Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

BACKGROUND: Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. METHODS: Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. RESULTS: Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. CONCLUSIONS: Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

Thromboembolism during neoadjuvant therapy for rectal cancer: a systematic review.

AIM: Thromboembolism (TE) is a common, costly and morbid complication that is also associated with decreased survival in cancer patients. However, the risk of cancer-associated TE varies because of the multitude of patient-, cancer- and treatment-related influences. Thromboprophylaxis (TP) is currently not widely adopted in the ambulant population. A review of the literature was undertaken to determine the rate of TE and the benefit of TP in patients with rectal cancer during neoadjuvant therapy (nT). METHOD: A systematic literature search of electronic databases, including PubMed and Embase, was performed (1995-2012) for all studies assessing nT in rectal cancer. Data were extracted and used to assess study design, patient demographic and clinical characteristics, treatment protocols and TE incidence. A systematic review was conducted to identify the rates of TE. The search strategy included text terms and MeSH headings for TP, rectal cancer and nT. RESULTS: Twelve of 86 studies met quality criteria for reporting TE complications and described 10 pulmonary emboli and three deep-vein thromboses in 3375 patients (overall TE rate = 0.38%). Ninety per cent of pulmonary emboli reported were fatal, suggesting significant under-reporting of TE events, even in high-quality studies. CONCLUSION: The risk of fatal pulmonary embolism in studies examining nT in rectal cancer that reported complications systematically was one in 375 (0.27%; 95% CI: 0.09-0.44%). The overall TE rate, as well as the effectiveness of TP during nT, remains unknown. TE events should be systematically reported using common terminology frameworks in cancer studies.

Short-term temperament tests in beef cattle relate to long-term measures of behavior recorded in the home pen.

Handling temperament tests for beef cattle have been related to production traits, with calmer temperaments having greater growth rates. In most tests of temperament or personality, observation of the animal takes place over a short period of time, sometimes completed in a matter of minutes. This study investigated whether behavior observed in a temperament test was reflective of the steer's behavior in the home pen. Indoor-housed, crossbred, Bos taurus beef steers (n = 67) were fitted with triaxial activity monitors (IceTags; IceRobotics Ltd., South Queensferry, Edinburgh, Scotland) and activity was recorded for 2 periods of 14 d each. Also, each steer was scored on 4 measures of temperament: 2 handling tests (flight speed and chute score) and 2 feeding behavior scores (aggression at feeders and ability to displace at feeders). Each temperament observation was repeated 4 times, with repeatability of the traits ranging from 0.23 (aggression) to 0.48 (flight speed). Activity measures derived from the accelerometer data, such as bout lengths, were found to be highly repeatable between the 2 periods of activity monitoring (repeatabilities of 0.67 and 0.70 for average lying bout duration and average standing bout duration, respectively). Steers with high flight speeds were also more active in the home pen (MotionIndex: rs = 0.35, P = 0.004; average step count: rs = 0.34, P = 0.005) than steers with low flight speeds. Steers that were more capable of displacing other steers at feeders had longer average standing bout durations (rs = 0.26, P = 0.036), which were more variable (standing time SD: rs = 0.27, P = 0.030), and lay down for less time (rs = -0.35, P = 0.004). No correlations were found between aggression at feeders or chute score and home pen behavior. Results of this study are the first to demonstrate that short-term temperament tests are related to longer-term behavior data in beef steers and these results should be taken into consideration for future research.

Enterocutaneous fistula: a single-centre experience.

BACKGROUND: Enterocutaneous fistulae (ECFs) present a difficult management problem and can cause significant morbidity. The aim of the study was to assess the outcome of these patients. METHODS: A retrospective chart review of all patients with ECF managed at a tertiary centre between 1996 and 2006 was performed. Demographic, management and outcome data including ECF closure, morbidity and mortality were recorded. RESULTS: A total of 33 patients (17 male) were identified with ECF (median age: 63 years, range: 27-84). The primary aetiology was Crohn's (30%), anastomotic leak (24%), iatrogenic (18%), mesh (6%), neoplasia (6%) and other (16%). Definitive surgery was undertaken in 21 (64%) at a median of 6.4 months (0.4-72 range) following presentation. Twenty percent of patients required emergency surgical intervention and 5 patients required preoperative total parenteral nutrition (TPN). Surgical management was formal resection and reanastomosis in all patients, with a mean operative time of 4.75 h (standard deviation = 1.8). The median hospital stay for the operative group was 19 days (7-85). Four patients required post-operative TPN with one patient requiring home TPN. Fistula closure rate was 97% (operative group: 21 out of 21; non-operative group: 11 out of 12). Mean follow-up was 37.3 months (0.5-217). Six (19%) operative patients developed fistula recurrence. There were two deaths at 2 and 5 months (fistula aetiology malignant colonic fistula and radiation enteritis, respectively). CONCLUSION: Patients with ECF can be treated with low morbidity and low recurrence rate in a multidisciplinary setting. We believe that patients with ECF should be referred to specialist units for management.

The role of intraoperative radiotherapy in solid tumors.

BACKGROUND: Combined multimodality therapy is becoming standard treatment for many solid tumors, but the role of intraoperative radiotherapy in the management of solid tumors remains uncertain. The aim is to review the indication, application, and outcomes of intraoperative radiotherapy in the management of nongynecological solid tumors. METHODS: A literature search was performed using Medline, Embase, Ovid, and Cochrane database for studies between 1965 and 2008 assessing intraoperative radiotherapy, using the keywords "intraoperative radiotherapy," "colorectal cancer," "breast cancer," "gastric cancer," "pancreatic cancer," "soft tissue tumor," and "surgery." Only publications in English with available abstracts and regarding adult humans were included, and the evidence was critically evaluated. RESULTS: Our search retrieved 864 publications. After exclusion of nonclinical papers, duplicated papers and exclusion of brachytherapy papers, 77 papers were suitable to assess the current role of intraoperative radiotherapy. The clinical application and evidence base of intraoperative radiotherapy for each cancer is presented. CONCLUSIONS: Current studies in all common cancers show an additional benefit in local recurrence rates when intraoperative radiotherapy is included in the multimodal treatment. However, intraoperative radiotherapy may not improve overall survival and has significant morbidity depending on the site of the tumor. Intraoperative radiotherapy does have a role in the multidisciplinary management of solid tumors, but further studies are required to more precisely determine the extent of benefit.

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.

Early feeding after elective open colorectal resections: a prospective randomized trial.

BACKGROUND: A period of starvation after colorectal resections to allow for resolution of the clinical evidence of ileus has been an unchallenged surgical doctrine until recent times. A prospective randomized trial comparing early feeding to traditional management in patients undergoing open elective colorectal resections is reported. METHODS: Patients undergoing elective intraperitoneal colorectal resections without stoma formation were randomized to either an early feeding or control group. The early feeding group were allowed free fluids from 4 h postoperatively progressing to a solid diet from the first postoperative day as they tolerated it. The control group remained nil orally until passage of flatus or bowel motion and were then commenced on fluids progressing to solids over 24-48 h. RESULTS: There were 40 patients in each group well matched for age, sex, type and duration of operation, method of analgesia and mobilization. Thirty-two patients (80%) in the early feeding group tolerated a diet within 48 h. There was no significant difference in the rate of vomiting, nasogastric reinsertion or complications. The early feeding group tolerated a diet, passed flatus, used their bowels, and were discharged from hospital significantly earlier than the control group. CONCLUSION: Early feeding after elective open colorectal resections is successfully tolerated by the majority of patients, leading to earlier resolution of ileus and hospital discharge.

Ileostomy dysfunction with adjuvant chemoradiation for rectal carcinoma requiring in-hospital management: a cause for concern.

The morbidity and mortality of 20 patients undergoing adjuvant chemoradiation for rectal carcinoma was documented. Of nine patients with defunctioning loop ileostomies, two suffered from dehydration and electrolyte disturbance during the treatment phase and required admission to hospital. These two cases suggest that dehydration and electrolyte disturbance from high stomal output could be a serious problem following chemoradiation therapy in patients with an ileostomy.

Early experience with postoperative adjuvant chemoradiation for rectal carcinoma: focus on morbidity.

The morbidity of postoperative adjuvant chemoradiation for primary extraperitoneal rectal carcinoma is documented in this ongoing study. Patients who presented electively for resection with ACPS Dukes' B and C extraperitoneal rectal carcinoma during the period January 1990 to June 1993 were studied. Twenty patients received postoperative adjuvant chemoradiation. At a mean follow up of 32.6 months (s.d. 7.1), three of the 20 patients who received combined adjuvant chemoradiation reported no side effects. In 10 patients (50%) complications were classified as minor. In the remaining seven patients (35%) major complications of therapy occurred. There were no deaths. These early results highlight the morbidity of postoperative adjuvant chemoradiation that has been presumed but not documented.

Reversal of Hartmann's procedure: effect of timing and technique on ease and safety.

PURPOSE: The optimal time for reversal of Hartmann's procedure is controversial. Significant operative difficulty and morbidity have been reported for Hartmann's reversal. The purpose of this study was to examine 11 years' experience with Hartmann's reversal, with particular attention to rate of reversibility, operative difficulty, and timing of reversal. METHODS: Case records of all patients undergoing either Hartmann's procedure or Hartmann's reversal at St. Vincent's Hospital between 1981 and 1991 were examined. Patients having Hartmann's reversal were divided into an early group (before 15 weeks) and a late group (after 15 weeks). These groups were compared in terms of morbidity and mortality, bed stay, and operative difficulty. RESULTS: Hartmann's procedure was performed on 111 patients, mostly for advanced cancer and complicated diverticular disease. Of 96 patients who survived, 50 (52 percent) underwent reversal. Of those with diverticular disease, 40 of 48 (83 percent) underwent reversal. Mortality for Hartmann reversal was 2 percent; anastomotic leak rate 4 percent; and overall complication rate 26 percent. Early reversal was performed in 13 patients and late reversal in 37 patients. There was no difference between these groups in mortality, morbidity, or anastomotic leakage. However, bed stay was longer in the early group and graded operative difficulty greater. In particular, cases in which adhesion density was most severe and in which accidental enterotomy occurred were more common in the early group (P = 0.02, Miettinen's modification of Fisher's exact test). CONCLUSIONS: Hartmann's reversal can be performed with an acceptable morbidity and mortality in most survivors of complicated diverticular disease. Operative difficulty appears to be less after a delay of 15 weeks.

Colonoscopy in a private hospital: continuous quality improvement in practice.

This paper documents serial audits on technical aspects of the performance of fibre-optic examination of the large intestine by a number of proceduralists, in one institution, over 7 years. The completeness of the procedure and the associated morbidity are recorded and compared with results reported in the world literature. The study provides a clear demonstration of continuous quality improvement in practice.

Pig-bel but no pig: enteritis necroticans acquired in Australia.

OBJECTIVE: To report a case of enteritis necroticans acquired in Australia, and to review the history, epidemiology, pathogenesis, clinical features, management and prevention of this disease. CLINICAL FEATURES: A 44-year-old diabetic and alcoholic restaurateur of Chinese-Malay origin, who had been living in Australia for over 20 years, was admitted to hospital with bloody diarrhoea which progressed to fulminant toxaemia and circulatory collapse, and ultimately required laparotomy. Typical pathological features and the isolation of Clostridium perfringens type C from faeces confirmed the diagnosis of enteritis necroticans. INTERVENTION AND OUTCOME: He was treated initially with ampicillin, gentamicin, metronidazole and chloramphenicol, and later with penicillin and metronidazole, and he required large volumes of intravenously administered fluid and blood for his toxaemic, hypotensive state. Laparotomy was performed as a life-saving procedure. Despite a lengthy convalescence, the patient recovered. CONCLUSIONS: Enteritis necroticans is a rare disease in developed countries, however it is likely to be underdiagnosed. Clinicians are encouraged to be on the alert for signs of severity that may indicate the need for laparotomy in a predisposed individual with features of this condition.

Splenectomy for trauma: morbidity, mortality and associated abdominal injuries.

Management of ruptured spleen still frequently requires splenectomy. A retrospective analysis of patients undergoing splenectomy for trauma at Box Hill Hospital, Melbourne, over a 14-year period was conducted; 141 of 145 cases were due to blunt trauma. The mortality rate was 10% and all deaths occurred as a result of road traffic accidents. The overall complication rate was 43%, varying from 25% in those with an isolated splenic injury to 100% with multiple system injuries. There was zero incidence of associated intra-abdominal injury in the group sustaining a ruptured spleen as a result of a fall, assault or sporting injury, in contrast to a nearly 50% incidence following road traffic and bicycle accidents. Whether these associated injuries would have been neglected had laparotomy for splenic trauma not been performed is uncertain, and so non-operative management of splenic trauma remains contentious, particularly in cases following vehicular accidents.

Relic pleistocene permafrost, Western arctic, Canada.

Icy layers and interbedded frozen sediments along the Arctic Coastal Plain of northwestern Canada have been subjected to glacial deformation. Radio-carbon dates indicate that the deformation took place more than 40,000 years ago.