Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon cancer: A cohort study of two cancer centres.

BACKGROUND/OBJECTIVES: Adjuvant chemotherapy for Stage II colon cancer offers a small (2-3%) overall survival benefit and is not universally recommended. Mismatch repair deficiency (dMMR) confers an improved prognosis identifying patients unlikely to benefit from adjuvant chemotherapy. The aim of this study was to investigate the use of dMMR immunohistochemistry in two major cancer treatment centres. METHODS: Prospective data were collected on all patients with resected Stage II colon cancer between 2010 and 2015 across two large Australian hospitals. Data collected included patient demographics, tumour histology, dMMR immunohistochemistry, chemotherapy use, and outcomes. RESULTS: All 355 patients (56.1% female, median age 81) with resected Stage 2 Colon cancer entered on to the surgical database were included in this analysis. MMR testing was performed on 167 patient samples (47%), most occurred post-2013 (73.1% vs. 26.9% patients). dMMR rates were 34.1%. 25 (7.3%) received adjuvant chemotherapy, with no patient >80 years receiving treatment. Presence of ≥2 high-risk feature increased the likelihood of adjuvant chemotherapy. Only 3.6% dMMR patients received chemotherapy; both were young with high-risk features. 27/288 (7.6%) patients (with follow up) relapsed, with 7 disease-free post-resection of metastatic disease, 9 are alive with metastatic disease, and 11 deceased. CONCLUSIONS: Unlike clinical trial populations, Stage 2 colon cancer patients are often elderly, have high rates of dMMR tumours, are rarely offered chemotherapy, yet still have excellent outcomes. dMMR immunohistochemistry is being increasingly used to identify Stage 2 patients who do not require chemotherapy.

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

BACKGROUND: 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. METHODS: A retrospective study of all patients treated with ECF between the period of January 2009 and June 2014 was conducted. Baseline demographic data assessed included the primary aetiology of the fistula, site of the fistula and output of the fistula. Outcomes measures assessed included re-fistulation rate, return to theatre, wound complications, fistula closure rate and death over the study period. RESULTS: A total of 16 patients with ECF were recorded within the study period. Mean age of the patient cohort was 55.8 ± 11.8 years with a female predominance (11 females, 5 males). Primary aetiology were Crohn's disease (31%), post intra-abdominal surgery not related to bowel neoplasia (50%) and post intra-abdominal surgery related to bowel neoplasia (19%). Majority of the fistulas developed from the small bowel (75%) and had low output (63%). Operative intervention was required in 81% of patients with an overall closure rate of 100%. Median operations required for successful closure was 1.15 operations. Mean duration between index operation and curative operation was 8 ± 12.7 months. CONCLUSION: Appropriate bundle of care (perioperative care, surgical timing and surgical technique) can produce excellent results in patients with ECF.

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

BACKGROUND: 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. METHODS: A retrospective clinical study of patients between 2010 and 2014 who underwent a Botox injection for CAF at a tertiary centre was performed. The effectiveness of Botox was measured using standardized outcomes including overall healing rate, presence of anal pain, recurrence and need for repeat botulinum injection. Binary outcomes were assessed using logistic regression model. The analysis was performed using Stata version 13 (StataCorp, College Station, TX, USA). RESULTS: One hundred and one patients underwent 126 Botox injections within the study period. The mean first post-operative visit was at 1 month. The overall recurrence rate was 32%. The majority of patients were given 33 U. No statistically significant relationship between dose and recurrence was identified. The presence of pain at the first post-operative visit was a predictor of future recurrence (odds ratio 3.92, confidence interval 1.58-9.74, P = 0.003). CONCLUSION: Botox is an effective strategy for CAF. Low doses can be given with good efficacy as highlighted by our audit and has the potential for great cost saving. The best predictor of recurrence is the presence of pain at the first post-procedure visit.

Clostridium colitis: challenges in diagnosis and treatment.

BACKGROUND: Clostridium difficile infection (CDI) has been reported to occur with increasing frequency and with more severe presentations being encountered. This article presents data from The Alfred Hospital highlighting the increased incidence, the increased severity and the broader clinical presentations observed. A case series highlights a variety of clinical scenarios that provided diagnostic and management challenges. We additionally describe a novel form of treatment for fulminant colitis. METHODS: A retrospective review of C. difficile toxin (CDT)-positive and culture-positive cases was performed at The Alfred Hospital (2010-2012). Six cases are then presented as a case series to highlight the broad and atypical types of presentations one may encounter. Finally, a novel method for managing fulminant colitis operatively is presented. RESULTS: A fourfold increase in cases of toxin-positive and culture-positive cases was noted over the initial 14 months of the period of analysis, the rate of cases detected then plateaued. This increase could not be explained by increased testing being undertaken. It is also not associated with increased usage of antibiotics nor with increased patient numbers being treated. CONCLUSION: CDI can present in various clinical forms. In our hospital, the number of cases of toxin-positive and culture-positive detection is increasing. A low threshold is required to identify and adequately treat patients with CDI. Fulminant colitis can be managed successfully with the creation of a diverting loop ileostomy, colonic washout and subsequent antegrade colonic vancomycin enemas.

Colonic transit: what is the impact of a diverting loop ileostomy?

BACKGROUND: Diverting loop ileostomy (DLI) is used following low anterior resections (LAR) or ultra-low anterior resections (ULAR) to reduce anastomotic leak (AL). Preoperative mechanical bowel preparation (MBP) is traditionally used with DLI. However, clearance of the left colon can be achieved with a fleet enema without the physiological compromise of MBP. We aimed to assess colonic transit following DLI in this context. METHODS: A prospective, observational study was performed with patients with rectal cancer undergoing LAR or ULAR in a tertiary colorectal unit with preoperative fleet enema. Radiopaque markers were inserted into the caecum following rectal resection and formation of a DLI with placement confirmed by image intensifier and endoscopy. X-rays were performed at days 1, 3, 5 and 14 post-operation with data collected prospectively. RESULTS: Ten patients (mean age 57, nine males) were enrolled. Mean time to functioning stoma was 1.9 days (range 1-3). There was no movement in the majority of markers in all patients at Day 5 post-operation. In all seven patients with Day 14 X-rays, the majority of markers remained in the right colon. Two patients had delayed AL, with markers found within the pelvis in both of these patients. CONCLUSIONS: This is the first study to assess colonic transit following DLI using fleet enema only, with results suggesting colonic motility is abolished in this setting. The use of a fleet enema without MBP may be sufficient prior to rectal resection surgery when DLI is employed. AL may actually increase colonic transit. Further research is warranted.

Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome.

BACKGROUND: Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. METHODS: A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. RESULTS: 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4-9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. CONCLUSIONS: The majority of patients showed some response to neoadjuvant treatment. Findings of this study indicate tumour response to neoadjuvant CRT improves the long-term outcome, with a better result in patients with pCR.

Distal intestinal obstruction syndrome in cystic fibrosis: presentation, outcome and management in a tertiary hospital (2007-2012).

BACKGROUND: Cystic fibrosis (CF) can result in distal intestinal obstruction syndrome (DIOS) due to inspissated mucus. This paper describes the clinicopathological characteristics of adult CF patients with DIOS and assesses risk factors for surgery. METHODS: A retrospective audit of CF patients at the Alfred Hospital from January 2007 to February 2012 was carried out. Patients who had 'bowel obstruction or constipation' were abstracted from the database, and medical records were reviewed for a diagnosis of DIOS. RESULTS: Forty-five encounters of 35 patients were extracted. Twenty-five (83%) patients were homozygous for the delta F508 mutations, 29 (85%) had pancreatic insufficiency and 15 (44%) had a lung transplant. Patients presented with abdominal pain (96% of encounters), nausea (76% of encounters) and vomiting (67% of encounters). Computed tomography (CT) was performed in 20 episodes. Compared with CT, abdominal X-ray had a sensitivity of 63% (95% confidence interval (CI) 30-89%) and specificity of 33% (95% CI 8-70%) for detecting DIOS with obstruction. Forty-one (91%) encounters resolved with medical management within 2-3 days. Three patients required surgical intervention in four episodes. Previous laparotomy (odds ratio (OR) 28.5, 95% CI 1.3-624, P=0.03) and history of meconium ileus (OR 14, 95% CI 1-192, P<0.05) were statistically significant predictors of progression to surgical management. CONCLUSION: In most patients with DIOS, the obstruction resolves with medical management. Early consultation with a CF service, assessment for a surgical abdomen and involvement of surgeons where appropriate is recommended. A history of previous laparotomy is a risk factor for the need for surgical intervention.

Elective versus emergency abdominal surgery following cardiac transplantation: a Victorian state transplant service experience.

BACKGROUND: Heart transplant patients constitute a unique patient cohort with multiple risk factors predictive of poor surgical outcome. The Alfred Hospital offers the only heart transplant service in Victoria, Australia. This article presents The Alfred Hospital's experience with outcomes of abdominal operations in the heart transplant patient population. METHODS: The statewide cardiothoracic registry was cross-referenced with The Alfred Hospital's electronic hospital database to identify heart transplant patients who had undergone abdominal surgery from 2002 to November 2012. Patients who met the inclusion criteria were evaluated in two groups: elective and emergency surgical settings. In the emergency group, risk factors recorded for poor surgical outcome were high-dose immunosuppression therapy, diabetes and other conventional vascular risk factors. Outcome measures assessed in both groups were length of stay, readmission within 30 days and 1-year mortality. RESULTS: Twelve patients were identified who underwent 13 abdominal operations. Eight were elective cases and five were emergent abdominal operations. The mean length of stay was shorter in the elective group than the emergency group (2.5 days versus 21.3 days). There was one readmission within 30 days, and no mortality at 1 year following elective surgery. In the emergency surgery group, two patients were readmitted within 30 days post-operatively, and there were two deaths observed in this group. CONCLUSION: The Alfred Hospital experience demonstrates that elective abdominal surgery following heart transplantation can be performed safely. Emergent surgery in this group of patients, however, is associated with poorer outcomes.

Continuous wound infusion of local anesthetic for the control of pain after elective abdominal colorectal surgery.

PURPOSE: Local anesthetic wound infusion has been investigated in recent years as a potential alternative to standard analgesic regimens after major surgery. This study investigates the efficacy of a continuous wound infusion of ropivacaine in conjunction with best practice postoperative analgesia after midline laparotomy for abdominal colorectal surgery. METHODS: We performed a randomized, participant and outcome assessor-blinded, placebo-controlled trial on patients presenting for major abdominal colorectal surgery at our institution between December 2003 and February 2006. Patients were allocated to receive ropivacaine 0.54 percent or normal saline via a dual catheter Painbuster Soaker (I-Flow Corporation, OH, USA) continuous infusion device into their midline laparotomy wound for 72 hours postoperatively. RESULTS: A total of 310 patients were included in this study. The continuous wound infusion of ropivacaine after abdominal colorectal surgery conveys minimal benefit compared with saline wound infusion. No statistically significant difference could be shown for: pain at rest, morphine usage, length of stay, mobility, nausea, or return of bowel function. There was a small, statistically significant difference in mean pain on movement on Day 1 for the ropivacaine group (adjusted mean difference -0.6 (range, -1.08 to -0.13)). Although this trend continued on Days 2 and 3, the differences between groups were no longer statistically significant. CONCLUSIONS: Management of pain after major abdominal colorectal surgery is best achieved through adopting a multimodal approach to analgesia. Delivery of ropivacaine to midline laparotomy wounds via a Painbuster Soaker device is safe, but we have not demonstrated any significant clinical advantage over current best practice.

Transanal endoscopic microsurgery: the first 50 cases.

BACKGROUND: Transanal endoscopic microsurgery is a form of minimally invasive rectal surgery first used at Cabrini Hospital in April 1997. This paper presents a prospective analysis of the first 50 cases with a median follow up of 33 months (range 20-48 months). METHODS: Prospective data was obtained from all cases between April 1997 and June 2000. RESULTS: Forty-nine patients (30 men and 19 women) underwent 50 procedures. Thirty-six had benign lesions and 14 malignant. The mean distance of the lower edge of the lesion from the anal verge was 8.7 cm. Three cases were converted to traditional transanal or transabdominal operations. Full-thickness excision was performed on 26 patients and the rectal wound was closed in 13 cases. The mean duration of transanal endoscopic microsurgery was 67 min (range 20-175), with a mean blood loss of 24 mL (0-300). The mean diameter and area of the fixed specimen was 3.7 cm (1.5-9.8) and 11.4 cm2 (0.8-18.9), respectively. Complications included postoperative fever (3), urinary retention (1) and per rectum bleeding (1). There was one death. The mean length of stay was 4 days. Histology confirmed complete excision in 39 (78%) cases and there have been two instances of local recurrence of adenoma (5%). CONCLUSIONS: Transanal endoscopic microsurgery is an effective, safe and cost-beneficial procedure for local excision of selected lesions in the middle and upper thirds of the rectum.