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JAMA Surgery Jul 2023Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection...
IMPORTANCE
Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients.
OBJECTIVE
To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer.
DESIGN, SETTING, AND PARTICIPANTS
This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0).
INTERVENTIONS
Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex.
MAIN OUTCOMES AND MEASURES
The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects.
RESULTS
A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02614534.
Topics: Humans; Male; Female; Hyperthermic Intraperitoneal Chemotherapy; Antineoplastic Combined Chemotherapy Protocols; Hyperthermia, Induced; Neoplasm Recurrence, Local; Colonic Neoplasms; Chemotherapy, Adjuvant
PubMed: 37099280
DOI: 10.1001/jamasurg.2023.0662 -
Journal of Clinical Oncology : Official... Jan 2024In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS.
PATIENTS AND METHODS
Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m and cisplatin 75 mg/m in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle.
RESULTS
Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% CRS + H, 43.6%; = .79).
CONCLUSION
This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.
Topics: Adult; Humans; Stomach Neoplasms; Peritoneal Neoplasms; Hyperthermic Intraperitoneal Chemotherapy; Combined Modality Therapy; Cytoreduction Surgical Procedures; Hyperthermia, Induced; Antineoplastic Combined Chemotherapy Protocols; Survival Rate; Retrospective Studies
PubMed: 37906724
DOI: 10.1200/JCO.22.02867 -
Turkish Journal of Ophthalmology Jun 2023Isolated from , mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It... (Review)
Review
Isolated from , mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It has been employed in pterygium surgery, ocular surface neoplasia, and refractive surgery. Currently, there is no definite consensus on the treatment protocols for each of the aforementioned applications. Although its benefits in the management of corneal and external diseases are promising, MMC use has potential complications including endothelial cell loss, corneal perforation, scleral melt, secondary glaucoma, iritis, and endophthalmitis. This article will review the literature regarding the use of MMC in the field of cornea and external disease and describe protocols employed with corresponding outcomes.
Topics: Humans; Mitomycin; Photorefractive Keratectomy; Lasers, Excimer; Cornea
PubMed: 37345314
DOI: 10.4274/tjo.galenos.2023.97932 -
Ophthalmology and Therapy Dec 2023Photorefractive keratectomy (PRK) is a safe and popular corneal surgery performed worldwide. Nevertheless, there is potential risk of corneal haze development after... (Review)
Review
Photorefractive keratectomy (PRK) is a safe and popular corneal surgery performed worldwide. Nevertheless, there is potential risk of corneal haze development after surgery. Proper management of post PRK haze is important for good visual outcome. We performed a comprehensive review of the literature on the various risk factors and treatments for PRK haze, searching the PubMed, Google Scholar, SCOPUS, ScienceDirect, and Embase databases using relevant search terms. All articles in English from August 1989 through April 2023 were reviewed for this study, among which 102 articles were chosen to be included in the study. Depending on the characteristics of and examination findings on post PRK haze, different management options may be preferred. In the proposed framework, management of PRK haze should include a full workup that includes patient's subjective complaints and loss of vision as well as visual acuity, biomicroscopy, anterior segment optical coherence tomography, epithelial mapping, and Scheimpflug densitometry. Topical steroid treatment for haze should be stratified based on early- or late-onset haze. Mechanical debridement or superficial phototherapeutic keratectomy (PTK) may be used to treat superficial corneal haze. Deep PTK and/or PRK can be used to treat deep corneal haze. Mitomycin-C and topical steroids are prophylactic post-surgery agents to prevent recurrence of haze.
PubMed: 37603162
DOI: 10.1007/s40123-023-00782-1 -
Cell Communication and Signaling : CCS Jun 2023Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness... (Review)
Review
Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness maintenance and cell fate determination would provide a new strategy for cancer therapy. Unregulated cellular energetics has been accepted as one of the hallmarks of cancer cells, but recent studies have revealed that mitochondrial metabolism can also actively determine CSC fate by affecting nuclear stemness gene expression. Herein, from the perspective of mito-nuclear communication, we review recent progress on the influence of mitochondria on CSC potential from four aspects: metabolism, dynamics, mitochondrial homeostasis, and reactive oxygen species (ROS). Video Abstract.
Topics: Humans; Neoplasm Recurrence, Local; Cell Differentiation; Mitomycin; Mitochondria; Neoplastic Stem Cells; Reactive Oxygen Species
PubMed: 37370081
DOI: 10.1186/s12964-023-01160-x -
Clinics and Practice Sep 2023Plantar fibromatosis (or Ledderhose's disease) is a rare benign condition, difficult to treat, defined by gradual-growing nodules in the central medial part of the... (Review)
Review
Plantar fibromatosis (or Ledderhose's disease) is a rare benign condition, difficult to treat, defined by gradual-growing nodules in the central medial part of the plantar fascia, with the possibility of sclerosis and shrinkage of the entire fascia or, rarely, contractures of the toes. From a histopathological point of view, it is linked to Dupuytren's contracture of the hand and Peyronie's disease of the penis, being part of a large group of fibromatoses, based on a proliferation of collagen and fibroblasts. Its etiology is still not fully understood, even though it has been associated with trauma, diabetes mellitus, use of anticonvulsants, frozen shoulder, alcohol consumption, and liver disease. Typically, ultrasound confirms the diagnosis, and magnetic resonance imaging is used for more aggressive and advanced types. Several conservative treatment techniques, such as steroid injections, verapamil, imatinib, radiation therapy, extracorporeal shock wave therapy, tamoxifen, sorafenib, mitomycin C, and collagenase, have been documented. When non-operative care fails, surgical measures may be considered, even though recurrence is expected. We attempted to provide a better understanding of this disease by covering all of the important aspects: its history, clinical and radiologic findings, diagnosis, pathophysiology features, conservative and surgical treatment, recurrence rate, and prognosis.
PubMed: 37887082
DOI: 10.3390/clinpract13050106 -
Journal of Thoracic Disease Jul 2023Benign tracheal stenosis can cause dyspnea, wheezing, and cough mimicking other obstructive lung diseases which often leads to a delay in the diagnosis. Risk factors and... (Review)
Review
Benign tracheal stenosis can cause dyspnea, wheezing, and cough mimicking other obstructive lung diseases which often leads to a delay in the diagnosis. Risk factors and etiologies for tracheal strictures include autoimmune diseases, infection, gastro-esophageal reflux disease (GERD), radiation injury and iatrogenic factors such as post-intubation and post-tracheostomy. Once suspected, tracheal strictures are diagnosed by performing a thorough evaluation involving clinical exam, laboratory workup, pulmonary function test, chest imaging and bronchoscopy. Bronchoscopy plays a pivotal role in the diagnosis of stenosis and along with the imaging and physiologic assessments leads to a proper description of the stenosis based on all parameters that matters for management. Surgical resection provides a definitive management in most patients with idiopathic or post intubation/tracheostomy stenosis, however, factors such as severe co-morbidities, length and location of the stricture can preclude patients from undergoing curative surgery. Several bronchoscopic interventions including mechanical or laser assisted dilation, electrosurgery (ES), airway stenting and pharmacological treatment with mitomycin C (MMC) and intralesional steroid have been reported in the literature for management of patients who are not surgical candidates. Herein, we review the role of bronchoscopy and illustrate the importance of a multi-disciplinary team (MDT) approach comprising of interventional pulmonologists, thoracic surgeons and otorhinolaryngologists in the diagnosis and management of patients with benign tracheal stenosis.
PubMed: 37559626
DOI: 10.21037/jtd-22-1734