Surgical vs general practitioner assessment: diagnostic accuracy in 2‐week‐wait colorectal cancer referrals

Aim It has been recommended that patients with suspected colorectal cancer should proceed straight to an endoscopic test to increase speed of diagnosis, using only the information in the general practitioner’s referral letter. This study aims to establish whether the diagnostic accuracy of the first surgical outpatient assessment is significantly greater than the general practitioner’s assessment and if so by what means. Method Demographic variables, symptoms and signs were collected from the first surgical outpatient assessment letters and the general practitioners’ referral letters in 2‐week‐wait colorectal cancer referrals made between 2002 and 2005. Multiple logistic regression models derived from both the surgeons’ and the general practitioners’ letters were compared with receiver operator characteristic curves. Results Variables were collected from 978 2‐week‐wait colorectal cancer referrals. The median age was 69 years (range 19–98) and the male to female ratio was 1:2. Seventy‐eight referrals were diagnosed with colorectal cancer. Surgeons’ models demonstrated significantly greater diagnostic accuracy than general practitioners’ models (area under the curve, 0.84 vs 0.73; P < 0.003). General practitioners’ letters contained significantly less information than surgeons’ letters (P < 0.001), but correcting for this did not account for the difference in diagnostic accuracy. The single variable that accounted for the difference in diagnostic accuracy was examination of the rectum by rigid sigmoidoscopy. Conclusion Rigid sigmoidoscopy significantly improves the diagnostic accuracy of clinical assessment in patients with suspected colorectal cancer. If rigid sigmoidoscopy were omitted in a straight‐to‐test pathway, some patients would be denied the opportunity for immediate diagnosis.     

Repeat 2‐week wait referrals for colorectal cancer

Aim The inappropriate use of the ‘2‐week wait’ pathway for suspected colorectal cancer (CRC2ww) may overload urgent clinics and delay the assessment and investigation of other patients. Those who have been previously referred and investigated for suspected colorectal cancer may present one group that does not warrant repeat urgent referral. This paper aims to identify the incidence and diagnostic yield of repeat CRC2ww referrals. Method All CRC2ww patients referred to our unit over a 4‐year period were identified retrospectively. Referral indication, outcome and instances of repeat referral were identified from multidisciplinary team, endoscopy and imaging databases. Results In all, 2735 CRC2ww referrals were made over the study period. Of these, 122 were repeated CRC2ww referrals, with the incidence increasing from 2% in 2008 to 6% in 2010 (P = 0.0006). The median time to repeat referral was 1070 days. After initial referral 267 cancers were detected, including 212 colorectal cancers. The diagnostic yield was lower but not significantly so after repeated referral (six cancers) compared with initial referral (5%vs 10%, P = 0.07). Conclusion The incidence of repeat referral is low but the diagnostic yield is not insignificant. Exclusion of these patients from urgent assessment and investigation will not significantly reduce workload and may risk missing some patients with cancer.     

Straight to test. Results of a pilot study in a hospital serving an inner city population

Objective  The main aims of the study were to determine the frequency with which two-week wait (2ww) referrals for colorectal cancer (CRC) could proceed directly to straight to test (STT), and the potential improvement in time to diagnosis.
Method  A telephone interview was attempted in all 2ww referrals not requiring an advocate and under 80 years. Data were assessed according to a test protocol, and where indicated a potential slot for the appropriate investigation was recorded (virtual test). All patients proceeded to clinic, following which differences in time from GP referral to virtual compared with actual requested test, and any discrepancies between virtual and requested tests were analysed.
Results  Between 8th January and 16th February 2007, there were 42 2ww referrals. Twenty-one patients were contacted, of whom 14 were suitable for STT: 13 virtual colonoscopies and one CT scan were booked. Following out-patient consultation, eight colonoscopies; three flexible sigmoidoscopies, one barium enema, and two CT scans were actually booked. There was a difference of 15.5 days between the median times of the virtual and actual test. During this 6-week period a total of nine patients were diagnosed with CRC, of whom three were referred via the 2ww pathway, but none were suitable for STT.
Conclusions  This 'straight to test' pilot study suggests a potential strategy for reducing the time to diagnosis and therefore first treatment of those identified with CRC, and offers a methodology for individual hospitals to assess their suitability to employ such a strategy.     

Prevention of peritoneal recurrence in high‐risk colorectal cancer and evidence of T4 status as a potential risk factor

Peritoneal metastasis (PM) following primary resection of colorectal cancer is common. The combined use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has significantly improved the survival outcome of patients with colorectal PM (CRPM). Diagnosing and treating early PM is essential as its extent is correlated with poorer outcomes. There are two novel therapies – second‐look surgery and synchronous hyperthermic intraperitoneal chemotherapy – that are proposed to prophylactically treat or intervene early in the disease process to reduce the incidence and adverse outcomes associated with PM. These strategies are limited to patients at high risk of developing CRPM, including those that had synchronous PM or ovarian metastases resected at primary tumour removal, or a perforated primary tumour. The data on advanced primary tumour (T4) as a prognostic factor for PM after primary resection suggest that T4a tumours are prognostically worse than T4b. This literature review outlines the evidence, feasibility and safety regarding the pre‐emptive treatments, as well as the relevance of T4a tumours as a risk factor for metachronous CRPM.     

Use of a patient consultation questionnaire and weighted numerical scoring system for the prediction of colorectal cancer and other colorectal pathology in symptomatic patients: A prospective cohort validation study of a Welsh population

Objective There is currently no system in widespread use that accurately prioritizes colorectal referrals in symptomatic patients with an acceptable degree of sensitivity and specificity. We have validated a weighted numerical scoring system for the prioritization of such colorectal referrals in an attempt to rectify this, with detection of colorectal cancer (CRC) the primary outcome. Method We conducted a prospective study of symptomatic patients referred by primary care to the colorectal service in a district general hospital. A computer‐generated weighted numerical score (WNS) was derived from the primary symptoms and symptom combinations. Patients underwent colorectal investigations and a final diagnosis was established. Sensitivity, specificity and accuracy of CRC detection as determined by the WNS, Department of Health (DOH) and National Institute for Health and Clinical Excellence guidelines was determined. Primary Care compliance with guidelines was analysed. Results A definitive diagnosis was established in 3457 patients. One hundred and eighty‐six (5.4%) had CRC. The mean score for the cancer patients (76.9, 95%CI 72–81) was significantly higher than that of non‐cancer patients (52, 95%CI 52–53) P < 0.001. Receiver Operator Curve analysis demonstrates a high discriminatory power for the Patient Consultation Questionnaire (PCQ) with an area under curve of 0.76. Compliance by primary care with the nationally recommended referral guidelines was poor with only 55% and 58% compliance with DOH and National Institute for Clinical Excellence referral guidelines for suspected cancer respectively. Conclusion The PCQ and the WNS is an efficient, objective system that allows the accurate prioritization of colorectal referrals with a high sensitivity for cancer and other serious colorectal pathologies.     

Downregulation of caspase‐9 is a frequent event in patients with stage II colorectal cancer and correlates with poor clinical outcome

Objective To evaluate the clinical significance of caspase‐9 mRNA expression and investigate its prognostic value in stage II colorectal cancer. Method Quantitative real‐time RT–PCR was used to analyse caspase‐9 mRNA expression in cancer tissue and corresponding normal mucosa from 120 patients. Results Compared with normal mucosa, the expression of caspase‐9 mRNA was found to be downregulated in cancer tissue (P = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation (P = 0.031). The Kaplan–Meier survival analysis demonstrated that patients with downregulated caspase‐9 showed a worse overall survival (P = 0.012) and disease‐free survival (P = 0.022). Cox’s proportional hazards regression model confirmed that expression of caspase‐9 was the strongest prognostic factor in stage II colorectal cancer. Conclusion The mRNA expression of caspase‐9 can be used as an independent prognostic factor for patients with stage II colorectal cancer.     

−509C>T polymorphism in the TGF‐β1 gene promoter is not associated with susceptibility to and progression of colorectal cancer in Chinese

Aim Colorectal cancer is common, accounting for nearly 10% of all cancers. Transforming growth factor‐β1 (TGF‐β1) is a pleiotropic cytokine that has been implicated in the pathogenesis of colorectal neoplasia. The most studied −509C>T polymorphism of TGF‐β1 gene has been associated with various kinds of cancer. This study investigated the association between this genetic variant and the risk and/or progression of colorectal cancer. Method A case–control study was carried out of 150 colorectal cancer cases and 503 healthy controls. DNA was extracted from blood cell nuclear materials, and −509C>T polymorphism in the TGF‐β1 gene promoter was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Colorectal cancer tissues (n = 70) were obtained from the studied cases for measurement of TGF‐β1 mRNA expression levels. We also assessed the plasma TGF‐β1 levels of cases (n = 88) and healthy subjects (n = 120). Results The TGF‐β1 producer genotype, −509TT, was not associated with an increased risk of colorectal cancer compared with other genotypes. Colorectal cancer patients especially those with a more aggressive disease behaviour were more frequently associated with C allele. Conclusion The results suggest that TGF‐β1 −509C>T polymorphism is not associated with either an increased risk or progression of colorectal cancer.     

Association between interleukin‐4R and TGF‐β1 gene polymorphisms and the risk of colorectal cancer in a Korean population

Aim Colorectal cancer is associated with inflammatory bowel disease. The mechanisms of how different genetic make‐ups of cytokines might influence the individual susceptibility to develop particular types of tumours are still unknown. The authors analysed the association between genetic polymorphisms in cytokine/cytokine receptor genes and the risk of colorectal cancer in a Korean population. Method The authors assessed polymorphisms of the interleukin: IL‐1, IL‐1R, IL‐2, IL‐4, IL‐4R, IL‐10, transforming growth factor (TGF)‐β1, IFN‐γ genes in Korean patients with colorectal cancer (n = 170) and in a normal healthy control group (n = 130) to investigate the association between theses cytokine gene polymorphisms and the risk of colorectal cancer. Results The IL‐4R 1902*T allele was found to be associated with an increased risk of colon cancer (P < 0.01, OR = 2.0) and rectal cancer (P < 0.05, OR = 1.8). The IL‐4R 1902*C allele was associated with a decreased risk of both colon cancer (P < 0.01, OR = 0.51) and rectal cancer (P < 0.05, OR = 0.5). The TFG‐β1 10*T allele was found to be associated with an increased risk of colon cancer (P < 0.00, OR = 2.3) and the TFG‐β1 10*C allele with a decreased risk of colon cancer (P < 0.00, OR = 0.43). Conclusion These results suggest that the genetic polymorphisms of IL‐4R and TGF‐β1 are associated with the risk of colorectal cancer in a Korean population.     

Previous transurethral resection of the prostate is not a contraindication to high‐dose rate brachytherapy for prostate cancer

OBJECTIVE

To analyse retrospectively the morbidity and efficacy of high‐dose rate (HDR) brachytherapy in patients who had a previous transurethral resection of the prostate (TURP).

PATIENTS AND METHODS

Morbidities documented in the records of 32 patients with previous TURP and 106 with no previous TURP, treated with HDR brachytherapy for prostate cancer at our institution, were analysed and compared. All patients received HDR brachytherapy as a boost before conformal external beam radiotherapy. We recorded and analysed genitourinary complications, rectal morbidity, and the biochemical control rate as assessed by the prostate‐specific antigen (PSA) level.

RESULTS

All complications of patients who received HDR brachytherapy were recorded during the follow‐up. All gastrointestinal and genitourinary complications were not significantly different in patients with or without previous TURP. There was little incontinence or severe morbidity associated with HDR brachytherapy. The PSA‐based biochemical control rates were similar in patients with or without previous TURP in each risk group.

CONCLUSIONS

HDR brachytherapy is a reasonable treatment for localized prostate cancer in patients who have had a previous TURP, with the expectation of low morbidity and satisfactory biochemical control.     

Ribociclib therapy in peritoneal carcinomatosis secondary to HER2‐negative metastatic breast cancer: A clinical case with a positive outcome

Although metastatic breast cancer can be fatal, a series of randomized double‐blind placebo‐controlled phase 3 trials (MONALEESA studies) have shown that ribociclib is an effective anticancer drug for the treatment of advanced breast cancer with bones, liver, lungs, and brain as major metastatic sites. Here, we report the clinical case of a woman with peritoneal carcinomatosis secondary to HER2‐negative estrogen receptor–positive breast cancer successfully treated with ribociclib and letrozole. After 9‐month follow‐up, total body computed tomography imaging showed resolution of hypodense areas surrounding the hepatic hilus with concomitant reduction in both bile duct dilatation and peritoneal effusion, and abdominal lymphadenopathy was excluded. Notably, therapy was well tolerated throughout the treatment with no side effects.