Identifying Factors and Techniques to Decrease the Positive Margin Rate in Partial Mastectomies: Have We Missed the Mark?

Breast conservation therapy (BCT) has a reported incidence of positive margins ranging widely in the literature from 20% to 70%. Efforts have been made to refine standards for partial mastectomy and to predict which patients are at highest risk for incomplete excision. Most have focused on histology and demographics. We sought to further define modifiable risk factors for positive margins and residual disease. A retrospective study was conducted of 567 consecutive partial mastectomies by 21 breast and general surgeons from 2009 to 2012. Four hundred fourteen cases of neoplasm were reviewed for localization, intraoperative assessment, excision technique, rates, and results of re‐excision/mastectomy. Histologic margins were positive in 23% of patients, 25% had margins 0.1–0.9 mm, and 7% had tumor within 1–1.9 mm. Residual tumor was identified at—in 61 cases: 38% (disease at margin), 21% (0.1–0.9 mm), and 14% (1–1.9 mm). Ductal carcinoma in situ (DCIS) was present in 85% of residual disease on re‐excision and correlated to higher rates of re‐excision (p = <0.001), residual disease, and subsequent mastectomy. The use of multiple needles to localize neoplasms was associated with 2–3 times the likelihood for positive margins than when a single needle was required. The removal of additional margins at initial surgery correlated with improved rates of complete excision when DCIS was present. Patients must have careful analysis of specimen margins at the time of surgery and may benefit from additional tissue excision or routine shaving of the cavity of resection. Surgeons should conduct careful patient selection for BCT, in the context of multifocal, and multicentric disease. Patients for whom tumor localization requires bracketing may be at higher risk for positive margins and residual disease and should be counseled accordingly.     

Managing Traps and Pitfalls During Initial Steps of an ECMO Retrieval Program Using a Miniaturized Portable System: What Have We Learned From the First Two Years?

The aim of this study was to provide early and mid‐term results of the newly established extracorporeal membrane oxygenation (ECMO) retrieval service in a tertiary cardiothoracic center using the miniaturized portable Cardiohelp System (Maquet, Rastatt, Germany). A particular attention was paid to organizational and logistic specifics as well as challenges and pitfalls associated with initial phase of the program. From January 2015 until January 2017 a heterogenic group of 28 consecutive patients underwent ECMO implantation in distant hospitals for acute cardiac, pulmonary or combined failure as a bridge‐to‐decision and were subsequently transported to our institution. Each cannulation was performed bedside on intensive care units (ICU) using the Seldinger's technique. Early outcomes and mid‐term overall survival with up to two‐year follow‐up along with the impact of ongoing cardiopulmonary resuscitation (CPR) on outcome were presented. Also, changes in hemodynamics and tissue perfusion factors 24 h after ECMO implantation were evaluated. ECMO implantations were performed in 15 distant departments with the median distance of 23(10;40) (maximum 60) km. A total of 15 patients (54%) were cannulated under CPR with the median duration of 30(20;110) (maximum 180) min. After 24 h of support there were significant improvements in SvO₂ (P = 0.021), mean arterial pressure (P = 0.027), FiO₂ (P = 0.001), lactate (P = 0.001), and pH (P < 0.001). The mean ECMO support duration was 96 ± 100 (maximum 384) hours, whereas 11 patients (40%) were weaned off support and discharged from hospital. Overall cumulative survival in patients without the need for CPR was 61.5% at one week and 38.5% at 1 month, 6 month, and 1 year, whereas patients requiring CPR survived in 40% at one week, and 33.3% at 1 month, 6 month, and 1 year (Log‐Rank (Mantel‐Cox) P = 0.374, Breslow (Generalized Wilcoxon) P = 0.162). Our initial experience shows that launching new ECMO retrieval programs in centers with sufficient ICU capacities and local ECMO experience can be feasible and associated with acceptable “real world” results despite the initial learning curve. Rapid logistical organization and team flexibility are the key points to ensure comparable survival of patients requiring prolonged CPR.     

Can We Learn From Viruses How to Prevent Type 1 Diabetes?: The Role of Viral Infections in the Pathogenesis of Type 1 Diabetes and the Development of Novel Combination Therapies

We will take a journey from basic pathogenetic mechanisms elicited by viral infections that play a role in the development of type 1 diabetes to clinical interventions, where we will discuss novel combination therapies. The role of viral infections in the development of type 1 diabetes is a rather interesting topic because in experimental models viruses appear capable of both accelerating as well as decelerating the immunological processes leading to type 1 diabetes. Consequently, I will discuss some of the underlying mechanisms for each situation and consider methods to investigate the proposed dichotomy for the involvement of viruses in human type 1 diabetes. Prevention of type 1 diabetes by infection supports the so-called “hygiene hypothesis.” Interestingly, viruses invoke mechanisms that need to be exploited by novel combinatorial immune-based interventions, the first one being the elimination of autoaggressive T-cells attacking the β-cells, ultimately leading to their immediate but temporally limited amelioration. The other is the invigoration of regulatory T-cells (Tregs), which can mediate long-term tolerance to β-cell proteins in the pancreatic islets and draining lymph nodes. In combination, these two immune elements have the potential to permanently stop type 1 diabetes. It is my belief that only combination therapies will enable the permanent prevention and curing of type 1 diabetes.It is a great honor for me to receive this year''s American Diabetes Association Outstanding Scientific Achievement Award, and I would like to express my sincere gratitude to my peers.What do we know about type 1 diabetes? Well, we can be pretty certain that it is an autoimmune disease. Data from partial pancreas transplants between monozygotic twins showed that the nondiabetic pancreas was rapidly destroyed following transplantation (1) and was accompanied by infiltration of the islets, called insulitis, which is indicative of a strong autoreactive response, in the affected diabetic twin who received the transplant. In addition, autoantibodies to β-cell antigens precede the clinical onset of hyperglycemia and can predict the risk of developing diabetes (2,3). It is, however, still unclear what causes this autoreactivity to begin with. In addition to a strong genetic component, environmental factors, such as viral infections, lifestyle, and nutrition, have been implicated.One noteworthy and striking observation in human type 1 diabetes is that the degree of islet inflammation is rather mild, that is, only a small percentage of islets are affected, especially in comparison with animal models. Pipeleers and colleagues (4) found that only 3–4% of all islets in pre-diabetic patients are affected by insulitis, a percentage that increased to somewhat higher levels at the time of diabetes diagnosis. Although the pathogenetic implication of this low degree of inflammation is unclear, it might be important in understanding how viral infections, as an additional factor, might contribute to the disease process. Thus, there are many open questions, some of which we will need to answer in order to cure this terrible disease. Usually, and this is also the case for our group, animal models are utilized to better understand these and other immunological processes in type 1 diabetes pathogenesis as well as to define novel interventions. However, translation of at least some of the findings to human type 1 diabetes has been frustrating and ineffective. In this presentation, I will touch on several of the aforementioned issues and delineate present and future strategies that could help improve our mechanistic understanding and translational successes.     

From distinct to indistinct,the life cycle of a medical heresy. Is osteopathic distinctiveness an anachronism?

Osteopathy began life as a medical heresy. In the USA, osteopathy embraced medicine and surgery, with an inevitable diminution of distinctiveness. Osteopaths elsewhere practice in much the same way as a century ago. Limited to manual intervention, categorised as ‘allied’, ‘complementary’ or ‘alternative’, distinctiveness is now diminished by similarity with other professional groups. In contrast though to late nineteenth century practice, osteopaths today are the beneficiaries of hitherto unimaginable medical and scientific knowledge, and the target of an omnipresent societal demand for evidence-based practice (EBP), that is requiring of professional and institutional support through explicit policy. There is an urgent need to overcome a cultural torpitude within osteopathy to subject any and all aspects of practice to robust scientific scrutiny, and in particular to relinquish those aspects that have assumed the dimensions of a bloated sacred cow, whose chief requirement for sustenance is faith. To manifest both distinctiveness and professional visibility, determined engagement with science (the evidence), and with other communities whether in clinical practice or in the basic sciences is now imperative. Marginalisation through progressive irrelevance is a poor alternative.     

The value of posterior levator repair in the treatment of anorectal incontinence due to rectal prolapse – a clinical and manometric study

BACKGROUND: When treating a complete rectal prolapse, the most important objective is elimination of the prolapse. In addition, restoration of sufficient anorectal continence is extremely important for the patients. We examined the value of posterior levator repair with respect to stabilization of the pelvic floor and to improvement in anorectal incontinence. METHODS: In patients with disabling anorectal incontinence, a posterior levatorplasty can be concomitantly performed during operative removal of the prolapse. To facilitate evaluation of the operative results, we implemented a scoring system to judge the patients' subjective symptoms of incontinence; in addition, we performed manometric measurements of resting and squeezing pressures of the anal sphincter to objectify the anorectal incontinence. RESULTS: From 1991 to 1997, 84 patients (mean age 65+/-10 years, 38-91 years; 79 women, 5 men) with complete rectal prolapse and severe incontinence were operatively treated; corresponding follow-ups were done. The following procedures were performed: Frykmann-Goldberg, 28 patients; Wells, 18 patients; Ripstein, 22 patients; and perineal proctectomy, 16 patients. Incontinence for liquid and solid stools was present in all of these patients. Posterior levatorplasty was implemented in 38 patients, and in this group we found significantly better postoperative results, both clinically and in the manometric measurements. Continence was improved by 84% in the group with levatorplasty, but improvement was only 67% in the other group (P<0.05). The incontinence score decreased significantly in the group with levatorplasty (preoperative 16.4+/-3.1, postoperative 9.3+/-4.5, P<0.05, vs the other group with preoperative 15.6+/-4.2, postoperative 11.5+/-5.1). Manometric observations in the group with levatorplasty demonstrated 55% improvement in resting pressure (preoperative 29+/-17 cm H2O, postoperative 45+/-21 cm H2O, P<0.05) and 40% improvement in squeezing pressure (preoperative 61+/-25 cm H2O, postoperative 85+/-31 cm H2O, P<0.05). In the group without levatorplasty, resting and squeezing pressure improved only by 20% (resting pressure: preoperative 32+/-16 cm H2O, postoperative 38+/-18 cm H2O; squeezing pressure: preoperative 64+/-29 cm H2O, postoperative 75+/-26 cm H2O). CONCLUSIONS: Posterior levatorplasty is an easy and efficient operative procedure which facilitates an improvement in anorectal continence. There are no apparent disadvantages. For this reason, levatorplasty can be part of operative procedures implemented in the treatment of a complete rectal prolapse accompanied by disabling anorectal incontinence.     

The cryosurgical ablation of bone tissue by means of a new miniature cryoprobe – evaluation of the probe and adaption of the method to in vitro human bone

Until now, modern miniature cryoprobes have been used successfully for the local destruction of soft-tissue tumors without damaging adjacent healthy tissue. In this study, the methodology of cryoablation was applied to bone, and the freezing effect as well as the cooling capacity of the probe were examined. Freezing was performed by cooling one or two probes, with a diameter of 3.2 mm, to -180 degrees C with liquid nitrogen. The cooling capacity of the probes was determined under optic and thermic control in a homogenous reference gel (gelatin), followed by an in vitro measurement on human bone. The simultaneous use of 2 probes resulted in a synergistic effect which produced an almost spherical expansion of frozen area in the homogenous gelatin. In vitro freezing of human tibiae produced equivalent freezing temperatures, with one or two probes, in comparison to the homogenous gelatin. An adequate tissue cooling of bone matrix can be achieved through the use of one or more miniature cryoprobes so that after in vivo testing, the use of this probe could possibly become an alternative or supplement to the surgical resection of pathologic bone processes.     

Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists.

Anesthesia groups may need to determine which clinical anesthesia outcomes to track as part of quality improvement efforts. The goal of this study was to poll a panel of expert anesthesiologists to determine which clinical anesthesia outcomes associated with routine outpatient surgery were judged to occur frequently and to be important to avoid. Outcomes scoring highly in both scales could then be prioritized for measurement and improvement in ambulatory clinical practice. A mailed survey instrument instructed panel members to rate 33 clinical anesthesia outcomes in two scales: how frequently they believe the outcomes occur and which outcomes they expect patients find important to avoid. A feedback process (Delphi process) was used to gain consensus rankings of the outcomes for each scale. Importance and frequency scores were then weighted equally to qualitatively rank order the outcomes. Of the 72 anesthesiologists, 56 (78%) completed the questionnaire. The five items with the highest combined score were (in order): incisional pain, nausea, vomiting, preoperative anxiety, and discomfort from IV insertion. To increase quality of care, reducing the incidence and severity of these outcomes should be prioritized. IMPLICATIONS: Expert anesthesiologists reached a consensus on which low-morbidity clinical outcomes are common and important to the patient. The outcomes identified may be reasonable choices to be monitored as part of ambulatory anesthesia clinical quality improvement efforts.     

Initial Presentation and Management of Hilar and Peripheral Cholangiocarcinoma: Is a Node-Positive Status or Potential Margin-Positive Result a Contraindication to Resection?

Background  

Cholangiocarcinoma (CC) frequently presents at an advanced stage and the majority of patients are unresectable at diagnosis. We sought to examine our recent experience with surgical resection for hilar and peripheral CC.     

The podocyte and diabetes mellitus: is the podocyte the key to the origins of diabetic nephropathy?

PURPOSE OF REVIEW: Podocyte injury plays a key role in the development of diabetic nephropathy. This review discusses recent advances in our understanding of mechanisms of podocyte injury in diabetes mellitus and the associated alterations in the function of the glomerular filtration barrier. RECENT FINDINGS: The effects of hyperglycemia on critical podocyte parameters including cell-cell interactions, attachment to the glomerular basement membrane, and podocyte apoptosis have been determined in both cell culture and in-vivo models of diabetes mellitus. The podocyte has also been identified as a target of action for insulin and growth hormone, hormones with significant roles in the altered homeostasis of diabetes mellitus. SUMMARY: Understanding the cellular and molecular basis for changes in podocyte structure and function in diabetes mellitus may lead to novel diagnostic tools and treatment strategies for diabetic nephropathy.