Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial: a systematic review of published responses.

OBJECTIVES: The objective of this review was to assess the nature and tone of the published responses to the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial. METHODS: Published articles that cited the PulMiCC trial were identified from Clarivate Web of Science (©. Duplicates and self-citations were excluded and relevant text was extracted. Four independent researchers rated the extracts independently using agreed scales for the representativeness of trial data and the textual tone. The ratings were aggregated and summarized. Two PulMiCC authors carried out a thematic analysis of the extracts. RESULTS: Sixty-four citations were identified and relevant text was extracted and examined. The consensus rating for data inclusion was a median of 0.25 out of 6 (range 0-5.25, interquartile range 0-1.5) and, for textual tone, the median rating was 1.87 out of 6 (range 0-5.75, interquartile range 1-3.5). The majority of citations did not provide adequate representation of the PulMiCC data and the overall textual tone was dismissive. Although some were supportive, many discounted the findings because the trial closed early and was underpowered to show non-inferiority. Two misinterpreted the authors' conclusions but there was an acceptance that 5-year survival was much higher than widely assumed. CONCLUSIONS: Published comments reveal a widespread reluctance to consider seriously the results of a carefully conducted randomized trial. This may be because the results challenge accepted practice because of 'motivated reasoning', but there is a widespread misunderstanding of the fact that though PulMiCC with 93 patients was underpowered to test non-inferiority, it still provides reliable evidence to undermine the widespread belief in a major survival benefit from metastasectomy.

The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) burden of care study: Analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort.

AIM: The aim of this work was to examine the burden of further treatments in patients with colorectal cancer following a decision about lung metastasectomy. METHOD: Five teams participating in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study provided details on subsequent local treatments for lung metastases, including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined. RESULTS: The five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 patients had one metastasectomy and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with nonelevated carcinoembryonic antigen, fewer metastases and no prior liver metastasectomy. These patients also had better Eastern Cooperative Oncology Group scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had one to five courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed, with no apparent reduction in chemotherapy usage. CONCLUSION: Repeated metastasectomy is associated with a higher risk of death without reducing the use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy.

The Pulmonary Metastasectomy in Colorectal Cancer cohort study: Analysis of case selection, risk factors and survival in a prospective observational study of 512 patients.

AIM: We wanted to examine survival in patients with resected colorectal cancer (CRC) whose lung metastases are or are not resected. METHODS: Teams participating in the study of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) identified potential candidates for lung metastasectomy and invited their consent to join Stage 1. Baseline data related to CRC and fitness for surgery were collected. Eligible patients were invited to consent for randomization in the PulMiCC randomized controlled trial (Stage 2). Sites were provided with case report forms for non-randomized patients to record adverse events and death at any time. They were all reviewed at 1 year. Baseline and survival data were analysed for the full cohort. RESULTS: Twenty-five clinical sites recruited 512 patients from October 2010 to January 2017. Data collection closed in October 2020. Before analysis, 28 patients with non-CRC lung lesions were excluded and three had withdrawn consent leaving 481. The date of death was known for 292 patients, 136 were alive in 2020 and 53 at earlier time points. Baseline factors and 5-year survival were analysed in three strata: 128 non-randomized patients did not have metastasectomy; 263 had elective metastasectomy; 90 were from the randomized trial. The proportions of solitary metastases for electively operated and non-operated patients were 69% and 35%. Their respective 5-year survivals were 47% and 22%. CONCLUSION: Survival without metastasectomy was greater than widely presumed. Difference in survival appeared to be largely related to selection. No inference can be drawn about the effect of metastasectomy on survival in this observational study.

Pulmonary metastasectomy in colorectal cancer: health utility scores by EQ-5D-3L in a randomized controlled trial show no benefit from lung metastasectomy.

AIM: The aim was to assess the health utility of lung metastasectomy in the treatment of patients with colorectal cancer (CRC) using the EQ-5D-3L questionnaire. METHODS: Multidisciplinary CRC teams at 14 sites recruited patients to a two-arm randomized controlled trial-Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC). Remote randomization was used, stratified by site and with minimization for seven known confounders. Participants completed the EQ-5D-3L questionnaire together with other patient reported outcome measures at randomization and then again at 3, 6, 12 and 24 months. These were returned by post to the coordinating centre. RESULTS: Between December 2010 and December 2016, 93 participants were randomized, 91 of whom returned questionnaires. Survival and patient reported quality of life have been published previously, revealing no significant differences between the trial arms. Described here are patient reported data from the five dimensions of the EQ-5D-3L and the visual analogue scale (VAS) health state. No significant difference was seen at any time point. The estimated difference between control and metastasectomy patients was -0.23 (95% CI -0.113, 0.066) for the composite 0 to 1 index scale based on the descriptive system and 0.123 (95% CI -7.24, 7.49) for the 0 to 100 VAS scale. CONCLUSIONS: Following lung metastasectomy for CRC, no benefit was demonstrated for health utility, which alongside a lack of a survival or quality of life benefit calls into question the widespread use of the procedure.

Pulmonary arteriovenous malformation-etiology, clinical four case presentations and review of the literature.

Pulmonary arteriovenous malformation (PAVM) is a rare clinical condition with abnormal direct communication between the branches of pulmonary artery and vein. It may occur as an isolated anomaly or in association with hereditary hemorrhagic telangiectasia (HHT). Although these vascular pulmonary pathologies are quite uncommon, they are the important part of the differential diagnosis of common pulmonary problems such as hypoxemia and pulmonary nodules. The diagnosis of PAVM in patients remains a diagnostic challenge to the emergency physician. The most common clinical signs of PAVM are recurrent episodes of epistaxis and hemoptysis, so surgical resection is deemed the best curative option to avoid further episodes and recurrence of hemoptysis. Quite often the diagnosis is established after pathohistological examinations. We report a case of a female patient with a massive recurrent hemoptysis and without pathologic radiological findings which would suggest to PAVM and who was successfully treated with lobectomy.

Semi-Fowler vs. lateral decubitus position for thoracoscopic sympathectomy in treatment of primary focal hyperhidrosis.

BACKGROUND AND OBJECTIVE: The aim of this study is to compare usefulness of Semi-Fowler position vs. lateral decubitus position for thoracoscopic sympathectomy in treatment of primary focal hyperhidrosis. MATERIALS AND METHODS: From January 2009 to January 2010, 263 consecutive patients with palmar and axillar hyperhidrosis underwent thoracoscopic sympathectomy Th2-Th4. Patients were divided into two groups: group A (n=133) underwent thoracoscopic sympathectomy through lateral decubitus using double lumen endotracheal intubation, and group B (n=130) underwent thoracoscopic sympathectomy through Semi-Fowler supine position (semi sitting with arm abducted) using single lumen endotracheal intubation without insufflation of CO2, but with short apnea period. All operations were performed through two 5 mm operating ports, videothoracoscopic camera 0° and endoscopic ultrasound activated harmonic scalpel. RESULTS: There were 107 males and 156 females with median age 30.31±8.35 years. Two groups were comparable in gender, age, severity of sweating. All operations were successfully performed with no complications or perioperative morbidity. For group A average operation time for both sides was 31.2±3.87 min and for group B average time was 14.19±4.98 min. In group B apnea period per one lung lasts 2.86±1.15 min and during that period observed saturation was 92.65%±5.66% without significant cardiorespiratory disturbances. Pleural drains were taken off on operation table after forced manually lung reexpansion. Patients were discharged from hospital for few hours, after the operation and radiologic confirmation of complete lung reexpansion. CONCLUSIONS: Based on this data (shorter operating time, lack of incomplete lung collapse, insignificant apnea and better reexpansion of lungs) we concluded that thoracoscopic sympathectomy through Semi-Fowler supine position is highly effective and easy to perform for primary hyperhidrosis.

Finding the evidence for pulmonary metastasectomy in colorectal cancer: the PulMicc trial.

The PulMiCC trial is a randomized controlled trial testing the effect on survival of pulmonary metastasectomy in patients with colorectal cancer. In stage 1 of the trial patients with treated primary colorectal cancer metastatic to the lungs are invited to consent for protocol-based evaluation of their suitability for metastasectomy. The evaluation is as in current practice and includes PET/CT. A decision for or against metastasectomy may be based on the opinion of the clinicians and the preference of the patient. If there is uncertainty the patient is invited to consent to have the treatment arm assigned by randomization in stage 2 of PulMiCC. More than 300 patients have entered stage 1 and more than 70 are in stage 2.

History and present status of pulmonary metastasectomy in colorectal cancer.

Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers, breast and lung, in that routine surveillance is recommended with the specific intent of detecting liver and lung metastases and undertaking liver and lung resections for their removal. We trace the history of this approach to colorectal cancer by reviewing evidence for effectiveness from the 1950s to the present day. Our sources included published citation network analyses, the documented proposal for randomised trials, large systematic reviews, and meta-analysis of observational studies. The present consensus position has been adopted on the basis of a large number of observational studies but the randomised trials proposed in the 1980s and 1990s were either not done, or having been done, were not reported. Clinical opinion is the mainstay of current practice but in the absence of randomised trials there remains a possibility of selection bias. Randomised controlled trials (RCTs) are now routine before adoption of a new practice but RCTs are harder to run in evaluation of already established practice. One such trial is recruiting and shows that controlled trial are possible.

Pulmonary metastasectomy: what is the practice and where is the evidence for effectiveness?

Pulmonary metastasectomy is a commonly performed operation and is tending to increase as part of a concept of personalised treatment for advanced cancer. There have been no randomised trials; belief in effectiveness of metastasectomy is based on registry data and surgical follow-up studies. These retrospective series are comprised predominately of solitary or few metastases with primary resection to metastasectomy intervals longer than 2-3 years. Five-year survival rates of 30-50% are recorded, but as case selection is based on favourable prognostic features, an apparent association between metastasectomy and survival cannot be interpreted as causation. Cancers for which lung metastasectomy is used are considered in four pathological groups. In non-seminomatous germ cell tumour, for which chemotherapy is highly effective, excision of residual pulmonary disease guides future treatment and in particular allows an informed decisions as to further chemotherapy. Sarcoma metastasises predominately to lung and pulmonary metastasectomy for both bone and soft tissues sarcoma is routinely considered as a treatment option but without randomised data. The commonest circumstance for lung and liver metastasectomy is colorectal cancer. Repeated resections and ablations are commonplace but without evidence of effectiveness for either. For melanoma, results are particularly poor, but lung metastases are resected when no other treatment options are available. In this review, the available evidence is considered and the conclusion reached is that in the absence of randomised trials there is uncertainty about effectiveness. A randomised controlled trial, Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), is in progress and randomised trials in sarcoma seem warranted.