Summary 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.
In the first full-length study in any modern language dedicated to the Meteorologica, Malcolm Wilson presents a groundbreaking interpretation of Aristotle's natural philosophy. Divided into two ...parts, the book first addresses general philosophical and scientific issues by placing the treatise in a diachronic frame comprising Aristotle's predecessors and in a synchronic frame comprising his other physical works. It argues that Aristotle thought of meteorological phenomena as intermediary or 'dualizing' between the cosmos as a whole and the manifold world of terrestrial animals. Engaging with the best current literature on Aristotle's theories of science and metaphysics, Wilson focuses on issues of aetiology, teleology and the structure and unity of science. The second half of the book illustrates Aristotle's principal concerns in a section-by-section treatment of the meteorological phenomena and provides solutions to many of the problems that have been raised since the time of the ancient commentators.
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.
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).
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.
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.
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.
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.
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.
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% (P
< 0.001); 5-year OS increased from 60% to 76% (P
= 0.001); and 5-year CCS increased from 62% in to 80% (P
= 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.
Current and predicted rates for 3-year LRF and 5-year survivals are considerably improved compared with those in historic trials.
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.
Adhesions after abdominal and pelvic surgery are important complications, although their basic epidemiology is unclear. We investigated the frequency of such complications in the general population ...to provide a basis for the targeting and assessment of new adhesion-prevention measures.
We used validated data from the Scottish National Health Service medical record linkage database to identify patients undergoing open abdominal or pelvic surgery in 1986, who had no record of such surgery in the preceding 5 years. Patients were followed up for 10 years and subsequent readmissions were reviewed and outcomes classified by the degree of adhesion. We also assessed the rate of adhesion-related admissions in 1994 for the population of 5 million people.
1209 (5·7%) of all readmissions (21 347) were classified as being directly related to adhesions, with 1169 (3·8%) managed operatively. Overall, 34·6% of the 29 790 patients who underwent open abdominal or pelvic surgery in 1986 were readmitted a mean of 2·1 times over 10 years for a disorder directly or possibly related to adhesions, or for abdominal or pelvic surgery that could be potentially complicated by adhesions. 22·1% of all outcome readmissions occurred in the first year after initial surgery, but readmissions continued steadily thoughout the 10-year period. In 1994, 4199 admissions were directly related to adhesions.
Postoperative adhesions have important consequences to patients, surgeons, and the health system. Surgical procedures with a high risk of adhesion-related complications need to be identified and adhesion prevention carefully assessed.
IntroductionGlobal 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 analysisPatients 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 disseminationEthical 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 numberClinicalTrials.gov Registry (NCT03409315).
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