Intrinsic predictors of prolonged length of stay in a colorectal enhanced recovery pathway: a prospective cohort study and multivariate analysis.

AIM: This was a prospective cohort study to determine the intrinsic non-modifiable factors influencing length of stay (LOS) in unselected consecutive patients undergoing elective colorectal surgery within an enhanced recovery pathway. METHODS: This study interrogated a prospective database of consecutive elective procedures from October 2006 to April 2011 at a tertiary referral academic hospital in the UK to identify independent predictors of prolonged length of stay (pLOS). pLOS was defined as longer than median length of stay (mLOS). Differences in determinants were identified in three groups of increasing operative complexity. RESULTS: In all, 872 procedures were identified and ranged from a simple ileostomy reversal to complex total pelvic exenteration. Preoperative anaemia and American Society of Anesthesiologists (ASA) Grade III+ predicted pLOS in stoma reversal surgery patients (n = 191, mLOS 4 days). In colonic and small bowel surgery (n = 444, mLOS 8 days), an open procedure, new stoma formation, planned critical care admission and ASA III+ predicted pLOS. New stoma formation and planned critical care admission predicted pLOS in patients undergoing pelvic rectal surgery (n = 237, mLOS 11 days). pLOS was associated with significantly higher morbidity across Dindo-Clavien grades and a longer time to postoperative functional recovery and discharge. CONCLUSIONS: Operative complexity is associated with longer LOS even with an established enhanced recovery pathway in place. Intrinsic non-modifiable predictors of pLOS differ with operative complexity, and this should be taken into account when planning benchmarking and research across units.

Perineal reconstruction after abdominoperineal excision using inferior gluteal artery perforator flaps.

BACKGROUND: Perineal wound complications following abdominoperineal excision (APE) for low rectal tumours remain an important cause of morbidity and prolonged hospital stay, particularly after chemoradiotherapy. The aim was to assess outcomes after using inferior gluteal artery perforator (IGAP) flaps for immediate perineal reconstruction, and to compare these with the authors' previous experience and published literature on myocutaneous flaps. METHODS: A series of patients who underwent immediate IGAP flap reconstruction after APE between April 2008 and December 2010 were examined retrospectively to determine patient demographics, length of operation, complications (perineal wound and general) and length of hospital stay. RESULTS: Forty patients with rectal adenocarcinoma (33 primary and 7 recurrent disease) underwent immediate IGAP flap reconstruction following APE. Median follow-up was 9 months. Neoadjuvant chemoradiotherapy was received by 98 per cent of the patients. Thirty-two patients underwent APE plus IGAP flaps (25 open, 7 laparoscopic), with a median operating time of 402 min, and eight patients had multivisceral resection (MVR) plus IGAP flaps (7 total pelvic exenteration (TPE), 1 abdominosacral resection), with a median duration of surgery of 561 min. There was one death (fatal stroke) and four major flap complications (10 per cent) (1 enteroperineal fistula, and 3 deep wound infections). Median length of hospital stay was 13 days after APE plus IGAP flaps and 27 days following MVR plus IGAP flaps. Late complications occurred in two patients who had vaginal reconstruction and developed perineal hernias requiring revisional surgery. CONCLUSION: Although operating times are long, the IGAP flap is robust, with no flap necrosis observed in this series.

Short- and long-term outcome of laparostomy following intra-abdominal sepsis.

AIM: This study reports the short- and long-term outcomes of laparostomy for intra-abdominal sepsis. METHOD: Twenty-nine sequential patients with intra-abdominal sepsis treated with a laparostomy over 6 years were included. RESULTS: The median age of the patients was 51 years, postoperative intensive care unit stay was 8 days, postoperative length of hospital stay was 87 days and follow up was 2 years. The expected mortality of 25% was insignificantly different from the observed mortality of 33% (P = 0.35). Seven per cent of patients required percutaneous drainage of intra-abdominal collections. An enterocutaneous fistula developed in 31% of all patients and in 15% of those treated with vacuum dressings. Component-separation fascial reconstruction was successful and uncomplicated in 83% of recipients compared with 25% of mesh repairs. CONCLUSION: Laparostomy does not significantly reduce mortality from the expected rate and commits the patient to a prolonged recovery with a high risk of enterocutaneous fistulation. Component-separation fascial reconstruction has a better outcome than mesh repair.

Complete clinical response to neoadjuvant chemoradiotherapy in patients with rectal cancer: opinions of British and Irish specialists.

INTRODUCTION: Advances in neoadjuvant treatment have highlighted the phenomenon of complete clinical response (CCR) in a proportion of patients with rectal cancer. Radical surgery may be associated with a poor functional outcome and quality of life and has a small but significant risk of mortality. This study aimed to assess opinion of colorectal surgeons on issues surrounding the question of nonoperative management in patients who demonstrate complete response after neoadjuvant therapy. METHOD: A questionnaire was sent to members of the Association of Coloproctology of Great Britain and Ireland regarding investigations, clinical management, pathological assessment and oncological outcome in rectal cancer patients with a complete response to neoadjuvant chemoradiotherapy. RESULTS: A total of 122 consultants responded (26% response rate). Most surgeons (58%) would not consider conservative management of patients with a complete response and even more (69%) expressed that they would never discuss nonoperative management in patients with rectal cancer who are fit for curative surgery. Over 70 different combinations of investigations and imaging modalities were suggested to define a CCR. Eighty-six per cent of consultants felt that a pathology report stating no evidence of residual adenocarcinoma did not rule out the presence of tumour cells and all respondents estimated the percentage of patients with pathological complete response as < 20%. CONCLUSIONS: No consensus exists as to what defines a complete response and at present there is resistance to offering nonoperative management in selected patients. With improvements in neoadjuvant treatment modalities, it will be increasingly important to consider nonoperative management in the future.

Use of myocutaneous flaps for perineal closure following abdominoperineal excision of the rectum for adenocarcinoma.

INTRODUCTION: Abdominoperineal excision (APE) following radiotherapy is associated with a high rate of perineal wound complications. The use of myocutaneous flaps may improve wound healing. We present our experience using myocutaneous flaps for immediate reconstruction. METHOD: Prospective data were collected on patients undergoing APE from October 2003 to December 2008. Patient demographics, operating time, wound complications and length of stay were recorded. RESULTS: Fifty-one patients underwent APE for rectal adenocarcinoma, 21 had primary closure and 30 had myocutaneous flap closure (24 VRAM, 6 gracilis). The proportion of patients undergoing preoperative radiotherapy in each group were 62% and 93% respectively (P = 0.011). There were no major complications following primary closure of the unirradiated perineum. Major perineal wound complications requiring reoperation or debridement were seen in three (14%) patients following primary closure and five (17%) patients with flap closure. After radiotherapy, closure with a flap reduced the length of stay from 20 to 15 days, but this difference was not statistically significant (P = 0.36). CONCLUSION: The use of flap closure in irradiated patients is associated with fewer perineal complications and a shorter hospital stay.

Outcome of patients on renal replacement therapy after colorectal surgery.

PURPOSE: Patients on renal replacement therapy are reported to have a high complication rate after abdominal surgery, the result of uremia and immunosuppression. A review of this group of patients undergoing colorectal surgery was undertaken. METHODS: Seventy-three separate colorectal operations were performed for 44 patients. Thirty-eight patients were on dialysis and 35 had a renal transplant. Data (coexisting disease, preoperative blood results, operative details, complications, and colorectal POSSUM score) were completed for each surgical event. RESULTS: Forty-two elective and 31 emergency procedures were performed. Infective complications were common (overall 60 percent). There were two anastomotic leaks in the elective group, but five leaks from seven emergency anastomoses. Stomas were frequently raised. Ninety percent of patients who survived and had a defunctioning stoma underwent a successful reversal. The overall major complication rate after elective and emergency surgery was 19 and 81 percent, respectively, and mortality was 5 and 26 percent, respectively. CONCLUSIONS: Renal patients have a high rate of complications after colorectal surgery, and emergency surgery has a significant risk of anastomotic leak. Primary anastomosis should be avoided in all patients undergoing emergency intestinal resections. Subsequent surgery to restore intestinal continuity is possible in 90 percent of patients with far fewer complications.

Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging?

Most studies measuring circulating vascular endothelial growth factor (VEGF) have sampled serum rather than plasma. There has been much debate whether the collection of sera (which causes the activation of platelets and VEGF release) is a true reflection of tumor angiogenic activity or whether platelets act as scavengers of VEGF. Addressing this issue, we measured serum and plasma VEGF, before and after colorectal resection, with reference to platelet counts. Serum and plasma samples were collected from 116 colorectal cancer (CRC) and 116 control patients. Ninety CRC and 32 benign resections were performed. Both plasma and serum VEGF were significantly higher in CRC patients (18.5 and 327 pg/ml, respectively) compared with controls (9.0 and 151.5 pg/ml, respectively; P < 0.0001). Paired serum and plasma VEGF measurements correlated in both CRC (r = 0.56) and control patients (r = 0.73; P < 0.0001). Serum and plasma VEGF levels correlated with platelet count in CRC patients (r = 0.58 and 0.44, respectively) but not in controls. Plasma and serum VEGF levels, and VEGF concentration per platelet, increased with advancing disease stage. The correlation of serum and plasma VEGF with platelet counts in CRC but not in benign disease may be attributable to the scavenging of VEGF from the tumor source by platelets, with plasma levels reflecting free circulating VEGF in equilibrium with platelet levels. VEGF levels in citrated plasma are low and lie close to the limits of ELISA sensitivity. We recommend that a standardized measurement of serum VEGF--normalized by the patient's platelet count to give a value of serum VEGF per platelet--be adopted.

VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression.

We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carcinoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA expression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenomatous polyps. Immunohistochemistry and ELISA assessed protein expression. VEGF-D mRNA expression was significantly lower in both polyps and CRCs compared with normal mucosa (P=.0002 and.002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and.004, respectively), but not polyps (P=.22 and P=.5, respectively). Receptor expression was similar in tumor tissue and normal mucosae. Tumors with lymph node metastases had significantly higher levels of VEGF-A compared with non-metastatic tumors (P=.043). There was no association between VEGF-C or VEGF-D and lymphatic spread. The decrease in VEGF-D occurring in polyps and carcinomas may allow the higher levels of VEGF-A and VEGF-C to bind more readily to the VEGF receptors, and produce the angiogenic switch required for tumor growth. Increased expression of VEGF-A within CRCs was associated with lymphatic metastases, and therefore, this member of the VEGF family may be the most important in determining metastatic spread.

Candidate defense genes from rice, barley, and maize and their association with qualitative and quantitative resistance in rice.

Candidate genes involved in both recognition (resistance gene analogs [RGAs]) and general plant defense (putative defense response [DR]) were used as molecular markers to test for association with resistance in rice to blast, bacterial blight (BB), sheath blight, and brown plant-hopper (BPH). The 118 marker loci were either polymerase chain reaction-based RGA markers or restriction fragment length polymorphism (RFLP) markers that included RGAs or putative DR genes from rice, barley, and maize. The markers were placed on an existing RFLP map generated from a mapping population of 116 doubled haploid (DH) lines derived from a cross between an improved indica rice cultivar, IR64, and a traditional japonica cultivar, Azucena. Most of the RGAs and DR genes detected a single locus with variable copy number and mapped on different chromosomes. Clusters of RGAs were observed, most notably on chromosome 11 where many known blast and BB resistance genes and quantitative trait loci (QTL) for blast, BB, sheath blight, and BPH were located. Major resistance genes and QTL for blast and BB resistance located on different chromosomes were associated with several candidate genes. Six putative QTL for BB were located on chromosomes 2, 3, 5, 7, and 8 and nine QTL for BPH resistance were located to chromosomes 3, 4, 6, 11, and 12. The alleles of QTL for BPH resistance were mostly from IR64 and each explained between 11.3 and 20.6% of the phenotypic variance. The alleles for BB resistance were only from the Azucena parent and each explained at least 8.4% of the variation. Several candidate RGA and DR gene markers were associated with QTL from the pathogens and pest. Several RGAs were mapped to BB QTL. Dihydrofolate reductase thymidylate synthase co-localized with two BPH QTL associated with plant response to feeding and also to blast QTL. Blast QTL also were associated with aldose reductase, oxalate oxidase, JAMyb (a jasmonic acid-induced Myb transcription factor), and peroxidase markers. The frame map provides reference points to select candidate genes for cosegregation analysis using other mapping populations, isogenic lines, and mutants.

Plasma basic fibroblast growth factor levels in colorectal cancer: a clinically useful assay?

Angiogenic cytokines in the plasma and serum of cancer patients may serve as 'surrogate' markers of tumour neoangiogenesis. Serum VEGF correlates with disease stage in colorectal cancer (CRC), but the role of bFGF in CRC is uncertain. This study aimed to assess plasma bFGF levels in CRC patients before treatment, during chemoradiotherapy and at one-year follow-up. Plasma samples were taken from 124 CRC patients, 26 polyp patients and 55 controls, and bFGF levels were measured by ELISA. 19 patients underwent pre-operative chemoradiotherapy. One-year follow-up samples were available from 48 disease-free patients and 18 patients with progressive disease. There were no detectable differences between plasma bFGF levels in polyp, Dukes' A or B patients (4.55, 5.77, 4.25 pg/ml, respectively), but there was a significant increase in metastatic CRC patients [Dukes' C and D (7.42 and 6.6 pg/ml; P = 0.004 and 0.048, respectively)], relative to median control levels of 4.14 pg/ml. At follow-up, there was a significant fall in plasma bFGF levels in disease-free patients (pre-op 6.09 and follow-up 3.45 pg/ml, P = 0.0004), but a non-significant rise in 18 patients with progressive disease (pre-treatment 5.90 and follow-up 9.99 pg/ml, P = 0.33). Pre-treatment plasma bFGF in patients receiving chemo-radiotherapy was similar in those with responsive and non-responsive tumours. There were no detectable changes in plasma bFGF through the adenoma-carcinoma sequence or patient groups with non-metastatic cancers. Elevated plasma bFGF was, however, associated with metastatic spread. The significant fall in bFGF in disease-free patients following therapy suggests that bFGF may be useful in clinical practice.

The use of neoadjuvant CMF to avoid mastectomy.

AIMS: Large operable cancers have traditionally been treated surgically by mastectomy. More recently centres have investigated the use of neoadjuvant chemotherapy to allow breast-conserving surgery. Between 1991 and 1995, a prospective study into the response of large operable breast cancers to CMF neoadjuvant chemotherapy was performed. METHODS: Patients with cancers requiring mastectomy, and with or without clinically involved non-fixed lymph nodes, were offered neoadjuvant CMF chemotherapy. Patients declining neoadjuvant treatment underwent mastectomy and appropriate axillary surgery. Clinical response was assessed after two cycles in the neoadjuvant group. Subsequent surgical or non-surgical management was planned after this. RESULTS: Thirty-eight patients were suitable for neoadjuvant treatment. Twenty-two underwent two cycles of CMF and were then reassessed. Seventy-three per cent achieved a response [three (14%) complete remission, 13 (60%) partial remission]. Fifteen (68%) patients avoided mastectomy, with six (27%) requiring no surgery at all with no clinically detectable residual disease. Sixteen (42%) declined neoadjuvant chemotherapy and opted for immediate mastectomy, seven of whom accepted chemotherapy post-operatively. After 3 years' follow-up there is no statistical difference in local recurrence, distant recurrence or overall survival. CONCLUSION: Approximately 40% of patients offered neoadjuvant chemotherapy will demand prompt surgical treatment but will consider the use of adjuvant chemotherapy post-operatively. Sixty-eight per cent of patients receiving neoadjuvant CMF will successfully avoid mastectomy.

Rapid Population Analysis of Magnaporthe grisea by Using rep-PCR and Endogenous Repetitive DNA Sequences.

ABSTRACT DNA samples from Magnaporthe grisea isolates were fingerprinted by using repetitive element-based polymerase chain reaction (rep-PCR) with two outwardly directed primer sequences from Pot2, an element found in approximately 100 copies in the fungal genome. Variable length fragments, defining the sequences lying between these elements, were generated, and fingerprint patterns specific for individual strains were established. "Long PCR" conditions, including higher pH (9.2) and increased extension time (10 min) were used to amplify DNA fragments ranging from 400 bp to longer than 23 kb. Polymorphisms specific to M. grisea strains were generated, allowing inference of their genetic relationships. Segregation analysis was used to confirm single-locus inheritance for the fragments amplified by rep-PCR. Cluster analysis revealed robust groupings that corresponded to previously determined MGR586 restriction fragment length polymorphism lineages of the rice-infecting strains of the pathogen. We have also demonstrated the utility of rep-PCR to differentiate isolates that infect rice from those that infect nonrice hosts. DNA fingerprinting by Pot2 rep-PCR provides an efficient means to monitor the population dynamics of the blast pathogen. Because of the method's low cost and ease in application, it is now feasible to conduct large-scale population studies to understand the impact of host genotypes on pathogen evolution.

Movement of Xanthomonas oryzae pv. oryzae in Southeast Asia Detected Using PCR-Based DNA Fingerprinting.

ABSTRACT Two outwardly directed primers complementary to sequences in IS1112, a repetitive element isolated from Xanthomonas oryzae pv. oryzae, were used to fingerprint DNA from a set of 71 bacterial blight pathogen strains using polymerase chain reaction (PCR), PCR-based restriction analysis, and ligation-mediated PCR. To allow amplification of long DNA fragments, standard amplification conditions were altered to increase the pH, add dimethylsulfoxide, decrease denaturation time, and increase extension time. Bands ranging in size from 100 bp to 7 kb and in number from 13 to 48 bands per strain were amplified. The three methods revealed useful polymorphisms among individual strains and allowed their genetic relationships to be efficiently deduced. Good correlation was found between the major clusters obtained by the three methods. The PCR method gave the most robust clusters and was most efficient in terms of speed, simplicity, and economy. Using PCR and restriction fragment length polymorphism to compare strains of the bacterial blight pathogen from Indonesia and the Philippines, we found that, whereas there is regional differentiation of the pathogen populations, the predominant strains in the pathogen collections from both countries are closely related. This indicates the occurrence of regional movement, perhaps as a consequence of germ plasm exchange.

Identification of Resistance Genes Effective Against Rice Bacterial Blight Pathogen in Eastern India.

Breeding for bacterial blight resistance in rice requires an understanding of the contemporary pathogen populations in the locations where resistance genes are to be deployed. We characterized 450 strains of Xanthomonas oryzae pv. oryzae collected from three states of India using polymerase chain reaction fingerprinting and virulence analysis. This pathogen collection was differentiated into 17 haplotypes (12 lineages at 80% similarity level). Significant differences in the distribution of haplotypes were observed among regions. Virulence analysis of the pathogen collection revealed nine pathotypes. Among the populations from three regions, the Orissa population was the most diverse, consisting of 11 out of 17 haplotypes and five out of nine pathotypes detected in the total collection. Representative pathotypes were used to evaluate seven near-isogenic lines carrying individual bacterial blight resistance genes (Xa3, Xa4, xa5, Xa7, Xa10, xa13, and Xa21) and gene pyramids. Pathogen strains compatible to individual genes were present in detectable frequencies, although no single strain could overcome all resistance genes. Gene combinations Xa4 + xa5, xa5 + Xa21, and Xa4 + xa5 + Xa21 conferred a broad spectrum of resistance to all the strains evaluated, supporting the strategy of pyramiding appropriate resistance genes.

Can haematological indices predict positive findings at endoscopy in anaemic patients?

INTRODUCTION: Patients with anaemia are commonly referred for bidirectional endoscopy. The aim of this study was to determine if any haematological parameters could predict positive findings at endoscopy. PATIENTS AND METHODS: A total of 209 patients had bidirectional endoscopies performed for anaemia between September 2002 and March 2004. The endoscopy reports, histology and full blood count results (haemoglobin [Hb], red blood cells [RBCs], packed cell volume [PCV], mean cell volume [MCV] and mean cell haemoglobin [MCH]) were then reviewed. Statistical analysis was performed using non-parametric tests. RESULTS: Overall, 197 patients had successful bidirectional endoscopies with 12 requiring completion barium enema. In 48 (23%) of these patients, a cause of anaemia was found with 15 (7.2%) carcinomas detected (2 upper GI and 13 lower GI). There was a significant difference in haemoglobin (9.2 g/dl versus 10.1 g/dl; P = 0.0044), RBCs (3.56 x 10(12)/l versus 3.83 x 10(12)/l; P = 0.0325) and PCV (0.279 l/l versus 0.31 l/l; P = 0.0112) between patients with positive findings at endoscopy and those with a normal investigation. Cancer patients had significantly lower haemoglobin (8.65 g/dl versus 10.1 g/dl; P = 0.0103), RBCs (3.45 x 10(12)/l versus 3.83 x 10(12)/l; P = 0.0179) and PCV (0.27 l/l versus 0.31 l/l; P = 0.0298) compared with patients with normal endoscopies. There was no significant difference in the other haematological parameters between those found to have positive findings and those that had normal endoscopies. CONCLUSIONS: Based on this study, the yield of bidirectional endoscopy is low, with haemoglobin and PCV being the most useful haematological indices of significant pathology. Ferritin and MCV did not predict the likelihood of finding a gastrointestinal cause for the anaemia.

Colocutaneous fistula complicating therapeutic mesenteric embolisation.

Percutaneous embolotherapy has now assumed an important role in the management of massive colonic haemorrhage. However, this therapeutic option is associated with a significant risk of irreversible segmental colonic ischaemia. We present a case where distal segmental ischaemia led to a colocutaneous fistula, a complication not reported so far in the literature.

Endoscopic sympathectomy in the treatment of facial blushing.

INTRODUCTION: Bilateral endoscopic thoracic sympathectomy (BETS) has been shown to be an effective, permanent, and safe treatment for severe upper limb hyperhydrosis. More recently, the possibility of using BETS to treat facial blushing, a redness of the face bought on by emotional or social stress, has been raised. This followed incidental reports from patients of relief from their blushing following this procedure for hyperhydrosis. At King's College Hospital, 120 patients underwent BETS over a 3-year period for both upper limb hyperhydrosis and facial blushing. In this study we report our results in relation to facial blushing. PATIENTS AND METHODS: The outcome was evaluated by questionnaire and symptoms assessed using the visual analogue scale. Questions on postoperative complications and overall quality of life were included. RESULTS: A total of 80 patients responded to our questionnaire of whom 59 (74%) experienced facial blushing. In 12 patients, this was their only symptom. Severity of facial blushing was reduced from a mean score of 78 before operation to 26 after BETS (P < 0.001); 29% reported complete resolution of their facial blushing. There was no mortality or conversion to open surgery. Quality of life was reported to be much better in 63% of facial blushers following the procedure. CONCLUSIONS: This study demonstrates both a statistically significant reduction in severity of facial blushing as well as a clear improvement in quality of life following a safe procedure with few complication rates. Facial blushing can, therefore, be considered as an indication for BETS on its own merit when not associated with hyperhydrosis.

Competition among Rhizobium leguminosarum bv. phaseoli strains for nodulation of common bean.

Six effective Rhizobium leguminosarum bv. phaseoli strains were examined for nodulation competitiveness on common bean (Phaseolus vulgaris L.), using all possible two-strain combinations of inoculum. Nodule occupancy was determined with strain-specific fluorescent antibodies. The strains were divided into three groups according to their overall competitive abilities on pole bean cv. Kentucky Wonder and bush bean cv. Bountiful. Strains TAL 182 and TAL 1472 were highly competitive (greater than 70% nodule occupancy); strains KIM-5, Viking 1, and CIAT 899 were moderately competitive (approximately 50% nodule occupancy); and strain CIAT 632 was poorly competitive (less than 5% nodule occupancy). The competitiveness of the six strains was similar on the two host cultivars. The proportion of competing strains in the inoculum influenced the nodule occupancy of the highly competitive and moderately competitive strains, but not that of the poorly competitive strain. Two outstanding strains (TAL 182 and TAL 1472) were identified as ideal model strains for molecular and genetic studies on nodulation competitiveness.