Open-source navigation system for tracking dissociated parts with multi-registration.

PURPOSE: During reconstructive surgery, knee and hip replacements, and orthognathic surgery, small misalignments in the pose of prosthesis and bones can lead to severe complications. Hence, the translational and angular accuracies are critical. However, traditional image-based surgical navigation lacks orientation data between structures, and imageless systems are unsuitable for cases of deformed anatomy. We introduce an open-source navigation system using a multiple registration approach that can track instruments, implants, and bones to precisely guide the surgeon in emulating a preoperative plan. METHODS: We derived the analytical error of our method and designed a set of phantom experiments to measure its precision and accuracy. Additionally, we trained two classification models to predict the system reliability from fiducial points and surface matching registration data. Finally, to demonstrate the procedure feasibility, we conducted a complete workflow for a real clinical case of a patient with fibrous dysplasia and anatomical misalignment of the right femur using plastic bones. RESULTS: The system is able to track the dissociated fragments of the clinical case and average alignment errors in the anatomical phantoms of [Formula: see text]  mm and [Formula: see text]. While the fiducial-points registration showed satisfactory results given enough points and covered volume, we acknowledge that the surface refinement step is mandatory when attempting surface matching registrations. CONCLUSION: We believe that our device could bring significant advantages for the personalized treatment of complex surgical cases and that its multi-registration attribute is convenient for intraoperative registration loosening cases.

Role of the pupillometer in the assessment of pain in the sedation of pediatric patients.

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic drugs in adults. The aim of this study was to verify the usefulness and effectiveness of the pupillometer to assess pain and depth of sedation in pediatric patients undergoing painful procedures and to optimize pain management by observing pupillary variations induced by opioids. PATIENTS AND METHODS: This is a prospective, monocentric study conducted in the sedation room of the Pediatric Intensive Care Unit of Fondazione Policlinico A. Gemelli in Rome. A population of 22 pediatric patients who underwent painful procedures was enrolled. Eleven children were sedated by opioid drugs. Heart rate, systolic blood pressure, diastolic blood pressure, bispectral index, maximum pupil size (Size), pupil change (CH), Neurological Pupil Index (NPi) were collected over four times: before starting the procedure; before the painful stimulus (when the patient was sedated); when the painful stimulus was applied; at the end of the procedure. A NeurOptics NPi-200 pupillometer was used for the study. RESULTS: Statistical significance in the variation of haemodynamic parameters was less significant than the variation obtained by analyzing the pupillary parameters: a significant change in NPi and CH in the transition from wakefulness to sedation and from the application of the painful stimulus to awakening was found in both study populations, patients who have received opioids and patients who have not received opioids. Changes in the mean CH of the pupil diameter correlate with the depth of sedation, and the size values vary in relation to the administration of opioids. CONCLUSIONS: Our findings highlight the potential role of pupillometry as a non-invasive method to objectively quantitate pain response in children to reach an efficient analgesic approach.

Computer-assisted surgery for replacement of the temporomandibular joint with customized prostheses: can we validate the results?

PURPOSE: Replacing the temporomandibular joint poses an important challenge to maxillofacial surgeons, and for certain disorders, it represents the treatment's gold standard. Computer-assisted surgery (comprising preoperative virtual planning, virtual intraoperative navigation and 3D printing) is a useful tool for this type of surgery. However, we do not know if and how much the final position of the prosthesis differs, in absolute values, from what was planned virtually in the preoperative phase. We propose a comparative result validation system for temporomandibular joint replacement METHODS: In the present study, we propose a comparative validation system using overlapping images, between the model obtained with preoperative virtual planning and the postoperative result. RESULTS: The mean difference for all screws of the glenoid prosthesis was 2.08 mm (range, 1.20-3.03) and for all screws of the condylar prosthesis it was 2.33 mm (range, 1.16-3.56). Mean overall difference between both prostheses in all patients was 2.21 mm (range, 1.16-3.56). CONCLUSIONS: The validation system proposed by overlapping pre- and postoperative images in temporomandibular joint replacement allowed us to establish differences in absolute values between the virtual preoperative model and the actual postoperative result expressed in millimeters.

Obtaining accurate and calibrated coil models for transcranial magnetic stimulation using magnetic field measurements.

Currently, simulations of the induced currents in the brain produced by transcranial magnetic stimulation (TMS) are used to elucidate the regions reached by stimuli. However, models commonly found in the literature are too general and neglect imperfections in the windings. Aiming to predict the stimulation sites in patients requires precise modeling of the electric field (E-field), and a proper calibration to adequate to the empirical data of the particular coil employed. Furthermore, most fabricators do not provide precise information about the coil geometries, and even using X-ray images may lead to subjective interpretations. We measured the three components of the vector magnetic field induced by a TMS figure-8 coil with spatial resolutions of up to 1 mm. Starting from a computerized tomography-based coil model, we applied a multivariate optimization algorithm to automatically modify the original model and obtain one that optimally fits the measurements. Differences between models were assessed in a human brain mesh using the finite-elements method showing up to 6% variations in the E-field magnitude. Our calibrated model could increase the precision of the estimated E-field induced in the brain during TMS, enhance the accuracy of delivered stimulation during functional brain mapping, and improve dosimetry for repetitive TMS. Graphical Abstract Geometrical model of TMS coil based on TAC images is optimally deformed to match magnetic field measurements. The calibrated model's induced electric field in the brain differs from the original.

Changing practices: The addition of a novel surgical approach to gynecomastia.

INTRODUCTION: Gynecomastia can be a significant impediment to quality of life for men who suffer from this affliction. Numerous surgical techniques have been described in the literature ranging from minimally invasive options such as liposuction to incision based reductions. The standard for the general surgeons at our institution has been subcutaneous mastectomy through a circumareolar incision, which often proved inadequate for patients with grade II or III gynecomastia. In November 2013 we adopted a new technique, the "double donut", that offers the post-operative appearance of a limited incision, with the additional benefits of mastopexy, skin reduction, and mastectomy through an enlarged incision which is not superficially evident at the completion of the procedure. METHODS: We reviewed our surgical database for all cases performed for gynecomastia in the period from May 2005 to August 2016. Basic demographic information, diagnostic modality, symptoms, indication for procedure, operation performed, and final pathology were collected and analyzed. RESULTS: There were 70 mastectomies performed on 52 subjects. All subjects were male; 14 were African American and 38 were Caucasian. The average age was 47 (23-73) years old. The majority of the patients were evaluated with mammogram and/or ultrasound. All but one patient presented with pain as the chief complaint. There were 41 mastectomies done prior to initiation of this technique and 29 were performed after. The average total volume of breast tissue excised via the previous technique was 97.4 cm3, this increased to 186.5 cm3 with the new technique. No necrosis of the NAC was seen and no wound infections resulted in complication. Cosmetic satisfaction was seen in 98% of patients. CONCLUSION: The "double donut" technique is particularly useful for males with grades II or III gynecomastia. It provides good wound results, with acceptable patient satisfaction and cosmetic outcomes. Although initially developed for patients with higher grade gynecomastia, the improved visibility and increased patient satisfaction allowed this to become the preferred technique at our institution.

Flat epithelial atypia on core needle biopsy, must we surgically excise?

Breast flat epithelial atypia (FEA) often coexists with more aggressive pathology and excision is currently recommended when diagnosed by core needle biopsy (CNB). Recent studies suggest isolated FEA has a low association with carcinoma and may warrant close surveillance. A radiology database containing 2189 breast CNB was reviewed for isolated FEA or FEA in combination with atypical pathology. 79 patients had FEA. There were 48/79 with isolated FEA and 31/79 concomitant FEA with ADH, ALH, or LCIS. 46 subsequent excisional biopsies of isolated FEA resulted: benign 38/46, ADH 5/46, LCIS 2/46, DCIS 1/46. Concomitant FEA + ADH/ALH/LCIS group resulted: benign 26/31, DCIS 3/31, DCIS and LCIS 1/31, tubular carcinoma 1/31. DCIS/invasive cancer on excision in the FEA + ADH group is 5/31 versus 1/46 for isolated FEA (p 0.0489). Findings support literature suggesting isolated FEA has a low association with carcinoma. These patients may not require surgical excision, but instead have close surveillance. Based on the higher cancer incidence in FEA combined with ADH, ALH, LCIS, or residual microcalcifications, we still recommend surgical excision. SUMMARY: Breast flat epithelial atypia (FEA) often coexists with more aggressive pathology and surgical excision is currently recommended when diagnosed by core needle biopsy. Recent studies have suggested isolated FEA has a low association with carcinoma and these patients may warrant close surveillance. Isolated FEA has a low association with carcinoma in our series. These patients may not require surgical excision, but instead have close surveillance.

Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor.

BACKGROUND: Estrogens may induce the proliferation of neoplastic cells by activating neo-angiogenesis. AIM: To evaluate the effect of estrogens on the expression of vascular endothelial growth factor (VEGF) and related receptors (VEGF-R) in human cholangiocarcinoma and the role played by VEGF in mediating the proliferative effects of estrogens. METHODS: Seven biopsies of intra-hepatic cholangiocarcinoma and the HuH-28 cell lines were investigated. Cell proliferation was measured by both PCNA Western blot and MTS proliferation assay. RESULTS: By immunohistochemistry, biopsies of human cholangiocarcinoma stained positively for VEGF-A and VEGF-C and related receptors. HuH-28 cells expressed VEGF-A, -C, and VEGFR-1, -2, -3 and, their protein level was enhanced by 17beta-estradiol in association with the stimulation of cell proliferation. 17beta-Estradiol-stimulated proliferation of HuH-28 cells was blocked by 70% by VEGF-TRAP, a receptor-based VEGF inhibitor. 17beta-Estradiol induced the secretion of VEGF in the supernatant of HuH-28 cells. The stimulatory effect of 17beta-estradiol on the protein expression of VEGF-A, VEGF-C and VEGFR-1, -2, -3 was blocked by antagonists of ER (Ici182,780) or insulin-like growth factor 1-receptor (alphaIR3). CONCLUSIONS: With the limitations of experiments performed in a cell line, our study indicates that VEGF plays a major role in mediating the proliferative effects of estrogens on human cholangiocarcinoma.

Bile salts regulate proliferation and apoptosis of liver cells by modulating the IGF1 system.

BACKGROUND: In different cell types, the insulin-like growth factor 1 and its receptor modulate growth, apoptosis and damage repair in cooperation with estrogen receptors. AIM: To evaluate the involvement of the insulin-like growth factor 1 system and estrogen receptors in bile salts modulation of apoptosis/proliferation of hepatocytes and cholangiocytes. Primary cultures of rat hepatocytes and cholangiocytes were exposed to glycochenodeoxycholate or tauro-CDC in the presence or absence of insulin-like growth factor 1 receptor blocking antibody (alphaIR3), small interfering RNA for insulin-like growth factor 1, 17beta-estradiol or estrogen receptor antagonist (ICI 182,780). Proliferation was evaluated by proliferating cell nuclear antigen Western blot and apoptosis by measuring caspase-3 activity or annexin-V. RESULTS: In hepatocytes, the insulin-like growth factor 1 receptor blocker enhanced glycochenodeoxycholate-induced apoptosis and caused tauro-CDC to promote apoptosis. 17Beta-estradiol or the estrogen receptor antagonist (ICI 182,780) did not influence the apoptotic effect of glycochenodeoxycholate. In cholangiocytes, both glycochenodeoxycholate and tauro-CDC induced proliferation at 100microM, while they induced apoptosis at 1mM with a more pronounced effect of glycochenodeoxycholate. Apoptosis induced by 1mM glycochenodeoxycholate or tauro-CDC in cholangiocytes was enhanced by blocking insulin-like growth factor 1 receptor or by silencing insulin-like growth factor 1. 17Beta-estradiol counteracts glycochenodeoxycholate-induced cholangiocyte apoptosis by enhancing insulin-like growth factor 1 secretion and activating the insulin-like growth factor 1 system. CONCLUSIONS: Modulation of the IGF1 system could represent a potential strategy for the management of bile salts-induced liver injury.

Oral isotretinoin and haemophilia A.

The effects of oral isotretinoin on the coagulation system are still not well known: some case reports describe thrombocytopenia or thrombocytosis, others present different effects on fibrinolysis. We report a case of severe acne treated with oral isotretinoin in a patient affected with haemophilia A. In this case, which differs from the only other case reported in the literature, oral isotretinoin did not appear to influence the haemophilic patient's need of factor VIII.

Reversal of bone loss in mice by nongenotropic signaling of sex steroids.

We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha,17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected].

Magnetic resonance imaging-guided core needle biopsy and needle localized excision of occult breast lesions.

BACKGROUND: Breast magnetic resonance imaging (MRI) has been reported to be twice as sensitive and three times more specific in detecting breast cancer. We report a series of MRI-guided stereotactic breast biopsies (SCNBB) and needle localized breast biopsies (NLBB) to evaluate MRI as a localization tool. METHODS: Forty-one breast lesions were identified in 39 patients who subsequently had SCNBB or NLBB. Suspicious areas of enhancement were stereotactically biopsied with 16-G core biopsy needles or localized with 22-G wires for excision under laser guidance. RESULTS: Forty-one breast lesions were identified from 1,292 breast MRIs. SCNBB identified three malignancies and two areas of atypia. Two additional cancers were found after NLBB. In patients having NLBB alone, five cancers and two areas of atypia were identified. CONCLUSIONS: In this initial series, breast MRI-guided SCNBB and NLBB were valuable tools in the management of patients with suspicious abnormalities seen only on MRI.

Racial differences in breast cancer survival: the effect of residual disease.

BACKGROUND: A survival difference has been seen in numerous studies between African-American (AA) and Caucasian (C) women with breast cancer. The purpose of this study was to elucidate the differences in patient characteristics and outcomes between AA and C women with breast cancer in our population. METHODS: We performed a retrospective analysis of 1345 women with newly diagnosed breast cancer who were entered into our tumor registry from October 1980 to December 1998. RESULTS: The association between race and stage at presentation was significant, as was the difference in the overall median survival between C and AA women. The data revealed no significant differences in survival between C and AA women presenting with Stage I or II disease. However, the differences between the median survival times for AA and C women presenting with Stage III and IV disease were both highly significant. A significantly lower percentage of AA women became "disease free" after initial therapy as compared with C women (P < 0.001). Interestingly, when data were stratified by stage, only in Stage III and IV were there significant differences between the races for becoming disease free. CONCLUSIONS: AA women tend to present at a later stage and have poorer survival from later-stage disease as compared with C women. The poorer survival appears to be related to the decreased ability to achieve disease-free status in AA women with advanced disease. The underlying causes of this difference in treatment outcome need further evaluation.

Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells.

BACKGROUND: Breast cancer metastasis to bone causes resorption of the mineralized matrix by osteoclasts. Macrophage colony stimulating factor (M-CSF)and receptor activator of the NF-kappaB ligand (RANKL) are produced by stromal cells and are essential for osteoclast formation. The human breast cancer cell line, MDA-MB-231, reliably forms bone metastases in a murine model and stimulates osteoclast formation in culture. We hypothesized that MDA-MB-231 stimulates osteoclast formation through secretion of M-CSF and/or RANKL. MATERIALS AND METHODS: We cocultured MDA-MB-231 and a bone marrow derived cell line, UAMS-33, and evaluated the expression of M-CSF and RANKL mRNA. Osteoclast formation was assessed using these cells added to hematopoietic cell cultures. RESULTS: MDA-MB-231 exhibited constitutive expression of M-CSF mRNA. As expected, addition of recombinant M-CSF (30 ng/ml) and RANKL (30 ng/ml) to hematopoietic osteoclast precursors supported osteoclast formation, while the addition of soluble RANKL alone or MDA-231 without added RANKL did not. Notably, coculture of MDA-231 with hematopoietic cells and added soluble RANKL stimulated significant osteoclast formation, indicating that MDA-231 served as an effective source for M-CSF. MDA-231 did not express RANKL. However, when cocultured with the murine bone marrow stromal cell line UAMS-33, RANKL expression was significantly increased in the latter cells. MDA-231 also stimulated osteoclast formation in coculture with UAMS-33 and hematopoietic cells. CONCLUSIONS: We conclude that MDA-MB-231 increases osteoclast formation by secreting adequate amounts of M-CSF protein and enhancing the expression of RANKL by stromal support cells. The ability to stimulate osteoclasts may explain the ability to metastasize to bone.

Hematoma-directed ultrasound-guided breast biopsy.

OBJECTIVE AND SUMMARY BACKGROUND DATA: The standard technique for removal of nonpalpable breast lesions is needle localization breast biopsy. Because traumatic hematomas can often be seen with ultrasound, the authors hypothesized that iatrogenically induced hematomas could be used to guide the excision of nonpalpable lesions using ultrasound. METHODS: Twenty patients with nonpalpable breast lesions detected by magnetic resonance imaging only were enrolled in this single-institution trial, approved by the institutional review board. A hematoma consisting of 2 to 5 mL of the patient's own blood was injected into the breast to target the nonpalpable lesion. Intraoperative ultrasound of the hematoma was used to direct the excisional biopsy. RESULTS: The average age of women was 53.8 +/- 10 years. Ninety-five percent of lesions detected by magnetic resonance imaging were localized by hematoma injection. All the hematomas used to recognize targeted lesions were identified at surgery by ultrasound and removed without complication. Eight (40%) of the lesions were malignant, with an average tumor size of 12 +/- 6 mm (range 4-25). The remaining 12 lesions (60%) comprised papillomas, sclerosing adenosis, radial scar, fibroadenoma, and areas of atypical ductal hyperplasia. CONCLUSION: The results of this pilot study show the effectiveness of hematoma-directed ultrasound-guided breast biopsy for nonpalpable lesions seen by magnetic resonance imaging. This new procedure is potentially more comfortable for the patient because no wire or needle is left in the breast. It is technically faster and easier because ultrasound is used to visualize directly the location of the hematoma at surgery and to confirm lesion removal in the operating room by specimen ultrasound. The hematoma can be placed several days before biopsy, easing scheduling, and without fear of the migration that may occur with needle localization. This method may have ready application to mammographically detected lesions.

Immunostimulant (1 --> 3)-D-glucans from the cell wall of Cryphonectria parasitica (Murr.) Barr strain 263.

A (1 --> 3)-beta-D-glucan with approximately 30% of the residues having a beta-D-Glc-(1 --> 6) branch is the main water-soluble component of the cell wall polysaccharide of Cryphonectria parasitica (Murr.) Barr strain 263. A (1 --> 3)-glucan with both alpha and beta anomeric linkages was found in the water-insoluble polysaccharide fraction. Both fractions possess immunological activity, being able to induce the production of either tumour necrosis factor alpha (TNF-alpha) or nitrite (NO2-).

Central venous catheter placement in patients with disorders of hemostasis.

BACKGROUND: Patients requiring central venous access frequently have disorders of hemostasis. The aim of this study was to identify factors predictive of bleeding complications after central venous catheterization in this group of patients. METHODS: A retrospective analysis of all central venous catheters placed over a 2-year period (1997 to 1999) at our institution were performed. The age, sex, clinical diagnosis, most recent platelet count, prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT), catheter type, the number of passes to complete the procedure, and bleeding complications were retrieved from the medical records. RESULTS: In a 2-year period, 2,010 central venous catheters were placed in 1,825 patients. Three hundred and thirty placements were in patients with disorders of hemostasis. In 88 of the 330 patients, the underlying coagulopathy was not corrected before catheter placement. In these patients, there were 3 bleeding complications requiring placement of a purse string suture at the catheter entry site. In the remaining 242 patients, there was 1 bleeding complication. Of the variables analyzed, only a low platelet count (<50 x 10(9)/L) was significantly associated with bleeding complications. CONCLUSION: Central venous access procedures can be safely performed in patients with underlying disorders of hemostasis. Even patients with low platelet counts have infrequent (3 of 88) bleeding complications, and these problems are easily managed.

Complication after laparoscopic donor nephrectomy: a case report and review.

BACKGROUND: Laparoscopic procedures are gaining acceptance in the treatment of benign and some malignant urologic disorders. Recently, laparoscopic techniques have been applied to transplant surgery and touted as a safe alternative to traditional open techniques. METHODS: We present a patient who developed a complication from laparoscopic donor nephrectomy that required open corrective surgery. RESULTS: A 25-year-old man underwent laparoscopic donor nephrectomy at a large medical center familiar with the operation. There were no operative or early postoperative complications. Within 6 weeks of the operation, the patient developed signs and symptoms of partial small bowel obstruction. Further evaluation revealed an internal hernia in the retroperitoneum at the site of the nephrectomy. This required a second operation to reduce the hernia and close the defect. CONCLUSION: Laparoscopic donor nephrectomy remains an evolving technique that has not stood the test of time. Larger series will eventually reveal whether this is the procedure of choice as compared to traditional open donor nephrectomy.

Can a one-day workshop alter surgeons' teaching practices?

BACKGROUND: A 1-day workshop, consisting of five sections with small group discussions and opportunities for practical application of participants' knowledge, was developed to enhance the teaching skills of practicing surgeons. Immediate and long-term follow-up surveys were completed by the participants. METHODS: Post-workshop evaluations were obtained from all participants who took the workshop; follow-up surveys were mailed 4 to 6 months later. RESULTS: Workshop quality was rated as good (25%) or excellent (75%) by all participants. Follow-up survey results indicated that many participants had rarely/never utilized cited references, looked for additional resources on specific topics, or referred to the section syllabus/handout materials provided during the workshop. However, 100% of the participant respondents reported that they had changed the way they teach as a result of their workshop attendance. CONCLUSION: An abbreviated course on surgical education can result in long-term changes in the participants' perceptions of their teaching practices. Further study is required to determine if these perceived changes in teaching practices, which the participants have directly attributed to their workshop attendance, have resulted in measurable improvement in their effectiveness and efficiency as teachers.

Laparoscopy for staging and palliation of gastrointestinal malignancy.

The use of laparoscopy in the treatment of malignant diseases is one of the great advances of surgery in the last few decades. Its roles as a diagnostic modality, a staging tool, and a therapeutic avenue for the various malignancies of the abdominal cavity continue to expand. The benefits to cancer patients with regard to reduced morbidity and shorter hospitalizations are well established. As video, optical, insufflation, and instrumentation technologies advance further, laparoscopic techniques for the treatment of cancer can only multiply in depth and breadth.