Adaptive clinical trials in surgery: A scoping review of methodological and reporting quality.

IMPORTANCE: Adaptive surgical trials are scarce, but adopting these methods may help elevate the quality of surgical research when large-scale RCTs are impractical. OBJECTIVE: Randomized-controlled trials (RCTs) are the gold standard for evidence-based healthcare. Despite an increase in the number of RCTs, the number of surgical trials remains unchanged. Adaptive clinical trials can streamline trial design and time to trial reporting. The advantages identified for ACTs may help to improve the quality of future surgical trials. We present a scoping review of the methodological and reporting quality of adaptive surgical trials. EVIDENCE REVIEW: We performed a search of Ovid, Web of Science, and Cochrane Collaboration for all adaptive surgical RCTs performed from database inception to October 12, 2023. We included any published trials that had at least one surgical arm. All review and abstraction were performed in duplicate. Risk of bias (RoB) was assessed using the RoB 2.0 instrument and reporting quality was evaluated using CONSORT ACE 2020. All results were analyzed using descriptive methods. FINDINGS: Of the 1338 studies identified, six trials met inclusion criteria. Trials were performed in cardiothoracic, oral, orthopedic, and urological surgery. The most common type of adaptive trial was group sequential design with pre-specified interim analyses planned for efficacy, futility, and/or sample size re-estimation. Two trials did use statistical simulations. Our risk of bias evaluation identified a high risk of bias in 50% of included trials. Reporting quality was heterogeneous regarding trial design and outcome assessment and details in relation to randomization and blinding concealment. CONCLUSION AND RELEVANCE: Surgical trialists should consider implementing adaptive components to help improve patient recruitment and reduce trial duration. Reporting of future adaptive trials must adhere to existing CONSORT ACE 2020 guidelines. Future research is needed to optimize standardization of adaptive methods across medicine and surgery.

Relationship of depth of invasion to survival outcomes and patterns of recurrence for T3 oral tongue squamous cell carcinoma.

INTRODUCTION: Current research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI. OBJECTIVES: Determine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10-20 mm). METHODS: Retrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified. Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology. Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy. Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm). RESULTS: One hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18-80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis. CONCLUSION: DOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients.

Survival outcomes of marijuana users in p16 positive oropharynx cancer patients.

BACKGROUND: Oropharynx squamous cell carcinoma (OPSCC) has become the predominant subsite for head and neck mucosal cancers (HNC) due to the rise of human papillomavirus (HPV) related disease. Previous studies have suggested an association between marijuana use and HPV-related OPSCC. Despite this, no study has examined the potential relationship between marijuana use and survival in this subset of patients. OBJECTIVE: To examine the survival outcomes of HPV-related OPSCC patients in marijuana users. METHODS: Patients who were marijuana users were identified from a prospectively collected database of HNC patients from January 2011 to 2015. A physical review of clinic records was undertaken to extract relevant patient, tumor, treatment, follow-up, as well as survival data. Patients greater than 17 years of age with pathologically proven p16 positive OPSCC were included. They were then case-matched in a 1-to-1 basis to patients who were non-marijuana users based on age, gender, and cTNM staging. RESULTS: Forty-Seven patients met inclusion criteria within each group. Univariate logistic regression analysis showed that age, gender, and cT-Stage were predictive of disease recurrence within both groups (p < 0.05). However, cN-stage, treatment modality, tumor subsite, tobacco use, and tobacco dose were not (p > 0.05). There was no statistically significant difference between marijuana and non-marijuana user groups in 5-year (p = 0.400) overall survival, disease-specific (p = 0.993), disease-free (p = 0.404), and metastasis-free survival (p = 0.384). CONCLUSIONS: No survival difference is found between HPV-related OPSCC marijuana users and non-users. This finding has implications for both de-escalation regimes and the use of cannabis as a therapeutic agent.

Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus.

The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.

Regional Variation across Canadian Centers in Radioiodine Administration for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer Diagnosed in 2000-2010.

Background. Use of radioactive iodine (RAI) ablation has been reported to vary significantly between studies. We explored variation in RAI ablation care patterns between seven thyroid cancer treatment centers in Canada. Methods. The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe and analyze patterns of care for thyroid cancer. We analyzed data from seven participating centers on RAI ablation in patients diagnosed with well-differentiated (papillary and follicular) thyroid cancer between 2000 and 2010. We compared RAI ablation protocols including indications (based on TNM staging), preparation protocols, and administered dose. We excluded patients with known distant metastases at time of RAI ablation. Results. We included 3072 patients. There were no significant differences in TNM stage over time. RAI use increased in earlier years and then declined. The fraction of patients receiving RAI varied significantly between centers, ranging between 20-85% for T1, 44-100% for T2, 58-100% for T3, and 59-100% for T4. There were significant differences in the RAI doses between centers. Finally, there was major variation in the use of thyroid hormone withdrawal or rhTSH for preparation of RAI ablation. Conclusion. Our study identified significant variation in use of RAI for ablation in patients with well-differentiated thyroid cancer both between Canadian centers and over time.

The utility of multidetector computed tomography for detection of parathyroid disease in the setting of primary hyperparathyroidism.

PURPOSE: The aim of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) in the detection of parathyroid adenoma and hyperplasia in the setting of primary hyperparathyroidism. METHODS: Records of 48 patients with biochemically confirmed primary hyperparathyroidism, who underwent preoperative imaging with 16- or 64-slice contrast-enhanced MDCT and subsequent successful parathyroidectomy over a 3-year period, were reviewed. Two radiologists, blinded to the operative and histologic findings, independently evaluated multiplanar computed tomographic images for all patients. RESULTS: On pathologic examination, 63 abnormal glands were confirmed in 41 female and 7 male patients (mean age, 63 years). Of the 63 abnormal glands, 40 were adenomatous and 23 were hyperplastic. MDCT demonstrated an 88% (95% confidence interval [CI], 77%-99%) positive predictive value for localizing abnormal hyperfunctioning parathyroid glands. The sensitivity of MDCT in detecting single-gland disease was 80% (95% CI, 68%-92%); whereas the specificity for ruling out hyperfunctioning parathyroid tissue, either adenomatous or hyperplastic, was 75% (95% CI, 51%-99%). The sensitivity for exclusively localizing parathyroid hyperplasia was 17% (95% CI, 2%-33%). The parathyroid adenomas were substantially larger and heavier than their hyperplastic counterparts, with an average weight of 1.51 g (range, 0.08-6.00 g) and 0.42 g (range, 0.02-2.0 g) for adenoma and hyperplasia, respectively. CONCLUSIONS: Contrast-enhanced MDCT demonstrated an 88% positive predictive value for localizing adenomatous and hyperplastic parathyroid glands. The poor sensitivity for detection of multigland disease was likely a result of the smaller size and weight of the abnormal hyperplastic glands.

Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

CONTEXT: An international workshop on primary hyperparathyroidism (PHPT) was convened on May 13, 2008, to review and update the previous summary statement on the management of asymptomatic PHPT published in 2002. EVIDENCE ACQUISITION: Electronic literature sources were systematically reviewed, addressing critical aspects of the surgical issues pertaining to the indications, imaging, surgical treatment, and cost-effective management of patients with PHPT. EVIDENCE SYNTHESIS: The surgical group concluded that many patients with "asymptomatic" PHPT have neurocognitive symptoms that may be unmasked after successful parathyroidectomy. Furthermore, reduced bone density and increased fracture risk can be improved with parathyroidectomy. When PHPT is symptomatic, it may be associated with nephrolithiasis, increased cardiovascular disease, and decreased survival. Preoperative imaging studies should only be performed to help plan the operation, and negative imaging should never preclude surgical referral. Noninvasive localization studies including ultrasound and sestamibi scans are often employed, especially in anticipation of focused explorations. Invasive localization studies should be reserved for remedial explorations where noninvasive imaging has been unsuccessful. CONCLUSIONS: When performed by expert parathyroid surgeons, parathyroid surgery is safe, cost-effective, and associated with very low perioperative morbidity. Minimally invasive approaches to parathyroid surgery appear to be as effective as the classic bilateral cervical exploration approach.

Pharyngo-cervical esophageal reconstruction.

Patients with advanced-stage hypopharyngeal or cervical esophageal carcinoma have a poor prognosis and may require a pharyngolaryngo-cervical esophagectomy. This treatment is usually palliative. In the past, the localized defect after resection has been reconstructed using many techniques. Currently, microsurgical techniques have become most common, both for full and partial circumferential defects. The jejunal free flap is the most frequently used, with free skin flaps as an alternative. The surgical complication rate is acceptable. Insufficient quantitative data exist to document postoperative swallowing function. Speech rehabilitation is often done with a tracheo-esophageal puncture technique, but studies documenting how the various methods of surgical reconstruction affect speech are lacking.

Oromandibular reconstruction after cancer resection.

The goals of this article are (1) to summarize the epidemiology of oromandibular cancer, (2) to describe the classification of defects after cancer extirpation, and (3) to discuss the principles of and state of the art in reconstruction of the oromandibular defect. The four commonly used flaps (fibula flap, radial forearm flap, scapula flap, and the iliac crest) and their key characteristics are summarized. Finally, some future speculations are entertained.

Effect of fibrin glue on air leak and length of hospital stay after pulmonary lobectomy.

AIM: Air leaks are a common cause of morbidity and prolonged hospital stay after pulmonary lobectomy. We reviewed our experience with intraoperative fibrin glue to determine if it reduced air leak and improved patient outcomes. METHODS: Records of patients undergoing pulmonary lobectomy for benign or malignant disease over a 4-year period (1998-2001) were reviewed. Data was collected on age, sex, pulmonary function, pulmonary pathology, use of fibrin glue, duration of chest tube drainage, length of hospital stay, and postoperative complications. RESULTS: Three hundred and sixty patients underwent lobectomy. Fibrin glue was used intraoperatively to seal air leaks in 102 of the 360 patients (study group: 102;control group: 258). Fibrin glue was used at the discretion of the surgeon, with some surgeons using it routinely. The groups did not differ in age (p=0.29), sex (p=0.42), FEV1 (p=0.57), or pathology (p=0.08). There were no differences in outcomes such as operative mortality (study: 2 of 102, control 6 of 258, p=0.85), empyema (study: 0 of 102, control: 3 of 258, p=0.55), prolonged (>7 days) air leaks (study: 10 of 20; control: 20 of 258, p=0.71), or length of hospital stay (study: 6.3+/-2.5 days, control:7.7+/-7.2 days, p=0.83). The use of fibrin glue was associated with a reduction in the duration of chest tube intubation (study: 4.1+/-3.2 days, control: 5.5+/-3.8 days, p=0.001). CONCLUSION: Patients treated intraoperatively with fibrin glue had a significantly shorter duration of chest tube intubation after pulmonary lobectomy than those treated conventionally. However, the use of fibrin glue did not significantly influence more clinically relevant outcomes such as length of hospital stay and incidence of prolonged (>7 days) air leaks.