Is ovarian cancer surgery stuck in the dark ages?: a commentary piece reviewing surgical technologies.

Ovarian cancer surgery endeavours to remove all visible tumour deposits, and surgical technologies could potentially facilitate this aim. However, there appear to be barriers around the adoption of new technologies, and we hope this article provokes discussion within the specialty to encourage a forward-thinking approach to new-age surgical gynaecological oncology.

[Historical evolution and research progress of perioperative therapy of locally advanced gastric cancer].

Based on the four major classic studies of perioperative treatment of locally advanced gastric cancer (LAGC), the North American Intergroup-0116 trial, the European MRC MAGIC trial, the Japan ACTS-GC trial and Korea-China CLASSIC trial, the perioperative therapy of LAGC was divided into three major patterns in the world, namely, postoperative adjuvant chemoradiotherapy in the North America, perioperative chemotherapy in the Europe and postoperative adjuvant chemotherapy in the East Asia. In recent years, scholars around the world have done many researches on the perioperative treatment of gastric cancer. For instance the German FLOT4-AIO trial pushed the perioperative chemotherapy of gastric cancer to a high point, so the NCCN guide changed perioperative chemotherapy to the preferred recommendation, and rewrote the perioperative chemotherapy regimen. The ARTIST trial in Korea showed that the addition of radiotherapy to the adjuvant chemotherapy after D2 radical resection of gastric cancer could not improve the overall survival rate, and further defined adjuvant chemotherapy as the standard treatment in D2 resection of gastric cancer. Asian scholars are actively exploring the application of perioperative chemotherapy in LAGC. For Bulky N cases, neoadjuvant chemotherapy has been recommended as the standard treatment in the Japanese guidelines. The JOCG1509,the RESOLVE and other studies will provide more effective evidence-based recommendations for the best perioperative therapy options of LAGC in Asian countries. At present, it is not clear whether perioperative chemotherapy or postoperative adjuvant chemotherapy is better. In this article, the development course of the three patterns of perioperative therapy of gastric cancer, the research progress in the perioperative period of gastric cancer in recent years, and the changes of guidelines are reviewed in order to provide reference for clinical practice.

Cushing's Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century.

Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing's disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing's disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

Frontline therapy of ovarian cancer: trials and tribulations.

PURPOSE OF REVIEW: The current article reviews the advances and challenges in the fight with cancer and the hope for cure, with a focus on clinical trials, at the one time with the best outcomes; first-line therapy. RECENT FINDINGS: To date there have been four great stories that bridge inception to development of new drugs in ovarian cancer: Serendipitous insight into the role of platinum, discovery of taxanes, understanding the microenvironment and angiogenesis, and following the science in the development of Poly (ADP-Ribose) Polymerase (PARP) inhibitors. There is a fundamental difference between overall survival (OS), simply living longer; and eradicating disease, cure. The scientific underpinning of both our understanding and the recent developments encourages an optimistic view of the remaining hurdles. SUMMARY: There has been an unprecedented explosion in the number of new drugs approved for the treatment of ovarian cancer with three new classes of agent, and five new drugs receiving food and drug administration approval in the last 3 years (Fig. 2). Getting the right drug truly transforms patients' experience with the seminal event being the development of imatinib in CML. In 1980, an average patient would have lived only 3 years, and now they only live 3 years less than a full lifespan [Bower et al. (2016). J Clin Oncol 34:2851].

The History of Multimodal Treatment of Wilms' Tumor.

Multimodal therapy-surgery, radiation therapy, and chemotherapy-the foundation of modern cancer treatment, has led to dramatic improvements in survival. How the three disciplines coalesced to conquer Wilms' tumor is a compelling story that includes two of history's greatest discoveries, X-rays and antibiotics. By the mid-20th century both fields had matured to where dedicated clinicians and creative scientists could apply them to Wilms' tumor and achieve successive improvements in survival. William Ladd was able to achieve a zero operative mortality by 1940, but was left with a 32 per cent survival with surgery alone. Robert Gross and Edwin Neuhauser combined surgery and radiotherapy and achieve 47 per cent survival rate in 1950. Sidney Farber and his colleagues added an antibiotic, dactinomycin, to the treatment regimen and reached 80 per cent survival rate in 1966. The National Wilms' Tumor Study, organized in 1968, was a multidisciplinary effort of surgeons, radiotherapists, and pediatric oncologists across the country. By the 1990s, the National Wilms' Tumor Study achieved survival rates above 95 per cent while minimizing long-term effects through shortening courses of chemotherapy and radiation. The story of Wilms' tumor serves as a paragon for all types of cancer, in both children and adults.

Spinal Traumas and their Treatments According to Avicenna's Canon of Medicine.

Spinal Traumas have been categorized as disabling diseases that cause irretrievable personal and social problems. Having conducted a rather comprehensive diagnosis of the anatomy of the backbone and spinal cord as well as their functions, Avicenna (Ibn Sina, 980-1037) stated the levels and kinds of spinal impairments that are caused by spinal traumas in his great masterpiece Al-Qanun fi al-Tibb (The Canon of Medicine). He also based his treatment process on his etiological diagnosis of such impairments. Avicenna had used the following methods to treat spinal traumas: food and drug therapy and regimental therapies such as massage, phlebotomy, cupping, dry sauna, and surgery. The authors of the present article review the bases of Avicenna's viewpoints regarding spinal traumas and their treatment.

Bromine, bear-claw scratch fasciotomies, and the Eagle effect: management of group A streptococcal necrotising fasciitis and its association with trauma.

Necrotising fasciitis is a rare, but potentially fatal, soft-tissue infection. Historical depictions of the disease have been described since classical times and were mainly recorded in wartime reports of battle injuries. Although several different species of bacteria can cause necrotising fasciitis, perhaps the most widely known is group A streptococcus (GAS). Infection control, early surgical debridement, and antibiotic therapy are now the central tenets of the clinical management of necrotising fasciitis; these treatment approaches all originate from those used in wars in the past 150 years. We review reports from the 19th century, early 20th century, and mid-20th century onwards to show how the management of necrotising fasciitis has progressed in parallel with prevailing scientific thought and medical practice. Historically, necrotising fasciitis has often, but not exclusively, been associated with penetrating trauma. However, along with a worldwide increase in invasive GAS disease, recent reports have cited cases of necrotising fasciitis following non-combat-related injuries or in the absence of antecedent events. We also investigate the specific association between GAS necrotising fasciitis and trauma. In the 21st century, molecular biology has improved our understanding of GAS pathogenesis, but has not yet affected attributable mortality.

High-dose therapy with autologous stem cell support for lymphoma--from experimental to standard treatment.

High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.

The impact of molecular targets in cancer drug development: major hurdles and future strategies.

The last decades were characterized by enormous technological advances resulting in a better understanding of disease pathologies and improvement of treatment strategies. The development of targeted drugs, whose beginning can be traced back to Paul Ehrlich's theory of the 'magic bullet' approximately 100 years ago, is today widely appraised as a promising strategy to combat benign, as well as malignant, diseases. Over 40 years after US President Nixon declared the 'war on cancer', treatment outcome, especially of solid tumors in the advanced stages of disease, still lies far behind expectations. In this perspective article, the authors discuss the recent development of targeted cancer drugs and identify major hurdles. The authors further highlight future strategies that might improve and accelerate the drug-development process.

The history of the combined supra- and infratentorial approach to the petroclival region.

Lesions of the ventrolateral brainstem, clivus, and cerebellopontine angle pose significant challenges for surgeons, and the rate of morbidity and mortality from classic neurosurgical approaches has proven to be unacceptably high. Early attempts to expose this region consisted primarily of an extended suboccipital craniectomy, with opening of the tentorium and ligation of the sigmoid sinus for additional exposure. During the 1960s, technological innovations including the surgical microscope and the pneumatic drill allowed surgeons to gain additional exposure by removing more bone from the base of the skull. This let surgeons define combined infra- and supratentorial approaches, which rely less on brain retraction to resect these difficult tumors successfully. These approaches rely on a combined posterior mastoid approach with an anterior petrosectomy. The evolution of this approach is discussed in this paper.

The history of pituitary surgery for Cushing disease.

Although he never performed a pituitary operation for the disease, Harvey Cushing was the first to describe and treat patients with Cushing disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)-secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD.

Splenectomy, interferon, and treatments of historical interest in hairy cell leukemia.

The evolution and "lessons learned" for therapeutic options and approaches in HCL, which subsequently evolved into the adenosine deaminase inhibitors as the treatment of choice, has been intriguing. The contributions to patient care and individual patient lives have been remarkable. Observation, splenectomy, and recombinant interferon are potential therapeutic are alternatives in select patients as initial therapy, and as therapeutic alternatives in the 10% of patients who have progressive disease after the purine nucleoside analogs.

Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies.

The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues. Group A patients (n = 22) had received alkylating agents and/or radiotherapy, and the majority (63.6%) had advanced Hodgkin disease. At univariate analysis, uncontrolled Hodgkin disease was the only risk factor for PML. In group B patients (n = 24), the most frequent treatments received were purine analogues (58.3%) and high-dose therapy with hematopoietic stem cell transplantation (33.3%; HDT/HSCT). B-cell chronic lymphocytic leukemia (45.8%) and aggressive non-Hodgkin lymphoma (24.9%) were the most frequent underlying LPDs. Patients treated with purine analogues were more likely to have active LPD, lower CD4 cell counts, and to be older and male than were HSCT recipients. The median interval from purine analogues or HDT/HSCT to PML was 11 months. In HDT/HSCT recipients, this interval was delayed for 10 months when peri-transplantation rituximab was used. Univariate analysis identified age >55 years, male sex, and CD4 cell counts