Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.

Anterior Chest Wall Reconstruction After Separation of Thoraco-Omphalopagus Conjoined Twins With Cadaveric Rib Grafts and Omental Flap.

BACKGROUND: Anterior chest wall defects have a wide range of etiologies in the pediatric population, ranging from infection, tumor, and trauma to congenital diseases. The reconstructive goals include restoring skeletal stability, obliterating dead space, preserving cardiopulmonary mechanics, and protecting vital underlying mediastinal organs. Although various reconstructive methods have been described in the literature, selecting the optimal method is challenging for the growing pediatric skeleton. Here, we report a case of previously thoraco-omphalopagus twins who underwent successful separation and reconstruction and presented for definitive anterior chest wall reconstruction. METHODS: A pair of previously thoraco-omphalopagus conjoined twins underwent definitive anterior chest wall defect reconstruction using cadaveric ribs and omental flap. Twin A received 2 cadaveric ribs, whereas twin B had a much larger sternal defect that required 3 cadaveric ribs combined with an omental flap for soft tissue chest coverage. Both twins were followed up for 8 months. RESULTS: Twin A's postoperative course was uneventful, and she was discharged on postoperative day 6. Twin B's course was complicated, and she was discharged on supported ventilation on postoperative day 10. At 8 months postoperatively, both twins healed well, and chest radiographs confirmed the stability of the chest reconstructions. The rib grafts in the twin with a tracheostomy were not mobile, and the patient had a solid sternum with adequate pulmonary expansion. The construct initially did not facilitate pulmonary functioning, but after a healing process, it eventually allowed for the twin with the tracheostomy who required pulmonary assistance to no longer need this device. CONCLUSIONS: Cryopreserved cadaveric ribs and omental flaps offer safe and reliable reconstructive methods to successfully reconstruct congenital anterior chest wall skeletal defects in the growing pediatric population. The involvement of multidisciplinary team care is key to optimizing the outcomes.

Robotic Rectus Abdominis Harvest for Pelvic Reconstruction after Abdominoperineal Resection.

The use of robotic surgical systems to perform abdominoperineal resection (APR) has recently become more prevalent. This minimally invasive approach produces fewer scars and potentially less morbidity for the patient. The rectus abdominis muscle is often used for reconstruction after APR if primary closure is not feasible or the surgical site is at high risk of wound complications. Since the traditional open harvest of this flap creates large incisions that negate the advantages of minimally invasive APR, there has been growing interest in harvesting the rectus abdominis in a similarly robotic fashion. This article reviews the technique, benefits, and limitations of this robotic technique. Compared to the traditional open harvest, robotic harvest of the rectus abdominis leaves smaller scars, provides technical benefits for the surgeon, and offers possible morbidity benefits for the patient. These advantages should be weighed against the added expense and learning curve inherent to robotic surgery.

Extracorporeal Pedicles for Free Flap Reconstruction in Diabetic Lower Extremity Wounds.

Diabetic foot ulcers are a severe complication of diabetes, and their management requires a multidisciplinary approach for optimal management. When treating these ulcers, limb salvage remains the ultimate goal. In this article, we present the "hanging" free flap for the reconstruction of chronic lower extremity diabetic ulcers. This two-staged approach involves standard free flap harvest and inset; however, following inset the "hanging" pedicle is covered within a skin graft instead of making extraneous incisions within the undisturbed soft tissues or tunnels that can compress the vessels. After incorporation, a second-stage surgery is performed in 4 to 6 weeks which entails pedicle division, flap inset revision, and end-to-end reconstruction of the recipient vessel. Besides decreasing the number of incisions on diabetic patients, our novel technique utilizing the "hanging" pedicle simplifies flap monitoring and inset and allows reconstruction of recipient vessels to reestablish distal blood flow.

RNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAFV600E metastatic colorectal cancer.

Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAFV600E colorectal cancer (mCRCBRAF-V600E). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery cohort of patients with mCRCBRAF-V600E treated with anti-BRAF/EGFR therapy, we found that inactivating mutations in RNF43, a negative regulator of WNT, predict improved response rates and survival outcomes in patients with microsatellite-stable (MSS) tumors. Analysis of an independent validation cohort confirmed the relevance of RNF43 mutations to predicting clinical benefit (72.7% versus 30.8%; P = 0.03), as well as longer progression-free survival (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.12-0.75; P = 0.01) and overall survival (HR, 0.26; 95% CI, 0.10-0.71; P = 0.008), in patients with MSS-RNF43mutated versus MSS-RNF43wild-type tumors. Microsatellite-instable tumors invariably carried a wild-type-like RNF43 genotype encoding p.G659fs and presented an intermediate response profile. We found no association of RNF43 mutations with patient outcomes in a control cohort of patients with MSS-mCRCBRAF-V600E tumors not exposed to anti-BRAF targeted therapies. Overall, our findings suggest a cross-talk between the MAPK and WNT pathways that may modulate the antitumor activity of anti-BRAF/EGFR therapy and uncover predictive biomarkers to optimize the clinical management of these patients.

Update on Thumb Basal Joint Arthritis Surgery.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Comprehend anatomy and biomechanics of the normal and arthritic trapeziometacarpal joint. 2. Evaluate best evidence for diagnosis and for operative and nonoperative treatment of thumb osteoarthritis. 3. Understand treatment pitfalls of basilar joint arthritis and complication avoidance. SUMMARY: Articular and ligamentous anatomy of the trapeziometacarpal joint enables complex motions. Disability from arthritis, common at the trapeziometacarpal joint, is debilitating. Furthering the understanding of how trapeziometacarpal arthritis develops can improve treatment. The authors provide current best evidence for diagnosis and treatment of basilar joint arthritis. Pitfalls in treatment are discussed.

Hinge Flap of Rectus Abdominis Muscle Combined with Component Separation Technique: Clinical Cases.

Some techniques to reconstruct the abdominal wall have been published, including the component separation procedure. The contribution of the rectus abdominis flap in the reconstruction of a giant incisional hernia is reported. The authors report three clinical cases in which the component separation technique was insufficient to reconstruct a giant midline incisional hernia. As a salvage technique, the rectus abdominis flap was dissected in the form of a hinge. The postoperative period was successful in all patients, combining both techniques. The rectus abdominis hinge flap could be used as a complementary technique to component separation to reconstruct a giant midline incisional hernia. There are several options to reconstruct the abdominal wall, such as anterior transposition of the posterior rectus sheath,1 or rotation of the anterior sheath toward the midline. This strategy is known as open book.2 The rectus turnover flap is also used.3 The anterior component separation technique closes defects less than 20 cm width.4 If it is wider, the reconstruction is more difficult. When the operative plan fails in the operating room, an additional technique should be considered. We report on the cases in which we use the rectus abdominis hinge flap.

ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study.

Background: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval. Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials. Results: The ERA-NET TRANSCAN Call 2011 on "Validation of biomarkers for personalized cancer medicine" was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project. Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become "old" as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.

Reconstructive Techniques in Melanoma for the Surgical Oncologist.

Wounds resulting from wide local excision of melanoma vary in size and complexity, and require individualized solutions to achieve satisfactory closure. Goals of reconstruction include restoration of form, function, and aesthetics while minimizing donor site morbidity without compromising the effectiveness and safety of oncologic melanoma treatment. Optimal reconstruction relies on an in-depth understanding of the defect, locoregional anatomy and vasculature, available donor tissues, and basic wound healing and surgical principles. This article provides a broad overview of preoperative patient, timing, and wound considerations; various surgical techniques for complex reconstruction throughout the body; and postoperative care and complication management.

Author Correction: Caring for patients with cancer in the COVID-19 era.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Caring for patients with cancer in the COVID-19 era.

The current COVID-19 pandemic challenges oncologists to profoundly re-organize oncological care in order to dramatically reduce hospital visits and admissions and therapy-induced immune-related complications without compromising cancer outcomes. Since COVID-19 is a novel disease, guidance by scientific evidence is often unavailable, and impactful decisions are inevitably made on the basis of expert opinions. Here we report how the seven comprehensive cancer centers of Cancer Core Europe have organized their healthcare systems at an unprecedented scale and pace to make their operations 'pandemic proof'. We identify and discuss many commonalities, but also important local differences, and pinpoint critical research priorities to enable evidence-based remodeling of cancer care during the COVID-19 pandemic. Also, we discuss how the current situation offers a unique window of opportunity for assessing the effects of de-escalating anticancer regimens, which may fast-forward the development of more-refined and less-toxic treatments. By sharing our joint experiences, we offer a roadmap for proceeding and aim to mobilize the global research community to generate the data that are critically needed to offer the best possible care to patients.

The Basics of Integra Dermal Regeneration Template and its Expanding Clinical Applications.

First developed for coverage of burn wounds, Integra (Integra LifeSciences) is a synthetic acellular dermal regeneration template that provides a base for revascularization and neodermal formation. The use of Integra has slowly grown and has now become an important consideration along the reconstructive ladder. This article reviews the basic science of Integra and provides an overview of the many expanding applications based on anatomic location.

Advances in Fetal Surgery: Current and Future Relevance in Plastic Surgery.

Scarless healing has long been the holy grail for plastic surgery. While historically fetal surgery has tempted plastic surgeons with the allure of scarless correction of congenital abnormalities, the risks far outweighed the benefits and these interventions never materialized. Current advances in fetal surgery with minimally invasive fetoscopic surgery have made these early fetal interventions safer, leading to expanding applications. While the plastic surgeon's role is limited as of yet, this article provides a review of the history of fetal surgery and the advances that may become relevant to the future plastic surgeon.

American Society of Plastic Surgeons Member Post-Operative Opioid Prescribing Patterns.

INTRODUCTION: Despite the widespread use of opioids in pain management, there are currently no evidence-based guidelines for the treatment of postoperative pain with opioids. Although other surgical specialties have begun researching their pain prescribing patterns, there has yet to be an investigation to unravel opioid prescribing patterns among plastic surgeons. METHODS: Survey Monkey was used to sample the American Society of Plastic Surgeons (ASPS) members regarding their opioid prescribing practice patterns. The survey was sent randomly to 50% of ASPS members. Respondents were randomized to 1 of 3 different common elective procedures in plastic surgery: breast augmentation, breast reduction, and abdominoplasty. RESULTS: Of the 5,770 overall active ASPS members, 298 responses (12% response rate) were received with the following procedure randomization results: 106 for breast augmentation, 99 for breast reduction, and 95 for abdominoplasty. Overall, 80% (N = 240) of respondents used nonnarcotic adjuncts to manage postoperative pain, with 75.4% (N = 181) using nonnarcotics adjuncts >75% of the time. The most commonly prescribed narcotics were Hydrocodone with Acetaminophen (Lortab, Norco) and Oxycodone with Acetaminophen (Percocet, Oxycocet) at 42.5% (N = 116) and 38.1% (N = 104), respectively. The most common dosage was 5 mg (80.4%; N = 176), with 48.9% (N = 107) mostly dispensing 20-30 tablets, and the majority did not give refills (94.5%; N = 207). CONCLUSIONS: Overall, plastic surgeons seem to be in compliance with proposed American College of Surgeon's opioid prescription guidelines. However, there remains a lack of evidence regarding appropriate opioid prescribing patterns for plastic surgeons.

Stacked Lateral Thigh Perforator Flap as a Novel Option for Autologous Breast Reconstruction.

BACKGROUND: Autologous breast reconstruction using perforator flaps offers excellent outcomes, minimizes donor-site morbidity, and allows for precise donor-site selection. The deep inferior epigastric artery perforator, profunda artery perforator, and gluteal artery perforator flaps along with the stacked flap technique are the most common options. This study reports the first series of the stacked lateral thigh perforator flap. METHODS: A retrospective review of all stacked lateral thigh perforator flaps done by a single group of surgeons was performed. Demographics, flap weights, complications, indications, and surgical technique were tabulated for each patient. RESULTS: Eight female patients with a history of breast cancer underwent delayed unilateral breast reconstruction with stacked lateral thigh perforator flaps for a total of 16 flaps. Mean patient age, body mass index, flap weight, and stacked flap weight were 47.3 years, 26.2 kg/m, 333.1 g, and 666.1 g, respectively. Microsurgical revascularization was completed in anterograde and retrograde fashion to the internal mammary vasculature. Flap survival was 100 percent and one subsequent flap revision was performed. Two patients developed a seroma at the donor site. Indications included insufficient abdominal tissue, prominent lateral thigh lipodystrophy, prior abdominal surgery, and failed prior abdominally based autologous reconstruction. CONCLUSIONS: This series demonstrates that the lateral thigh perforator flap is a reliable and effective option for a stacked breast reconstruction. Its ease of harvest (stemming from reliable anatomy), straightforward dissection, and intraoperative positioning make it an appealing flap option. The stacked lateral thigh perforator flap allows the reconstructive surgeon to tailor breast reconstruction to the patient, focusing on body habitus and minimizing morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

New clinical trial designs in the era of precision medicine.

Cancer treatment has made significant strides towards the promise of personalized medicine. Recent scientific advances have shown that there are numerous genetic deregulations that are common in multiple cancer types, raising the possibility of developing drugs targeting those deregulations irrespective of the tumour type. Precision Cancer Medicine (PCM) was born out of accumulated evidence matching targeted agents with these tumour molecular deregulations. At the same time, the therapeutic armamentarium is rapidly increasing and the number of new drugs (including immune-oncology agents) entering drug development continues to rise. These factors, added to strong collaboration with regulatory agencies, which have approved novel agents based on data obtained from phase 1/2 trials, have led to unprecedented evolution in the design of early-stage clinical trials. Currently, we have seen rapid phase 1 dose-escalation trials followed by remarkably large expansion cohorts, and are witnessing the emergence of new trials, such as adaptive studies with basket and umbrella designs aimed at optimizing the biomarker-drug co-development process. Alongside the growing complexity of these clinical trials, new frameworks for stronger and faster collaboration between all stakeholders in drug development, including academic institutions and frameworks, clinicians, pharma companies and regulatory agencies, have been established. In this review article, we describe the main challenges and opportunities that these new trial designs may provide for a more efficient drug development process, which may ultimately help ensure that PCM becomes a reality for patients.

Interrogating open issues in cancer medicine with patient-derived xenografts.

This corrects the article DOI: 10.1038/nrc.2016.140.

Interrogating open issues in cancer precision medicine with patient-derived xenografts.

Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research.

El tiempo libre como heurístico del self: una metodología para el análisis de la complejidad del sujeto / Free time as a heuristic for the self: a methodology to anlyze the complexity of the subject

Las actividades de ocio y tiempo libre se han considerado importantes para el desarrollo del self - sí mismo - como proceso psicosocial (entre otros, Csikszentmihalyi y Kleiber, 1991; Cuenca, 2008a; Grossman y O'Connell, 2000; Kleiber, 1999; Munné y Codina, 1996, 2002; Wearing y Wearing, 1992). El análisis empírico de este vínculo y los procesos que se generan entre ellos es lo que pretende mostrar la Metodología Cualitativa Secuencial (MCS; Codina, 1999, 2005a y b). Esta estrategia metodológica permite poner de manifiesto la complejidad del tiempo libre, del self y de las relaciones entre ambos (Codina, 2004a y b; Codina y Pestana, 2008; Pestana, 2007; Pestana y Codina, 2005). Como muestra del potencial explicativo de la MCS, en este trabajo se ejemplifica una aproximación empírica al self con base en la dialogicidad derivada de las ideas de M. Bajtín (1961/2003a, 1974/2003b) y en los aspectos complejos -no linealidad, fractalidad, borrosidad- descritos por F. Munné (1997a, 2000) en su modelo del self. Investigar empíricamente propuestas teóricas sobre el self como las de Bajtín y Munné posibilita aprehender las relaciones del desarrollo de la persona con un comportamiento más libre. En un sentido más general, la MCS contribuye a resaltar el carácter vertebrador de la libertad y la mismidad en el análisis del sujeto contemporáneo.

Both leisure and free time activities have been considered important for self development as a psychosocial process (among others, Csikszentmihalyi & Kleiber, 1991; Cuenca, 2008a; Grossman & O'Connell, 2000; Kleiber, 1999; Munné & Codina, 1996, 2002; Wearing & Wearing, 1992). Putting into evidence the processes derived from the relationship between leisure/free time activities and self has been the purpose of the Sequential Qualitative Methodology (SQM; Codina, 1999, 2005a & b). This methodological strategy has made possible to show the complexity among free time, self and their relationships (Codina, 2004a & b; Codina & Pestana, 2008; Pestana, 2007; Pestana & Codina, 2005). As an example of the SQM potential of explanation, this contribution offers an empirical approximation to the self, based on M. M. Bakhtin's dialogical perspective (1961/2003a, 1974/2003b), and the complex aspects (non-linearity, fractality and fuzziness) described by F. Munné (1997a, 2000) in his model of the self. Empirical research about both Bakhtin and Munné proposals makes possible apprehending the relationships between a person's development and a free behavior. In a more general sense, the SQM contributes to underline the significance of freedom and selfhood in analyzing the contemporary subject.