RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases.

BACKGROUND: Genetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT). PATIENTS AND METHODS: Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004-2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan-Meier curves were used to determine overall survival. RESULTS: One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4-184.9 months) and median OS was 38.7 months (95% CI 32.4-44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402-16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995-2.843, p = 0.052). CONCLUSIONS: RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.

Temporal improvements in loco-regional failure and survival in patients with anal cancer treated with chemo-radiotherapy: treatment cohort study (1990-2014).

BACKGROUND: We evaluated oncological changes in patients with squamous cell carcinoma of the anus (SCCA) treated by chemoradiotherapy (CRT) from a large UK institute, to derive estimates of contemporary outcomes. METHODS: We performed a treatment-cohort analysis in 560 patients with non-metastatic SCCA treated with CRT over 25 years. The primary outcomes were 3-year loco-regional failure (LRF), 5-year overall survival (OS), and 5-year cancer-specific survival (CSS). We developed prediction models; and overlaid estimates on published results from historic trials. RESULTS: Age distributions, proportions by gender and cT stage remained stable over time. The median follow-up was 61 (IQR: 36-79) months. Comparing the first period (1990-1994) with the last period (2010-2014), 3-year LRF declined from 33 to 16% (Ptrends < 0.001); 5-year OS increased from 60% to 76% (Ptrends = 0.001); and 5-year CCS increased from 62% in to 80% (Ptrends = 0.001). For 2020, the models predicted a 3-year LRF of 14.7% (95% CIs: 0-31.3); 5-year OS of 74.7% (95% CIs: 54.6-94.9); and 5-year CSS of 85.7% (95% CIs: 75.3-96.0). Reported oncological outcomes from historic trials generally underestimated contemporary outcomes. CONCLUSIONS: Current and predicted rates for 3-year LRF and 5-year survivals are considerably improved compared with those in historic trials.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei (PMP) from perforated low-grade appendiceal mucinous neoplasms (LAMN II). In a selected group of LAMN II patients without established PMP, CRS/HIPEC can be performed laparoscopically (L-CRS/HIPEC); however the short-term benefits and safety of this approach have yet to be determined. This study aims to determine the short-term outcomes from a series of L-CRS/HIPEC LAMN II patients compared to those who have undergone a similar open operation (O-CRS/HIPEC) for low-volume PMP. METHODS: LAMN II patients undergoing L-CRS/HIPEC at a UK national peritoneal tumour centre were compared to O-CRS/HIPEC patients (peritoneal cancer index ≤ 7). Outcomes of interest included Clavien-Dindo complication grade, operative time, blood transfusions, high dependency unit (HDU) admission, length of hospital stay, and histopathological findings. RESULTS: 55 L-CRS/HIPEC were compared to 29 O-CRS/HIPEC patients (2003-2017). Groups were matched for age, sex, and procedures. Median operative time was 8.8 (IQR 8.1-9.5) h for L-CRS/HIPEC versus 7.3 (IQR 6.7-8) h for O-CRS/HIPEC (Mann-Whitney test p < 0.001). Post-operative HDU admission was 56% versus 97% (OR 0.04 95% CI 0.01-0.34) and median length of stay = 6 (IQR 5-8) versus 10 (IQR 8-11) days (p < 0.001) for L- versus O-CRS/HIPEC. Despite a normal pre-operative CT scan, 13/55 (23.6%) L-CRS/HIPEC patients had acellular mucin and 2/55 (3.5%) had mucin with epithelium present in their specimens. Residual appendix tumour was identified in 2/55 patients (3.6%). Clavien-Dindo Grade 1-4 complications were similar in both groups with no mortality. CONCLUSION: L-CRS/HIPEC for LAMN II takes longer; however patients have significantly reduced length of HDU and overall stay, without increased post-operative complications. A significant proportion of LAMN II patients undergoing L-CRS/HIPEC have extra-appendiceal acellular mucin with some cases demonstrating residual cellular epithelium from the LAMN II. The risk of these patients developing PMP without surgery is under current review.

Laparoscopic Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (L-CRS/HIPEC) for Perforated Low-Grade Appendiceal Mucinous Neoplasm (LAMN II).

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei resulting from a perforated low-grade appendiceal mucinous neoplasm (LAMN II). In patients with localized disease, a laparoscopic procedure (L-CRS/HIPEC) can be undertaken. METHODS: This video demonstrates L-CRS/HIPEC in a 66-year-old male who had previously undergone an appendicectomy for an LAMN II lesion. The preoperative computed tomography (CT) scan suggested disease localized to the right iliac fossa. However, laparoscopic assessment unexpectedly revealed disease in the pelvis and on the right hemidiaphragm and liver surface. RESULTS: A technique for treating the thin film of mucin in the pelvis and on the right hemidiaphragm is demonstrated. The liver is mobilized to facilitate ablation of mucin on the serosal surface of the right lobe. Tips and tricks for starting the omentectomy, dealing with the vascular pedicle, and completing the dissection in the left upper quadrant are shown. The Peritoneal Cancer Index (PCI) score was 5 (3 for the right upper quadrant, 1 for the pelvis, 1 for the small bowel), and the cytoreduction score was CC-1. The operative duration was 8.5 h, and length of hospital stay was 5 days. The patient returned to work after 6 weeks. DISCUSSION: L-CRS/HIPEC can be performed when patients are unexpectedly found to have disease, provided the appendiceal pathology is low grade and the PCI score is low. There are potential benefits to this approach, with a shorter length of hospital stay and faster functional recovery when compared with traditional open surgery.

Tuberculosis in Far North Queensland, Australia: a retrospective clinical audit.

BACKGROUND: Compared with global numbers, Australia has enjoyed relatively good tuberculosis control over the past 30 years, with an annual incidence of 5.7 per 100 000 population. Thanks to its unique geography and proximity to high-burden countries, such as Papua New Guinea (PNG), Far North Queensland (FNQ) has previously been shown to have higher rates of tuberculosis compared with both the state and national average. AIMS: To document tuberculosis epidemiology in FNQ compared to two previous audits of the region. METHODS: Retrospective clinical audit of all cases of tuberculosis reported to the Cairns Tuberculosis Control Unit between 2006 and 2016. RESULTS: A total of 453 cases were identified, 374 with microbiological/histological confirmation. There were 312 cases of pulmonary tuberculosis, 155 extrapulmonary and 21 disseminated. Three-quarters (327/453) were identified in the overseas-born population. Of the remaining 126 cases, 40 were Torres Strait Islander and 19 Aboriginal Australians. Where drug susceptibility was known, two-thirds (247/368) were fully sensitive, 42 mono-resistant, 78 multidrug resistant and 1 extensively drug resistant. Rates of human immunodeficiency virus co-infection were less than 3% (10/362). CONCLUSION: Tuberculosis remains a significant problem in FNQ. Case numbers have increased threefold since the 1990s. Much of the increase comes from the overseas-born population. Although PNG accounts for the majority, the number of positive notifications among those born abroad has increased fivefold since 2010. Tuberculosis among Aboriginal Australians has decreased following policy changes in response to previous audits. However, tuberculosis in Torres Strait residents has increased from 12 cases (1993-2002) to 40 cases (2006-2016).

Long-term Quality of Life After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei: A Prospective Longitudinal Study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are an established treatment for pseudomyxoma peritonei (PMP), but it is a major surgical procedure and may be associated with long-term morbidity. To date, health-related quality-of-life (HRQL) data among survivors are lacking. METHODS: A two-period qualitative study investigated patients undergoing CRS-HIPEC for PMP at a national peritoneal tumor center between 2003 and 2011. First, the European Organization for Research and Treatment (EORTC)-QLQ C30 HRQL questionnaire was used longitudinally preoperatively and at postoperative months 3, 6, 9, 12, 18, and 24, then yearly thereafter. Second, it was updated in 2016 as a cross-sectional study. Both studies were compared with age- and sex-matched reference populations (one-way t tests). RESULTS: A total of 553 longitudinal HRQL questionnaires were completed for 137 patients, truncated at 60 months. In the 2016 update, 85 responses were received from 103 survivors (mean follow-up period, 8.11 years). Patients' physical, role, and social function scores were impaired until 12 months postoperatively, after which the scores did not differ significantly from those of with reference populations. Similarly, fatigue, appetite loss, insomnia, and financial difficulties worsened significantly compared with reference populations in the first 12-months and then normalized. In contrast, impaired cognitive function (82.3 vs 88.5; P = 0.017), constipation (13.7 vs 7.3; P = 0.032), and diarrheal symptoms (15.1 vs 4.9; P = 0.0006) persisted through both periods. Global health scores did not differ significantly from those of the reference population. CONCLUSIONS: Beyond 12 months postoperatively, CRS-HIPEC for PMP is associated with a good quality of life except for some cognitive functional impairment and bowel disturbances.

Predicting Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendix Adenocarcinoma.

BACKGROUND: Appendix adenocarcinomas are rare tumors with propensity for peritoneal metastasis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an established treatment with curative intent, but, to date, studies reporting survival have been heterogeneous with regard to their patient groups (including other tumor types), interventions (not all patients receiving intraperitoneal chemotherapy), and follow-up (varying surveillance protocols). OBJECTIVE: The aim of this study is to quantify the impact of this intervention on survival in a homogeneous group of patients with appendix adenocarcinoma receiving standardized treatment and follow-up, and to determine the impact of prognostic indicators on survival. DESIGN: This is a retrospective analysis of a prospective database at a national peritoneal tumor center where all patients had their appendix pathology reviewed and management planned by a specialized peritoneal tumor multidisciplinary team. MAIN OUTCOME MEASURES: Data were extracted on prognostic indicators including peritoneal cancer index, completeness of cytoreduction score, preoperative tumor markers, and histological features. Overall and disease event-free survival from the date of intervention were evaluated using Kaplan Meier curves and univariate Cox proportional hazards regression analysis. RESULTS: A total of 65 patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma between 2005 and 2015. Median follow-up was 44.3 months. The overall survival was 55.5% and disease event-free survival was 36.1% (5-year rate). Peritoneal Cancer Index <7, complete cytoreduction score of 0, and preoperative CEA of <6 were all associated with significantly higher overall and disease event-free survival. CA19-9 <38 and CA125 <31 were not associated with a significantly higher overall or disease event-free survival. LIMITATIONS: The sample size was limited because of the rarity of this tumor type. CONCLUSIONS: This study quantifies the impact of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy on overall and disease event-free survival for appendix adenocarcinoma, identifying key prognostic indicators that may guide treatment. It supports the referral of these rare tumors to specialist centers with appropriate expertise for initial management and follow-up. See Video Abstract at http://links.lww.com/DCR/A595.

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis.

BACKGROUND: Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care). METHODS: Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses. FINDINGS: 259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19-43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30-48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75-94] with watch and wait vs 78% [63-87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88-98] vs 87% [77-93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64-82] vs 47% [37-57]; hazard ratio 0·445 [95% CI 0·31-0·63; p<0·0001), with a 26% (95% CI 13-39) absolute difference in patients who avoided permanent colostomy at 3 years between treatment groups. INTERPRETATION: A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy. FUNDING: Bowel Disease Research Foundation.

Risk-reducing laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for low-grade appendiceal mucinous neoplasm: early outcomes and technique.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion of pseudomyxoma peritonei, which, if treated suboptimally, may later disseminate throughout the abdominal cavity. We previously demonstrated the role of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) to reduce the dissemination risk. Here we describe the feasibility and safety of minimal access cytoreductive surgery (MACRS) and HIPEC as an alternative to the open approach. METHODS: We evaluated patients with LAMNs at risk of dissemination (known as LAMN II) who were referred to a national treatment centre between 2010 and 2012 and comparison is made between this group and patients undergoing open CRS and HIPEC for the same pathology over the same time period. RESULTS: Of the 39 patients with LAMN II, 10 patients were treated by MACRS and HIPEC and 7 were treated by an open approach. Among the MACRS procedures, there were no conversions to open surgery; median procedure length, median length of stay, and complication rates were similar between groups and there were no 30-day deaths. After 3- and 11-months median follow-up respectively, no patients have evidence of disease progression. CONCLUSIONS: The present series demonstrates that MACRS and HIPEC is a feasible and safe alternative to the open procedure with the advantage of smaller abdominal wounds and comparable morbidity and inpatient stay. Longer follow-up is needed to assess the impact on disease progression.

Poor performance of paired tests of latent tuberculosis in highly immune-compromised individuals exposed to multidrug-resistant tuberculosis: time for new diagnostic markers.

Guideline-based recommendations for diagnosis of latent TB in highly immune suppressed populations are difficult to interpret and poorly characterised. More accurate biomarkers independent of T-cell functions are urgently required. https://bit.ly/41P8vTa.

Clinical and economic impact of adhesiolysis during repeat cesarean delivery.

OBJECTIVE: To estimate adhesiolysis rates at cesarean delivery (CD) and to estimate costs and clinical implications of performing adhesiolysis at repeat CD. DESIGN: Retrospective cohort using secondary data. SETTING: Over 500 acute care hospitals in the USA. POPULATION: Women ≥15 years old with a medical claim for CD between 1 January 2007 and 31 December 2008 who were treated in a hospital that contributed data to the Premier Perspective™ database. METHODS: Using data from hospital discharge records, rates of adhesiolysis at the time of CD were calculated. Among patients with repeat CD, a propensity score was used to create matched cohorts with and without adhesiolysis. Unadjusted rates and means were compared between these cohorts. MAIN OUTCOME MEASURES: Cost, length of stay and selected clinical complications between repeat CD patients with and without adhesiolysis. RESULTS: Adhesiolysis was performed in 0.5% of primary and 6.1% of repeat CD patients. Using propensity scores, 10 261 women who experienced repeat CD with adhesiolysis were matched to 10 261 control women. Hospital cost ($5739 vs. $5448), length of stay (2.97 vs. 2.88 days) and operative time (84.0 vs. 74.2 min) were significantly greater in the adhesiolysis than in the non-adhesiolysis group (p < 0.01 for all comparisons), as was the overall complication rate (6.3 vs. 3.5%). CONCLUSIONS: Adhesiolysis rates were higher in repeat compared with primary CD. Among repeat CD patients, costs and complications were higher in the adhesiolysis group. Reducing adhesion formation after primary CD could reduce cost and complications at the time of repeat CD.

The inpatient burden of abdominal and gynecological adhesiolysis in the US.

BACKGROUND: Adhesions are fibrous bands of scar tissue, often a result of surgery, that form between internal organs and tissues, joining them together abnormally. Postoperative adhesions frequently occur following abdominal surgery, and are associated with a large economic burden. This study examines the inpatient burden of adhesiolysis in the United States (i.e., number and rate of events, cost, length of stay [LOS]). METHODS: Hospital discharge data for patients with primary and secondary adhesiolysis were analyzed using the 2005 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. Procedures were aggregated by body system. RESULTS: We identified 351,777 adhesiolysis-related hospitalizations: 23.2% for primary and 76.8% for secondary adhesiolysis. The average LOS was 7.8 days for primary adhesiolysis. We found that 967,332 days of care were attributed to adhesiolysis-related procedures, with inpatient expenditures totaling $2.3 billion ($1.4 billion for primary adhesiolysis; $926 million for secondary adhesiolysis). Hospitalizations for adhesiolysis increased steadily by age and were higher for women. Of secondary adhesiolysis procedures, 46.3% involved the female reproductive tract, resulting in 57,005 additional days of care and $220 million in attributable costs. CONCLUSIONS: Adhesiolysis remain an important surgical problem in the United States. Hospitalization for this condition leads to high direct surgical costs, which should be of interest to providers and payers.

Management of isoniazid-monoresistant tuberculosis (Hr-TB) in Queensland, Australia: a retrospective case series.

OBJECTIVES: Drug-resistance represents a major threat in the fight against tuberculosis. Globally, isoniazid-monoresistant tuberculosis (Hr-TB) is twice as common as multidrug/rifampicin-resistant (MDR/RR)-TB. Recently updated WHO guidelines now recommend treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide and levofloxacin for at least six months. Our primary objective was to define the frequency, treatment and outcomes for Hr-TB in Queensland, Australia. We also sought to determine the frequency of fluoroquinolone use and whether its inclusion improved outcomes. METHODS: Retrospective case series of tuberculosis notifications in Queensland between 2000 and 2017 with at least low-level isoniazid resistance and preserved susceptibility to other first-line oral agents. RESULTS: Hr-TB was identified in 7.2% of all notifications. Where outcomes were assessable (163/198), 76.1% were treated with first-line agents only and 11.0% received at least six months of a fluoroquinolone-containing regimen (consistent with recent WHO guidelines). Favourable outcomes were achieved in 95.7%, comparable to fully susceptible disease (94.9%). Inclusion of a fluoroquinolone did not significantly improve outcomes compared with a regimen containing first-line agents only, although these cases were more likely to have high-level resistance. Previous treatment made an unfavourable outcome more likely. CONCLUSIONS: Hr-TB is prevalent in Queensland. Treatment outcomes in our cohort were comparable to fully susceptible disease. The current WHO-recommended regimen did not confer advantage over an appropriately constructed regimen containing first-line agents only. Our findings suggest that, in a well-resourced setting with good programmatic management, the addition of a fluoroquinolone may not substantially improve outcomes - potentially allowing these agents to be reserved for more extensively resistant disease.

Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study.

INTRODUCTION: Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls. METHODS AND ANALYSIS: Patients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0 and t=5 hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM. ETHICS AND DISSEMINATION: Ethical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03409315).

Referral pathways and outcome of patients with colorectal peritoneal metastasis (CRPM).

INTRODUCTION: Traditionally patients with colorectal peritoneal metastases (CRPM) were offered palliative chemotherapy and best supportive care. With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients in the UK have been referred to nationally approved centres. This study describes the pattern of referral and outcomes of patients managed through one UK centre. METHODS: and Methods: A prospective register recorded referrals, demographics, prior treatment pathways, and specialist multidisciplinary team (MDT) decisions (2002-2015). Peritoneal cancer index (PCI) was recorded intra-operatively; complete cytoreduction was deemed when a CC0/1 was achieved. Complications were classified using NCI CTCAE. v.4. Median overall survivals (OS) were described for those treated by CRS/HIPEC and in derived estimates for patients with isolated peritoneal metastases treated by chemotherapy alone in the ARCAD trials consortium. RESULTS: Two-hundred-eighty-six patients with CRPM were referred. Despite increasing numbers of referrals annually, the proportion of patients selected for CRS/HIPEC decreased from 64.5%, to 40%, and to 37.1% for 2002-09, 2010-12, and 2013-15, respectively (p < 0.017). CRS/HIPEC was undertaken in 117 patients with a median PCI of 7 and CC0/1 achieved in 86.3%. NCI CTCAE grade 3/4 complication rates were 9.4%; 30-day mortality was 0.85%. Median OS following CRS/HIPEC was 46.0 months: that for patients not receiving CRS/HIPEC was 13.2 months. CONCLUSION: The evolution of the national peritoneal treatment centre over 14 years has been associated with increased referral numbers, refinement of selection for major surgery, matched with achievements of low complication rates and survival advantages in selected patients compared with traditional non-surgical treatments.

Cost and economics of adhesions.

The burden and cost of adhesions is considerable. Products are available which might reduce these problems. The costing of these products will have a significant effect on their usage. A low-cost product with a 25% efficacy could potentially generate a cost saving of 55 million Pounds over a 10-year period in the UK.

Successful Management of Jejunal Perforation in Burkitt's Lymphoma: A Case Report.

Burkitt's lymphoma (BL) is rare, rapidly growing, and highly aggressive. Urgent commencement of chemotherapy is vital to prevent complications and promote a favourable prognosis. Any factor causing a delay in the initiation of chemotherapy will affect prognosis significantly. Intestinal perforation is a well-known complication with devastating consequences. It inevitably leads to a delay in the initiation of chemotherapy. There are few reports in the literature that discuss this complication. Furthermore, there are no reports of patients that have survived intestinal perforation occurring prior to the commencement of chemotherapy. We present a case of a 55-year-old male who survived perforation of advanced sporadic BL of the jejunum occurring prior to the commencement of chemotherapy. Critical aspects of the patients care are discussed.