A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Impact of Postoperative Antibiotic Prophylaxis on Surgical Site Infections Rates After Mastectomy with Drains but Without Immediate Reconstruction: A Multicenter, Double-Blinded, Randomized Control Superiority Trial.

BACKGROUND: There is no consensus on the use of postoperative antibiotic prophylaxis (PAP) after mastectomy with indwelling drains. We explored the utility of continued PAP in reducing surgical site infection (SSI) rates after mastectomy without immediate reconstruction and with indwelling drains. PATIENTS AND METHODS: A multicenter, two-armed, randomized control superiority trial was conducted in Pakistan. We enrolled all consenting adult patients undergoing mastectomy without immediate reconstruction. All patients received a single preoperative dose of cephalexin within 60 min of incision, and postoperatively were randomized to receive either continued PAP using cephalexin (intervention) or a placebo (control) for the duration of indwelling, closed-suction drains. The primary outcome was the development of SSI within 30 days and 90 days postoperatively. Secondary outcomes included study-drug-associated adverse events. Intention-to-treat analysis was performed using multivariable Cox regression. RESULTS: A total of 369 patients, 180 (48.8%) in the intervention group and 189 (51.2%) in the control group, were included in the final analysis. Overall cumulative SSI rates were 3.5% at 30 days and 4.6% at 90 days postoperatively. PAP was not associated with SSI reduction at 30 (hazard ratio, HR 1.666 [95% confidence interval CI 0.515-5.385]) or 90 (1.575 [0.558-4.448]) days postoperatively, or with study-drug-associated adverse effects (0.529 [0.196-1.428]). CONCLUSIONS: Continuing antibiotic prophylaxis for the duration of indwelling drains after mastectomy without immediate reconstruction offers no additional benefit in terms of SSI reduction. There is a need to update existing guidelines to provide clearer recommendations regarding use of postoperative antibiotic prophylaxis after mastectomy in the setting of indwelling drains.

Practice Patterns of Antibiotic Prophylaxis in Patients Undergoing Mastectomy: A Survey of Members of the American Society of Breast Surgeons.

BACKGROUND: Surgical site infections after breast surgery range from 1 to 16%. Both the American Society of Breast Surgeons (ASBrS) and the American Association of Plastic Surgeons guidelines lack clarity on postoperative antibiotic prophylaxis (AP) after mastectomy. We surveyed the ASBrS membership to understand their practice patterns of AP after mastectomy and familiarity with ASBrS guidelines. METHODS: A self-designed, 19-question survey was emailed to all 2934 ASBrS members. Information was obtained on the participants' training, familiarity with ASBrS guidelines, and practices of prescribing perioperative AP after mastectomy with/without reconstruction and with indwelling drains. RESULTS: In total, 556 (19%) responses were analyzed. Half were fellowship-trained breast surgeons/surgical oncologists (50.2%), with 55.6% having practiced for > 15 years and 66.9% in community/private practice. Only 53.6% reported familiarity with ASBrS guidelines for perioperative AP. Most (> 90%) surgeons reported "always" placing drains after mastectomy and "always" prescribing preoperative AP. Postoperatively, preference for continuing AP in cases with drains in place varied by procedure: 7.7% when no reconstruction, 29.1% when autologous-only, and 52.5% when implant reconstruction. Academic surgeons were less likely than surgeons in community/private practice to continue postoperative AP, whether for the duration of indwelling drains (5.1% versus 9.4%) or even till 7 days postoperatively (0.6% versus 3.2%) (p < 0.05). CONCLUSIONS: Surgeons uniformly adhere to ASBrS guidelines for preoperative AP. However, there is wide variation in AP postoperatively in patients with/without reconstruction and with indwelling drains. Our results highlight the need for high-quality evidence based on which guidelines must be updated, and the need to familiarize surgeons with current guidelines.

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy.

INTRODUCTION: Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2]. RESULTS: Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change. CONCLUSIONS: Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

Changes in utilization of axillary dissection in women with invasive breast cancer and sentinel node metastasis after the ACOSOG Z0011 trial.

The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial demonstrated no survival advantage for women with clinical T1-T2 invasive breast cancer with 1-2 positive sentinel lymph nodes (SLN) who received whole-breast radiation, and no further axillary surgery when compared to women who did undergo axillary lymph node dissection (ALND). We used the National Cancer Database (NCDB) to study changes in utilization of ALND after the publication of this trial. NCDB was queried for female patients from 2012 to 2015 who met Z0011 criteria. Patients were divided into four groups based on Commission on Cancer facility accreditation. Outcome measures include the rate of ALND (nonadherence to Z0011) and the average number of nodes retrieved with ALND. 27,635 patients were identified, with no significant differences in T stage and receptor profiles between groups. Overall rate of ALND decreased from 34.0% in 2012 to 22.7% in 2015. Nonadherence was lowest in Academic Programs (decreasing from 30.1% in 2012 to 20.5% in 2015) and was highest in Community Cancer Programs (41.2% in 2012 to 29.1% in 2015). Median number of positive SLN did not differ between groups (p = .563). Median number of nodes retrieved on ALND decreased from 9 (IQR 5-14) in 2012 to 7 (IQR 4-12) in 2015 (p < .001). In patients who met the ACOSOG Z11 trial guidelines, rates of ALND have decreased over time. However, rates of nonadherence to Z0011 are significantly higher in Community Cancer Programs compared to Academic Programs.

Use of the End to End Anastomotic Stapler From Above for Difficult Pelvic Surgery for Distal Rectal Disease.

INTRODUCTION: Transabdominal utilization (TAU) of the end to end anastomotic (EEA) stapler in low anterior resection (LAR) for rectal cancer is an excellent alternative to the most widely performed techhnique. METHODS: We performed a retrospective analysis of a prospectively maintained database which obtained data on 104 patients with rectal disease who underwent EEA-assisted LAR with TAU. Records of all patients were used to evaluate demographics, complications, tumor location, margin status, postoperative complications, clinical sphincter function, adjuvant or neoadjuvant treatment, disease stage, and survival. RESULTS: Of the 104 patients, 48% were women with a mean age of 64 years (range 34-85 years). The average tumor location was 8 cm above the dentate line, and the mean tumor distance from the distal margin was 1.9 cm. All distal margins in cases for patients with rectal cancer were negative. Hospital length of stay averaged 8.7 days (6-15 days). There were no anastomotic complications (leaks, bleeding, or obstruction), and there were no leaks at the separate colotomy site. All patients have had normal postoperative sphincter function. CONCLUSION: Transabdominal utilization of the EEA stapler in LAR for colorectal carcinoma is an alternative to the conventional approach and may be advantageous in avoidance of the lithotomy position with potential nerve injury, risk of deep venous thrombosis, and stapler-induced sphincter trauma.

Factors associated with general surgery residents' decisions regarding fellowship and subspecialty stratified by burnout and quality of life.

BACKGROUND: Although most surgery residents pursue fellowships, data regarding those decisions are limited. This study describes associations with interest in fellowship and specific subspecialties. METHODS: Anonymous surveys were distributed to 607 surgery residents at 19 US programs. Subspecialties were stratified by levels of burnout and quality of life using data from recent studies. RESULTS: 407 (67%) residents responded. 372 (91.4%) planned to pursue fellowship. Fellowship interest was lower among residents who attended independent or small programs, were married, or had children. Residents who received AOA honors or were married were less likely to choose high burnout subspecialties (trauma/vascular). Residents with children were less likely to choose low quality of life subspecialties (trauma/transplant/cardiothoracic). CONCLUSIONS: Surgery residents' interest in fellowship and specific subspecialties are associated with program type and size, AOA status, marital status, and having children. Variability in burnout and quality of life between subspecialties may affect residents' decisions.

The Clinicopathological Aspects of Primary Presacral Neuroendocrine Neoplasms: One Center Experience.

OBJECTIVES: Presacral neuroendocrine neoplasms (NENs) are rare entities that are found at the presacral space. We report our experience in the diagnosis, management, and outcomes of primary presacral NENs. METHODS: This was an institutional review board-approved retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of NENs at Cedars-Sinai Medical Center between January 2000 and April 2016. RESULTS: Ten patients were identified. The median age at presentation was 38 years (range, 20-77 years), and 8 were women. One patient presented with carcinoid-like symptoms, 2 were diagnosed incidentally, and 7 presented with symptoms related to mass effect. The median size of the tumor was 7.0 cm (range, 3-12 cm). On pathologic review, 3 of 10 were low-grade and well-differentiated, 5 of 10 were intermediate-grade and well-differentiated, 2 of 10 were grade 3 and classified as high-grade and poorly differentiated neuroendocrine tumors. Seven cases were metastatic on presentation with lymph node, liver, lung, or skeletal metastasis. Seven of 8 cases were detectable using Octreoscan. Eight patients were treated with a somatostatin analog and 5 patients were treated surgically. CONCLUSIONS: Presacral NENs are clinically similar to gastroenteropancreatic tumors. Octreoscan imaging and somatostatin analog therapies were frequently applied. Further biologic characterization of this rare subtype is needed.

Breast cancer following ovarian cancer in BRCA mutation carriers.

IMPORTANCE: BRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized. OBJECTIVES: To determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers. MAIN OUTCOMES AND MEASURES: Incidence of breast cancer and methods of surveillance. RESULTS: Of 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%. CONCLUSIONS AND RELEVANCE: The risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.

Genetic risk factors for major bleeding in patients treated with warfarin in a community setting.

The influence of warfarin pharmacogenomics on major bleeding risk has been little studied in long-term users and non-specialist care settings. We conducted a case-control study to evaluate associations between CYP2C9*2/*3, VKORC1(1173), and CYP4F2*3 variants and major bleeding among patients treated with warfarin in a community setting. We calculated major bleeding odds ratios, adjusting for race, duration of warfarin use, age, gender, and body mass index. In 265 cases and 305 controls with 3.4 and 3.7 mean years of warfarin use, respectively, CYP4F2*3 was associated with decreased major bleeding risk (odds ratio: 0.62; 95% confidence interval: 0.43-0.91). CYP2C9*2/*3 and VKORC1(1173) had null associations overall, but there was a nonsignificant increase in major bleeding risk in patients with duration <6 months (odds ratio: 1.30; 95% confidence interval: 0.60-2.83; odds ratio: 1.23; 95% confidence interval: 0.57-2.64, respectively). In summary, in the largest study of warfarin pharmacogenomics and major bleeding to date, we found a 38% lower risk in patients with CYP4F2*3, potentially reflecting interaction with warfarin and dietary vitamin K intake and warranting additional evaluation.

Telesonography: virtual 3D image processing of remotely acquired abdominal, vascular, and fetal sonograms.

PURPOSE: To design and test a new telesonography technique using remote volume acquisition by untrained operators in locations without access to trained sonographers, postprocessing, and interpretation done at expert centers. MATERIALS AND METHODS: The technique was tested with 84 sonograms of organs acquired in pregnant women (n = 8) and patients with various abdominal pathologic conditions (n = 11) located in French Guyana (France), Ceuta (Spain), and Murighiol (Romania). An operator inexperienced in sonography (US) placed the transducer over the predetermined acoustic window for each organ, then swept it from a -45° to a +45° position to scan the targeted organ. The acquired volume dataset was sent to an expert center via the Internet and reconstructed using a proprietary software, which allowed a trained sonographer to navigate through the appropriately reconstructed sonograms. RESULTS: After three-dimensional processing at the expert center, the organs scanned in the obstetrical cases were adequately visualized by the expert in seven of eight (88%) examinations of the fetal head, femur, and umbilical cord and eight of eight (100%) examinations of the fetal abdomen and placenta, whereas in the general abdominal cases, the liver, gallbladder, portal vein, and right kidney were correctly visualized in 10 of 11 (91%) examinations. CONCLUSIONS: Telesonography allowed untrained operators to scan and transfer the US volume datasets over the Internet to an expert center where an expert sonographer could navigate through the reconstructed US volume and visualize sonograms of diagnostic quality.

The effect of nicotinamide on gene expression in a traumatic brain injury model.

Microarray-based transcriptional profiling was used to determine the effect of nicotinamide on gene expression in an experimental traumatic brain injury (TBI) model. Ingenuity Pathway Analysis (IPA) was used to evaluate the effect on relevant functional categories and canonical pathways. At 24 h, 72 h, and 7 days, respectively, 70, 58, and 76%, of the differentially expressed genes were up-regulated in the vehicle treated compared to the sham animals. At 24 h post-TBI, there were 150 differentially expressed genes in the nicotinamide treated animals compared to vehicle; the majority (82%) down-regulated. IPA analysis identified a significant effect of nicotinamide on the functional categories of cellular movement, cell-to-cell-signaling, antigen presentation and cellular compromise, function, and maintenance and cell death. The canonical pathways identified were signaling pathways primarily involved with the inflammatory process. At 72 h post-cortical contusion injury, there were 119 differentially expressed genes in the nicotinamide treated animals compared to vehicle; the majority (90%) was up-regulated. IPA analysis identified a significant effect of nicotinamide on cell signaling pathways involving neurotransmitters, neuropeptides, growth factors, and ion channels with little to no effect on inflammatory pathways. At 7 days post-TBI, there were only five differentially expressed genes with nicotinamide treatment compared to vehicle. Overall, the effect of nicotinamide on counteracting the effect of TBI resulted in significantly decreased number of genes differentially expressed by TBI. In conclusion, the mechanism of the effect of nicotinamide on secondary injury pathways involves effects on inflammatory response, signaling pathways, and cell death.

Transcriptome correlation analysis identifies two unique craniosynostosis subtypes associated with IRS1 activation.

The discovery of causal mechanisms associated with nonsyndromic craniosynostosis has proven to be a difficult task due to the complex nature of the disease. In this study, differential transcriptome correlation analysis was used to identify two molecularly distinct subtypes of nonsyndromic craniosynostosis, termed subtype A and subtype B. In addition to unique correlation structure, subtype A was also associated with high IGF pathway expression, whereas subtype B was associated with high integrin expression. To identify a pathologic link between altered gene correlation/expression and the disease state, phosphorylation assays were performed on primary osteoblast cell lines derived from cases within subtype A or subtype B, as well as on primary osteoblast cell lines with novel IGF1R variants previously reported by our lab (Cunningham ML, Horst JA, Rieder MJ, Hing AV, Stanaway IB, Park SS, Samudrala R, Speltz ML. Am J Med Genet A 155A: 91-97, 2011). Elevated IRS1 (pan-tyr) and GSK3ß (ser-9) phosphorylation were observed in two novel IGF1R variants with receptor L domain mutations. In subtype A, a hypomineralization phenotype coupled with decreased phosphorylation of IRS1 (ser-312), p38 (thr-180/tyr-182), and p70S6K (thr-412) was observed. In subtype B, decreased phosphorylation of IRS1 (ser-312) as well as increased phosphorylation of Akt (ser-473), GSK3ß (ser-9), IGF1R (tyr-1135/tyr-1136), JNK (thr-183/tyr-187), p70S6K (thr-412), and pRPS6 (ser-235/ser-236) was observed, thus implicating the activation of IRS1-mediated Akt signaling in potentiating craniosynostosis in this subtype. Taken together, these results suggest that despite the stimulation of different pathways, activating phosphorylation patterns for IRS1 were consistent in cell lines from both subtypes and the IGF1R variants, thus implicating a key role for IRS1 in the pathogenesis of nonsyndromic craniosynostosis.

Intraductal papillary lesions of the breast: clinical and pathological correlation.

Papillary lesions of the breast range from a spectrum of benign intraductal papillomas with and without atypia to papillary carcinoma. Distinction between benign and malignant lesions on core needle biopsy (CNB) is difficult without surgical excision. We examined if clinical findings in patients with benign intraductal papillomas (IP) on CNB correlate with pathology at surgical excision. Between 1998 and 2011, 103 patients were identified with a papillary lesion on CNB. Clinical variables were studied to determine if there was clinical correlation with pathological outcomes at final surgical excision. Of the 103 patients, 59 (57%) patients had IP on initial CNB and were included in our analysis. On final pathology, 17 (29%) of these were upstaged to intraductal papilloma with atypia and six (10%) were found to have carcinoma. A clinically palpable mass was the only significant predictor of upstaging to malignancy (P<0.05). No radiographic findings were found to be significant predictors of pathological upstaging. In conclusion, surgical excision is still recommended for benign papillary lesions diagnosed on CNB because the correlation with clinical and radiological findings does not assure benign pathology.

[System of telesonography with synchronous teleconsultations and asynchronous telediagnoses (Togo)]. / Système de télé-expertise échographique temps réel et de télédiagnostic échographique temps différé. Étude pilote au Togo.

INTRODUCTION: Ultrasonography is an important nonirradiating diagnostic medical imaging procedure, frequently used, especially in urgent circumstances. This relatively inexpensive noninvasive examination makes it possible to diagnose disorders in various parts of the human body, by examining, for example, the abdomen and pelvis, the cardiovascular system, and the muscles and joints. Ultrasound is also an operator-dependent examination, in that the quality of the result depends on precision in the manipulation of the probe. Unfortunately, many small medical centers and isolated sites do not have an appropriate well-trained sonographer to perform initial evaluations, and an untrained operator cannot capture the appropriate echographic views required for a safe diagnosis of current patients, even with realtime vocal guidance (personal data). The lack of experienced physicians or qualified technicians means that diagnostic ultrasound is not always accessible to patients for rapid examination worldwide, especially in Africa, Amazonia or near the North or South Poles. This situation has led to the development of a new concept of telemedicine: telesonography, with a remote ultrasound diagnosis either in real time (synchronous) or delayed (asynchronous; store-and-forward). These systems of real-time telesonography and data transmission require expensive and complex technology with sophisticated equipment not available in many developing countries. The purpose of this study is to design a low-cost real-time system of telesonography for teleconsultations with experts and a delayed telediagnostic mode between isolated peripheral hospitals and a University Hospital center (UHC). METHODS AND MATERIALS: An IP camera and an internet video server were installed in a geographically isolated site equipped with an ultrasound machine and an operator with basic training in its use. Synchronous teleconsultation (second-opinion diagnosis) is possible via internet with a UHC expert. If no ultrasound operator is available at the isolated center, volume capture-and-store software is used. Later on, the UHC expert uses Echo-Cnes 3D software to reconstruct the organs scanned. The expert can then navigate within the reconstructed volume and display any plane. Volume capture is performed by tilting (± 40°) to both sides vertically to the skin. To locate the probe on the organ acoustic window, the novice operator uses acoustic window mapping designed by our laboratory (UMPS-Tours). The system was tested between the Tsévié regional hospital in Togo (40 km from Lomé, Togo, and 4500 km from Tours, France) and the UHC at Lomé and the Trousseau UHC in Tours. RESULTS: With an average internet connection of 2 Mbps, the quality of transmission of the background video and ultrasound sequence videos from Tsévié towards Lomé was satisfactory (16 images/s) with a maximal transmission delay of 1.5 s (almost in real time). A video conference between the Trousseau UHC in Tours, the UHC Campus in Lomé and the Tsévié Hospital was possible and the bandwidth allowed the Lomé experts (radiologists) to perform real-time telesonography with very satisfactory results (ultrasound diagnoses obtained) for abdominal (n = 5), pelvic (n = 3), obstetric (n = 2), prostate (n = 2) and mammary (n = 2) ultrasound, both normal and pathological. Because the doctors at Tsévié had minimal experience with ultrasound, complete ultrasound diagnoses were obtained by combining remote voice instruction for image capture and full diagnosis by Echo-Cnes. Asynchronous telediagnosis was also performed with Tsévié operators who lacked ultrasound expertise but could perform the required tilt movements (after 3 training sessions). The expert at Trousseau UHC performed real-time telesonography with the Tsévié Hospital for two cases requiring abdominal images and another viewing of the prostate. He also performed asynchronous reconstruction of the abdominal organs with Echo-Cnes. A demonstration seminar of our platform was organized successfully for 2 days during the 9(th) Congress of the French-speaking Black Africa Society of Radiology (SRANF in French) held from 4 till 6 May 2011 at the hotel EDA OBA. During this seminar, 4 ultrasound teleconsultations were performed from the hotel by eminent African radiologists. DISCUSSION AND CONCLUSION: This preliminary study, although limited in the number of patients, allowed us to assess the technical features of our telesonography system. Togo, a developing country with a very modest infrastructure for information and communication, was an ideal site for a first test of this platform. Our system of remote ultrasound requires the local patient center to be equipped simply with a 2D ultrasound machine. The cost is quite low, in comparison to the asynchronous techniques requiring 3D devices. The high cost of 3D or 4D ultrasound machines and their fragility make it difficult to install them at the isolated sites and was a serious obstacle in the development of this system. If the center already has a 2D device and a computer, the cost to equip it with the remaining communications materials is 1,500 €. The experience in Togo clearly highlighted the possibility of teletraining and complete teleradiology with our system. The next stage of this work will seek to validate the results of this preliminary experience on a larger sample with more precise assessment criteria in 2012. The results will allow the widespread dissemination and routine use of this system in developing countries.

Preliminary experience with tele-sonography and tele-mammography in Togo.

Many medical centres are equipped with a sonograph. However, a sonographist is not always present or is not trained in all of the specialised domains of sonography. . A sonogram is not always possible due to a lack of physicians. This situation has given rise to the concept of remote-controlled sonography: tele-sonography, a medical procedure used in remote sonographic diagnosis in real time or deferred time. Tele-sonography can now be carried out in real time by the transmission of the expert's procedure (robotic system) or by the use of a 3D sonograph in real time. These modes of real time tele-sonography rely on expensive technologies requiring budgets and an infrastructure that is not always possible in developing countries where the needs in tele-medicine are increasing. This paper aimed to present a preliminary evaluation of a "low cost" system of sonographic tele-expertise in real time and the deferred sonographic telediagnosis accompanied by a tele-mammography between expert sites (university hospitals) and isolated sites (peripheral hospitals, dispensaries).

Activation of CCR9/CCL25 in cutaneous melanoma mediates preferential metastasis to the small intestine.

PURPOSE: Specific chemokines and their respective receptors have been implicated in distant tumor cell metastasis. Cutaneous melanoma has a distinct pattern of metastasis, preferentially targeting the submucosa of the small intestine. However, the underlying pathogenic mechanism remains unknown. Migration of CCR9(+) lymphocytes to the small intestine is known to occur in response to the chemoattractant effects of CCL25 (thymus-expressed chemokine). The integrin heterodimers alphabeta are also known to be important mediators of cellular adhesion. We hypothesize that the mechanism of small intestinal metastasis by melanoma is via the CCR9-CCL25 axis and specific integrins. EXPERIMENTAL DESIGN: Quantitative reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to assess melanoma tumors for CCR9 and CCL25. Integrin expression was assessed using flow cytometry. CCR9 expression by quantitative reverse transcription-PCR was assessed in primary (n = 23) and metastatic (n = 198) melanomas, and melanoma lines derived from small intestinal metastases (n = 23). RESULTS: We showed CCR9 expression in 88 of 102 paraffin-embedded metastatic melanomas from the small intestine, 8 of 8 melanoma lines derived from metastases in the small intestine, and 0 of 96 metastatic melanomas from other sites. In vitro migration and invasion studies done on CCR9(+) melanoma lines showed migration in response to CCL25 that was inhibited by anti-CCR9 antibody or by short interfering RNA CCR9. Flow cytometric analysis confirmed CCR9 expression by melanomas to the small intestine and showed concomitant alpha(4)beta(1) integrin expression. CONCLUSIONS: Our findings show that functionally active CCR9 on melanoma cells facilitates metastasis to the small intestine. The CCR9-CCL25 axis may explain the high incidence of melanoma metastasis to this specific location.