Rectal cancer lateral pelvic sidewall lymph nodes: a review of controversies and management.

BACKGROUND: The management of lateral pelvic lymphadenopathy in low rectal cancer poses an oncological and technical challenge. Interpretation of the literature is confounded by different approaches to management in the East and West, and a lack of randomized data from which to draw accurate conclusions regarding the optimal approach. Recent collaboration between Eastern and Western centres has increased the standardization of care. Despite this, significant differences in international guidelines remain. The aim of this review was to appraise the available literature and propose a management algorithm. METHODS: A literature review of all relevant studies was performed to summarize the historical evidence, as well as establish the significance of clinically positive lateral pelvic sidewall nodes, and the role of neoadjuvant chemoradiotherapy and lateral pelvic node dissection. A management algorithm was developed based on this review of the literature. RESULTS: The management of pelvic sidewall lymphadenopathy in rectal cancer is non-standardized, with geographical differences. The mechanism of lateral lymphatic spread is well defined; the risk increases with lower tumour height and advanced T category. Existing data indicate that acceptable disease-free and overall survival can be achieved by neoadjuvant chemoradiotherapy with selective lateral pelvic node dissection. CONCLUSION: Suspicious lateral pelvic sidewall nodes, particularly in the internal iliac chain, should be considered as resectable locoregional disease, and surgery offered for enlarged nodes that do not respond to neoadjuvant chemoradiotherapy.

ANTECEDENTES: El tratamiento de las adenopatías en la pared pélvica lateral en el céncer de recto inferior plantea un desafío oncológico y técnico. La interpretación de la literatura es confusa por los diferentes abordajes en Oriente y Occidente y la falta de estudios aleatorizados a partir de los cuales extraer conclusiones precisas sobre cuél es el enfoque óptimo. La reciente colaboración entre los centros orientales y occidentales ha aumentado la estandarización del tratamiento. A pesar de ello, persisten diferencias significativas en las guías internacionales. El objetivo de esta revisión fue evaluar la literatura disponible y proponer un algoritmo terapéutico. MÉTODOS: Se realizó una revisión de la literatura de todos los estudios relevantes para resumir las evidencias existentes, así como para determinar la importancia de las adenopatías de la pared lateral pélvica clínicamente positivas, el papel de la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiotherapy, NCRT) y de la linfadenectomía pélvica lateral (lateral pelvic node dissection, LPND). Se desarrolló un algoritmo de tratamiento basado en esta revisión de la literatura. RESULTADOS: El tratamiento de las adenopatías de la pared lateral de la pelvis en el céncer de recto no esté estandarizado y sigue habiendo diferencias geogréficas. El mecanismo de la diseminación linfética lateral esté bien definido con un mayor riesgo en los tumores de recto inferior y con un estadio T avanzado. Los datos existentes demuestran que se puede obtener una supervivencia libre de enfermedad y global aceptables mediante NCRT con LPND selectiva. CONCLUSIÓN: Las adenopatías sospechosas en la pared lateral de la pelvis, en particular en la cadena ilíaca interna, deben considerarse enfermedad locorregional resecable y se debe ofrecer cirugía para los ganglios aumentados de tamaño que no responden a la NCRT.

Inguinal hernias associated with a single strenuous event.

INTRODUCTION: There is debate regarding the role of physical activity and, in particular, a single strenuous event (SSE) in the development of inguinal hernia. This study aims to identify the incidence and associated features of hernias perceived to be due to a single strenuous event and to compare their features with published guidelines. MATERIALS AND METHODS: All consecutive patients surgically treated for primary inguinal hernia at a single NHS trust between April 2010 and April 2011 were identified and contacted to participate in a questionnaire. Clinical details from operative records and case notes were compared with patients' responses to identify features of their presentation attributable to a single strenuous event according to previously published guidelines. RESULTS: Three hundred and thirty five eligible patients were contacted with a response rate of 292 (87 %). 41/292 (14 %) of patients reported an SSE associated with the onset of their hernia. Only 2 of 41 (5 %) patients reporting a hernia associated with SSE met published criteria for association of the hernia with SSE, and this represented less than 1 % of all patients treated for inguinal hernia at a single centre in a 1-year period. CONCLUSION: The relationship between physical activity and development of inguinal hernia is under debate; however, we find that inguinal hernia that can be attributed to SSE is a rare event, despite the fact that many patients present with acute symptoms. Updated guidelines for the assessment of 'cause' in industrial claims for the association of hernia with workplace activity are required.

Approaches by the US National Institutes of Health to support rigorous scientific research on dietary supplements and natural products.

Mechanistic, clinical, and epidemiological research relevant to dietary supplements (DS) is supported by the U.S. National Institutes of Health. The Office of Dietary Supplements and the National Center for Complementary and Integrative Health promote the development and appropriate use of rigorous and comprehensive DS analyses which are critical for research reproducibility, particularly when the investigational DS include chemically complex natural products with unclear mechanisms of action.

Acute choke zone effects: Lessons from radioactive and fluorescent microspheres in a pig model muscle flap.

BACKGROUND: Choke vessels dilate and contract to regulate blood flow between adjacent arterial angiosomes. In skin flap surgery, when arterial inflow to an angiosome is ligated, choke vessels allow blood supply from an adjacent angiosome. In muscle flap surgery, the vascular anatomy is analogous to skin flaps; however, while it is established that the choke vessels will fully dilate irreversibly after two to three days, no study has yet analyzed the acute changes in each vascular region immediately following ligation of one pedicle. OBJECTIVE: To establish whether the choke vessels open or close immediately following ligation of a pedicle, and how this change affects blood flow in the adjacent proximal and distal vascular regions. METHODS: Radioactive and fluorescent microspheres in a pig model were used to study the regional intramuscular blood flow in each anatomical zone of a rectus abdominis flap. Blood flow measurements for each zone were calculated relative to the entire muscle at preligation, ligation and various times (15 min to 90 min) postligation. RESULTS: There was no statistically significant difference in blood flow across choke zones as a result of ligation. This signifies that the choke vessels do not significantly dilate to produce a statistically significant measureable change in blood flow. CONCLUSIONS: Given these results and previous literature findings, the anatomical presence of choke vessels in a muscle is the strongest determining factor for acute flap viability in surgery.

HISTORIQUE: Les vaisseaux anastomotiques se dilatent et se contractent pour réguler le débit sanguin entre les angiosomes artériels adjacents. Dans le cadre d'une chirurgie par lambeau cutané, lors de la ligature du débit artériel vers un angiosome, les vaisseaux anastomotiques assurent un débit sanguin en provenance d'un angiosome adjacent. L'anatomie vasculaire est alors analogue aux lambeaux cutanés. Cependant, bien qu'il soit établi que les vaisseaux anastomotiques se dilatent pleinement et de manière irréversible au bout de deux ou trois jours, aucune étude n'a encore analysé les changements aigus de chaque région vasculaire immédiatement après la ligature d'un pédicule. OBJECTIF: Établir si les vaisseaux anastomotiques s'ouvrent ou se ferment immédiatement après la ligature d'un pédicule et examiner l'effet de ce changement sur le débit sanguin des régions proximales et distales adjacentes. MÉTHODOLOGIE: Les chercheurs ont utilisé les microsphères radioactives et fluorescentes d'un porc pour étudier le débit sanguin intramusculaire régional de chaque zone anatomique d'un lambeau du grand droit. Ils ont mesuré le débit sanguin de chaque zone par rapport au muscle entier avant la ligature, au moment de la ligature et à divers moments (de 15 à 90 minutes) après la ligature. RÉSULTATS: Il n'y avait pas de différence statistiquement significative du débit sanguin dans les diverses zones anastomotiques après une ligature. Ainsi, les vaisseaux anastomotiques ne se dilatent pas au point de produire un changement du débit sanguin pouvant être mesuré de manière statistiquement significative. CONCLUSIONS: Compte tenu de ces résultats et des conclusions de publications scientifiques, la présence anatomique de vaisseaux anastomotiques dans un muscle est le principal déterminant de viabilité aiguë d'un lambeau lors d'une chirurgie.

Outcomes in locally advanced rectal cancer with highly selective preoperative chemoradiotherapy.

BACKGROUND: This study compared outcomes after surgery alone for stage II/ III rectal cancer in a tertiary cancer unit versus highly selective use of preoperative chemoradiotherapy (CRT). METHODS: This was a single-centre retrospective cohort study of consecutive patients receiving potentially curative surgery for stage II and III primary rectal cancer. CRT was given only for magnetic resonance imaging-predicted circumferential resection margin (CRM) involvement and nodal disease (at least N2). Primary endpoints were CRM involvement and local recurrence rates. Secondary endpoints were systemic recurrence and overall survival. Data were analysed by log rank test, and univariable and multivariable analysis. RESULTS: Between 2002 and 2012, 363 patients were treated for rectal cancer. After applying exclusion criteria, 266 patients with stage II/III mid or low rectal cancer were analysed. Of these, 103 received neoadjuvant CRT and 163 proceeded directly to surgery, seven of whom required postoperative radiotherapy; the latter patients were included in the neoadjuvant CRT group for analysis. There was a significant difference in local recurrence between the CRT and surgery-alone groups (6·5 versus 0 per cent at 5 years; P = 0·040), but not in CRM involvement (7·2 versus 5·1 per cent; P = 0·470), 5-year systemic recurrence (37·2 versus 43·0 per cent; P = 0·560) and overall survival (64·2 versus 64·6 per cent; P = 0·628) rates. Metastatic disease developed more frequently in low rectal cancers (odds ratio 0·14; P < 0·001), regardless of whether neoadjuvant treatment was delivered. CONCLUSION: Locally advanced rectal cancer does not necessarily require neoadjuvant CRT.

Spontaneous resolution of an inferior epigastric artery pseudoaneurysm secondary to surgical drain placement.

We report the case of a 73-year-old woman who was found to have an inferior epigastric artery pseudoaneurysm caused by surgical drain placement during a laparotomy for an appendix abscess. She presented with pain around the drain site two months following surgery and intravenous contrast computed tomography (CT) revealed a right inferior epigastric artery pseudoaneurysm. A decision was made to manage this expectantly as she remained stable with no other complications. Following a period of nine months of observation, repeat intravenous contrast CT showed evidence of spontaneous regression and thrombosis of the pseudoaneurysm. She remains well and her symptoms have now resolved.

Quality of life after treatment of laryngeal carcinoma: a single centre cross-sectional study.

INTRODUCTION: Laryngeal cancer treatment inherently affects life's most basic functions and significantly affects quality of life (QOL). We aimed to identify which aspects of QOL and which patients are most affected by the various treatment options. METHODS: The University of Washington Quality of Life (UW-QOL) questionnaire was administered to all patients with laryngeal cancer treated at a single institution over a seven-year period (2003-2010). RESULTS: In total, 41 patients responded. All had been treated for squamous cell carcinoma of the larynx. Questionnaires were completed at a median of 18.5 months after treatment. The overall quality of life was 81.1/100 as assessed by the UW-QOL scale, with only 4.9% reporting 'poor' or worse QOL. Neither patient age nor time after treatment significantly affected any aspect of QOL. Patients undergoing primary radiotherapy reported the best QOL. Those undergoing chemoradiotherapy or combined surgical treatment and chemoradiotherapy reported the worst QOL, particularly in terms of social eating, taste and saliva production. Patients with a T stage ≥2 and those with nodal metastases reported a significantly worse QOL. CONCLUSIONS: Overall, QOL in our patients was good. This study highlights the aspects of QOL most affected by various treatments for laryngeal cancer and identifies areas in which therapeutic intervention may be focused. It also provides information to guide clinicians when assisting patients to make informed decisions regarding treatment of their head and neck cancer.

Pseudo-peptides derived from isomannide: inhibitors of serine proteases.

In this paper, we describe the synthesis of a novel class of pseudo-peptides derived from isomannide and several oxazolones as potential inhibitors of serine proteases as well as preliminary pharmacological assays for hepatitis C. Hepatitis C, dengue and West Nile fever are among the most important flaviviruses that share one important serine protease enzyme. Serine proteases belong to the most studied class of proteolytic enzymes and are a primary target in the drug development field. Several pseudo-peptides were obtained in good yields from the reaction of isomannide and oxazolones, and their anti-HCV potential using the HCV replicon-based assay was shown.

Pseudo-peptides derived from isomannide as potential inhibitors of serine proteases.

Hepatitis C, Dengue and West Nile virus are among of the most important flaviviruses that share one important serine protease enzyme. Serine proteases belong to the most studied class of proteolytic enzymes, and are a primary target in the drug development field. In this paper, we describe the synthesis and preliminary molecular modeling studies of a novel class of N-t-Boc amino acid amides derived of isomannide as potential serine proteases inhibitors.

N- t-Boc-amino acid esters of isomannide. Potential inhibitors of serine proteases.

Hepatitis C, Dengue and West Nile virus are some of the most important flaviviruses, that share one important serine protease enzyme. Serine proteases are the most studied class of proteolytic enzyme and, in these cases, a primary target for drug discovery. In this paper, we describe the synthesis and preliminary molecular modeling studies of a novel class of N- t-Boc amino acid esters derived of isomannide as potential serine proteases inhibitors.

Anti-Helicobacter pylori agents. An update.

Helicobacter pylori infection is the major causative factor of a number of gastric pathologies. Several classes of compounds have been identified as anti-H. pylori agents. Here we provide a review of anti-H. pylori compounds that have recently appeared in the literature, including the guanidino, antibiotics, acetamide, pyrazole and benzimidazole compounds.

Transformation of artemisinin by Cunninghamella elegans.

Semi-synthetic derivatives of the anti-malarial drug artemisinin hold great promise in the search for an effective and economical treatment of chloroquine-resistant forms of malaria. Unfortunately, synthetic functionalization of the artemisinin skeleton is often tedious and/or impractical. We seek to utilize 7beta-hydroxyartemisinin, obtained from microbial transformation, as a semi-synthetic precursor for the synthesis of novel 7beta-substituted artemisinin anti-malarial agents. Here we employ liquid cultures of Cunninghamella elegans as a means for the rational and economical bioconversion of artemisinin to 7beta-hydroxyartemisinin in 78.6% yield. In addition, there were three other bioconversion products: 7beta-hydroxy-9alpha-artemisinin (6.0%), 4alpha-hydroxy-1-deoxoartemisinin (5.4%), and 6beta-hydroxyartemisinin (6.5%).

Hydroxamic acids as pharmacological agents.

A variety of hydroxamic acid derivatives have recently been touted for their potential use as inhibitors of hypertension, tumor growth, inflammation, infectious agents, asthma, arthritis, and more. Here we provide a comprehensive review of the basic medicinal chemistry and pharmacology of hydroxamic acid derivatives that have been examined as inhibitors of zinc metalloproteases, matrix metalloproteinases, leukotriene A(4) hydrolases, ureases, lipoxigenases, cyclooxygenases, as well as peptide deformilases.

A review of cancer chemopreventive agents.

In the late 20(th) century, the treatment of cancer began to include its prevention. Today, compounds exist that will lower the risk of developing certain types of cancer. This has been demonstrated in studies where chemically induced tumor growth has been slowed or reversed. Anti-inflammatory compounds having chemopreventive activity are piroxicam, sulindac, aspirin, celecoxib and curcumin. The selective estrogen receptor modulators, tamoxifen and raloxifene, are beneficial in the prevention of estrogen dependent tumors. Retinoids, vitamin A derivatives, such as targretin and fenretinide are useful in the prevention of tumors. Compounds containing sulfur, such as sulforaphane and oltipraz, are even useful as radioprotective agents. The steroid dehydroepiandosterone can inhibit experimental carcinogenesis. All of these chemical classes provide a start for the medicinal chemist to design more effective chemopreventive agents. The biomarkers used to determine the chemopreventive activity of new compounds are quite often activities of enzymes. The identification of those individuals at high risk is still in its infancy and presents a troubling dilemma.

Toe-to-finger transfer for post-traumatic reconstruction of the fingerless hand.

OBJECTIVE: To assess the utility of toe-to-finger transfers (TFTs) for post-traumatic reconstruction of the fingerless hand. DESIGN: A case series. SETTING: A regional trauma centre. PATIENTS: Eight men, mean age was 36 years (range from 25-59 yr), who had lost all the fingers from a hand due to a crush-degloving injury (6 patients), frostbite (1 patient) or a burn injury (1 patient). INTERVENTION: TFT. Twelve TFTs were cone and the mean time from injury to reconstruction was 17.2 months. MAIN OUTCOME MEASURES: Objective (range of motion, moving 2-point discrimination, grip strength, key pinch, Jebsen-Taylor hand assessment, return to work) and subjective (activities of daily living and a questionnaire) measures. RESULTS: Eleven of the 12 transfers survived. Six of the 7 in whom the transfer was successful were available for follow-up (mean 45 mo). Range of motion was 10 degrees at the distal interphalangeal joint, 18 degrees at the proximal interphalangeal joint and 59 degrees at the metacarpophalangeal joint. Sensation was protective in all. Grip strength and key pinch were 26.1% and 70.2% of the contralateral hand respectively. Jebsen-Taylor assessment indicated that basic activities were possible but slowed. All 6 patients returned to work and could perform 92.6% of the activities of daily living unassisted. Hand and foot symptoms were mild. Two-thirds were appearance conscious, 5 of the 6 went on to altered vocations and all reported overall satisfaction as high. CONCLUSION: This study supports TFT for reconstruction of the fingerless hand in that, although transferred toe function may be poorer than a normal finger, the hand is restored to a useful, sensate and versatile functional unit, such that global hand and patient function, as well as patient satisfaction, are very good.

Vascular resistance in human muscle flaps.

Important differences in free muscle flap survival have been reported in the setting of long arterial and venous vein grafts. The authors provide insight into the etiology of flap failure by addressing the following question: Do differences in flap type result in clinically significant different vascular resistances and consequently anastomotic patency? A total of 15 human flaps were studied intraoperatively: 9 gracilis, 3 rectus abdominis, and 3 latissimus dorsi. The muscle was isolated on a single pedicle and hemodynamic stability was ensured. The venous pedicle was then divided. A timed collection of effluent was used to determine flow. Vascular resistance was calculated by dividing the change in pressure by the flow, and standardizing this for temperature and hematocrit. Average vascular resistance and standard deviation for the gracilis, rectus, and latissimus flaps was 10.34 +/- 7.77 mmHg per milliliter per minute, 2.79 +/- 1.50 mmHg per milliliter per minute, and 3.17 +/- 1.05 mmHg per milliliter per minute respectively. An inverse relationship between muscle vascular resistance and flap mass was found (p < 0.001). This indicates that larger muscles have less vascular resistance. The decreased resistance gives rise to higher flow rates and, as a result, potentially improved vein graft patency. The clinical implication is that a larger flap should be used when high flow-through is critical. The role of flap vascular territory makeup continues to be pursued.

Helicobacter pylori: current chemotherapy and new targets for drug design.

Helicobacter pylori infection is a major cause of many diseases of the gastrointestinal tract, including gastritis, non-ulcer dyspepsia, peptic ulcer disease, and gastric cancers. It is estimated that more than half of the human race is affected by this organism. Although effective treatments are available which will eliminate the organism in about 90 percent; of cases in developed countries, the pandemic occurrence of Helicobacter pylori infection coupled with its ability to develop resistance to our current arsenal of antimicrobial regimens and subsequently reinfect patients makes the pathogenic potential of this microorganism a major global health concern. Provided is a review of the current and evolving therapeutic regimens used in the eradication of Helicobacter pylori, the difficulties associated with in vitro drug screening, as well as potentially new therapeutic targets. In addition, the discovery, the unique physiology, biochemistry, and pathogenicity of this remarkable microorganism is examined.