Development and validation of a symptom-based severity score for haemorrhoidal disease: the Sodergren score.

AIM: One major obstacle in assessing the efficacy of treatment of haemorrhoids and the comparison of trials has been the lack of a standardized, validated symptom severity score. This study aimed to develop an objective, validated symptom-based score of severity for haemorrhoids that can be used to compare treatments, monitor disease and assist in surgical decisions. METHOD: A symptom and quality-of-life questionnaire was developed from the literature in conjunction with expert surgical opinion. The questionnaire was circulated to patients with confirmed haemorrhoids. A statistical model was used to derive a weighted score of symptoms most affecting patients' quality of life. Patients who were offered operative treatment were independently judged by specialists to have more severe symptoms, with further validation of the scoring system against treatment. RESULTS: Forty-five patients were included in final validation analysis, of whom 44 (98%) reported multiple symptoms, the most common being rectal bleeding. Patient-reported effects on quality of life were 47.5 ± 36.3 (1-100 visual analogue scale). Calculated symptom severity scores were used to compare patients receiving operative or ambulatory care, with significant difference in the scores (7.7 ± 3.9 vs 2.8 ± 3.5, P = 0.002) and a receiver operating characteristic area under the curve of 0.842. CONCLUSION: A novel validated score for the assessment of haemorrhoidal disease adopting a standardized global score for symptom severity may have important implications in future for research, assessment and the management of this common pathology.

A pilot randomised controlled trial evaluating postoperative packing of the perianal abscess.

PURPOSE: Traditional management of a perianal abscess involves incision and drainage followed by packing of the cavity until healing by secondary intention is complete. The evidence supporting this is lacking however, and regular postoperative packing is time-consuming, painful and costly. This pilot study aimed to assess whether healing could be achieved safely without packing and to obtain preliminary results to enable sample size calculation in order to facilitate the implementation of a large multicentre randomised controlled trial. ClinicalTrials.gov Identifier: NCT01853267. METHODS: Fourteen patients with perianal abscesses were randomised to packing or non-packing of the abscess cavity postoperatively. Outcome measures were time to healing, abscess recurrence, fistula formation and postoperative pain. RESULTS: Healing in the non-packing group was faster compared to the packing group: mean 26.8 days (95 % confidence interval 22.7 to 30.7) vs 19.5 days (13.6 to 25.4); P = 0.047. There were no differences in recurrence rates between the groups (37.5 % packing group vs 33.3 % non-packing group; P = 0.580) at a median follow-up of 90.0 weeks (interquartile range (IQR) 26.0). In patients presenting with recurrence, one fistula was found in the packing group with no fistulas in the non-packing group. The non-packing group reported less pain 2 weeks postoperatively: median (IQR) 2.00 (3.00) vs 0.00 (1.00); (P = 0.030). CONCLUSION: Within the limitations of a small sample population, the results of this pilot study suggest that not packing the perianal abscess cavity after incision and drainage is safe. Our results show not packing confers less pain with a faster healing time compared with the conventional packing method, and this is a novel finding. These results need to be corroborated in the setting of a larger multicentre randomised controlled trial.

Linked hospital and primary care database analysis of the impact of short-term complications on recurrence in laparoscopic inguinal hernia repair.

OBJECTIVE: To study the effects of short-term complications on recurrence following laparoscopic inguinal hernia repair using routine data. BACKGROUND: Linked primary and secondary care databases can evaluate the quality of inguinal hernia surgery by quantifying short- and long-term outcome together. METHODS: Longitudinal analysis of linked primary care (Clinical Practice Research Datalink) and hospital administrative (Hospital Episodes Statistics) databases quantified 30-day complications (wound infection and bleeding) and surgery for recurrence after primary repair performed between 1st April 1997 and 31st March 2012. RESULTS: Out of 41,545 primary inguinal hernia repairs, 10.3% (4296/41,545) were laparoscopic. Complications were less frequent following laparoscopic (1.8%, 78/4296) compared with open (3.5%, 1288/37,249) inguinal hernia repair (p < 0.05). Recurrence was more frequent following laparoscopic (3.5%, 84/2541) compared with open (1.2%, 366/31,859) repair (p < 0.05). Time to recurrence was shorter for laparoscopic (26.4 months SD 28.5) compared with open (46.7 months SD 37.6) repair (p < 0.05). Overall, complications were associated with recurrence (3.2%, 44/1366 with complications; 1.7%, 700/40,179 without complications; p < 0.05). Complications did not significantly increase the risk of recurrence in open hernia repair (OR = 1.49; 95% CI 0.97-2.30, p = 0.069). Complications following laparoscopic repair was significantly associated with increased risk of recurrence (OR = 7.86; 95% CI 3.46-17.85, p < 0.05). CONCLUSIONS: Complications recorded in linked routine data predicted recurrence following laparoscopic inguinal hernia repair. Focus must, therefore, be placed on achieving good short-term outcome, which is likely to translate to better longer term results using the laparoscopic approach.

Essential genes in the hDf6 region of chromosome I in Caenorhabditis elegans.

In this paper we describe the analysis of essential genes in the hDf6 region of chromosome I of Caenorhabditis elegans. Nineteen complementation groups have been identified which are required for the growth, survival or fertility of the organism (essential genes). Since ten of these genes were represented by more than one allele, a Poisson calculation predicts a minimum estimate of 25 essential genes in hDf6. The most mutable gene in this region was let-354 with seventeen alleles. An average mutation rate of 5 x 10(-5) mutations/gene/chromosome screened was calculated for an ethyl methanesulfonate dose of 15 mM. Mutations were recovered by screening for lethal mutations using the duplication sDp2 for recovery. Our analysis shows that duplications are very effective for maintenance and mapping of large numbers of lethal mutations. Approximately 600 lethal mutations were mapped in order to identify the 54 that are in the deficiency hDf6. The hDf6 region appears to have a lower proportion of early arresting mutations than other comparably sized regions of the genome.

The effects of translocations on recombination frequency in Caenorhabditis elegans.

In the nematode Caenorhabditis elegans, recombination suppression in translocation heterozygotes is severe and extensive. We have examined the meiotic properties of two translocations involving chromosome I, szT1(I;X) and hT1(I;V). No recombination was observed in either of these translocation heterozygotes along the left (let-362-unc-13) 17 map units of chromosome I. Using half-translocations as free duplications, we mapped the breakpoints of szT1 and hT1. The boundaries of crossover suppression coincided with the physical breakpoints. We propose that DNA sequences at the right end of chromosome I facilitate pairing and recombination. We use the data from translocations of other chromosomes to map the location of pairing sites on four other chromosomes. hT1 and szT1 differed markedly in their effect on recombination adjacent to the crossover suppressed region. hT1 had no effect on recombination in the adjacent interval. In contrast, the 0.8 map unit interval immediately adjacent to the szT1(I;X) breakpoint on chromosome I increased to 2.5 map units in translocation heterozygotes. This increase occurs in a chromosomal interval which can be expanded by treatment with radiation. These results are consistent with the suggestion that the szT1(I) breakpoint is in a region of DNA in which meiotic recombination is suppressed relative to the genomic average. We propose that DNA sequences disrupted by the szT1 translocation are responsible for determining the frequency of meiotic recombination in the vicinity of the breakpoint.

Alpha-1-antitrypsin in duodenal fluid and gallbladder bile.

Using the immunoelectrophoretic method alpha-1-antitrypsin was detected in all but 6 of 26 samples of duodenal fluid obtained from 16 patients with various gastroenterological problems. The concentrations (mg/100 ml) of alpha-1-antitrypsin in duodenal aspirates from children with liver disease (7.32 plus or minus 6.1) were less than those from children with cystic fibrosis, Shwachman Diamond syndrome, or Hirschsprung's disease (16.7 plus or minus 11.9; p smaller than 0.02). Alpha-1-antitrypsin was detected in all but one of 6 samples of gallbladder bile, the exception being that from a patient with extrahepatic biliary atresia. No significant correlation was found between the alpha-1-antitrypsin concentration in the samples studied and the corresponding total antitrypsin activity.

How should perineal wounds be closed following abdominoperineal resection in patients post radiotherapy--primary closure or flap repair? Best evidence topic (BET).

This best evidence topic was investigated according to a described protocol. The question posed was: should the irradiated perineal wound following abdominoperineal resection (APR) be closed with primary repair or a myocutaneous flap. Using the reported search 364 papers were found of which eight represented the best evidence to answer the clinical question. The conclusion drawn is that there is some limited evidence for recommending flap closure in abdominoperineal resection post radiotherapy. The best evidence available was from a systematic review of cohort studies and case series. Although no meta-analysis was performed, overall wound healing was improved using flap closure with a low frequency of flap necrosis. Other studies providing evidence were case-control series or cohort studies. Three papers prospectively compared vertical rectus abdominus muscle (VRAM) flap with primary closure; two of which demonstrated statistically significant improvement in complication rates with flap closure. Two retrospective case control series showed significant improvement in major wound complication rates in the flap group. Two studies retrospectively compared gracilis flap repair with primary closure and showed significantly lower incidence of major perineal complications. Most studies suffered from significant limitations, small sample sizes and no direct comparisons between matched groups with respect to type of anatomic flap, wound size, tumour recurrence or radiation dose. Whilst there is evidence that myocutaneous flap closure following APR in radiotherapy patients can reduce wound related complications, prospective randomized controlled trials are warranted.

Isolation and mapping of DNA probes within the linkage group I gene cluster of Caenorhabditis elegans.

We have isolated probes for DNA polymorphisms across the linkage group I gene cluster in Caenorhabditis elegans, using Tc1-linkage selection. The probes detect strain polymorphism between the wild-type strains of var. Bristol and var. Bergerac. As a result of mapping the sites hP4, hP5, hP6, hP7, hP9, and sPl, more than 1000 kilobases (kb) of cloned cosmid DNA has been positioned on the genetic map. We found there is more DNA per map unit in the center of the gene cluster than expected on the basis of the genomic average. Furthermore, the amount is not constant across the entire region but reaches a peak in the hP9 unc-13 interval. To find the coding regions, we examined DNA cross-homology between two species, Caenorhabditis elegans and Caenorhabditis briggsae. Approximately one-third of the DNA in the hP5 hP9 interval was examined for coding regions and 21 sequences were identified within 318 kb of DNA.

Lethal mutations defining 112 complementation groups in a 4.5 Mb sequenced region of Caenorhabditis elegans chromosome III.

The central gene cluster of chromosome III was one of the first regions to be sequenced by the Caenorhabditis elegans genome project. We have performed an essential gene analysis on the left part of this cluster, in the region around dpy-17III balanced by the duplication sDp3. We isolated 151 essential gene mutations and characterized them with regard to their arrest stages. To facilitate positioning of these mutations, we generated six new deficiencies that, together with preexisting chromosomal rearrangements, subdivide the region into 14 zones. The 151 mutations were mapped into these zones. They define 112 genes, of which 110 were previously unidentified. Thirteen of the zones have been anchored to the physical sequence by polymerase chain reaction deficiency mapping. Of the 112 essential genes mapped, 105 are within these 13 zones. They span 4.2 Mb of nucleotide sequence. From the nucleotide sequence data, 920 genes are predicted. From a Poisson distribution of our mutations, we predict that 234 of the genes will be essential genes. Thus, the 105 genes constitute 45% of the estimated number of essential genes in the physically defined zones and between 2 and 5% of all essential genes in C. elegans.