The benefits of index telephone consultations in patients referred on the two-week wait colorectal cancer pathway.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) clinic appointments, conducted using telephone calls at a district general hospital in England. METHODS: Patients undergoing index outpatient 2-ww LGI clinic assessment between 1 June 2019 and 31 October 2019 (FtF group) and 1 June 2020 and 31 October 2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets was assessed. Environmental and financial impact analyses were performed. RESULTS: In total, 1,531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF (n=774, 50.6%). Ninety-two (6%, VC=44, FtF=48) patients had malignant pathology and 64 (4.2%) had colorectal cancer (CRC); of these, 46 (71.9%, VC=26, FtF=20) underwent treatment with curative intent. The median waiting times to index appointment, investigation and diagnosis were significantly lower following VC assessment (p<0.001). The cancer detection rates (p=0.749), treatments received (p=0.785) and median time to index treatment for CRC patients (p=0.156) were similar. A significantly higher proportion of patients were seen within two weeks of referral in the VC group (p<0.001). VC appointments saved patients a total of 9,288 miles, 0.7 metric tonnes of CO2 emissions and £7,482.97. Taxpayers saved £80,242.00 from VCs. No formal complaints were received from patients or staff in the VC group. CONCLUSION: Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits.

The Oncormed approach to genetic testing.

This report describes a commercial laboratory's novel approach to providing genetic testing services to detect BRCA1 mutations in persons with hereditary breast/ovarian cancer. The approach involves the use of institutional review board (IRB)-approved protocols as a paradigm for conducting genetic testing in a commercial setting. We discuss the rationale for this approach and the key elements of the protocol. In addition, we provide data on the first 6 months of implementation of the protocol in 32 clinical sites. A phased testing approach was used, consisting of an allele-specific oligonucleotide assay for the 8 most common BRCA1 mutations, a protein truncation test of exon 11, and direct sequencing of the remaining regions of the gene. Data are presented on the yield of mutation carriers by category of family history and by stage of analysis.

Serosal imprint cytology in colonic cancer: a simple staging technique.

Accurate staging of colonic cancer is essential in defining the rational use of adjuvant treatments. Recent studies have shown that prognostic accuracy can be significantly improved by recognition of primary tumour extension to the free serosal surface. This study compares the technical results of serosal imprint cytology with the results of histology in assessing serosal involvement. When analysed in terms of the modified Dukes' staging the results of cytology imprints taken from the peritoneum overlying the colonic primary were positive for tumour cells in 4/13 Dukes' B, 7/14 Dukes' C, and 5/9 metastatic cancers. Imprint cytology was positive in 6/7 Dukes' B and C cases with histological serosal invasion and was suspicious in the remaining case. However, a further 5/20 cases without identified invasion on routine histology also had positive cytology. Imprint cytology is an adjunct to routine histology which is easily performed and allows more precise staging of serosal involvement in Dukes' B and C colonic cancers. Final evaluation of this technique requires long-term follow-up of patients.

Molecular confirmation of alpha 1-antitrypsin genotypes in newborn dried blood specimens.

Deficiency of alpha 1-antitrypsin (alpha 1AT), a common hereditary disorder of Caucasians, is associated with an increased risk for early-onset chronic obstructive pulmonary disease and childhood liver dysfunction. The two most common deficiency variants, PiS and PiS, are both single base-pair substitutions causing amino acid modifications, although neither mutation creates or destroys a naturally occurring restriction site. Dried blood specimens (DBS) submitted to the New York State Department of Health for mandated newborn screening tests were tested for alpha 1AT activity using a fluorometric elastase inhibition assay. A second DBS from specimens determined to be alpha 1AT deficient was phenotyped on an agarose isoelectric focusing gel. Genotypic confirmation was performed by amplifying, directly from a DBS, the regions of the DNA containing the S and Z mutation. The Z mutation was analyzed with a modified primer designed to create an artificial restriction site in the normal allele. TaqI digestion produces two bands, a 157- and a 22-bp fragment. The single base substitution in PiS individuals eliminates this TaqI restriction site, thus showing the same 179-bp fragment before and after digestion. A primer mismatch placed close to the S mutation creates a restriction site in the normal allele, producing a 100-bp product after TaqI digestion. The restriction site is abolished in individuals that carry the S mutation, with a 121-bp product observed before and after digestion. Of 11,081 specimens screened, 3 PiS neonates, all Caucasian, were detected by these methodologies for an estimated incidence of 1:2019 in the Caucasian or 1:3694 in the general population in New York State.(ABSTRACT TRUNCATED AT 250 WORDS)

Free peritoneal tumour cell identification in patients with gastric and colorectal cancer.

The finding of free tumour cells within the peritoneum at the time of laparotomy for gastrointestinal cancer is an important indicator of prognosis and may help select treatment. The aim of this study was to improve the methods whereby these cells could be retrieved and identified. Free peritoneal cancer cells were found in 6 out of 18 gastric cancer patients. All 6 patients had tumour invasion through to the serosa and subsequently died of tumour recurrence. None of the 18 Dukes' B and C colorectal cancer patients had free peritoneal cancer cells. Only 2 of a further 5 patients with extensive colorectal tumour spread had positive cytologies. The conventional mucin stain Periodic Acid Schiff (after diastase digestion) and the monoclonal antibody stain B72.3 were the most useful in identifying free peritoneal cancer cells. Peritoneal brushings did not offer any advantages over conventional peritoneal washings in the retrieval of free tumour cells.

Ten-year review of treatment of the undescended testis in the west of Ireland.

Advances continue to be made in the treatment of the undescended testis, and treatment recommendations are continually changing. We reviewed 543 patients admitted for treatment of undescended testes in the 10-year period 1977 to 1986. The side and position of the testis were recorded, the patient's age at operation and the procedure carried out. The presence of an associated inguinal hernia was noted. The necessity for reoperation was recorded and predisposing factors sought. We found the mean age at operation to be 9.5 years and this decreased significantly over the study period. Dartos pouch orchiopexy was the commonest operation (69%). No significant link was found between the procedure performed or the presence of a hernia and the need for further procedures; 2.7% of patients required such further procedures. A coherent classification of position is lacking for abnormally descended testes. We report a classification which we used to tackle this situation.

Prenatal diagnosis of fragile X syndrome: results from parallel molecular and cytogenetic studies.

Since 1985, we have provided coordinated DNA-based and cytogenetic prenatal analysis for couples at risk for offspring afflicted with the fragile X [fra(X)] syndrome. To date, 40 pregnancies have been studied (22 males, 18 females). There were 5 males and 3 females identified to be at high risk by DNA but only 2 males and one female were demonstrated to be cytogenetically expressing the fra(X) prenatally. Of the other 3 males, one was a cytogenetic false negative (i.e. confirmed fra(X)+ at termination of pregnancy). The other 2 remain fra(X)- and are developing normally (undetected recombinants or non-penetrant male carriers). All fetuses at low risk were carried to term and are reported to be normal.

An annual strategy for total quality.

The total quality management (TQM) revolution that is fueling the interest of CEOs and the JCAHO will present big leadership challenges to department administrators. Successfully implementing TQM concepts will require basic changes in operational methods and highly visible leadership commitment. Lasting change can only occur with a strategy that is understood by all employees and is periodically updated. Operational improvements will result from actions you take to better serve internal and external customers, as well as personal commitment from each employee. Quality teams are the core of TQM philosophy. Any strategy to implement TQM will require extensive training and/or study of quality improvement tools and methods, as well as a plan for managing cultural change. Aligning the department within the organization requires input from the rank and file as well as those at the executive level.

Adenocarcinoma of the gallbladder--a 5 year review of outcome in Newcastle upon Tyne.

Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon Tyne over a 5 year period (1980-1985) were reviewed retrospectively. The mean age of patients on diagnosis was 74 years. Of the 29 patients diagnosed, two were detected after routine cholecystectomy. Laparotomy was performed in 21 patients (72%) of which only 14 patients had a cholecystectomy performed. Mean survival after surgery was 6.6 months with only one patient alive after 5 years. Metastatic disease was present in 72% of patients. The poor prognosis of carcinoma of the gallbladder reflects its late diagnosis and early metastasis to distant sites. Improvement in survival will depend upon early detection of in situ lesions and identification of at risk patients.

DNA-based genetic testing in fifty fragile X families.

During the past 4 years (1985-1989), we have analyzed 171 cases in 50 fragile X [fra(X)] families by DNA linkage methods. Most (140 cases; 81%) were for carrier detection, both female (98 cases; 57%) and male (41 cases; 24%). Women who were obligate carriers of the fra(X) mutation accounted for an additional 6 "prior-to-pregnancy" cases. Four pregnancies have subsequently occurred with 3 having been successfully monitored (one male, 2 females). One pregnancy miscarried early prior to testing. Prenatal diagnoses (26 cases; 15%) accounted for the remainder of cases (15 males, 11 females). These will be discussed in the companion paper by Shapiro et al. (Am J Med Genet, 1991). A diagnosis in the cytogenetically uninformative carrier cases was reached in greater than 75% of analyses with a panel of 5 probes: 3 proximal (F9, DXS105, DXS98) and 2 distal (F8, DSX52). Five additional probes, 3 proximal (DXS10, DSX51, DSX102) and 2 distal (DSX15, DXS33), were used in cases that were resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Given this panel, only 5% of cases did not have any informative markers identified. Thus, molecular methods can provide a useful adjunct to cytogenetic analysis in most situations. An unusual association between the rare allele (A1) of DXS10 with the X chromosome carrying the fra(X) mutation was observed. This occurred in both male and female carriers in the uppermost generation tested. The basis for this association is uncertain at the present time.

Prenatal diagnosis of the fragile X syndrome: possible end of the experimental phase for amniotic fluid.

We have had experience with 260 prenatal diagnosis cases for the fragile X syndrome [fra(X)]; amniotic fluid was received in 230. There was a documented family history of fra(X) in 148 amniotic fluid cases. Our sample includes 91 males. Eleven were correctly identified as fra(X)-positive and 2 were false-negative. Eight of 57 females were fra(X) positive and one was a false-negative. CVS were received in 21 cases with a family history of fra(X), and there were 2 positive results in females and 3 false-negative results in males which were ultimately detected by means of molecular analysis or a subsequent amniotic fluid specimen. RFLPs were utilized in 29 cases (amniotic fluid and CVS); RFLPs identified 2 false-negative cytogenetic results in CVS. Two male fetuses were found to have a high probability of being affected by means of RFLPs, but on the basis of prenatal and postnatal negative fra(X) cytogenetic results and subsequent normal growth and development, they are either unaffected transmitting males or are double recombinants. Three female fetuses were also found to be cytogenetically negative in CVS but had a 90%, 93%, and 99% probability of being affected by RFLPs. On the basis of the data, it can be concluded: 1. Amniotic fluid experience is adequate to eliminate the "experimental" designation providing the limitations are understood and an experienced laboratory is involved. 2. Chorionic villus cells for cytogenetic analysis should still be considered experimental. 3. Negative results with CVS should be confirmed by molecular methods and/or by cytogenetic analysis of another tissue. 4. Multiple approaches can maximize reliability of fra(X) prenatal diagnosis.

Molecular markers of fragile X: clinical aspects of carrier detection and prenatal diagnosis.

In our families, a determination of carrier or affected status was made in more than 75% of cases using a standard panel of five marker systems: three proximal (F9, DXS105, DXS98) and two distal (F8, DXS52). Five additional systems, three proximal (DXS10, DXS51, DXS102) and two distal (DXS15, DXS33), were used in cases resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Utilizing the complete panel, only 5% of cases did not have any informative markers identified. In order to facilitate the appropriate application of molecular methods, several simple rules should be followed by the genetic service provider when dealing with fra(X) families: 1. Cytogenetic prescreening of females may be helpful. Only negative or ambiguous fra(X) expression levels justify the labor-intensive DNA-based family studies. 2. At present, DNA-based studies are the only way to ascertain male carrier status. 3. Every effort should be made to perform DNA-based studies under maternal phase-known conditions. 4. Information should be collected and pedigrees prepared for both sets of maternal grandparents. 5. Fathers of female consultands should be directly DNA-typed to rule out non-paternity. 6. Genetic counseling should be conservative, i.e. the "worst" scenario presented to these families, in order to avoid underestimating the risk of transmission to the next generation.

Experience with multiple approaches to the prenatal diagnosis of the fragile X syndrome: amniotic fluid, chorionic villi, fetal blood and molecular methods.

We have had experience with 160 prenatal diagnosis cases for the fragile X syndrome [fra(X)] or Martin-Bell Syndrome. In 140, amniotic fluid was utilized; 98 had a documented family history of fra(X). The 94 completed cases included 4 no growth; 56 males of which 7 were fra(X)-positive and 2 false-negative; 38 females of which 5 were fra(X) positive. There was no fra(X) positive result when a family history of mental retardation was not documented as fra(X). Molecular methods (RFLPs) were utilized in 10 amniotic fluid and 5 chorionic villus specimens (CVS). Percutaneous umbilical blood sampling was used in 2 negative cases and 1 fra(X) positive case because of timing, tissue culture failure or confirmation of another method. CVS were received in 13 cases, and RFLPs were utilized in 5 of the CVS cases. There was no positive fra(X) CVS chromosome result in males, 1 positive result in a female, but 2 false negatives were detected by RFLPs. On the basis of the results, it can be concluded that cytogenetic and molecular methods are complementary and best used together and that multiple approaches can enhance the efficiency and reliability of fra(X) prenatal diagnosis.