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Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4–6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.Advances in surgical technique and chemotherapy regimens have improved the survival outcomes of patients with pancreatic cancer, although these remain dismal relative to most other solid tumours. Attempts to further improve outcomes have led to increasing research interest in neoadjuvant therapy, which is beginning to improve the outcomes of certain subgroups of patients. In this Review, the authors provide an overview of the various neoadjuvant therapy approaches for patients with pancreatic cancer, including discussions of several promising future research directions

Rectal cancer treatment has evolved during the past 40 years with the use of a standardized surgical technique for tumour resection: total mesorectal excision. A dramatic reduction in local recurrence rates and improved survival outcomes have been achieved as consequences of a better understanding of the surgical oncology of rectal cancer, and the advent of adjuvant and neoadjuvant treatments to compliment surgery have paved the way for a multidisciplinary approach to disease management. Further improvements in imaging techniques and the ability to identify prognostic factors such as tumour regression, extramural venous invasion and threatened margins have introduced the concept of decision-making based on preoperative staging information. Modern treatment strategies are underpinned by accurate high-resolution imaging guiding both neoadjuvant therapy and precision surgery, followed by meticulous pathological scrutiny identifying the important prognostic factors for adjuvant chemotherapy. Included in these strategies are organ-sparing approaches and watch-and-wait strategies in selected patients. These pathways rely on the close working of interlinked disciplines within a multidisciplinary team. Such multidisciplinary forums are becoming standard in the treatment of rectal cancer across the UK, Europe and, more recently, the USA. This Review examines the essential components of modern-day management of rectal cancer through a multidisciplinary team approach, providing information that is essential for any practising colorectal surgeon to guide the best patient care.Rectal cancer treatment has evolved towards a multidisciplinary approach to disease management. This Review examines the essential components of rectal cancer management through a multidisciplinary team, with a focus on the effect of this approach and the elements used for staging and developing the treatment plan.

Key Points Near-infrared (NIR) fluorescence imaging has been demonstrated to be feasible during cancer surgery using available imaging systems and contrast agents Clinical applicability has been described in sentinel lymph-node mapping, tumour imaging, visualization of vital structures and imaging of vascularization and perfusion NIR fluorescence image-guided surgery has properties that make it a good candidate for clinical acceptance, as it fulfils a clinical need, is versatile and is fast Targeted contrast agents, necessary for full evaluation of this technique, are in advanced stages of clinical approval As novel contrast agents are developed and camera systems are optimized, the technique should prove its true clinical value Well-designed outcomes studies have yet to be performed in the field Optical imaging that exploits invisible near-infrared (NIR) fluorescent light (700–900 nm) has the potential to improve cancer surgery outcomes, minimize anaesthesia time and lower health-care costs via its improved contrast and depth of tissue penetration relative to visible light. This Review introduces the concept of NIR fluorescence imaging and examines imaging system and contrast agent optimization. Paradigm shifts in surgery arise when surgeons are empowered to perform surgery faster, better and less expensively than current standards. Optical imaging that exploits invisible near-infrared (NIR) fluorescent light (700–900 nm) has the potential to improve cancer surgery outcomes, minimize the time patients are under anaesthesia and lower health-care costs largely by way of its improved contrast and depth of tissue penetration relative to visible light. Accordingly, the past few years have witnessed an explosion of proof-of-concept clinical trials in the field. In this Review, we introduce the concept of NIR fluorescence imaging for cancer surgery, examine the clinical trial literature to date and outline the key issues pertaining to imaging system and contrast agent optimization. Although NIR seems to be superior to many traditional imaging techniques, its incorporation into routine care of patients with cancer depends on rigorous clinical trials and validation studies.

Patients with advanced-stage ovarian cancer are widely believed to have a dismal prognosis; however, around 20% of women with this disease survive beyond 12 years after treatment and are effectively cured. In this Perspectives, Steven Narod presents the case that this proportion could be substantially increased through the combination of maximal debulking surgery and intraperitoneal chemotherapy. Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer.

Key Points Patients with high-risk prostate cancer have a significant chance of developing systemic or local recurrence, and are at higher risk for symptoms and/or death from the disease Definitions vary for what constitutes high-risk disease in localized prostate cancer, but are historically based on clinicopathological findings including clinical stage, Gleason score, and PSA The literature is limited as a consequence of variations in definition, lack of prospective randomized trials, limitations in statistical plan (underpowered studies), the need for long-term follow-up, and suboptimal end points Several key principles for radiotherapy have been established, including the importance of dose, and the addition of androgen-deprivation therapy Optimal surgical management requires completely removing the gland itself, confirming negative margins intraoperatively, and discussing the potential need for post-operative radiotherapy Treatment of potential lymph-node involvement, either surgically or with extended pelvic radiation, is favoured in high-risk disease, but lacks level I evidence High-risk prostate cancer includes a heterogeneous group of patients with a range of prognoses, with some that can be fatal. The optimal management of this patient subgroup is evolving. We critically evaluate the existing literature focused on defining the high-risk population, the management of patients with high-risk prostate cancer, and future directions to optimize care. Approximately 15% of patients with prostate cancer are diagnosed with high-risk disease. However, the current definitions of high-risk prostate cancer include a heterogeneous group of patients with a range of prognoses. Some have the potential to progress to a lethal phenotype that can be fatal, while others can be cured with treatment of the primary tumour alone. The optimal management of this patient subgroup is evolving. A refined classification scheme is needed to enable the early and accurate identification of high-risk disease so that more-effective treatment paradigms can be developed. We discuss several principles established from clinical trials, and highlight other questions that remain unanswered. This Review critically evaluates the existing literature focused on defining the high-risk population, the management of patients with high-risk prostate cancer, and future directions to optimize care.

Technical advances in microsurgery have enabled complex oncological reconstructions by performing free tissue transfers, nerve and lymphatic reconstructions. However, the manual abilities required to perform microsurgery can be affected by human fatigue and physiological tremor resulting in tissue damage and compromised outcomes. Robotic assistance has the potential to overcome issues of manual microsurgery by improving clinical value and anastomoses’ outcomes. The Symani Surgical System, a robotic platform designed for microsurgery, was used in this in-vivo preclinical study using a rat animal model. The tests included anastomoses on veins and arteries performed by microsurgeons manually and robotically, with the latter approach using Symani. The anastomoses were assessed for patency, histopathology, and execution time. Patency results confirmed that the robotic and manual techniques for venous and arterial anastomoses were equivalent after anastomosis, however, the time to perform the anastomosis was longer with the use of the robot (p < 0.0001). Histological analysis showed less total average host reaction score at the anastomotic site in robotic anastomosis for both veins and arteries. This study demonstrates the equivalence of vessel patency after microsurgical anastomoses with the robotic system and with manual technique. Furthermore, robotic anastomosis has proven to be slightly superior to manual anastomosis in terms of decreased tissue damage, as shown by histological analysis.

The prognosis for patients with advanced stage ovarian cancer is poor. Here, Gooitzen van Dam and colleagues demonstrate the first human application of a tumor-specific intraoperative fluorescence imaging methodology using a folate receptor-α (FR-α)-targeted fluorescent agent that exploits the overexpression of FR-α in the majority of epithelial ovarian cancers. It is hoped this approach may lead to improved intraoperative staging and more radical cytoreductive surgery. The prognosis in advanced-stage ovarian cancer remains poor. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and thereby improve prognosis. The overexpression of folate receptor-α (FR-α) in 90–95% of epithelial ovarian cancers prompted the investigation of intraoperative tumor-specific fluorescence imaging in ovarian cancer surgery using an FR-α–targeted fluorescent agent. In patients with ovarian cancer, intraoperative tumor-specific fluorescence imaging with an FR-α–targeted fluorescent agent showcased the potential applications in patients with ovarian cancer for improved intraoperative staging and more radical cytoreductive surgery.

Background: Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival. Methods: Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated ‘on-demand’. Results: We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively ( P =0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE ( P <0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE ( P =0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival ( P <0.05). Conclusions: The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.

Late-stage distribution and bulky intraperitioneal disease are the hallmarks of ovarian cancer presentation, which is managed primarily by surgical resection and chemotherapy. However, advances in surgical resection objectives, alternative chemotherapy administration schedules, and novel therapeutics based on increasing knowledge of disease biology are making strides to improve outcomes. This Review covers all elements of the definition, treatment, and biology of ovarian cancer. The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics, despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free survival and overall survival, although the cure rates have been affected only modestly. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, growth in our armamentarium offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial 'ovarian' cancer and describes the direction and early results of clinical investigation. Key Points Ovarian cancer continues to be characterized by late-stage presentation and bulky intraperitoneal disease burden at presentation Surgery and chemotherapy are the mainstays of primary therapy; 'optimal' surgical cytoreduction is being re-defined as resection of all macroscopic disease Advances in adjuvant chemotherapy have leveraged intraperitoneal administration, dose-dense paclitaxel and the addition of biological agents predominately targeting angiogenesis Maintenance therapy is a promising strategy as a primary or subsequent adjuvant approach, but as yet is not been proven to increase overall survival Recurrence therapy has improved post-progression outcomes, although cures are elusive Closely tied to a wider understanding of the underlying biology of ovarian cancer, drug development is increasingly focused on specific new targets in the hope of optimizing the therapeutic index