Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: analysis of histopathology and outcome

To examine the histopathologic effect of neoadjuvant therapy and its impact on survival in patients with carcinoma of the pancreas, we retrospectively reviewed the records of 116 patients who underwent resections for pancreatic cancer from 1987 to 2000. Median follow-up of surviving patients was 19 mo(range 4-150 mo). Preoperative chemotherapy was administered in 61 patients (53%) and consisted of 5-fluorouracil/mitomycin C in 35 patients and gemcitabine in 26 patients, given concurrently with external beam radiation (5040 cGy). All resections were performed with curative intent (98 Whipples, 11 total, 6 distal, and 1 central pancreatectomy). Histopathologic examination included an estimation of the amount of fibrosis present in the tumor specimen (expressed as the percentage of fibrosis identified relative to the amount of neoplastic cells present). The mean fibrosis level for the series was 56% (range 5% to 100%). The administration of neoadjuvant therapy resulted in greater fibrosis (73%) than no preoperative treatment (38%) (p = 0.0001). Higher mean fibrosis levels were observed in patients with negative lymph nodes (p = 0.0006) and negative margins (p = 0.05). Factors associated with improved survival(log rank test) included: negative margins (p = 0.001), negative lymph nodes (p = 0.03), and use of neoadjuvant therapy (p = 0.03). Median survival in the neoadjuvant group was 23 mo vs 16 mo without preoperative therapy (p = 0.03). In conclusion, the use of neoadjuvant therapy resulted in a greater degree of fibrosis in the specimen. Patients with negative margins and negative lymph nodes had a greater amount of fibrosis present, and these were significant predictors of improved outcome. Although retrospective,this series suggests an improvement in survival in patients treated with neoadjuvant therapy.     

Platelets modulate the proteolysis of factor VIII:C protein by plasmin

Factor VIII coagulant protein (VIII:C) functions as a critical cofactor with factor IXa, calcium ions, and phospholipid during the activation of factor X. In the course of this reaction, the activity of VIII:C is first increased and then is destroyed by one or more serine proteases that are part of the coagulation sequence. In this study, we have investigated the influence of platelets on the inactivation of VIII:C by plasmin. Platelets were separated from plasma proteins in the presence of granule release inhibitors and were incubated with plasmin and isolated VIII:C or the complex of purified VIII:C/von Willebrand factor (vWF); VIII:C activity and antigen levels were assessed over time. In the presence of platelets, the isolated VIII:C showed an initial increase in VIII:C activity that was not present when platelets were absent, and the VIII:C/vWF showed an increase in VIII:C activity over that seen when platelets were absent. In addition, platelets stabilized VIII:C activity over a one-hour time course when compared with buffer. The VIII:C antigen did not increase and decreased slowly whether platelets were present or absent. Preincubating the platelets with ristocetin, collagen, or plasmin did not alter the results, and experiments using platelets from a patient with severe von Willebrand's disease also showed a pattern similar to that seen with normal platelets. Experiments using fixed platelets or phospholipid vesicles showed that they did not support the activation reaction or delay the inactivation reaction. These studies demonstrate that platelets modulate the activation and inactivation of VIII:C by plasmin, apparently by a mechanism that is independent of the platelet release reaction.     

Medical cannabis: A forward vision for the clinician

Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence‐based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care ‘primum non nocere’ and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy.

Significance

Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.     

Care planning for long‐term conditions – a concept mapping

Objective

This article focuses on approaches within clinical practice that seek to actively involve patients with long‐term conditions (LTCs) and how professionals may understand and implement them. Personalized care planning is one such approach, but its current lack of conceptual clarity might have impeded its widespread implementation to date. A variety of overlapping concepts coexist in the literature, which have the potential to impair both clinical and research agendas. The aim of this article is therefore to explore the meaning of the concept of care planning in relation to other overlapping concepts and how this translates into clinical practice implementation.

Methods

Searches were conducted in the Cochrane database for systematic reviews, CINHAL and MEDLINE. A staged approach to conducting the concept mapping was undertaken, by (i) an examination of the literature on care planning in LTCs; (ii) identification of related terms; (iii) locating reviews of those terms. Retrieved articles were subjected to a content analysis, which formed the basis of our concept maps. (iv) We then appraised these against knowledge and experience of the implementation of care planning in clinical practice.

Results and Conclusions

Thirteen articles were retrieved, in which the core importance of patient‐centredness, shared decision making and self‐management was highlighted. Literature searches on these terms retrieved a further 24 articles. Our concept mapping exercise shows that whilst there are common themes across the concepts, the differences between them reflect the context and intended outcomes within clinical practice. We argue that this clarification exercise will allow for further development of both research and clinical implementation agendas.