Peter Carne

KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer

Purpose: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse. Experimental Design: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial. Results: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial. Conclusions: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies. Clin Cancer Res; 17(5); 1122–30. ©2011 AACR.

RADICAL LYMPH NODE DISSECTION FOR MELANOMA

Background:  Therapeutic lymph node dissection for melanoma aims to achieve regional disease control. Radical lymphadenectomy (RLND) can be a difficult procedure associated with significant postoperative morbidity.

Maternal and Fetal Outcome After Colectomy for Fulminant Ulcerative Colitis During Pregnancy: Case Series and Literature Review

PurposePrevious studies have reported high morbidity and mortality in mothers and their offspring after colectomy for ulcerative colitis during pregnancy. This study was designed to assess the maternal and fetal outcomes of pregnant females undergoing colectomy for ulcerative colitis in the current era.MethodsA retrospective analysis was performed at our institution of all pregnant females undergoing operation for ulcerative colitis between 1980 and 2004. To compare this data to that of past literature, a MEDLINE search from 1951 to 2004 reviewed all cases reported on this topic.ResultsBetween 1980 and 2004, five females underwent an operation at our institution for fulminant ulcerative colitis while pregnant. All five patients underwent subtotal colectomy with Brooke ileostomy. Postoperative maternal morbidity included a superficial wound infection and a small asymptomatic intra-abdominal abscess. All females had successful pregnancies, and no maternal or fetal deaths occurred. Two patients went on to have an ileal pouch-anal anastomosis, one had a completion proctectomy and end ileostomy, oneis scheduled for an ileal pouch-anal anastomosis, andone patient is lost to follow-up. The literature review revealed 37 cases. The overall fetal and maternal mortality was 49 and 22 percent respectively. Postoperative maternal morbidity was reported in 24 percent.ConclusionsIn contrast to historic data, the maternal and fetal mortality from our series was zero and maternal morbidity was low. Subtotal colectomy and Brooke ileostomy for ulcerative colitis during pregnancy is safe. A multidisciplinary team that includes a gastroenterologist, high-risk obstetrician, and experienced surgeon is necessary for an optimal outcome.

ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer.

Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts.

The first 1000 patients on an internet-based colorectal neoplasia database across private and public medicine in Australia: development of a binational model for the Colorectal Surgical Society of Australia and New Zealand

BACKGROUND: Collection of multi-institutional data pertaining to the treatment of bowel cancer has been hindered by poor clinician compliance with data entry and the lack of incentive to participate. OBJECTIVE: This study aimed to establish if a novel browser-based model of data collection results in complete data capture. DESIGN: A Web-based data collection interface was custom written, offering automated reporting modules for clinical outcome to participants and an automated reporting system for outstanding data fields, and summary reporting of surgical quality outcomes. The software was combined with a clinical feedback system incorporating fortnightly data review meetings, at the time of clinical multidisciplinary meetings. PATIENTS AND SETTING: Selected were 932 consecutive patients with opt-out consent from 3 hospital sites, including public and private medicine. MAIN OUTCOME MEASURES: The primary outcomes measured were the analysis of data completeness and accuracy and ensuring that the highest-quality data were used for clinical audit of the surgical practices of Australian colorectal surgeons for the purpose of quality assurance. RESULTS: A total of 932 men and women, 22 to 94 years of age, treated for colorectal neoplasia were evaluated. We obtained 100% completion (>27,000 data points) of perioperative data registered by 8 specialist colorectal surgeons and a full-time database manager. CONCLUSIONS: Data completeness and validity are essential for clinical databases to serve the purpose of quality assurance, benchmarking, and research. The results confirm the safety and efficacy of colorectal cancer surgery in both the public and private sector in Australia. The combination of a simple multiuser interface, defined data points, automated result-reporting modules, and data-deficiency reminder module resulted in 100% data compliance in nearly 1000 clinical episodes. The unprecedented success of this model has lead to the Colorectal Surgical Society of Australia and New Zealand adopting this model for data collection for Australia and New Zealand as the binational database.

Squamous-cell carcinoma developing in an ileostomy stoma

A 66-year-old male presented with an enlarging peristomal mass for investigation. A 10-cm diameter fungating mass involving his stoma was present (Fig. 1). Forty-one years previously, a proctocolectomy and formation of an end ileostomy had been performed for ulcerative colitis. For 38 years after that procedure, he did not consult a medical practitioner or stomal therapist with regard to his stoma. Biopsy of the ileostomy mass revealed well-differentiated to moderately well-differentiated keratinising squamous-cell carcinoma. Laparotomy, excision of the tumor, and relocation of the end ileostomy were performed. There was no evidence of intra-abdominal tumor. The ileostomy with carcinoma was widely excised, including the full thickness of the anterior abdominal wall. Histology confirmed squamous-cell carcinoma, with resection margins clear of tumor. The patient’s postoperative recovery was unremarkable, and he remains well on last review, four months postsurgery. Squamous-cell carcinoma may arise in areas of chronic irritation or injury. An ileostomy is one such area, with peristomal skin irritation from stomal effluent a potential mechanism of injury. Recurrent irritation, difficulties with appliance application, and subsequent further skin irritation can occur—a cycle that is difficult to break. Other factors such as parastomal hernia, stomal prolapse, stomal retraction, and regional scars or skin folds can all contribute to difficulty with appliance application. The development of squamous-cell carcinoma around an ileostomy is extremely rare; only two other cases have been reported. Wide local excision and stoma relocation would seem to be appropriate treatment in the setting of localized disease. This case illustrates the importance of ongoing follow-up of patients with stomas to allow the early recognition of stomal management problems and the early diagnosis and treatment of the rare, but significant, late complication of parastomal squamous-cell carcinoma.

Botulinum toxin therapy for chronic anal fissures: where are we at currently?

Botulinum toxin (Botox) injection for chronic anal fissure (CAF) is commonly performed, yet there remains no consensus on optimal dosage or frequency of injections required to achieve complete resolution of anal fissure. The aim of this study was to determine the effectiveness of Botox and side‐effect profile in the management of CAF.

Complete Pathological Response After Neoadjuvant Long-course Chemoradiotherapy for Rectal Cancer and Its Relationship to the Degree of T3 Mesorectal Invasion

BACKGROUND: Many studies have shown significantly improved outcomes (reduced local recurrence and improved overall survival) for patients achieving a complete pathological response from neoadjuvant chemoradiotherapy. OBJECTIVE: This study aimed to document the complete pathological response rate and outcomes in patients receiving preoperative long-course chemoradiotherapy stratified for the extent of T3 mesorectal invasion measured on preoperative imaging. DESIGN: This is a retrospective study of prospectively collected data, of patients with rectal cancer in the Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from Cabrini Hospital and The Alfred Hospital, identifying patients entered between January 2010 and June 2014. PATIENTS AND SETTINGS: One hundred eighteen patients with T3 rectal cancer met the selection criteria for the study; 26 achieved complete pathological response (22%). MAIN OUTCOME MEASURES: Outcomes in terms of complete pathological response and oncological outcomes such as disease-free and overall survival were analyzed. RESULTS: Patients with complete pathological response had significantly less preoperative invasion than those with no complete pathological response (p < 0.001). Depth of invasion was the only variable associated with complete pathological response (p < 0.002), and the likelihood of complete pathological response decreased by 35% for every millimeter of invasion. Complete pathological response was associated with increased disease-free survival (p = 0.018) and a lower risk of cancer progression (p = 0.046). Depth of invasion was associated with an increased risk of death after surgery; HR increased by 1.07 (95% CI, 1.00–1.15) for each 1-mm increase in invasion. LIMITATIONS: This was a retrospective study with the usual limitations, although these were minimized through the use of a clinician-driven prospective database. CONCLUSIONS: The smaller the degree of T3 invasion, the higher the chance of achieving complete pathological response (up to 35%), which is associated with improved disease-free and overall survival. A higher complete pathological response rate is observed in early T3 disease in comparison with more extensive T3 invasion.

Establishing a robotic colorectal surgery programme.

This paper aimed to describe the training available and the process taken to establish a robotic colorectal surgery programme in a large Australian academic private hospital. Through this we hope to guide other surgeons and hospitals planning to introduce this technology in circumstances where such guidelines do not exist.

Enterocutaneous fistula: analysis of clinical outcomes from a single Victorian tertiary referral centre

Enterocutaneous fistulas (ECFs) are complex and can result in significant morbidity and mortality. The study aimed to evaluate ECF outcomes in a single tertiary hospital.