[cancer of the rectum and rectosigmoid]

It is the purpose of this thesis to examine this evidence, and also to consider the anatomical and technical factors governing the use of restorative resections, so as to determine the place that they may legitimately assume during this interim period in the treatment of rectal and rectosigmoid cancer.1. In this thesis an attempt has been made to ascertain how far sphincter conservation and restoration of continuity can be reconciled with the requirements of radical surgery in the treat - ruent of carcinoma of the rectum and rectosigaoid, and to decide which are the best technical methods of achieving this end.2. A study of 1500 combined excision specimens has disclosed the following facts: - (a) In approximately 40 of the combined excision cases the growth was situated in the anal canal or lower 1 /3rd of the rectum and the removal of the anal sphincters and related levator muscles was essential for radical treatment. (b) In the remaining 60%, however, in which the growth lay in the upper 2/3rds of the rectum or in the rectosignoid, it was not apparent that the sacrifice of the sphincter apparatus had in any way increased the prospects of eradication of the disease. It seemed that preservation of the anus and rectum from a level 1" below the lower margin of the primary tumour mass would not have adversely affected the chances of ultimate cure. The rare occurrence of retrograde venous and lymphatic extension below this level is not denied, but such cases, by reason of their wide spread in other directions, must be regarded as incurable by any operation. (c) The most important avenue of extension of carcinoma of the rectum and rectosignoid is by the upgoing lymphatics and veins accompanying the superior haeinorrhoidal and inferior mesenteric arteries. No operation for these conditions can be considered adequate unless it provides for removal of these vessels to a high level. Spread to the sigmoid paracolic glands only occurs when the growth arises in the rectosigmoid and they lie in sequence between it and the inferior mesenteric glands. Consequently all but the basal and possibly the lowest part of the sigmoid mesocolon and attached colon may always be safely preserved.3. An examination of the arrangement of the blood vessels to the rectum and distal half of the colon in 75 necropsy room bodies, supplemented by observations on living patients at operation, has established the following-points :- (a) The left colic and first sigmoid arteries generally spring conjointly from the inferior mesenteric trunk opposite the bifurcation of the abdominal aorta; in a combined excision the ligature on the inferior mesenteric vessels is generally placed immediately below this point. (b) With the main ligature so sited, it is, however, possible in practically every case to prepare a sufficiently long well vascular - ized piece of sigmoid colon to permit of endto-end union with an anorectal stump after resection. One method of preparation provides for a direct blood supply to the end of the sigmoid stump through the first sigmoid branch; if this stump should not be long enough additional length may be secured by preserving the intersigmoid marginal artery and colon for 2 or 3" below the first sigmoid, or by severing the latter branch and relying on the descending division of the left colic artery. Our preference is for the latter method whenever possible. (c) When an abdomino -anal "pull through" type of operation is contemplated a very much longer sigmoid stump is required. In our experience this can also be provided by a combination of methods in the great majority of cases, though not in all. (d) When the entire si :g,aoid colon has to be sacrificed, as for example in some cases of double carcinoma, restoration of continuity may still be possible by resetting up to the splenic flexure or middle of the transverse colon and swinging down the remainder of this to the anorectal stump or anus. Occasionally a graft taken from the lower ileum with its blood supply intact may be useful in this type of case. (e) The blood supply to the anorectal stump after resection with division of the superior, and often the middle, haemorrhoidal vessels is surprisingly abundant. It would appear to be derived not only from the inferior haemorrhoidal arteries but also from numerous unnamed branches in the levator ani muscles.4. The highest point at which the superior haemorrhoidal or inferior mesenteric vessels can be tied through a sacral approach is usually 3 or 4" lower than the site generally chosen for this ligature in a combined excision. Sacral resections are therefore condemned as pathologically inadequate, and the recorded results support this condemnation.5. An abdominal phase, to permit of high division of the inferior mesenteric vessels and proper preparation of the colon stump, is an essential part of any radical resection operation. The steps of the abdominal dissection are described in detail. The operation may be carried out entirely through the abdomen or completed as an abdomino-sacral or abdoinino-anal resection.6. Our experience has been chiefly with abdominal resection and it has been found possible to remove nearly all growths, that are suitable for resection, by this method. An "open" suture technique has been used for making the anastomosis in the bowel. We have not been able to reach any firm conclusion as to the advantage of establishing a preliminary or simultaneous transverse colostomy. Post- operative septic complications and fistulae have not been common. There have been 5 hospital deaths in 45 cases. The functional results have been uniformly excellent.7. For some low growths in the middle 1 /3rd of the rectum in individuals with narrow pelves an abdoinino- sacral or abdoin ino -anal techni4ue of resection may be advisable. We have had no personal experience of the former, but hAve used abdomino -anal resection of Maunsell -Weir type in 21 cases with one operative death. All the survivors possessed good rectal function, but troublesome stenosis at the suture line was a frequent sequel.S. Most of our-resection operations have been performed recently and no full account of the late results is yet possible. But in a few cases further growth has appeared in the region of the anastomosis in the bowel or in the rectal stump. It is suggested that this may have been due to:- (a) incomplete removal at the original operation, (b) the development of a fresh primary carcinoma, or (c) the occurrence of metastases by implantation. The latter two seem the more likely explanations, and measures calculated to minimise these dangers are described.9. In view of these unfavourable results an optimistic assessment of the value of resection procedures in the treatment of rectal or recto - sigmoid cancel is not at the present stage justified

Effects of bromopride on the healing of left colon anastomoses of rats

Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. Métodos: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados: Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group- C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day

Bayesian Joint Modeling for Longitudinal Magnitude Data with Informative Dropout: an Application to Critical Care Data

In various biomedical studies, the focus of analysis centers on the magnitudes of data, particularly when algebraic signs are irrelevant or lost. To analyze the magnitude outcomes in repeated measures studies, using models with random effects is essential. This is because random effects can account for individual heterogeneity, enhancing parameter estimation precision. However, there are currently no established regression methods that incorporate random effects and are specifically designed for magnitude outcomes. This article bridges this gap by introducing Bayesian regression modeling approaches for analyzing magnitude data, with a key focus on the incorporation of random effects. Additionally, the proposed method is extended to address multiple causes of informative dropout, commonly encountered in repeated measures studies. To tackle the missing data challenge arising from dropout, a joint modeling strategy is developed, building upon the previously introduced regression techniques. Two numerical simulation studies are conducted to assess the validity of our method. The chosen simulation scenarios aim to resemble the conditions of our motivating study. The results demonstrate that the proposed method for magnitude data exhibits good performance in terms of both estimation accuracy and precision, and the joint models effectively mitigate bias due to missing data. Finally, we apply proposed models to analyze the magnitude data from the motivating study, investigating if sex impacts the magnitude change in diaphragm thickness over time for ICU patients

The HubBLe Trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for symptomatic second- and third-degree haemorrhoids: a multicentre randomised controlled trial and health-economic evaluation.

BACKGROUND: Optimal surgical intervention for low-grade haemorrhoids is unknown. Rubber band ligation (RBL) is probably the most common intervention. Haemorrhoidal artery ligation (HAL) is a novel alternative that may be more efficacious. OBJECTIVE: The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids. DESIGN: A multicentre, parallel-group randomised controlled trial. PERSPECTIVE: UK NHS and Personal Social Services. SETTING: 17 NHS Trusts. PARTICIPANTS: Patients aged ≥ 18 years presenting with grade II/III (second- and third-degree) haemorrhoids, including those who have undergone previous RBL. INTERVENTIONS: HAL with Doppler probe compared with RBL. OUTCOMES: Primary outcome - recurrence at 1 year post procedure; secondary outcomes - recurrence at 6 weeks; haemorrhoid severity score; European Quality of Life-5 Dimensions, 5-level version (EQ-5D-5L); Vaizey incontinence score; pain assessment; complications; and cost-effectiveness. RESULTS: A total of 370 participants entered the trial. At 1 year post procedure, 30% of the HAL group had evidence of recurrence compared with 49% after RBL [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.42 to 3.51; p = 0.0005]. The main reason for the difference was the number of extra procedures required to achieve improvement/cure. If a single HAL is compared with multiple RBLs then only 37.5% recurred in the RBL arm (adjusted OR 1.35, 95% CI 0.85 to 2.15; p = 0.20). Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year (9% HAL and 29% RBL), suggesting significant deterioration in both groups over the year. Symptom score, EQ-5D-5L and Vaizey score improved in both groups compared with baseline, but there was no difference between interventions. Pain was less severe and of shorter duration in the RBL group; most of the HAL group who had pain had mild to moderate pain, resolving by 3 weeks. Complications were low frequency and not significantly different between groups. It appeared that HAL was not cost-effective compared with RBL. In the base-case analysis, the difference in mean total costs was £1027 higher for HAL. Quality-adjusted life-years (QALYs) were higher for HAL; however, the difference was very small (0.01) resulting in an incremental cost-effectiveness ratio of £104,427 per additional QALY. CONCLUSIONS: At 1 year, although HAL resulted in fewer recurrences, recurrence was similar to repeat RBL. Symptom scores, complications, EQ-5D-5L and continence score were no different, and patients had more pain in the early postoperative period after HAL. HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY. LIMITATIONS: Blinding of participants and site staff was not possible. FUTURE WORK: The incidence of recurrence may continue to increase with time. Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness. The polysymptomatic nature of haemorrhoidal disease requires a validated scoring system, and the data from this trial will allow further assessment of validity of such a system. These data add to the literature regarding treatment of grade II/III haemorrhoids. The results dovetail with results from the eTHoS study [Watson AJM, Hudson J, Wood J, Kilonzo M, Brown SR, McDonald A, et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial. Lancet 2016, in press.] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy. Combined results will allow expansion of analysis, allowing surgeons to tailor their treatment options to individual patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41394716. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 88. See the NIHR Journals Library website for further project information

Utility and safety of draining pleural effusions in mechanically ventilated patients: a systematic review and meta-analysis

Abstract Introduction Pleural effusions are frequently drained in mechanically ventilated patients but the benefits and risks of this procedure are not well established. Methods We performed a literature search of multiple databases (MEDLINE, EMBASE, HEALTHSTAR, CINAHL) up to April 2010 to identify studies reporting clinical or physiological outcomes of mechanically ventilated critically ill patients who underwent drainage of pleural effusions. Studies were adjudicated for inclusion independently and in duplicate. Data on duration of ventilation and other clinical outcomes, oxygenation and lung mechanics, and adverse events were abstracted in duplicate independently. Results Nineteen observational studies (N = 1,124) met selection criteria. The mean PaO2:FiO2 ratio improved by 18% (95% confidence interval (CI) 5% to 33%, I 2 = 53.7%, five studies including 118 patients) after effusion drainage. Reported complication rates were low for pneumothorax (20 events in 14 studies including 965 patients; pooled mean 3.4%, 95% CI 1.7 to 6.5%, I 2 = 52.5%) and hemothorax (4 events in 10 studies including 721 patients; pooled mean 1.6%, 95% CI 0.8 to 3.3%, I 2 = 0%). The use of ultrasound guidance (either real-time or for site marking) was not associated with a statistically significant reduction in the risk of pneumothorax (OR = 0.32; 95% CI 0.08 to 1.19). Studies did not report duration of ventilation, length of stay in the intensive care unit or hospital, or mortality. Conclusions Drainage of pleural effusions in mechanically ventilated patients appears to improve oxygenation and is safe. We found no data to either support or refute claims of beneficial effects on clinically important outcomes such as duration of ventilation or length of stay

Effect of different pressure-targeted modes of ventilation on transpulmonary pressure and inspiratory effort

Spontaneous breathing during mechanical ventilation improves gas exchange and might prevent ventilator- induced diaphragm dysfunction. In pressure-targeted modes, transpulmonary pressure (PL) is the sum of pres- sure generated by the ventilator and muscular pressure. When inspiratory effort increases, PL and tidal volume (VT) increase, potentially resulting in lung injury. This effect depends on the degree of inspiratory synchroniza- tion (i-sync); pressure-targeted modes can be classified into fully, partially, and non i-sync modes. A bench study [1] demonstrated that non-i-sync mode resulted in lower PL and VT than other modes, protecting the lungs from injury. We undertook to assess the effect of varying synchronization during pressure-targeted venti- lation in critically ill patients

Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort

In pressure-controlled (PC) ventilation, tidal volume (V) and transpulmonary pressure (P) result from the addition of ventilator pressure and the patient's inspiratory effort. PC modes can be classified into fully, partially, and non-synchronized modes, and the degree of synchronization may result in different V and P despite identical ventilator settings. This study assessed the effects of three PC modes on V, P, inspiratory effort (esophageal pressure-time product, PTP), and airway occlusion pressure, P. We also assessed whether P can be used for evaluating patient effort. Prospective, randomized, crossover physiologic study performed in 14 spontaneously breathing mechanically ventilated patients recovering from acute respiratory failure (1 subsequently withdrew). PC modes were fully (PC-CMV), partially (PC-SIMV), and non-synchronized (PC-IMV using airway pressure release ventilation) and were applied randomly; driving pressure, inspiratory time, and set respiratory rate being similar for all modes. Airway, esophageal pressure, P, airflow, gas exchange, and hemodynamics were recorded. V was significantly lower during PC-IMV as compared with PC-SIMV and PC-CMV (387 ± 105 vs 458 ± 134 vs 482 ± 108 mL, respectively; p < 0.05). Maximal P was also significantly lower (13.3 ± 4.9 vs 15.3 ± 5.7 vs 15.5 ± 5.2 cmHO, respectively; p < 0.05), but PTP was significantly higher in PC-IMV (215.6 ± 154.3 vs 150.0 ± 102.4 vs 130.9 ± 101.8 cmHO × s × min, respectively; p < 0.05), with no differences in gas exchange and hemodynamic variables. PTP increased by more than 15% in 10 patients and by more than 50% in 5 patients. An increased P could identify high levels of PTP. Non-synchronized PC mode lowers V and P in comparison with more synchronized modes in spontaneously breathing patients but can increase patient effort and may need specific adjustments. Clinical Trial Registration Clinicaltrial.gov # NCT02071277