The straight to test endoscopy service for suspected colorectal cancer: meeting national targets but are we meeting our patients' expectations?

AIM: The NHS Cancer Plan describes initiatives to improve patient care in the UK, including the two-week rule cancer referral pathway. To meet this target a straight to test (STT) endoscopy service was devised to expedite diagnosis of suspected colorectal cancer. Our novel study aimed to determine patient satisfaction with this new approach to rapid access investigation. METHOD: An anonymized questionnaire was posted to 300 patients who had undergone STT endoscopy in our unit between January and June 2010. It assessed satisfaction with the service overall, time from referral to investigation, pre-test information, bowel preparation instructions and time to results as well as preference for a traditional pre-test or post-test outpatient appointment and awareness that the referral was for suspected bowel cancer. RESULTS: In all, 174 questionnaires were obtained (58% yield; mean age 68.8; 44.8% men). 82.2% of patients were 'very satisfied' with the service overall, 82.8% with time from referral to test, 75.2% with time from test to results, 73% with endoscopy information and 69.5% with bowel preparation instructions. Eight per cent would rather have seen a specialist prior to endoscopy, 31.6% would have preferred a post-test appointment and 68.4% of patients were aware that referral was for suspected bowel cancer. CONCLUSION: Straight to test is popular with patients. It offers a fast and cost effective service in the diagnosis of colorectal cancer and meets national targets whilst reducing the volume burden on outpatient clinics. However, its success heavily relies on accurate communication between general practitioner, patient and secondary care.

Exocrine pancreatic insufficiency following esophagectomy.

Weight loss following esophagectomy is a management challenge for all patients. It is multifactorial with contributing factors including loss of gastric reservoir, rapid small bowel transit, malabsorption, and adjuvant chemotherapy. The development of a postoperative malabsorption syndrome, as a result of exocrine pancreatic insufficiency (EPI), is recognized in a subgroup of patients following gastrectomy. This has not previously been documented following esophageal resection. EPI can result in symptoms of flatulence, diarrhea, steatorrhea, vitamin deficiencies, and weight loss. It therefore has the potential to pose a significant level of morbidity in postoperative patients. There is some evidence that patients with proven EPI (fecal elastase-1 < 200 µg/g) may benefit from a trial of pancreatic enzyme replacement therapy (PERT). We observed symptoms compatible with EPI in a subgroup of patients following esophagectomy. We hypothesized that this was contributing to malabsorption and malnutrition in these patients. To investigate this, fecal elastase-1 was measured in postoperative patients, and in those with proven EPI, a trial of PERT was commenced in combination with specialist dietary education. At routine postoperative follow-up, which included assessment by a specialist dietitian, those patients with symptoms suggestive of malabsorption were given the opportunity to have their fecal elastase-1 measured. PERT was then offered to patients with fecal elastase-1 less than 200 µg/g (EPI) as well as those in the 200-500 µg/g range (mild EPI) with more severe symptoms. Fecal elastase-1 was measured in 63 patients between June 2009 and January 2011 at a median of 4 months (range 1-42) following surgery. Ten patients had fecal elastase-1 less than 200 µg/g, and all had failed to maintain preoperative weight. All accepted a trial of PERT. Nine (90%) had symptomatic improvement, and seven (70%) increased their weight. Thirty-nine patients had a fecal elastase-1 in the 200-500 µg/g range. Twelve were given a trial of PERT based on level of symptoms, five (42%) reported an improvement in symptoms, but only two (17%) gained weight. Our early results support the observation that EPI is a factor contributing to postoperative morbidity in patients recovering from esophagectomy and that these patients can benefit from a trial of PERT. Our study has limitations, and a formal trial is required to evaluate the impact of EPI and PERT following esophagectomy. Currently, our practice is to measure fecal elastase-1 in any patient with unexplained weight loss or symptoms of malabsorption. In patients with proven EPI or those who are symptomatic with mild EPI, a trial of PERT should be offered and symptoms reassessed.

Defects in the Drosophila myosin rod permit sarcomere assembly but cause flight muscle degeneration.

We have determined the molecular and ultrastructural defects associated with three homozygous-viable myosin heavy chain mutations of Drosophila melanogaster. These mutations cause a dominant flightless phenotype but allow relatively normal assembly of indirect flight muscle myofibrils. As adults age, the contents of the indirect flight muscle myofibers are pulled to one end of the thorax. This apparently results from myofibril "hyper-contraction", and leads to sarcomere rupture and random myofilament orientation. All three mutations cause single amino acid changes in the light meromyosin region of the myosin rod. Two change the same glutamic acid to a lysine residue and the third affects an amino acid five residues away, substituting histidine for arginine. Both affected residues are conserved in muscle myosins, cytoplasmic myosins and paramyosins. The mutations are associated with age-dependent, site-specific degradation of myosin heavy chain and failure to accumulate phosphorylated forms of flightin, an indirect flight muscle-specific protein previously localized to the thick filament. Given the repeating nature of the hydrophobic and charged amino acid residues of the myosin rod and the near-normal assembly of myofibrils in the indirect flight muscle of these mutants, it is remarkable that single amino acid changes in the rod cause such severe defects. It is also interesting that these severe defects are not apparent in other muscles. These phenomena likely arise from the highly organized nature and rigorous performance requirements of indirect flight muscle, and perhaps from the interaction of myosin with flightin, a protein specific to this muscle type.

Recovery of dominant, autosomal flightless mutants of Drosophila melanogaster and identification of a new gene required for normal muscle structure and function.

To identify further mutations affecting muscle function and development in Drosophila melanogaster we recovered 22 autosomal dominant flightless mutations. From these we have isolated eight viable and lethal alleles of the muscle myosin heavy chain gene, and seven viable alleles of the indirect flight muscle (IFM)-specific Act88F actin gene. The Mhc mutations display a variety of phenotypic effects, ranging from reductions in myosin heavy chain content in the indirect flight muscles only, to reductions in the levels of this protein in other muscles. The Act88F mutations range from those which produce no stable actin and have severely abnormal myofibrillar structure, to those which accumulate apparently normal levels of actin in the flight muscles but which still have abnormal myofibrils and fly very poorly. We also recovered two recessive flightless mutants on the third chromosome. The remaining five dominant flightless mutations are all lethal alleles of a gene named lethal(3)Laker. The Laker alleles have been characterized and the gene located in polytene bands 62A10,B1-62B2,4. Laker is a previously unidentified locus which is haplo-insufficient for flight. In addition, adult wild-type heterozygotes and the lethal larval trans-heterozygotes show abnormalities of muscle structure indicating that the Laker gene product is an important component of muscle.

Mucosal transport of Eimeria tenella in the cecum of the chicken.

A study of the early life history of Eimeria tenella with the electron microscope confirmed that sporozoites do not directly enter the enterocytes of the crypts, in which they develop, but are carried there by host cells. However, these cells are not macrophages, as previously thought, but intraepithelial lymphocytes. The evidence presented demonstrates that sporozoites first penetrate surface enterocytes and then enter intraepithelial lymphocytes that leave the epithelium, pass through the lamina propria and enter the crypts.

Presence of a complete endothelial barrier between lymph and lymphoid tissue in the lumbar lymph nodes of the duck (Anas platyrhynchos).

The ultrastructure of the lumbar lymph nodes of the domestic duck is described and compared with published accounts of mammalian lymph nodes. The barrier to cell migration between lymphoid tissue and lymph is more formidable in the duck than in the mammal. In the duck the lymphatic endothelium lining the lymph spaces is continuous and bonded with desmosomes whereas in the mammal it is unbonded and fenestrated. In both types of node there are filtering zones and areas of dense lymphatic tissue but their topographical organisation differs. There is no cortex or medulla in the duck lymph node and filtration occurs in extensive lymphatic spaces traversed by numerous trabeculae to which are attached rounded phagocytic macrophages. Dense lymphoid tissue is scattered throughout the node, suspended by trabeculae or attached to the capsule and there are blood vessels analogous to the post capillary venules of mammalian nodes where lymphocytes migrate between blood and lymphoid tissue.

Necrotising soft tissue infection following mastectomy.

Necrotising fasciitis is a rare but rapidly progressive soft tissue disease which can lead to extensive necrosis, systemic sepsis and death. Including this case, only 7 other cases have been reported in the world literature with only 2 others affecting the patient post mastectomy. This 59 year old Caucasian lady presented with severe soft tissue infection soon after mastectomy, which was successfully treated with a combination of debridement, triangulation, VAC© dressing and skin grafting. Necrotising soft tissue infections following mastectomy are rapidly progressive and potentially extremely serious. It is essential that a high index of clinical suspicion is maintained together with prompt aggressive treatment in a multidisciplinary environment to prevent worsening physical and psychological sequelae.

Haemopoietic cells in peripheral nerves of SPF chickens.

Foci of haemopoiesis were found in the peripheral nerves of SPF Rhode Island Red chickens and conventionally reared Brown Leghorn chickens. They contained cells which closely resembled the development stages in the bone marrow of erythrocytes, heterophil leukocytes or thrombocytes, but did not include lymphocytes. When birds from these flocks are used to study neuropathological disease, ectopic haemopoiesis in nerves must be distinguished from pathological lesions.

Comparison of the flagellins from different flagellar morphotypes of Escherichia coli.

The molecular weights of the flagellins of 13 strains of Escherichia coli, each with a different H antigen, were estimated using polyacrylamide gel electrophoresis. In each case only one major polypeptide was demonstrated, although some strains possessed apparently sheathed flagella. Considerable differences in the molecular weight of flagellin accompanied the previously described structural differences between flagella from strains with different H antigens. The relationship between flagellar diameter and the molecular weight of the corresponding flagellins was similar for both unsheathed and apparently sheathed flagella. Crosss-polymerization occurred between seed consisting of fragment of unsheathed flagella and flagellin solution from apparently sheathed flagella and vice versa. Co-polymerization of flagellin from unsheathed flagella and flagellin from apparently sheathed flagella was also demonstrated. These polymerization experiments indicate that the assembly pattern of flagellin molecules is probably the same in all E. coli flagella. The above and other evidence suggests that there is no true sheath, but that the differences in flagellar surface structure between different E. coli flagella are the result of differences in the superficial parts of the flagellin molecules.

Ultrastructure of the central nervous system in Marek's disease and the effect of route of infection on lesion incidence in the central nervous system.

The ultrastructure of the lesions of the central nervous system (CNS) of chickens was examined at intervals after intra-abdominal inoculation of Marek's disease virus (MDV). No transient paralysis occurred. Peri-vascular accumulations of lymphocytes and macrophages (cuffing) were accompanied by invasion of the CNS by these blood-borne leukocytes in the most severe lesions. Only minor damage to axons, myelin or glial cells was detected and no structural evidence for viral replication was observed. Intracerebral inoculation of cell-free MDV induced similar lesions in the CNS and there was no evidence for local exacerbation of their severity, although a few chickens developed transient paralysis. It is concluded that replication of MDV in the CNS is unlikely to be the direct cause of the CNS lesions.

Chronological study of ultrastructural changes in the peripheral nerves in Marek's disease.

A chronological study was made of the ultrastructural changes in peripheral nerves following inoculation of 1-day-old chicks with a neurogenic strain of Marek Disease virus. No virus particles were found in nerves. Cellular infiltration of nerves was detected as early as 5 days after inoculation and by 3 weeks some nerves contained proliferative lesions which possessed many of the ultrastructural features characteristic of normal, reactive lymphoid tissue. About 4 weeks after inoculation, coinciding with the onset of neurological signs, areas of widespread demyelination appeared within these lesions; lymphocytes and macrophages penetrated and destroyed the myelin sheath, but spared Schwann cells and most axons. Later oedematous, sparsely infiltrated B type lesions were observed, some of which contained demyelinated nerve fibres undergoing repair; these were therefore a stage in the regression of the proliferative lesions. Our observations do not favour the hypothesis that cellular infiltration of nerves in Marek's disease is the direct result of auto-sensitization to normal myelin. They are consistent with the hypothesis that demyelination is a secondary feature and that the primary lesions are preferential sites for immune demyelination.

Parasite-host relationships during the development of Eimeria dispersa Tyzzer 1929, in the turkey (Meleagris gallopavo gallopavo) with a description of intestinal intra-epithelial leucocytes.

An electron microscopical study was made on the development of Eimeria dispersa in the small intestine of the domestic turkey. Turkey poults, 10-14 days of age, were inoculated with oocysts and pieces of intestinal tissue were fixed at intervals between 3.5 and 114 h after inoculation. Sporozoites were occasionally seen in enterocytes but more often in 'pale' cells closely resembling lymphocytes. These cells were insinuated between enterocytes and in this study are referred to as intestinal intra-epithelial leucocytes (IEL). Maturation of the first-generation of schizogony occurred in this type of cell. Other generations of schizonts and gametogony occurred in epithelial cells and were characterized by the presence of 'spines' arranged around the parasitophorous vacuole extending into the cytoplasm of the host cell. A limited study of the parasite in the Bobwhite quail, Colinis virginianus, showed that development occurred in similar cells to those of the turkey. The 'spines', which were characteristic of later stages of E. dispersa in the turkey, were also present in this host and seemed to be a characteristic of E. dispersa, not of the host species.

Serotypes of sex pili.

There are situations in which direct observation of the attachment of antibody molecules may be the simplest method of detecting antigen-antibody reactions. Applied to the study of the sex pili determined by a number of transmissible bacterial plasmids, the method has distinguished four serotypes in the F-like class and two in the I-like class. Antibody was usually attached haphazardly to the pili; however, in a few cases a regular periodicity could be observed. When few antibody molecules were attached, they could frequently be individually resolved and in certain antibody-pilus combinations large antibody molecules, tentatively identified as IgM, could be seen to predominate.

The effect of immunity on the early events in the life-cycle of Eimeria tenella in the caecal mucosa of the chicken.

A comparison was made between the early events (asexual stages) in the life-cycle of Eimeria tenella in specifically immunized and control chickens. Particular attention was paid to the quantitative aspects and to the transport of sporozoites within intra-epithelial lymphocytes (IEL) from the enterocytes of the surface epithelium to the enterocytes of the crypts. There was a moderate decrease in the number of parasites initially seen in the mucosa of the immune birds, suggesting that some of the effects of immunity are exerted before penetration of the surface enterocytes, but the reduction in the numbers of developing parasites was more marked. This latter effect was due, at least partly, to failure of transfer of sporozoites from IELs to crypt enterocytes. These findings are discussed in relation to the efficacy of the immunity induced.

Interactions of TRIC agents with macrophages and BHK-21 cells observed by electron microscopy.

TRIC agents do not multiply in mouse peritoneal macrophages in culture but have a toxic effect on them, whereas they multiply readily in BHK-21 cells. Sections of macrophages and of BHK-21 cells fixed during the first 90 min after inoculation were examined by electron microscopy. Macrophages ingested all forms of the organism, which were eventually degraded in lysosomes. However, elementary bodies were distinguished from other TRIC particles by the delay in their transfer to lysosomes. BHK-21 cells ingested elementary bodies selectively, and in these cells the organisms were neither found in lysosomes nor degraded. Instead they showed morphological changes that probably represented an early stage of development.

Morphological distinction between different H serotypes of Escherichia coli.

The structure of the flagellar filaments of 50 Escherichia coli strains, each with a different H antigen, was examined. Although the flagella within each strain were structurally identical, there was variability in flagellar surface pattern between strains with differrent H antigens. Investigation of additional strains confirmed that flagella structure was the same in all strains having the same H antigen. In three pairs of strains with cross-reacting H antigens, the antigenic relatedness was associated with identical flagella structure.