or placebo daily for 12 months. During these trials, the bone resorption markers urinary Ca, pyridinoline (Pyd), deoxypyridinoline (Dpd), type I collagen cross-linked N-telopeptide and type I collagen cross-linked C-telopeptide revealed clear dose-dependent responses in accordance with the appropriate dose of ibandronate. The bone formation markers serum osteocalcin, carboxy-terminal propeptide of type I collagen and bone-specific alkaline phosphatase demonstrated also dose-dependent changes in long-term treatment. Thus, for dose finding and monitoring of ibandronate treatment in osteoporosis and in patients with malignant metastatic bone disease urinary type I collagen cross-linked N-telopeptide and C-telopeptide are the most responsive biochemical markers of bone resorption. For bone formation monitoring serum osteocalcin and serum bone-specific alkaline phosphatase should be employed.

Administration of the bisphosphonate ibandronate (BM 21.0955) by intravenous bolus injection.

Bisphosphonates (BPs) are used for the treatment of both benign and malignant diseases characterized by increased bone resorption. Because of their potential nephrotoxicity, currently available BPs have to be administered by slow intravenous infusion, with conventional doses requiring an infusion time of at least 2 h. In the present investigation, we evaluated the safety and efficacy of the new BP ibandronate as administered by intravenous bolus injection. On day 0, 15 normocalcemic breast cancer patients with bone metastases were treated with 3 mg of ibandronate injected intravenously over 60-120 s. Ibandronate treatment led to significant decreases in serum levels of calcium (p < 0.0001) and phosphate (p < 0.0001) and to subsequent increases in serum concentrations of parathyroid hormone (p <0.0001) and calcitriol (p <0.0001). Moreover, there was a significant reduction in the urinary excretion of calcium (p <0.0001), pyridinoline (p <0.001), and deoxypyridinoline (p < 0.0001). Three serious adverse events were observed: vomiting (WHO grade 3), pulmonary infection (WHO grade 2), and deterioration of a pre-existing impaired glucose tolerance (WHO grade 3). Only vomiting appeared to be related to administration of the drug. The most frequent nonserious adverse events were 10 cases of transient clinically asymptomatic hypocalcemia and 8 cases of asymptomatic hypophosphatemia. Serum levels of creatinine and urea nitrogen did not increase, nor did creatinine clearance deteriorate. When tested with the dipstick method, proteinuria was present in five (33%) patients prior to ibandronate treatment (median protein concentration, 30 mg/dl). Following the BP injection, seven (47%) patients showed slight (highest protein concentration, 30 mg/dl) transient proteinuria at at least one time point, of which six cases appeared in conjunction with leucocyturia and three with microhematuria. Side effects specific to aminosubstituted BPs (fever, reduction in white blood cell counts, and lymphocyte counts) were not seen in these 15 patients. In conclusion, a single intravenous injection of 3 mg of ibandronate significantly inhibited osteoclast activity as reflected by the decrease in serum calcium and in urinary parameters of bone resorption. Serum creatinine levels and estimates of creatinine clearance were not affected by therapy. However, before repeated bolus injections of ibandronate at this dosage can be recommended for further clinical trials, whether a relationship exists between the transient pathological urinary findings and injected ibandronate needs to be determined.