Multivisceral Transplant in a Patient With Portopulmonary Hypertension: A Case Report.

Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was <30 mm Hg with a pulmonary vascular resistance of <300 dynes.s/cm5 on oral sildenafil and intravenous epoprostenol. Intraoperatively, management required comprehensive transfusion protocols, a careful balance between correcting blood loss and preventing thrombosis. Intravenous epoprostenol, sildenafil, milrinone, and inhaled nitric oxide were used to reduce elevated mean pulmonary artery pressure and right ventricular strain associated with vascular clamping, reperfusion, and massive fluid shifts. Nitric oxide and epoprostenol use unleashed antiplatelet effects on a patient already susceptible to coagulopathy. A multimodal and multidisciplinary approach continued throughout the surgery and in the postoperative period, which led to a successful outcome.

A Monte Carlo model of synchrotron radiotherapy shows good agreement with experimental dosimetry measurements: Data from the imaging and medical beamline at the Australian Synchrotron.

Experimental measurement of Synchrotron Radiotherapy (SyncRT) doses is challenging, especially for Microbeam Radiotherapy (MRT), which is characterised by very high dynamic ranges with spatial resolutions on the micrometer scale. Monte Carlo (MC) simulation is considered a gold standard for accurate dose calculation in radiotherapy, and is therefore routinely relied upon to produce verification data. We present a MC model for Australian Synchrotron's Imaging and Medical Beamline (IMBL), which is capable of generating accurate dosimetry data to inform and/or verify SyncRT experiments. Our MC model showed excellent agreement with dosimetric measurement for Synchrotron Broadbeam Radiotherapy (SBBR). Our MC model is also the first to achieve validation for MRT, using two methods of dosimetry, to within clinical tolerances of 5% for a 20×20 mm2 field size, except for surface measurements at 5 mm depth, which remained to within good agreement of 7.5%. Our experimental methodology has allowed us to control measurement uncertainties for MRT doses to within 5-6%, which has also not been previously achieved, and provides a confidence which until now has been lacking in MRT validation studies. The MC model is suitable for SyncRT dose calculation of clinically relevant field sizes at the IMBL, and can be extended to include medical beamlines at other Synchrotron facilities as well. The presented MC model will be used as a validation tool for treatment planning dose calculation algorithms, and is an important step towards veterinary SyncRT trials at the Australian Synchrotron.

Ultra-fast prompt gamma detection in single proton counting regime for range monitoring in particle therapy.

In order to fully exploit the ballistic potential of particle therapy, we propose an online range monitoring concept based on time-of-flight (TOF)-resolved prompt gamma (PG) detection in a single proton counting regime. In a proof of principle experiment, different types of monolithic scintillating gamma detectors are read in time coincidence with a diamond-based beam hodoscope, in order to build TOF spectra of PG generated in a target presenting an air cavity of variable thickness. Since the measurement was carried out at low beam currents (< 1 proton/bunch) it was possible to reach excellent coincidence time resolutions, of the order of 100 ps (σ). Our goal is to detect possible deviations of the proton range with respect to treatment planning within a few intense irradiation spots at the beginning of the session and then carry on the treatment at standard beam currents. The measurements were limited to 10 mm proton range shift. A Monte Carlo simulation study reproducing the experiment has shown that a 3 mm shift can be detected at 2σ by a single detector of ∼1.4 × 10-3 absolute detection efficiency within a single irradiation spot (∼108 protons) and an optimised experimental set-up.

Computer hexapod-assisted orthopaedic surgery provides a predictable and safe method of femoral deformity correction.

AIMS: Computer hexapod assisted orthopaedic surgery (CHAOS), is a method to achieve the intra-operative correction of long bone deformities using a hexapod external fixator before definitive internal fixation with minimally invasive stabilisation techniques. The aims of this study were to determine the reliability of this method in a consecutive case series of patients undergoing femoral deformity correction, with a minimum six-month follow-up, to assess the complications and to define the ideal group of patients for whom this treatment is appropriate. PATIENTS AND METHODS: The medical records and radiographs of all patients who underwent CHAOS for femoral deformity at our institution between 2005 and 2011 were retrospectively reviewed. Records were available for all 55 consecutive procedures undertaken in 49 patients with a mean age of 35.6 years (10.9 to 75.3) at the time of surgery. RESULTS: Patients were assessed at a mean interval of 44 months (6 to 90) following surgery. The indications were broad; the most common were vitamin D resistant rickets (n = 10), growth plate arrest (n = 6) and post-traumatic deformity (n = 20). Multi-planar correction was required in 33 cases. A single level osteotomy was performed in 43 cases. Locking plates were used to stabilise the osteotomy in 33 cases and intramedullary nails in the remainder. Complications included two nonunions, one death, one below-knee deep vein thrombosis, one deep infection and one revision procedure due to initial under-correction. There were no neurovascular injuries or incidence of compartment syndrome. CONCLUSION: This is the largest reported series of femoral deformity corrections using the CHAOS technique. This series demonstrates that precise intra-operative realignment is possible with a hexapod external fixator prior to definitive stabilisation with contemporary internal fixation. This combination allows reproducible correction of complex femoral deformity from a wide variety of diagnoses and age range with a low complication rate. Cite this article: Bone Joint J 2017;99-B:283-8.

Absorbed dose determination in kilovoltage X-ray synchrotron radiation using alanine dosimeters.

Alanine dosimeters from the National Physical Laboratory (NPL) in the UK were irradiated using kilovoltage synchrotron radiation at the imaging and medical beam line (IMBL) at the Australian Synchrotron. A 20 × 20 mm2 area was irradiated by scanning the phantom containing the alanine through the 1 mm × 20 mm beam at a constant velocity. The polychromatic beam had an average energy of 95 keV and nominal absorbed dose to water rate of 250 Gy/s. The absorbed dose to water in the solid water phantom was first determined using a PTW Model 31014 PinPoint ionization chamber traceable to a graphite calorimeter. The alanine was read out at NPL using correction factors determined for 60Co, traceable to NPL standards, and a published energy correction was applied to correct for the effect of the synchrotron beam quality. The ratio of the doses determined by alanine at NPL and those determined at the synchrotron was 0.975 (standard uncertainty 0.042) when alanine energy correction factors published by Waldeland et al. (Waldeland E, Hole E O, Sagstuen E and Malinen E, Med. Phys. 2010, 37, 3569) were used, and 0.996 (standard uncertainty 0.031) when factors by Anton et al. (Anton M, Büermann L., Phys Med Biol. 2015 60 6113-29) were used. The results provide additional verification of the IMBL dosimetry.

Routes of early enteral nutrition following oesophagectomy.

Introduction Oesophagectomy for cancer is a challenging procedure with a five-year overall survival rate of 15-20%. Early enteral nutrition following oesophagectomy is a crucial component of the postoperative recovery and carries a significant impact on the outcome. Different methods of enteral feeding were conducted in our unit. The aim of this study was to examine the efficacy and safety of nasojejunal tube (NJT), jejunostomy tube (JT) and pharyngostomy tube (PT) feeding after oesophagectomy. Methods A retrospective review was carried out of prospectively collected data on patients with oesophageal cancer who underwent an oesophagectomy between 2011 and 2014. The primary outcome was feeding tube related complications such as occlusion, dislocation and leak. The secondary outcomes were length of stay and 30-day morbidity. Results A total of 90 oesophagectomies were included in the study. A NJT was inserted in 41 patients (45.6%), a JT was used in 14 patients (15.5%) and a PT was the route for enteral nutrition in 35 patients (38.9%). In total, five patients (5.5%) developed tube related complications. There were no tube related complications in the NJT group but one JT patient (7.1%) developed tube related cellulitis (p=0.189) and four PT patients (11.4%) developed tube related haemorrhage (p=0.544), tube dislocation (p=0.544) or cellulitis (p=0.189). The median length of stay and 30-day postoperative morbidity were similar between the groups. Conclusions NJT feeding is a less invasive, feasible route for early enteral nutrition following oesophagectomy. A randomised controlled trial is recommended to verify these findings.

Absolute dosimetry on a dynamically scanned sample for synchrotron radiotherapy using graphite calorimetry and ionization chambers.

The absolute dose delivered to a dynamically scanned sample in the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter anticipated to be established as a primary standard for synchrotron dosimetry. The calorimetry was compared to measurements using a free-air chamber (FAC), a PTW 31 014 Pinpoint ionization chamber, and a PTW 34 001 Roos ionization chamber. The IMBL beam height is limited to approximately 2 mm. To produce clinically useful beams of a few centimetres the beam must be scanned in the vertical direction. In practice it is the patient/detector that is scanned and the scanning velocity defines the dose that is delivered. The calorimeter, FAC, and Roos chamber measure the dose area product which is then converted to central axis dose with the scanned beam area derived from Monte Carlo (MC) simulations and film measurements. The Pinpoint chamber measures the central axis dose directly and does not require beam area measurements. The calorimeter and FAC measure dose from first principles. The calorimetry requires conversion of the measured absorbed dose to graphite to absorbed dose to water using MC calculations with the EGSnrc code. Air kerma measurements from the free air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. The two ionization chambers are secondary standards requiring calibration with kilovoltage x-ray tubes. The Roos and Pinpoint chambers were calibrated against the Australian primary standard for air kerma at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Agreement of order 2% or better was obtained between the calorimetry and ionization chambers. The FAC measured a dose 3-5% higher than the calorimetry, within the stated uncertainties.

High spatial resolution dosimetric response maps for radiotherapy ionization chambers measured using kilovoltage synchrotron radiation.

Small circular beams of synchrotron radiation (0.1 mm and 0.4 mm in diameter) were used to irradiate ionization chambers of the types commonly used in radiotherapy. By scanning the chamber through the beam and measuring the ionization current, a spatial map of the dosimetric response of the chamber was recorded. The technique is able to distinguish contributions to the large-field ionization current from the chamber walls, central electrode and chamber stem. Scans were recorded for the NE 2571 Farmer chamber, the PTW 30013, IBA FC65-G Farmer-type chambers, the NE 2611A and IBA CC13 thimble chambers, the PTW 31006 and 31014 pinpoint chambers, the PTW Roos and Advanced Markus plane-parallel chambers, and the PTW 23342 thin-window soft x-ray chamber. In all cases, large contributions to the response arise from areas where the incident beam grazes the cavity surfaces. Quantitative as well as qualitative information about the relative chamber response was extracted from the maps, including the relative contribution of the central electrode. Line scans using monochromatic beams show the effect of the photon energy on the chamber response. For Farmer-type chambers, a simple Monte Carlo model was in good agreement with the measured response.

The outcome following fixation of bicondylar tibial plateau fractures.

Unstable bicondylar tibial plateau fractures are rare and there is little guidance in the literature as to the best form of treatment. We examined the short- to medium-term outcome of this injury in a consecutive series of patients presenting to two trauma centres. Between December 2005 and May 2010, a total of 55 fractures in 54 patients were treated by fixation, 34 with peri-articular locking plates and 21 with limited access direct internal fixation in combination with circular external fixation using a Taylor Spatial Frame (TSF). At a minimum of one year post-operatively, patient-reported outcome measures including the WOMAC index and SF-36 scores showed functional deficits, although there was no significant difference between the two forms of treatment. Despite low outcome scores, patients were generally satisfied with the outcome. We achieved good clinical and radiological outcomes, with low rates of complication. In total, only three patients (5%) had collapse of the joint of > 4 mm, and metaphysis to diaphysis angulation of 75º, and five patients (9%) with displacement of > 4 mm. All patients in our study went on to achieve full union. This study highlights the serious nature of this injury and generally poor patient-reported outcome measures following surgery, despite treatment by experienced surgeons using modern surgical techniques. Our findings suggest that treatment of complex bicondylar tibial plateau fractures with either a locking plate or a TSF gives similar clinical and radiological outcomes.

Transgenic IGF-IR overexpression induces mammary tumors with basal-like characteristics, whereas IGF-IR-independent mammary tumors express a claudin-low gene signature.

Molecular profiling has allowed a more precise classification of human cancers. With respect to breast cancer, this approach has been used to identify five subtypes; luminal A, luminal B, HER2-enriched, basal-like and claudin-low. In addition, this approach can be used to determine the type of tumor represented by particular cell lines or transgenic animal models. Therefore, this approach was utilized to classify the mammary tumors that develop in MTB-IGFIR transgenic mice. It was determined that the primary mammary tumors, which develop due to elevated expression of the type I insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells, most closely resemble murine tumors with basal-like or mixed gene expression profiles and with human basal-like breast cancers. Downregulation of IGF-IR transgene in MTB-IGFIR tumor-bearing mice leads to the regression of most of the tumors, followed by tumor reappearance in some of the mice. These tumors that reappear following IGF-IR transgene downregulation do not express the IGF-IR transgene and cluster with murine mammary tumors that express a mesenchymal gene expression profile and with human claudin-low breast cancers. Therefore, IGF-IR overexpression in murine mammary epithelial cells induces mammary tumors with primarily basal-like characteristics, whereas tumors that develop following IGF-IR downregulation express a gene signature that most closely resembles human claudin-low breast tumors.

A rare case of segmental small bowel pneumatosis intestinalis: A case report.

INTRODUCTION: Pneumatosis intestinalis is a rare condition affecting 0.03% of the population. It has a myriad of aetiological causes and hence presentation can vary immensely. The management of symptomatic pneumatosis intestinalis in an acute and outpatient setting remains a challenge to both physicians and surgeons. CASE PRESENTATION: We present a case of a 79 year old who presented in a gastroenterology outpatients department with a history suggestive of intermittent small bowel obstruction associated with abdominal pain aggravated by eating and posture. He was found to have signs suggestive of Marfan's syndrome. Computed tomography demonstrated extensive pneumatosis intestinalis of the small bowel. Due to deterioration in symptoms, an exploratory laparotomy was performed demonstrating segmental small bowel pneumatosis intestinalis secondary to a hypermobile mesentery. CONCLUSION: This case highlights the importance of both surgical and gastroenterology expertise in successfully managing symptomatic pneumatosis intestinalis.

Arteriovenous fistulae vs. arteriovenous grafts: a retrospective review of 1,700 consecutive vascular access cases.

OBJECTIVE: Vascular access (VA) procedures are rapidly becoming the most prevalent surgery in the United States. It is estimated that there will be over 500,000 VA procedures done this year. Previously, surgeons in the US were attempting many more non-autogenous grafts than autogenous fistulae. In recent years, there has been a great push called 'Fistula First' to promote arteriovenous fistulae (AVF) as the first line of treatment vs. nonautogenous grafts. The goal of this investigation is to determine if too many fistulae are now being performed without attention to specific patient profiles. METHODS: A retrospective review of 1700 consecutive cases was performed by one surgeon at one institution between 1997 and 2005. Patients were categorized by demographics, co-morbidities, previous access procedures, access location, and type of graft. Patency was calculated. Kaplan-Meier, Cox regression and the Log Rank Test were used to analyze data. Access endpoints and complications were also documented. RESULTS: The study reviewed 1700 procedures. The median age was 52 (60.2% male) with 58.7% fistulae and 41.3% grafts. Median patency time was 10 months, with no statistically significant difference between access types. There was no significant difference in length of patency when comparing upper arm (70.1%), lower arm (24.5%) and thigh (5.4%). Graft infection rate was 9.5% and fistula infection rate was 0.9% (p<0.001). The overall infection rate was 4.5%, and decreased patency significantly (4 vs. 11 months). Thrombosis occurred in 24.7% of grafts and 9.0% of fistulae. Thrombosed grafts had better salvage rates (8 vs. 4 months, p<0.001). The data showed diabetes, HTN and HIV have no overall impact on patency. CONCLUSIONS: AVF and grafts are both useful in providing VA for patients requiring hemodialysis. Our data shows that grafts are equivalent in long-term patency. Therefore, it is apparent in those patients who are not candidates for an AV fistula; an AV graft for VA should be placed.

Complete clinical response after preoperative chemoradiation in rectal cancer: is a "wait and see" policy justified?

PURPOSE: A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of "waiting to see" and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery. RESULTS: In total, 218 Phase I/II or retrospective studies and 28 Phase III trials of preoperative radiotherapy or chemoradiation were identified: 96 percent of trials documented the pathologic complete response, but only 38 trials presented data on the achievement of a complete clinical response/partial clinical response. Only five studies were found in which patients with clinically staged T2/T3 tumors were treated with radiotherapy/chemoradiation and did not routinely proceed to surgery and also reported on the long-term outcome of a "wait and see" policy. DISCUSSION: It remains uncertain whether the degree of response to chemoradiation in terms of complete clinical response or pathologic complete response is a useful clinical end point. Studies that include T3 rectal cancer are associated with high local recurrence rates after nonsurgical treatment. Few studies report long-term outcome after achievement of a complete clinical response. CONCLUSIONS: The end point of complete clinical response is inconsistently defined and seems insufficiently robust with only partial concordance with pathologic complete response. The rationale of a "wait and see" policy when complete clinical response status is achieved relies on retrospective observations, which are currently insufficient to support this policy except in patients who are recognized to be unfit for or refuse radical surgery.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the preoperative staging of thoracic oesophageal and gastro-oesophageal junction cancer: a prospective study.

BACKGROUND: The pre-operative staging in oesophageal cancer is often challenging and underestimation of the extent of the disease may lead to unnecessary surgery. AIM: To audit the use and assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) as a staging tool for thoracic oesophageal and gastro-oesophageal junction (GOJ) cancers in our oncological surgical practice. PATIENTS AND METHODS: Over a 3 year period, between 2002 and 2004, 134 patients with thoracic oesophageal or GOJ cancer were referred to our unit for treatment. The standard preoperative staging investigation in all cases was CT (thorax, abdomen and pelvis). A preoperative FDG-PET scan was further requested in 22 patients. The case notes of all the patients that underwent a FDG-PET scan were reviewed and compared with the preoperative imaging, the operative findings and the histopathology of the resected tumours. RESULTS: Eighteen men and 4 women with a median age of 65 (range 43-79) years were studied. After FDG-PET, 13 out of 22 patients (59%) were deemed suitable for tumour resection. Twelve of the 13 patients were fit to undergo surgery. At laparotomy, 2 of those (17%) were found inoperable due to widespread disease. The sensitivity of CT versus FDG-PET to detect infiltrated lymph nodes was 29% (95% CI: 3-70) versus 71% (95% CI: 29-96) (P=0.0412), whereas both tests had 67% specificity (95% CI: 9-99) in detecting lymph nodes. The sensitivity and the specificity of CT versus FDG-PET to detect distant organ metastases (M1b) were 33% (95% CI: 4-77) and 88% (95% CI: 47-99) versus 50% (95% CI: 6-93) and 100% (95% CI: 69-100), respectively (P>0.05). The FDG-PET regarding the N and M status differed from the CT in 11 patients and led to modification of the planned management in 5 of them. CONCLUSIONS: FDG-PET is more accurate than CT in defining N and M status. It can result in a reduction of unnecessary surgery in a significant number of patients. The combined PET-CT scan as a single imaging modality is expected to further improve diagnostic accuracy of FDG-PET.

Reproducibility of the Gartland classification for supracondylar humeral fractures in children.

PURPOSE: To evaluate the intra- and inter-observer reproducibility of the Gartland radiographic classification for supracondylar humeral fractures in children. METHODS: Anteroposterior and lateral radiographs of 50 supracondylar humeral fractures in children were graded on 2 separate occasions by 4 orthopaedic surgeons according to the Wilkins modification of the Gartland classification. Data were analysed by calculating the Kappa values for intra- and inter-observer agreement to indicate the reproducibility of the classification. RESULTS: There was moderate inter-observer agreement, except for poor agreement over type I fractures. Type II fractures only showed fair to moderate agreement. Type III fractures and the flexion group showed good to very good agreement. Intra-observer agreement was good to very good. CONCLUSION: Surgeons should treat paediatric supracondylar humeral fractures based on an assessment of the degree of displacement rather than by employing the Gartland classification.

Combined surgery and chemoradiation as a treatment for the Buschke-Löwenstein tumour.

BACKGROUND: The Buschke-Löwenstein tumour (BLT) or giant condyloma acuminata is a rare disease which affects the anogenital region. Although histologically benign, it behaves in a malignant fashion, infiltrating the surrounding tissues. The morbidity and mortality from this tumour is high, as is the risk of recurrence following treatment. It lies on the continuum between the benign condylomata acuminata and squamous cell carcinoma. The human papillomavirus is implicated in its aetiology. Treatment is controversial, with topical chemotherapy, radiotherapy, immunotherapy and radical surgery all having been employed. Chemoradiation remains the mainstay of treatment for anal cancers but has not been routinely employed in the management of the BLT without squamous cell carcinoma transformation. METHODS: Two cases of extensive perineal BLT treated with chemoradiation and subsequent surgical excision are presented. RESULTS: The first patient had a good symptomatic response to the chemoradiation but unfortunately died of recurrent disease following surgery. The second patient had a macroscopically complete response to chemoradiation and remains well following abdominoperineal excision. CONCLUSION: Pre-operative chemoradiation has proved to be useful in management for histologically proven benign BLT

Tube pharyngostomy: a simple method for prolonged intubation of the foregut following oesophagogastric surgery.

Tube pharyngostomy involves the percutaneous passage of a tube through the pharynx as an alternative to nasogastric intubation. We use this method for upper gastrointestinal decompression after oesophagectomies and total gastrectomies where prolonged intubation of the foregut is anticipated. It is simple to perform and very well tolerated as compared to a nasogastric tube. The pharyngostomy tube can also be used for enteral feeding. We present here the technique in detail and our experience with 67 procedures over the last 6 years where only few minor complications were encountered. We also review the literature for previous reports of pharyngostomy.

Endoscopic palliation of malignant dysphagia: a challenging task in inoperable oesophageal cancer.

BACKGROUND: The main goal when managing patients with inoperable oesophageal cancer is to restore and maintain their oral nutrition. The aim of the present study was to assess the value of endoscopic palliation of dysphagia in patients with oesophageal cancer, who either due to advanced stage of the disease or co-morbidity are not suitable for surgery. PATIENTS AND METHODS: All the endoscopic palliative procedures performed over a 5-year period in our unit were retrospectively reviewed. Dilatation and insertion of self-expandable metal stents (SEMS) were mainly used for tight circumferential strictures whilst ablation with Nd-YAG laser was used for exophytic lesions. All procedures were performed under sedation. RESULTS: Overall 249 palliative procedures were performed in 59 men and 40 women, with a median age of 73 years (range 35-93). The median number of sessions per patient was 2 (range 1-13 sessions). Palliation involved laser ablation alone in 24%, stent insertion alone in 22% and dilatation alone in 13% of the patients. In 41% of the patients, a combination of the above palliative techniques was applied. A total of 45 SEMS were inserted. One third of the patients did not receive any other palliative treatment, whilst the rest received chemotherapy, radiotherapy or chemoradiotherapy. Swallowing was maintained in all patients up to death. Four oesophageal perforations were encountered; two were fatal whilst the other two were successfully treated with covered stent insertion and conservative treatment. The median survival from diagnosis was 10.5 months (range 0.5-83 months) and the median survival from 1st palliation was 5 months (range 0.5-68.5 months). CONCLUSION: Endoscopic interventions are effective and relatively safe palliative modalities for patients with oesophageal cancer. It is possible to adequately palliate almost all cases of malignant dysphagia. This is achieved by expertise in combination treatment.

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3-T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.

The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy.

AIMS: To determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer. MATERIALS AND METHODS: One hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6-12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m2 via a 60-min infusion on days 1-5 and 29-33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (< or = 1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40). RESULTS: After SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0-21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36-1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26-0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55-5.97). CONCLUSIONS: The number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.