Targeting MYC effector functions in pancreatic cancer by inhibiting the ATPase RUVBL1/2.

OBJECTIVE: The hallmark oncogene MYC drives the progression of most tumours, but direct inhibition of MYC by a small-molecule drug has not reached clinical testing. MYC is a transcription factor that depends on several binding partners to function. We therefore explored the possibility of targeting MYC via its interactome in pancreatic ductal adenocarcinoma (PDAC). DESIGN: To identify the most suitable targets among all MYC binding partners, we constructed a targeted shRNA library and performed screens in cultured PDAC cells and tumours in mice. RESULTS: Unexpectedly, many MYC binding partners were found to be important for cultured PDAC cells but dispensable in vivo. However, some were also essential for tumours in their natural environment and, among these, the ATPases RUVBL1 and RUVBL2 ranked first. Degradation of RUVBL1 by the auxin-degron system led to the arrest of cultured PDAC cells but not untransformed cells and to complete tumour regression in mice, which was preceded by immune cell infiltration. Mechanistically, RUVBL1 was required for MYC to establish oncogenic and immunoevasive gene expression identifying the RUVBL1/2 complex as a druggable vulnerability in MYC-driven cancer. CONCLUSION: One implication of our study is that PDAC cell dependencies are strongly influenced by the environment, so genetic screens should be performed in vitro and in vivo. Moreover, the auxin-degron system can be applied in a PDAC model, allowing target validation in living mice. Finally, by revealing the nuclear functions of the RUVBL1/2 complex, our study presents a pharmaceutical strategy to render pancreatic cancers potentially susceptible to immunotherapy.

Abdominal Panniculectomy Can Simplify Kidney Transplantation in Obese Patients.

BACKGROUND: Obesity is frequently present in patients suffering from end-stage renal disease (ESRD). However, overweight kidney transplant candidates are a challenge for the transplant surgeon. Obese patients tend to develop a large abdominal panniculus after weight loss creating an area predisposed to wound-healing disorders. Due to concerns about graft survival and postoperative complications after kidney transplantation, obese patients are often refused in this selective patient cohort. The study aimed to analyze the effect of panniculectomies on postoperative complications and transplant candidacy in an interdisciplinary setting. METHODS: A retrospective database review of 10 cases of abdominal panniculectomies performed in patients with ESRD prior to kidney transplantation was conducted. RESULTS: The median body mass index was 35.2 kg/m2 (range 28.5-53.0 kg/m2) at first transplant-assessment versus 31.0 kg/m2 (range 28.0-34.4 kg/m2) at panniculectomy, and 31.6 kg/m2 (range 30.3-32.4 kg/m2) at kidney transplantation. We observed no major postoperative complications following panniculectomy and minor wound-healing complications in 2 patients. All aside from 1 patient became active transplant candidates 6 weeks after panniculectomy. No posttransplant wound complications occurred in the transplanted patients. CONCLUSION: Abdominal panniculectomy is feasible in patients suffering ESRD with no major postoperative complications, thus converting previously ineligible patients into kidney transplant candidates. An interdisciplinary approach is advisable in this selective patient cohort.

Novel imaging methods reveal positive impact of topical negative pressure application on tissue perfusion in an in vivo skin model.

The influence of topical negative pressure application (TNPA) on tissue perfusion still remains controversial. TNPA was applied for 30 minutes on intact skin of 21 healthy participants. Measurements of tissue oxygen saturation and tissue temperature as signs of tissue perfusion were performed before application of the TNPA, directly after removal of the TNPA and 5, 10, 15, 20, and 30 minutes after removal of the dressing using the near infrared imaging (NIRI) and a thermal imaging camera. Tissue oxygen saturation showed an increase from 67.7% before applying the TNPA to 76.1% directly after removal of TNPA, followed by a decrease of oxygen saturation 30 minutes after removal of TNPA. The measured temperature of the treated skin area increased from 32.1°C to 36.1°C after removal of TNPA with a consecutive decrease of the temperature 30 minutes after removal. TNPA resulted in both a higher tissue oxygen saturation and a higher skin temperature after 30 minutes compared to the beginning. TNPA increases both tissue oxygen saturation and skin temperature as sign of an increase of tissue perfusion. NIRI and thermal imaging proved to be useful for measuring changes in tissue perfusion.

Results on the spatial resolution of repetitive transcranial magnetic stimulation for cortical language mapping during object naming in healthy subjects.

BACKGROUND: The spatial resolution of repetitive navigated transcranial magnetic stimulation (rTMS) for language mapping is largely unknown. Thus, to determine a minimum spatial resolution of rTMS for language mapping, we evaluated the mapping sessions derived from 19 healthy volunteers for cortical hotspots of no-response errors. Then, the distances between hotspots (stimulation points with a high error rate) and adjacent mapping points (stimulation points with low error rates) were evaluated. RESULTS: Mean distance values of 13.8 ± 6.4 mm (from hotspots to ventral points, range 0.7-30.7 mm), 10.8 ± 4.8 mm (from hotspots to dorsal points, range 2.0-26.5 mm), 16.6 ± 4.8 mm (from hotspots to apical points, range 0.9-27.5 mm), and 13.8 ± 4.3 mm (from hotspots to caudal points, range 2.0-24.2 mm) were measured. CONCLUSIONS: According to the results, the minimum spatial resolution of rTMS should principally allow for the identification of a particular gyrus, and according to the literature, it is in good accordance with the spatial resolution of direct cortical stimulation (DCS). Since measurement was performed between hotspots and adjacent mapping points and not on a finer-grained basis, we only refer to a minimum spatial resolution. Furthermore, refinement of our results within the scope of a prospective study combining rTMS and DCS for resolution measurement during language mapping should be the next step.

Preoperative language mapping by repetitive navigated transcranial magnetic stimulation and diffusion tensor imaging fiber tracking and their comparison to intraoperative stimulation.

INTRODUCTION: Repetitive navigated transcranial magnetic stimulation (rTMS) can be used for preoperative language mapping, but it still suffers from comparatively high sensitivity and low specificity when compared to direct cortical stimulation (DCS). Therefore, this study evaluates whether the additional consideration of rTMS-based diffusion tensor imaging fiber tracking (DTI FT) for identifying language-positive brain regions improves specificity when compared to DCS. METHODS: We performed rTMS, rTMS-based DTI FT, and DCS during awake surgery combined with object naming in 20 patients suffering from left-sided perisylvian brain lesions. For rTMS, different error rate thresholds (ERTs) and error types were considered, and DTI FT was conducted with individualized fractional anisotropy thresholds (FATs). Then, receiver operating characteristics (ROC) for rTMS vs. DCS, rTMS-based DTI FT vs. DCS, and rTMS spots confirmed by rTMS-based DTI FT vs. DCS were calculated. RESULTS: In general, rTMS vs. DCS was in good accordance with previous literature (sensitivity/specificity: 92.7/13.3 % for all naming errors without ERT). In addition, rTMS-based DTI FT vs. DCS led to balanced results when tracking was based on all errors as well (sensitivity/specificity: 62.8/64.3 % for 100 % FAT). However, rTMS combined with rTMS-based DTI FT vs. DCS did not lead to any improvement in specificity when compared to rTMS vs. DCS alone. CONCLUSION: The additional use of rTMS-based DTI FT to rTMS did not improve the identification of DCS-positive language areas during awake surgery. Yet, concerning rTMS-based DTI FT, this new technique must be validated itself by intraoperative subcortical stimulation.

Stimulation frequency determines the distribution of language positive cortical regions during navigated transcranial magnetic brain stimulation.

BACKGROUND: Although language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) gains importance in neuropsychological research and clinical utility, neuroscientists still use different mapping protocols including different stimulation frequencies. To refine the existing language protocol, we tested two different repetition rates of 5 Hz/10 pulses and 7 Hz/10 pulses with a 0 ms delay in 19 healthy subjects. We furthermore investigated differences between both frequencies in case of performance of four different language tasks: object naming, pseudoword reading, verb generation, and action naming. RESULTS: Even the small variance in frequencies revealed statistically significant differences concerning the number and type of language errors. Stimulation with 5 Hz evoked a higher number of all occurred language errors in all language tasks (error rate object naming 14% (5 Hz) vs. 12% (7 Hz); pseudoword reading 4% (5 Hz) vs. 3% (7 Hz); verb generation 13% (5 Hz) vs. 11% (7 Hz); action naming 11% (5 Hz) vs. 9% (7 Hz)), whereas 7 Hz evoked specifically more total speech arrests. CONCLUSION: These findings suggest that the stimulation frequency has to be adapted to the aim of the rTMS language investigation.

The impact of preoperative language mapping by repetitive navigated transcranial magnetic stimulation on the clinical course of brain tumor patients.

BACKGROUND: Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is used for resection planning in patients suffering from brain lesions within regions known to be involved in language function. Yet we also need data that show whether patients benefit clinically from preoperative rTMS for language mapping. METHODS: We enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011-2013), with the mapping results not being available for the surgeon, and we matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013-2014), but the mapping results were taken into account during tumor resection. Additionally, cortical language maps were generated by analyzing preoperative rTMS and intraoperative direct cortical stimulation (DCS) data. RESULTS: Mean anterior-posterior (ap) craniotomy extents and overall craniotomy sizes were significantly smaller for the patients in GROUP 2 (Ap: p = 0.0117; overall size: p = 0.0373), and postoperative language deficits were found significantly more frequently for the patients in GROUP 1 (p = 0.0153), although the preoperative language status did not differ between groups (p = 0.7576). Additionally, there was a trend towards fewer unexpected tumor residuals, shorter surgery duration, less peri- or postoperative complications, shorter inpatient stay, and higher postoperative Karnofsky performance status scale (KPS) for the patients in GROUP 2. CONCLUSIONS: The present study provides a first hint that the clinical course of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. However, a significant difference between both groups was only found for craniotomy extents and postoperative deficits, but not for other clinical parameters, which only showed a trend toward better results in GROUP 2. Therefore, multicenter trials with higher sample sizes are needed to further investigate the distinct impact of rTMS language mapping on the clinical course of brain tumor patients.

Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy.

BACKGROUND: Repetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas. METHODS: Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later. RESULTS: Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients. CONCLUSIONS: This report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard.

Inter- and intraobserver variability in motor mapping of the hotspot for the abductor policis brevis muscle.

BACKGROUND: For accuracy in navigated transcranial magnetic stimulation (nTMS), determination of the hotspot location of small hand muscles is crucial because it is the basis for the resting motor threshold (RMT) and, therefore, its spatial resolution. We investigated intra- and interobserver differences of hotspot mapping to provide evidence for the reproducibility of this method.Ten subjects underwent nTMS motor mapping of the hotspot for the abductor pollicis brevis muscle (APB) three times. The first two sessions were performed by the same examiner; the third mapping was performed by a different examiner. Distances between the first and second mappings (intraobserver variability) and between the second and third mappings (interobserver variability) were measured. RESULTS: Intraobserver variability had a mean of 8.1 ± 3.3 mm (limits of agreement (LOA) 1.7 to 14.6 mm), whereas mean interobserver variability was 10.3 ± 3.3 mm (LOA 3.8 to 16.7 mm). Concerning RMT, CCC was 0.725 (95% CI: 0.276; 0.914). The mean variability in the same cortical depth was measured as 5.7 ± 3.3 mm (LOA -0.7 to 12.2 mm) for intraobserver and 9.2 ± 3.3 mm (LOA 2.7 to 15.8 mm) for interobserver examinations. When evaluating the RMT, CCC was 0.709 (95% CI: 0.244; 0.909). CONCLUSIONS: Overall, intraobserver variability showed higher reliability than interobserver variability. Our findings show that we can achieve good reliability in hotspot determination, ranging within the calculated precision of the system.

Intra- and interobserver variability of language mapping by navigated transcranial magnetic brain stimulation.

BACKGROUND: Repetitive navigated transcranial magnetic stimulation (rTMS) has been used for studying language organization in healthy volunteers and patients, and to detect cortical areas involved in language processing. However, little is known about the reliability of this method. To determine the reliability of rTMS language mapping, we conducted both an interobserver and an intraobserver investigation. METHODS: Ten right-handed healthy subjects underwent language mapping by rTMS and the same object-naming task three times. Intraobserver and interobserver reliability of seven different error types were tested by two investigators. Analysis was performed blinded to the previous results and stimulated cortical sites. RESULTS: Overall, the results of both the interobserver and the intraobserver investigations show variable accordance. This is demonstrated by comparing the error rates of all different error types of the three examinations. Considering the most important error type, "no response", there is only small variability in inter- and intraobserver mapping. CONCLUSIONS: With our current protocol, interobserver and intraobserver comparisons only corresponded partially. Thus, although rTMS seems a promising method for preoperative planning as well as neuropsychological research, the current protocol needs further improvement.

Does indocyanine green fluorescence angiography impact the intraoperative choice of procedure in free vascularized medial femoral condyle grafting for scaphoid nonunions?

Background: Free vascularized medial femoral condyle (MFC) bone grafts can lead to increased vascularity of the proximal pole and restore scaphoid architecture in scaphoid nonunions. The intraoperative perfusion assessment of the bone graft is challenging because the conventional clinical examination is difficult. Indocyanine green (ICG) angiography has previously been shown to provide a real-time intraoperative evaluation of soft tissue perfusion in reconstructive surgery. The present study investigated the utility of ICG angiography in patients treated with a free medial femoral condyle graft for scaphoid nonunions. Methods: We performed a retrospective analysis of patients with scaphoid nonunions, in which ICG angiography was used intraoperatively for perfusion assessment. The medical records, radiographs, intraoperative imaging, and operative reports of all patients were reviewed. Intraoperative ICG dye was administered intravenously, and laser angiography was performed to assess bone perfusion. The scaphoid union was examined using postoperative CT scans. Results: Two patients had documented osteonecrosis of the proximal pole at the time of surgery. Four patients received a nonvascularized prior bone graft procedure, and a prior spongiosa graft procedure was performed in one patient. The mean time from injury to the MFC bone graft surgery was 52.7 months, and the mean time from prior failed surgery was 10.4 months. Perfusion of the vascular pedicle of the MFC and the periosteum could be detected in all patients. In two patients, even perfusion of the cancellous bone could be demonstrated by ICG angiography. Following transplantation of the bone graft, patency of the vascular anastomosis and perfusion of the periost were confirmed by ICG angiography in the assessed cases. No additional surgery regarding a salvage procedure for a scaphoid nonunion advanced collapse was necessary for the further course. Conclusion: ICG-angiography has shown to be a promising tool in the treatment of scaphoid nonunion with medial femoral condyle bone grafts. It enables intraoperative decision making by assessment of the microvascular blood supply of the periosteum and the vascular pedicle of the MFC bone graft. Further studies need to evaluate the impact on union rates in a long-term follow-up.

Corrigendum: Does indocyanine green fluorescence angiography impact the intraoperative choice of procedure in free vascularized medial femoral condyle grafting for scaphoid non-unions?

[This corrects the article DOI: 10.3389/fsurg.2022.962450.].

Improving the Safety of DIEP Flap Transplantation: Detailed Perforator Anatomy Study Using Preoperative CTA.

Background: Deep inferior epigastric perforator and muscle sparing transverse rectus abdominis muscle flaps are commonly used flaps for autologous breast reconstruction. CT-angiography allows to analyse the perforator course preoperatively. Our aim was to compare the different aspects of perforator anatomy in the most detailed study. Methods: CT-angiographies of 300 female patients with autologous breast reconstruction of 10 years were analysed regarding the anatomy of the deep inferior epigastric artery and every perforator. Results: Overall, 2260 perforators were included. We identified correlations regarding the DIEA branching point and number of perforators and their intramuscular course. The largest perforator emerged more often from the medial branch of the DIEA than the smaller perforators (70% (416/595) vs. 54% (878/1634), p < 0.001) and more often had a direct connection to the SIEV (large 67% (401/595) vs. small 39% (634/1634), p < 0.01). Medial row perforators were larger than the laterals (lateral 1.44 mm ± 0.43 (n = 941) vs. medial 1.58 mm ± 0.52 (n = 1304) (p < 0.001)). The larger and more medial the perforator, the more likely it was connected to the SIEV: perforators with direct connection to the SIEV had a diameter of 1.65 mm ± 0.53 (n = 1050), perforators with indirect connection had a diameter of 1.43 ± 0.43 (n = 1028), perforators without connection had a diameter of 1.31 mm ± 0.37 (n = 169) (p < 0.001). Medial perforators were more often directly connected to the SIEV than lateral perforators (medial 56% (723/1302) vs. lateral 35% (327/941), p < 0.001). A lateral perforator more often had a short intramuscular course than medial perforators (69% (554/800) vs. 45% (474/1055), p < 0.001), which was also more often observed in the case of a small perforator and a caudal exit of the rectus sheath. Conclusion: The largest perforator emerges more often from the medial branch of the DIEA and frequently has a direct connection to the SIEV, making medial row perforators ideal for DIEP flap transplantation.

The third dimension in perforator mapping-Comparison of Cinematic Rendering and maximum intensity projection in abdominal-based autologous breast reconstruction.

BACKGROUND: Cinematic Rendering (CR) is a recently introduced post-processing three-dimensional (3D) visualization imaging tool. The aim of this study was to assess its clinical value in the preoperative planning of deep inferior epigastric artery perforator (DIEP) or muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps, and to compare it with maximum intensity projection (MIP) images. The study presents the first application of CR for perforator mapping prior to autologous breast reconstruction. METHODS: Two senior surgeons independently analyzed CR and MIP images based on computed tomography angiography (CTA) datasets of 20 patients in terms of vascular pedicle characteristics, the possibility to harvest a DIEP or MS-TRAM flap, and the side of the flap harvest. We calculated inter- and intra-observer agreement in order to examine the accordance of both image techniques. RESULTS: We observed a good inter- and intra-observer agreement concerning the type of flap and the side of the flap harvest. However, the agreement on the pedicle characteristics varies depending on the considered variable. Both investigators identified a significantly higher number of perforators with MIP compared with CR (observer 1, p<0.0001 and observer 2, p<0.0385). CONCLUSION: The current study serves as an explorative study, showing first experiences with CR in abdominal-based autologous breast reconstruction. In addition to MIP images, CR might improve the surgeon's understanding of the individual's anatomy. Future studies are required to compare CR with other 3D visualization tools and its possible effects on operative parameters.

Influence of the autotaxin-lysophosphatidic acid axis on cellular function and cytokine expression in different breast cancer cell lines.

Previous studies provide high evidence that autotaxin (ATX)-lysophosphatidic acid (LPA) signaling through LPA receptors (LPAR) plays an important role in breast cancer initiation, progression, and invasion. However, its specific role in different breast cancer cell lines remains to be fully elucidated to offer improvements in targeted therapies. Within this study, we analyzed in vitro the effect of LPA 18:1 and the LPAR1, LPAR3 (and LPAR2) inhibitor Ki16425 on cellular functions of different human breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF-7, BT-474, SKBR-3) and the human breast epithelial cell line MCF-10A, as well as Interleukin 8 (IL-8), Interleukin 6 (IL-6) and tumor necrosis factor (TNF)-alpha cytokine secretion after LPA-incubation. ATX-LPA signaling showed a dose-dependent stimulatory effect especially on cellular functions of triple-negative and luminal A breast cancer cell lines. Ki16425 inhibited the LPA-induced stimulation of triple-negative breast cancer and luminal A cell lines in variable intensity depending on the functional assay, indicating the interplay of different LPAR in those assays. IL-8, IL-6 and TNF-alpha secretion was induced by LPA in MDA-MB-468 cells. This study provides further evidence about the role of the ATX-LPA axis in different breast cancer cell lines and might contribute to identify subtypes suitable for a future targeted therapy of the ATX-LPA axis.

An Innovative Arteriovenous (AV) Loop Breast Cancer Model Tailored for Cancer Research.

Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate-fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.

Topical negative-pressure wound therapy: emerging devices and techniques.

Introduction: The treatment of chronic wounds constitutes a massive financial burden to society and our health-care system. Therefore, efficient wound care is of great importance to all kinds of medical fields. The implementation and modification of negative-pressure wound therapy can be seen as a major improvement in wound healing. Many different NPWT applications evolved trying to address various wound etiologies.Areas covered: This review aims to give an overview of various NPWT applications, show its effects on wound healing, and discuss future modifications.Expert opinion: NPWT as a delivery device for cold plasma, growth factors, or targeted stem cells to the wound bed and the ability to monitor the inflammatory activity, bacterial load and wound healing factors can be seen as possible future steps to individualized wound care. In addition, it requires high-quality experimental studies to develop the ideal foam in terms of microstructure, pore size, and material properties.

Body Contouring Surgery Improves Physical Activity in Patients After Massive Weight Loss-a Retrospective Study.

BACKGROUND: The aim of the study was to compare physical activity (PA) in patients who had undergone massive weight loss (MWL), before and after body contouring procedures. METHODS: All patients undergoing body contouring surgery after MWL between 2007 and 2017 with a minimum follow-up of 6 months after the last procedure were included in this retrospective study. Excluded were those with a body mass index > 35 kg/m2 and those with comorbidities leading to impaired PA. Quality of life (QOL) was assessed using the Moorehead-Ardelt QOL Questionnaire II. Evaluation of PA was obtained with the International Physical Activity Questionnaire (IPAQ) short form and the Freiburg PA Questionnaire. Functional impairment during exercise was analyzed using a self-designed functional impairment score (FIS). RESULTS: In the 45 patients completing the survey (37 female, 8 male), an improvement in QOL (p < 0.001) and PA scored by the IPAQ (p = 0.017) was found. The Freiburg PA Questionnaire showed no difference in PA before and after body contouring surgery (p = 0,274). Furthermore, scores of the FIS indicated a decrease of functional impairment during physical activity after body contouring surgery (p < 0.001). CONCLUSION: Body contouring improves QOL and PA in patients after massive weight loss. The results of our study confirm the important role of plastic surgery in the treatment and maintenance of health of patients with former obesity.

Language function shows comparable cortical patterns by functional MRI and repetitive nTMS in healthy volunteers.

In preoperative planning, fMRI and repetitive navigated transcranial magnetic stimulation (rTMS) repeatedly revealed differences in the detected language sites, which can be attributed to tumor-induced oxygenation changes impairing the accuracy of fMRI. We therefore compared the accordance of those techniques in healthy subjects using exactly the same tasks in both investigations. 19 healthy right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during fMRI at 3 T and rTMS. For rTMS language mapping, we stimulated 46 cortical spots over the left hemisphere; each site was stimulated for three times. Language positive points during rTMS for one, two, or three errors out the three stimulations per spot (1/3, 2/3, 3/3) were exported via DICOM, and compared to the positive fMRI clusters. As a result of this comparison, the best correlation was observed between 3/3 errors and fMRI for pseudoword reading and verb generation with t-values of pu < 0.001, uncorrected for multiple comparisons, on average across the whole rTMS-spot map. We found a close spatial agreement between several rTMS-spots (2/3 and 3/3 errors) and fMRI clusters accentuated in the frontal lobe, followed by the parietal lobe and less in the temporal lobe. Compared to the fMRI clusters, there was a higher congruence for 2/3 and 3/3 errors than for 1/3 errors. Overall, results of language mapping in healthy subjects by fMRI and rTMS correspond well yet depending on the used language task.