Survival impact of the Australian National Bowel Cancer Screening Programme.

BACKGROUND: The Australian National Bowel Cancer Screening Program (NBCSP) has been offering age-based faecal occult blood testing since 2006. With the rapid expansion of this programme, the NBCSP will ultimately offer biennial screening to all 50-74 years old by 2020. Participation rates remain low. Previous reports have described an increased proportion of earlier stage cancers in patients with NBCSP-detected tumours. METHODS: Data on consecutive patients enrolled into a prospective, comprehensive, multidisciplinary database at six Victorian hospitals were examined. Clinicopathologic and outcome data were compared for NBCSP and symptomatic presentation patients. RESULTS: We identified 3743 patients that presented with colorectal cancer (CRC) at participating hospitals since May 2006. Of 1930 patients aged between 50 and 70 years, 141 (7.3%) had a NBCSP detected cancer, 1441 (74.7%) presented with symptoms and 266 (13.8%) were diagnosed through screening outside of the NBCSP. Based on the American Society of Anaesthesiology score, the NBCSP patients were fitter. They had an earlier stage of diagnosis and were more likely to be female and less likely to have lymphovascular invasion or to present as an emergency. NBCSP detected patients had a lower rate of recurrence (HR 0.17, P = 0.0001) and fewer deaths (HR 0.19, P = 0.005). CONCLUSIONS: Patients with NBCSP-detected CRC have a markedly reduced risk of CRC recurrence and death compared with patients with a symptomatic presentation. The dominant driver of this appears to be earlier stage at diagnosis. Increased promotion of the impact of the NBCSP, including data related to the survival impact, should be undertaken to increase participation rates and achieve further survival gains.

Comparing oncological outcomes of laparoscopic versus open surgery for colon cancer: Analysis of a large prospective clinical database.

BACKGROUND: Oncological outcomes of laparoscopic colon cancer surgery have been shown to be equivalent to those of open surgery, but only in the setting of randomized controlled trials on highly selected patients. The aim of this study is to investigate whether this finding is generalizable to real world practice. METHODS: Analysis of prospectively collected data from the BioGrid Australia database was undertaken. Overall and cancer specific survival rates were compared with cox regression analysis controlling for the confounders of age, sex, BMI, ASA score, hospital site, year surgery performed, procedure, tumor stage, and adjuvant chemotherapy. RESULTS: Between 2003 and 2009, 1,106 patients underwent elective colon cancer resection. There were differences between the laparoscopic and open cohorts in BMI, procedure, post-operative complication rate, and tumor stage. When baseline confounders were accounted for using cox regression analysis, there was no difference in 5 year overall survival (χ(2) test 1.302, P = 0.254), or cancer specific survival (χ(2) test 0.028, P = 0.866). CONCLUSION: This large prospective clinical study validates previous trial results, and confirms that there is no difference in oncological outcome between laparoscopic and open surgery for colon cancer.

The role of tissue diagnosis prior to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

AIM: Neoadjuvant chemoradiotherapy is the standard of care for locally advanced rectal cancer, with diagnostic work-up routinely including a biopsy confirming invasive carcinoma. For the occasional patient where initial biopsies reveal only dysplasia, or even normal epithelium, repeat biopsy is currently advised, but this may delay therapy and repeat biopsy has potential adverse effects. The study aimed to determine, in the setting of clinical findings and imaging demonstrating locally advanced rectal cancer, whether the absence of a tissue diagnosis prior to commencing chemoradiation compromises patient outcome. METHOD: A review was conducted of our database, including comprehensive treatment and outcome details, in which consecutive patients with colorectal cancer have been enrolled since 1997 at a single institution. All records for patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer were reviewed to identify patients for whom treatment was initiated before a tissue diagnosis was obtained, and to assess any consequences of this. RESULTS: Of 254 patients who had received neoadjuvant treatment for rectal cancer, 16 (6.3%) were found to have had neoadjuvant therapy without a tissue diagnosis of invasive cancer. Compared with cases where a tissue diagnosis had been obtained, median age (59 vs 63 years, P = 0.497), sex (75% vs 71.3% male, P = 0.955) and tumour location (56.3% vs 73.5% < 8 cm, P = 0.230) were similar. Of these, 14 (87.5%) had adenocarcinoma identified on histopathology review of the surgical specimen. Three patients were considered to have had complete pathological responses with mucin lakes within the muscularis propria (n = 2) or lymph nodes (n = 1) or fibrosis (n = 3). One of these had no mucin evident and only fibrosis; thus final pathological proof of invasive cancer was present in 15 (93.5%) patients. There were no local recurrences, but three of the 16 (18.8%) cases developed distant recurrence. CONCLUSION: For the small number of cases without a confirmatory tissue diagnosis before chemoradiation, no adverse consequences were identified. In particular the initial diagnosis was confirmed in 15 out of 16 cases following pathological examination of the operative specimen. We would suggest that, where clinical and radiological features support a diagnosis of locally advanced rectal cancer, proceeding directly to neoadjuvant chemoradiotherapy in the absence of a biopsy demonstrating invasive cancer may not be unreasonable, particularly where repeat biopsy would delay the commencement of treatment.

Not all patients need to be discussed in a colorectal cancer MDT meeting.

AIM: It is recommended that patients with cancer should be managed in the context of a multidisciplinary team (MDT). Alternatively, proponents of the standard model of care propose that the well-informed treating doctor is able to make the appropriate plan for each patient, making the need for a MDT meeting redundant. We compared the management plans made within a colorectal cancer MDT with routine care. METHOD: Consecutive cases presenting to the colorectal MDT were prospectively assessed. Before the meeting management plans were made, based on routine care pathways. These were compared with plans made at the MDT meeting and discrepancies recorded. The number of patients who generated beneficial discussion was recorded. RESULTS: There were 261 discussions regarding the care of 197 patients. In the 203 cases where the pathways were relevant, patient management was consistent with the pathway in 94% of the cases discussed. Discussion of routine cases of colon cancer rarely changed management (3.4%). Conversely, management changed after MDT discussion in 50% of complex cases (the preoperative management of rectal cancer, recurrence, metastatic disease and malignant polyps). The postoperative discussion of pathology findings rarely generated beneficial discussion. CONCLUSION: Discussion of routine cases of colon cancer in our MDT rarely changed management, but it did change the decisions regarding complex cases or in patients with unusual pathology. We propose a two-tiered approach to the MDT where all patients are listed for a MDT meeting but only patients with complex pathology are discussed in detail.

Hospital discharge criteria following colorectal surgery: a systematic review.

AIM: The aim of this study was to identify and synthesize the hospital discharge criteria that have been used in the colorectal surgery literature. METHODS: A systematic literature search was conducted using eight bibliographic databases. Searches were limited to English language journal articles published between January 1996 and October 2009. Primary research applying hospital discharge criteria following colorectal surgery was included. Study selection was made independently by two reviewers. Discharge criteria were extracted from each included study. RESULTS: The 156 studies identified by the search strategy described 70 different sets of criteria to indicate readiness for discharge. The majority of studies applied a combination of three or four criteria; those most frequently cited were tolerance of oral intake (80%), return of bowel function (70%), adequate pain control (44%) and adequate mobility (35%). End-points employed to determine the achievement of criteria were generally poorly defined. CONCLUSION: A variety of hospital discharge criteria were applied in the colorectal surgery literature. Development of standardized criteria will allow more accurate comparison of results between studies assessing hospital length of stay or other discharge-related outcome measures.

Managing fistula-in-ano with ligation of the intersphincteric fistula tract procedure: the Western Hospital experience.

AIM: To review the preliminary results of the ligation of the intersphincteric fistula tract (LIFT) technique in treating complex anal fistulas at our hospital. METHOD: Between March and November 2010, patients with cryptoglandular anal fistulas were recruited prospectively from the colorectal clinic and treated using the LIFT procedure. A database was set up to collect information on demographics, past surgical treatments, fistula characteristics, MRI scan results, operative data and follow-up findings. The primary end-point measured was cure of the disease. The secondary end-point was the degree of postoperative continence. Preoperative and postoperative incontinence rates were recorded using Wexner's Incontinence Scale. RESULTS: Twenty-five patients (eight women and 17 men; median age, 40 years) underwent the LIFT procedure. Ten patients had recurrent fistulas and previous fistula surgery. The median operating time was 39 min. No intraoperative complications were documented. The median follow-up duration was 22 (3-43) weeks. Primary healing was observed in 17 (68.0%) patients and the median healing time was 6 weeks; one wound remained incompletely healed. Seven patients (28.0%) had disease recurrence presenting between 7 and 20 weeks postoperatively. No patients reported any incontinence postoperatively. CONCLUSION: The LIFT procedure has favourable healing rates with little or no risk of incontinence. This operation is safe and easy to learn. The early results from this pilot study show promise and affirm some of the findings of other researchers. These results will suggest opportunities to conduct further controlled studies comparing the LIFT procedure with standard therapies.

Current practice in preoperative therapy and surgical management of locally advanced rectal cancer: a bi-national survey.

AIM: The Australasian colorectal surgeon's current approach to preoperative rectal cancer management was compared with international guidelines. METHOD: Members of the Colorectal Surgical Society of Australia and New Zealand were surveyed in 2010, on the use of MRI and the management of locally advanced rectal cancer. Surgeons had to decide the appropriate management in five scenarios that were developed from national guidelines. RESULTS: Of 174 invitations sent, 108 (62.1%) replies were received. Most surgeons (98.1%) had access to MRI. Ninety-three (86.1%) would use MRI routinely for staging. The majority selected a tumour-specific mesorectal resection for upper rectal cancer (58.2%) and a total mesorectal excision for distal cancer (100%). Almost all restorative operations included a covering ileostomy. One third of surgeons recommended that patients with a favourable cT3 mid-rectal tumour (N0, clear circumferential resection margins) should not have preoperative therapy and should proceed directly to surgery. When high-risk features, such as threatened resection margins or cN1 stage, were present, 5% and 15% of surgeons, respectively, would continue to treat by standard resection without preoperative therapy. CONCLUSION: Evidence-based international guidelines for the management of rectal cancer have changed little in the last 10 years. Despite this, there is a clear gap between these and clinical practice. The main variance relates to the role of radiotherapy in locally advanced rectal cancer. Despite considerable evidence that radiotherapy reduces local recurrence for all stages of rectal cancer, current practice in Australasia is for its selective use.

Immunomodulation does not alter histology in resected Crohn's disease.

BACKGROUND: The use of immunomodulators (Azathioprine, 6-Mercaptopurine and Methotrexate) and biological agents (Infliximab and adalimumab) for the treatment of Crohn's disease (CD) has increased in the recent years with the aim of treating the inflammatory component of the disease and hoping to change the natural history of the disease. The aim of this study was to determine if the use of immunomodulators or biological agents in the 2 years prior to resection affects the histopathological characteristics of the patient's disease. METHODS: A retrospective review was conducted over a 10-year period (1996-2005) of patients who underwent resection for CD. Clinical case notes and histology specimens were reviewed. Patients treated with Azathioprine, 6-Mercaptopurine, Methotrexate or Infliximab for more than 3 months within the 2 years preceding surgery were deemed to have been immunomodulated. The results were also analysed by Montreal phenotype. RESULTS: A total of 165 patients were identified. 52 patients had been treated with either immunomodulator or biological agent. Of 20 histological features examined, only muscular hypertrophy approached significance (P = 0.05), Montreal A and Montreal L phenotypes were the same regardless on immunomodulators, however, there was a significant difference (P = 0.03) with regard to Montreal B in patients with stricturing disease being more likely to have received an immunomodulator. CONCLUSIONS: In this cohort of patients requiring resection for CD, those with stricturing disease were more likely to receive immunomodulators or biologics than those without stricturing disease. However, there were no significant histological differences in the resected specimens between those who did and those who did not receive these drugs.

Intradermal injection of methylene blue for the treatment of refractory pruritus ani.

OBJECTIVE: Idiopathic pruritus ani is a common perianal condition that can be refractory to diligent perineal care. We wished to evaluate the efficacy and side effects of intradermal methylene blue for the treatment of refractory pruritus ani. METHOD: A prospective series of 49 patients with idiopathic pruritus ani, who had failed to improve with perineal care, were treated by a single surgeon. All patients received intradermal injections of methylene blue. Endpoints were patient symptom score, and complications (pain, dysaesthesia, skin necrosis, incontinence and anaphylaxis). RESULTS: Symptoms improved in 96% and resolved in 57% of patients after one treatment. All four patients who had a second treatment became symptom-free. Seven patients noticed changes in continence, all resolved between 10 days and 6 weeks. Two patients were distressed by their decrease in their perianal sensation. There was no skin necrosis or anaphylaxis. CONCLUSION: Treatment of refractory pruritus ani by intradermal injection of methylene blue is effective and generally well tolerated.

Sacrococcygeal pilonidal disease.

BACKGROUND: Sacrococcygeal pilonidal is a common disease in active young adults. Many surgical methods have been proposed, although no clear consensus as to the optimal treatment has been reported. This review looks at the different surgical techniques available and examines the reported results of primary healing, recurrent disease and complications (including delayed healing). METHOD: A literature search using the Medline database was performed to locate English language articles on surgery for pilonidal disease. Further articles were obtained from the references cited in the literature initially reviewed. RESULTS: Management should be tailored according to the individual and whether the disease is acute or chronic. Treatment should take into consideration hospital stay and return to work. Simple excision, curettage, partial lateral wall excision, or marsupialisation, are simple techniques with good results. They can be used for the initial surgery but their use is not recommended for recurrent disease. The modified rhomboid flap for recurrent disease has consistently shown positive results in terms of complication rates and recurrence. CONCLUSION: We would recommend tailored treatment with simple excision for initial presentation and the modified rhomboid flap for recurrent disease.

Single-institution experience of adjuvant 5-fluorouracil-based chemotherapy for stage III colon cancer.

BACKGROUND: Adjuvant 5-flourouracil-based chemotherapy is standard care for patients with stage III colon cancer. Limited data are available regarding use of adjuvant treatment in routine clinical practice, where patients are often frail and/or elderly. METHODS: A review of patients with stage III colon cancer over a 7-year period at Western Hospital using a prospective, comprehensive colorectal database was carried out. Results were compared to recent clinical trial data. RESULTS: We identified 554 patients with colon cancer, including 165 patients (30%) with stage III disease. Median patient age was 69 years, with a median follow up of 38 months. There were nine early postoperative deaths. Thirty other patients (19%) were not offered adjuvant chemotherapy, mainly because of advanced patient age and/or comorbidity. Of 124 patients offered adjuvant therapy 12 (10%) elected not to pursue treatment. Thirty-four of the 112 patients that commenced treatment had a dose reduction, with 30 not completing treatment because of toxicity (14) or other reasons (16). The 5-year progression-free survival was 50% and 5-year overall survival 59%. CONCLUSION: In routine practice many patients with stage III colon cancer do not receive adjuvant chemotherapy. For those receiving treatment the experience is not significantly different from that reported in the carefully selected clinical trial group.

Long-term results of palliative stenting or surgery for incurable obstructing colon cancer.

OBJECTIVE: Self-expanding metal stents are an effective means of relieving left-sided malignant colonic obstruction, and in the setting of incurable disease may provide palliation while allowing the patients to avoid surgery altogether. With modern chemotherapy regimes, patients may have a long-life expectancy, even in the presence of metastases. The purpose of this study was to investigate the long-term results of palliative stent placement, compared with patients undergoing palliative surgery. METHOD: This is a retrospective study of 55 consecutive patients who underwent colonic stenting or palliative surgery for incurable, obstructing adenocarcinoma of the left colon. RESULTS: Twenty-nine patients underwent colonic stenting, and 26 had surgery during the study period. Survival was similar in the two groups (14 months in the stent group, 11 months in the surgery group). Median hospital stay was shorter in the stent group (4 vs 13.5 days), and fewer patients in the stent group had complications (2 vs 14). Only four patients in the stent group went on to require later surgery. The median time to failure of the stents was 14 months. CONCLUSION: Colonic stenting provides effective and durable palliation for patients with incurable, obstructing adenocarcinomas of the left colon. It can be performed with less morbidity than palliative surgery, and offers similar long-term survival.

Value of database linkage: are patients at risk of familial colorectal cancer being referred for genetic counselling and testing?

BACKGROUND: Unique research opportunities are being created in an era of increasingly sophisticated data collection and data linkage. There are Familial Cancer Clinics (FCC) to counsel patients and families about risk reduction strategies and to carry out genetic testing where appropriate. There is currently no objective evidence as to whether appropriate patients are being referred to the FCC. METHODS: Using a unique resource, the BIO21:MMIM informatics platform, we were able to link data from a prospective colorectal cancer (CRC) database at four Melbourne hospitals with the FCC database for the 4-year period from 2002 to 2005. We determined the number of patients that, on the basis of at least one risk factor suggestive of hereditary CRC, could have been considered for FCC referral, the number that was referred and the number that attended. RESULTS: Of the 829 new diagnoses of CRC 228 (27.5%) would potentially have benefited from FCC referral. Of these, 50 persons (21.9%) were referred and 32 (14.0%) attended. The highest referral rates were in young, early-stage CRC patients with a family history and the lowest in late-stage and multiple-polyp patients. Patient sex, language and insurance status did not influence referral or attendance. CONCLUSION: The database linkage capability provided by MMIM has enabled us to carry out a unique study. The results suggest that the rate of appropriate FCC referral is low, that certain subgroups are at particular risk of non-referral and that many referred patients do not ultimately attend. Interventions that increase referral rates and encourage attendance need to be considered.

Application of 10 percent formalin for the treatment of radiation-induced hemorrhagic proctitis.

PURPOSE: Rectal instillation of 4 percent formalin solution has been described as a successful treatment for hemorrhagic radiation proctitis recalcitrant to medical treatment. We present our experience with a new method of treatment involving the topical application of 10 percent buffered formalin, which is well tolerated and suitable for office use. METHODS: Patients with marked or refractory rectal bleeding and clinical features consistent with radiation proctitis were reviewed. Treatment involved direct application of a 10 percent buffered formalin solution to the affected mucosa using a 16-inch cotton tip applicator applied through a proctoscope in the office setting. RESULTS: A total of 100 patients with a mean age of 75 (range, 49-91) years were followed for 18 (range, 1-79) months. The interval from radiation exposure to formalin treatment was 21 months. Overall, 93 percent of patients had cessation of bleeding after an average of 3.5 formalin applications at two-week to four-week intervals. Patients with severe (Grade 3) proctitis and those taking aspirin required an average of 1.5 additional treatments. A total of eight patients rebled at a mean of 24 months from treatment; however, all responded to further applications of formalin. Three patients complained of anal pain and one experienced dizziness postprocedure for a complication rate of 1.1 percent. CONCLUSIONS: We present a simple, cost-effective, and well-tolerated method of controlling hemorrhagic radiation proctitis. It is performed by using materials readily available in the office of a colon and rectal surgeon, eliminating the need for bowel preparation, anesthesia, or a surgical suite.

Colorectal cancer audit: a comparative study before and after establishing a specialty colorectal surgery unit.

OBJECTIVE: A prospective audit was kept for colorectal cancer after the establishment of a special-interest colorectal unit at a Melbourne metropolitan teaching hospital. METHODS: These data were compared with data collected retrospectively on surgical management of colorectal cancer by general surgeons in the hospital. RESULTS: The groups were well matched with respect to age, sex, pathological staging and elective vs urgent surgery. Differences were found in postoperative length of stay (9 vs 12 days, P = 0.01) in favour of the colorectal special interest group. Differences were found in the permanent stoma rate with regard to rectal cancer with the colorectal special interest group having a lower permanent stoma rate. CONCLUSION: Specialisation improved the results of treatment.

Rapid diagnostic test for hereditary nonpolyposis colon cancer kindred using polymerase chain reaction.

PURPOSE: We have identified a mutation in the hMLH1 gene from the proband of a hereditary nonpolyposis colorectal cancer kindred. We wished to develop a rapid test for this specific mutation to facilitate screening of other family members. METHOD: An allele-specific polymerase chain reaction strategy was used to detect a T insertion at the + 3 splice site post exon 9 in the hMLH1 gene. The test was evaluated on DNA in which the mutation status was known. RESULTS: A 130-base pair fragment was reliably amplified using the allele-specific polymerase chain reaction. The test is able to identify the mutant allele and to distinguish between normal, carriers (heterozygous), and tumor DNA samples. The mutant allele is not present in an unrelated hereditary nonpolyposis colorectal cancer cell line or in a sample of the normal population (n=49). CONCLUSIONS: This is a simple, rapid test that can determine carrier status in the members of a kindred at risk for this mutation. This mutation is unlikely to be a polymorphism. This test may now be evaluated in a clinical setting.

RNA-based mutation screening in hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a cancer syndrome inherited in an autosomal dominant fashion. Four susceptibility genes are known, which code for DNA mismatch repair enzymes. The purpose of this study was to identify the HNPCC gene defects in a cohort of Australian HNPCC families and to evaluate the use of RNA-based screening methods. Six mutations were identified, four in the hMLH1 gene and two in hMSH2, by using a combination of DNA-based and RNA-based methods. One of the hMLH1 defects was a missense mutation, and the other five mutations would be expected to result in a shortened protein. These included a rare type of mRNA splicing mutation in hMLH1 exon 17. By use of reverse-transcriptase (RT) PCR, defective transcripts were detectable for three of the hMLH1 mutations but not for the fourth one, which was predicted to cause skipping of exon 15. Furthermore, many more alternative transcripts for the hMLH1 gene were found than previously described, and these were more abundant in the RNA samples prepared from whole blood than from lymphoblastoid cell lines. This confounded RNA-based screening for HNPCC mutations, because it was difficult to determine which aberrant RT-PCR fragment was the real hereditary defect. One of the splice-site mutations reported here causes skipping of exons 9 and 10, which also occurs as an alternative transcript. When the protein-truncation test was used, the results were indistinguishable between the patients in this family and controls. Other aberrant transcripts were also observed that varied in size between individuals but were unrelated to the hereditary defects. This study has important implications for the design of reliable diagnostic tests for HNPCC gene defects.

Hereditary non-polyposis colorectal cancer (Lynch syndrome I) in a 13 year old male.

A case of adenocarcinoma of the colon is reported. It presented in a family with hereditary non-polyposis colorectal cancer (HNPCC). Colonoscopic screening at a young age is recommended in such families. It also suggests a genetic basis for colorectal carcinogenesis in this family. Three of the members of this family also have peptic ulceration and an association between this syndrome and HNPCC is postulated.

Primary malignant fibrous histiocytoma of the retroperitoneum.

A 38 year old woman presenting with minimal digestive symptoms was found on ultrasound and computerized tomography scanning to have a large, solid, uniform mass arising in the region of the right adrenal gland. Preoperative investigations indicated a non-functioning tumour. At operation a well-circumscribed, ovoid tumour was removed and found subsequently to be a malignant fibrous histiocytoma arising adjacent to the right adrenal gland. It is believed that sarcomas arising in the retroperitoneum should be included in the differential diagnosis of masses presumed to be adrenal tumours on scanning. The limitations of computerized tomography scanning in distinguishing between benign and malignant tumours and between adrenal and juxta-adrenal masses should be recognized. Tumour size is the best indicator of malignancy and it is recommended that non-functioning tumours greater than 5 cm in diameter be presumed malignant until proven otherwise histologically. Surgical removal of all non-functioning retroperitoneal masses greater than 5 cm in diameter is therefore recommended.