The clinical utility of pre-operative neutrophil-to-lymphocyte ratio as a predictor of outcomes in patients undergoing elective laparoscopic cholecystectomy.

BACKGROUND: In recent years, there has been an increasing trend towards day-case surgery for patients undergoing laparoscopic cholecystectomy (LC). We investigated the predictive value that pre-operative neutrophil-to-lymphocyte ratio (PNLR) had on surgical outcomes. METHODS: A review of all patients who underwent LC during a 6-year period in a single institution was performed and PNLR recorded. A PNLR cutoff value of 3 was utilised. We compared operation time, length of stay (LOS), and conversion to open between those with PNLR less and greater than 3. RESULTS: A total of 567 patients underwent elective LC. Those with PNLR>3 had associated prolonged operation time (p < 0.005), prolonged LOS (p < 0.005), and higher rates of conversion to open surgery (p < 0.005). CONCLUSIONS: PNLR correlates with outcomes following LC. It is useful in delineating patients that have higher risk of conversion or prolonged length of hospital stay and is helpful in assessing suitability of day-case surgery.

Iterative assembly line synthesis of polypropionates with full stereocontrol.

The polypropionate motif is ubiquitous, being characteristic of the most important family of natural products for human health, the polyketides. Numerous strategies have been devised to construct these molecules with high stereocontrol, but certain stereoisomers remain challenging to prepare. We now describe the development of an iterative assembly line strategy for the construction of polypropionates. An assembly line strategy for the synthesis of deoxypolypropionates has already been described. However, the introduction of carbinol units required the development of new building blocks and new reaction conditions. This has been achieved by the use of enantioenriched lithiated α-chlorosilanes [1-((2'-lithiochloromethyldimethylsilyl)-methyl)-2-(methoxymethyl)-pyrrolidine], thus enabling the programmed synthesis of polypropionates in a fully stereocontrolled manner, including the stereochemically challenging anti-anti isomers. The versatility of the approach is exemplified in its extension to the synthesis of 1,3-related polyols. The methodology now allows access to a much wider family of polyketide natural products with stereochemistry being dialled in at will.

International, Expert-Based, Consensus Statement Regarding the Management of Acute Diverticulitis.

IMPORTANCE: This Delphi study provides consensus related to many aspects of acute diverticulitis and identifies other areas in need of research. OBJECTIVE: To generate an international, expert-based, consensus statement to address controversies in the management of acute diverticulitis. DESIGN, SETTING, AND PARTICIPANTS: This study was conducted using the Delphi technique from April 3 through October 21, 2014. A survey website was used and a panel of acute diverticulitis experts was formed via the snowball method. The top 5 acute diverticulitis experts in 5 international geographic regions were identified based on their number of publications related to acute diverticulitis. INTERVENTIONS: The Delphi study used 3 rounds of questions, after which the consensus statement was collated. MAIN OUTCOMES AND MEASURES: A consensus statement related to the management of acute diverticulitis. RESULTS: Twenty items were selected for inclusion in the consensus statement following 3 rounds of questioning. A clear definition of uncomplicated and complicated diverticulitis is provided. In uncomplicated diverticulitis, consensus was reached regarding appropriate laboratory and radiological evaluation of patients as well as nonsurgical, surgical, and follow-up strategies. A number of important topics, including antibiotic treatment, failed to reach consensus. In addition, consensus was reached regarding many nonsurgical and surgical treatment strategies in complicated diverticulitis. CONCLUSIONS AND RELEVANCE: Controversy continues internationally regarding the management of acute diverticulitis. This study demonstrates that there is more nonconsensus among experts than consensus regarding most issues, even in the same region. It also provides insight into the status quo regarding the treatment of acute diverticulitis and provides important direction for future research.

Clinical, MRI, and PET-CT criteria used by surgeons to determine suitability for pelvic exenteration surgery for recurrent rectal cancers: a Delphi study.

BACKGROUND: Surgical resection with clear margins is the major predictor of long-term survival in recurrent rectal cancer. The extent of pelvic exenteration surgery depends on many factors including clinical and radiological criteria. OBJECTIVE: The aim of this study was to establish which clinical, MRI, and PET criteria were considered important by surgeons who perform pelvic exenteration surgery, when assessing a patient with recurrent rectal cancer for pelvic exenteration surgery. DESIGN: A 2-stage Delphi study was conducted among an international panel of 36 colorectal surgeons recruited via a snowball-sampling method. Surgeons rated the importance of 99 clinical and radiological criteria by using a 9-point scale. MAIN OUTCOME MEASURES: Consensus was attained when at least 85% of the panel rated criteria within 3 points. RESULTS: Clinical factors suggestive of systemic disease, symptoms of advanced local recurrence such as pain, surgical fitness, and cognitive impairment were considered important by the panel when considering suitability for surgery. Agreement regarding the indication for surgery was reached for 20 radiological factors. Strong agreement was achieved for factors associated with tumor involvement in the axial and anterior compartments. For only 16 of these 20 radiological factors was there an agreement that a clear resection margin was likely to be achieved. LIMITATIONS: Further rounds of Delphi may have yielded greater consensus. CONCLUSION: This study has identified a set of criteria considered by experts to be important in evaluating patients' suitability for pelvic exenteration surgery. Evaluation of these criteria is required to determine their clinical utility in predicting a negative resection margin at pelvic exenteration surgery.

A predictive model of suitability for minimally invasive parathyroid surgery in the treatment of primary hyperparathyroidism [corrected].

BACKGROUND: Improved preoperative localizing studies have facilitated minimally invasive approaches in the treatment of primary hyperparathyroidism (PHPT). Success depends on the ability to reliably select patients who have PHPT due to single-gland disease. We propose a model encompassing preoperative clinical, biochemical, and imaging studies to predict a patient's suitability for minimally invasive surgery. METHODS: For the purposes of the present study, 180 consecutive patients were included for analysis. A 5-variable model based on preoperative ionized serum calcium (>1.4 mmol/l), intact parathyroid hormone level (≥ 2 times the upper limit of normal), positive sestamibi scan for a single affected gland, positive ultrasound scan for a single gland, and concordance between the two imaging modalities for single-gland disease at a similar location was employed, where a score of 1 was allocated for each variable present. RESULTS: Of the 180 patients, 62 (34%) underwent bilateral exploration, 63 (36%) underwent unilateral exploration, and 55 (30%) underwent minimally invasive parathyroidectomy. The results showed that 92% had single-gland disease, 3% had double adenomas, and 5% had hyperplasia. Biochemical cure was achieved in 98.9%. Mean follow-up was 153 days (range: 80-342 days). With the predictive scoring model, a score of ≥ 3 had a positive predictive value of 100% for single-gland disease. CONCLUSIONS: A scoring model encompassing preoperative biochemical and imaging data can be successfully employed to predict suitability for minimally invasive surgery in the majority of patients with single-gland disease.

The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

BACKGROUND: The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated. OBJECTIVE: This study aimed to determine the prognostic significance of extramural nodules and extracapsular lymph node extension in colon cancer. DESIGN: A pathological review of 114 stage III and 80 stage II colon cancers was undertaken to analyze for p-T stage, p-N stage (using the fifth, sixth, and seventh editions), and the size and contour of nodal and extramural deposits. Multivariate Cox regression models were used to determine the prognostic significance of clinicopathological parameters on survival estimates. RESULTS: According to the sixth and seventh editions of the guidelines, extramural deposits were present in 29% and 31% of patients with stage III colon cancer and in 5% of patients with stage II colon cancer. Extracapsular lymph node invasion was present in 68% of cases. Multivariate analysis demonstrated that lymph node ratio, extracapsular lymph node extension, and adjuvant chemotherapy were independent prognostic factors affecting 5-year disease-free survival. The same 3 variables, in addition to extramural deposits, were independent prognostic factors affecting overall survival. The presence of extramural deposits was associated with an 11% 5-year survival, and extracapsular lymph node invasion was associated with a 33% 5-year survival. CONCLUSIONS: Instead of extramural nodules being included as part of the T category or as site-specific tumor deposits, they should perhaps be classified in the metastasis category. This has major prognostic implications and may broaden the application of a number of adjuvant agents.

Laparoscopic (TEP) versus Lichtenstein inguinal hernia repair: a comparison of quality-of-life outcomes.

BACKGROUND: Laparoscopic inguinal hernia repair has emerged as a viable alternative to the open procedure. To date, few studies have included validated measures of quality of life as end points. We compared quality-of-life outcomes following laparoscopic versus open repair of inguinal hernia. METHODS: All laparoscopic repairs were performed via the totally extraperitoneal route (TEP). All open procedures were Lichtenstein repairs (LR). Hernia repairs performed between January 1999 and December 2006 were included in the study. Data was recorded prospectively and each TEP repair was matched with a LR for analysis. The SF-36 form was used to assess quality of life. Statistical significance was determined using the two-sample Wilcoxon rank-sum (Mann-Whitney) test. RESULTS: Three hundred fourteen procedures were performed during the study period, 164 (52%) had a TEP repair and 150 (48%) had a LR. Ninety TEP repairs were matched with 90 LR. Recurrence rates were 3% following TEP repair and 2% following LR. There was a significant difference between the laparoscopic and open groups in terms of physical function (p = 0.0001), physical role (p < 0.0001), bodily pain (p = 0.0029), general health (p = 0.0025), and emotional role (p < 0.0001). There was no significant difference between the groups in terms of vitality (p = 0.2501), mental health (p = 0.08), or social functioning (p = 0.1677). CONCLUSIONS: These data suggest that the TEP repair results in less postoperative pain, a quicker return to normal functional status, and improved quality-of-life outcomes with equivalent recurrence rates when compared to the LR.

The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Small bowel obstruction secondary to migration of a fragment of lithobezoar: a case report.

INTRODUCTION: Small bowel obstruction is a common world-wide condition that has a range of etiological factors. The management is largely dependent on the cause of the obstruction. Small bowel obstruction caused by foreign body ingestion is rare; many items have been reported as responsible, but there are no reports implicating polyurethane foam. CASE PRESENTATION: We report the case of a 44-year-old Irish male who presented following ingestion of polyurethane foam. He was asymptomatic on presentation but developed a small bowel obstruction shortly thereafter. CONCLUSION: Patients presenting following ingestion of polyurethane foam should be scheduled for elective laparotomy, gastrotomy, and retrieval of the cast on the next available theatre list - given that they are suitable for surgery.

Incarcerated transmesosigmoid hernia presenting in a 60-year-old man: a case report.

INTRODUCTION: Internal hernias are a rare cause of small bowel obstruction and are estimated to account for 1% to 5% of cases. Herniation through a defect in the sigmoid mesocolon constitutes 6% of all internal hernias. CASE PRESENTATION: In this case report we describe a rare case of a fit and healthy 60-year-old man, with no previous history of abdominal surgery, who presented with signs and symptoms of small bowel obstruction as a result of an incarcerated transmesosigmoid hernia. The hernia was reduced and the incarcerated loop of small bowel was found to be viable. The patient made a good recovery and was discharged home on the fourth post-operative day. CONCLUSION: Internal hernias can cause considerable morbidity and mortality, so prompt diagnosis is paramount. Transmesosigmoid hernias are most common in the paediatric population; however, our patient was 60 years old. This report highlights the importance of considering an internal hernia as a cause of small bowel obstruction in individuals of all age groups and especially in those without a previous history of abdominal surgery.

Mesenteric desmoid tumor causing ureteric obstruction.

Desmoid tumors are rare, accounting for just 0.03% of all neoplasms and less than 3% of all soft tissue tumors. Although these tumors are benign, they are locally invasive and can cause considerable morbidity and mortality. We describe the case of a 16-year-old female who presented with hydronephroureter secondary to an intra-abdominal desmoid tumor. This case report draws the attention of urologists to the diagnostic dilemma and therapeutic challenges associated with an intra-abdominal mass causing ureteral obstruction especially in young patients.

CA 15-3 is predictive of response and disease recurrence following treatment in locally advanced breast cancer.

BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and is the most widely used serum marker in breast cancer. METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC. RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer.

Associations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast cancer.

PURPOSE: Associations between p160 coactivator proteins and the development of resistance to endocrine treatment have been described. We hypothesized that nuclear receptor coregulatory proteins may interact with nonsteroid receptors. We investigated the mitogen-activated protein kinase-activated transcription factors, Ets, as possible interaction proteins for the coactivators SRC-1 and AIB1 and the corepressor NCoR in human breast cancer. EXPERIMENTAL DESIGN: Expression and coexpression of Ets and the coregulatory proteins was investigated using immunohistochemistry and immunofluorescence in a cohort of breast tumor patients (N = 134). Protein expression, protein-DNA interactions and protein-protein interactions were assessed using Western blot, electromobility shift, and coimmunoprecipitation analysis, respectively. RESULTS: Ets-1 and Ets-2 associated with reduced disease-free survival (P < 0.0292, P < 0.0001, respectively), whereas NCoR was a positive prognostic indicator (P < 0.0297). Up-regulation of Ets-1 protein expression in cell cultures derived from patient tumors in the presence of growth factors associated with tumor grade (P < 0.0013; n = 28). In primary breast tumor cell cultures and in the SKBR3 breast cell line, growth factors induced interaction between Ets and their DNA response element, induced recruitment of coactivators to the transcription factor-DNA complex, and up-regulated protein expression of HER2. Ets-1 and Ets-2 interacted with the coregulators under basal conditions, and growth factors up-regulated Ets-2 interaction with SRC-1 and AIB1. Coexpression of Ets-2 and SRC-1 significantly associated with the rate of recurrence and HER expression, compared with patients who expressed Ets-2 but not SRC-1 (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: These data describe associations and interactions between nonsteroid transcription factors and coregulatory proteins in human breast cancer.