Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Thursday, December 3, 2020

A Performance Comparison of Commonly Used Assays to Detect RET Fusions

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Purpose: Selpercatinib and pralsetinib induce deep and durable responses in advanced RET fusion-positive lung and thyroid cancer patients. RET fusion testing strategies with rapid and reliable results are critical given recent FDA approval. Here, we assess various clinical assays in a large pan-cancer cohort. Experimental Design: Tumors underwent DNA-based next generation sequencing (NGS) with reflex to RNA-based NGS if no mitogenic driver or if a RET structural variant of unknown significance (SVUS) were present. Canonical DNA-level RET fusions and RNA-confirmed RET fusions were considered true fusions. Break-apart fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) performance were assessed in subgroups. Results: 171 of 41,869 patients with DNA NGS harbored RET structural variants, including 139 canonical fusions and 32 SVUS. 12/32 (37.5%) SVUS were transcribed into RNA-level fusions, resulting in 151 oncogenic RET fusions. The most common RET fusion-positive tumor types were lung (65.6%) and thyroid (23.2%). The most common partners were KIF5B (45%), CCDC6 (29.1%), and NCOA4 (13.3%). DNA NGS showed 100% (46/46) sensitivity and 99.6% (4459/4479) specificity. FISH showed 91.7% (44/48) sensitivity, with lower sensitivity for NCOA4-RET (66.7%, 8/12). 87.5% (7/8) of RET SVUS negative for RNA-level fusions demonstrated rearrangement by FISH. The sensitivity of IHC varied by fusion partner: KIF5B sensitivity was highest (100%, 31/31), followed by CCDC6 (88.9%, 16/18) and NCOA4 (50%, 6/12). Specificity of RET IHC was 82% (73/89). Conclusions: While DNA sequencing has high sensitivity and specificity, RNA sequencing of RET SVUS is necessary. Both FISH and IHC demonstrated lower sensitivity for NCOA4-RET fusions.

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Minimal Invasive Esophagectomy—a New Dawn of EsophagealSurgery

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Abstract

Surgery is the mainstay of esophageal cancer. However, esophagectomy is a major surgical trauma on a patient with high morbidity and mortality. The intent of minimally invasive esophagectomy (MIE) is to decrease the degree of surgical trauma and perioperative morbidity associated with open surgery, and provide faster recovery and shorter hospital stay with the equivalent oncological outcome. It also allows for lesser pulmonary morbidity, less blood loss, less pain, and a better quality of life. MIE is safe and effective but has a steep learning curve with high technical expertise. Recently, it is increasingly accepted and adopted all over the globe. In this article, we discuss the safety, efficacy, short-term, and oncological outcomes of thoracoscopic- and laparoscopic-assisted minimally invasive esophagectomy and robotic surgery compared with open esophagectomy with a special focus on the Indian perspective.

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Minimal Access Surgery for Thymoma

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Abstract

Thymoma is a rare epithelial tumor of the thymus gland. Despite rarity, it is the most common tumor of the anterior mediastinum. Surgical resection in the form of extended thymectomy is the gold standard operation. Conventionally and even in the current era of significant advances in the minimally invasive surgery, open transsternal extended thymectomy is considered the gold standard, particularly for advanced-stage tumors. There is however significant evidence now available for the use of minimally invasive approaches for early-stage thymomas. This article aims to discuss the various minimally invasive approaches currently being employed for thymomas.

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Differentiating Benign from Malignant Adrenocortical Tumors by a Single Morphological Parameter—a Clinicopathological Study on 837 Adrenocortical Neoplasias

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Abstract

The morphological differentiation between benign and malignant adrenocortical tumors is an ongoing problem in diagnostic pathology. In recent decades the complex scoring systems have been widely used to calculate the probability of malignancy in adrenocortical tumors on the basis of a variety of histomorphological parameters. We herewith present a substantially simplified method to diagnose adrenocortical carcinoma by a single histomorphological parameter on a consecutive series of more than 800 adrenocortical tumors. Between January 2000 and May 2019, altogether 2305 adrenalectomies for of all types of diseases were removed, approximately 98% by minimally invasive approaches. After exclusion of pheochromocytomas, adrenal ganglioneuromas, adrenal metastases, Cushing's disease related specimens, and Conn's adenomas, the present series finally consisted of 837 adrenocortical tumors. All tumors were analyzed by experienced pathologists of a single institution using standard histopathological methods (Hematoxylin-Eosin and Ki67 stained sections). Clinical and histopathologic data were prospectively collected and retrospectively analyzed. Clinically, 385 patients had 420 functioning tumors (FT), and 417 had non-functioning adrenal tumors (NFT). The mean size of FT was 3.8 ± 1.4 cm (range 0.5–16 cm) and for NFT 4.5 ± 1.6 cm (range 1.5–18 cm). Histomorphologically, 32 adrenal tumors were classified as adrenocortical carcinoma (ACC; 3.8%). In all 32 cases (tumor size 9.1 ± 4.0 cm, range 3–18 cm), confluenting tumor necrosis could be demonstrated. The remaining 805 tumors (control group) completely lacked this highly reproducible single morphological feature. Ki67 levels above 10% were found in 31 of 32 ACCs and never in adrenocortical adenomas (ACA). With a mean follow-up of 8.2 years, 24 out of 32 patients primarily diagnosed as ACC developed distant metastases (75.0%), whereas all patients in the control group remained free of local or distant recurrence. We conclude that a single morphological parameter (confluenting tumor necrosis) is sufficient to predict a poor clinical course in adrenocortical tumors. The histomorphological diagnosis of this parameter is straightforward and highly reproducible.

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Robotic Complete Mesocolic Excision with Central Vascular Ligation for Right Colon Cancer: Surgical Technique and Short-term Outcomes

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Abstract

Background

Minimally invasive colorectal surgery has demonstrated to have the same oncological results as open surgery, with better clinical outcomes. Robotic assistance is an evolution of minimally invasive technique.

Purpose

The study aims to present technical details and short-term oncological outcomes of robotic-assisted complete mesocolic excision (CME) with central vascular ligation (CVL) for right colon cancer.

Methodology

Fifty-two consecutive patients affected by right colon cancer were operated between May 2016 and February 2020 with da Vinci Xi platform. Data regarding surgical and short-term oncological outcomes were systematically collected in a colorectal specific database for statistical analysis.

Results

Thirty-seven (71.15%) and 15 (28.85%) patients underwent right and extended right hemicoletomy with an extracorporeal anastomosis. Median age was 55 years. Mean operative time was 182 ± 36 min. Mean blood loss was 110 ± 90 ml. Conversion rate was 3.84% (two cases). 78.84% (41 cases) were pT3 and mean number of harvested lymph nodes was 28 ± 4. 1/52 (1.92%) had a documented anastomotic leak requiring exploratory laparotomy and diversion proximal ileostomy. Surgery-related grade IIIa–IIIb Calvien Dindo morbidity were noted in 9.61% and 1.92%, respectively.

Conclusion

Robotic assistance allows performance of oncological adequate dissection of the right colon with radical lymphadenectomy as in open surgery, confirming the safety and oncological adequacy of this technique, with acceptable results and short-term outcomes.

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Silver Prussian blue analogue nanomedicine for future cancer therapy

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Future Oncology, Ahead of Print.
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Dostarlimab in the treatment of recurrent or primary advanced endometrial cancer

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Future Oncology, Ahead of Print.
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Lymph Node Harvest After Neoadjuvant Treatment for Rectal Cancer and Its Impact on Oncological Outcomes

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Abstract

The aim of this study was to analyze the influence of neoadjuvant treatment on nodal harvest after rectal cancer surgery and its impact on long-term oncological outcomes. A retrospective analysis of patients with rectal cancer who received curative intent treatment from 2002 to 2012 in our institution was performed. Data on various clinic-pathological and treatment details were recovered from the records. The number of nodes harvested after surgery was analyzed. The influence of number of nodes harvested on overall survival and disease free survival was analyzed. Among the 459 patients included in this study, 326 underwent surgery after neoadjuvant treatment (NAT). The mean number of nodes harvested was significantly lower in patients who received NAT compared with those who did not (8.9 ± 5.77 vs 14 ± 9.84, p < 0.001). However, the mean number of pathologically positive nodes was not significantly different. A minimum of 12 nodes were harvested in only 27.9% of patients who received NAT. No lymph nodes were identified in the specimen in 15 patients (4.6%) who underwent surgery after NAT. The only independent factors influencing harvest of a minimum of 12 nodes were patient age and NAT. The 5-year overall survival was not significantly different in patients in whom < 12 or ≥ 12 nodes were harvested (64% vs 69% respectively, p = 0.5). Neoadjuvant chemoradiation significantly reduces nodal harvest in patients undergoing treatment for rectal cancer. However, this reduced nodal harvest did not adversely impact survival in patients. However, every effort must be made by the surgeon and the pathologist to maximize the nodal harvest.

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Robotic Total Mesorectal Excision for Rectal Cancer: Short-Term Oncological Outcomes of Initial 178 Cases

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Abstract

Emerging techniques in minimally invasive rectal resection include robotic total mesorectal excision (R-TME). The Da Vinci Surgical System offers precise dissection in narrow and deep confined spaces and is gaining increasing acceptance during recent times. The aim of this study is to analyse our initial experience of R-TME with Da Vinci Xi platform in terms of perioperative and oncological outcomes in the context of data from recently published randomised ROLARR trial amongst minimally invasive novice surgeons. Patients who underwent R-TME or tumour specific mesorectal excision for rectal cancer between May 2016 and November 2019 were identified from a prospectively maintained single institution colorectal database. Demographic, clinical-pathological and short-term oncological outcomes were analysed. Of the 178 patients, 117 (65.7%) and 31 (17.4%) patients had lower and mid third rectal cancer. Most of the tumours were locally advanced, cT3–T4: 138 (77.5%). One hundred/178 (56.2%) underwent sphincter preserving TME. Eighty-seven (48.8%) were grade II adenocarcinoma. Nonmucinous adenocarcinoma was the predominant histology, 138 (78.4%). One hundred one cases (56.7%) were pT3. The mean number of lymph node yield was 13 ± 5. Distal resection margin and circumferential resection margin were positive in 2 (1.12%), 12 cases (6.74%) respectively. Eleven cases (6.7%) had to be converted to open TME. Mean blood loss and duration of surgery was 170 ± 60 ml and 286 ± 45 min respectively. Five percent cases had an anastomotic leak. Grade IIIa–IIIb Clavien Dindo (CD) morbidity score was reported to be in 12 (6.75%) and 10 (5.61%) cases. Median length of hospitalisation was 7 days (range 4–14 days). Perioperative and pathologic outcomes following robotic rectal resection is associated with good short-term oncological outcomes and is safe, effective, and reproducible by a minimally invasive novice surgeon.

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Comparative Evaluation of the Short-Term Treatment Outcomes Between Open, Laparoscopic- and Robotic-Assisted Surgical Approaches for Rectal Cancer Treatment

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Abstract

The open surgeries and more recently minimal invasive surgeries aided by laparoscopic or robotic approaches are employed for rectal cancer treatment procedures. The open approach is the most commonly opted technique, but recent studies have also shown that laparoscopic total mesorectal excision (TME) has become the standard of care. There are certain shortcomings of laparoscopic surgery such as long learning curve, inadequate counter traction, limited dexterity, lack of tactile feedback and limited two-dimensional visions. Robotic surgery also offers several benefits to overcome the drawbacks of laparoscopic procedures, such as providing better dexterity and a more stable visualization. This study aims to analyse the surgical results in terms of completion of TME, short-term surgical outcomes and hospital stay in after open, laparoscopic- and robotic-assisted rectal resections respectively. A retrospective review of prospectively maintained dat abase of patients operated for carcinoma rectum between January 2013 and August 2018 at Manipal Comprehensive Cancer Centre, Manipal-Vattikuti Institute of Robotic Surgery, Bangalore, was analysed in this study. The surgical parameters like completion of total mesorectal excision; proximal, distal and circumferential resection margins; number of nodes retrieved; and total post operative hospital stay were analysed in the open, laparoscopic-assisted and robotic-assisted groups. A total of 100 patients were included in the study consisting of 25, 25 and 50 patients each in the open, laparoscopic and robotic arms respectively. In case the desired results were not obtained using the advanced technique the procedure was converted and open technique was adopted. The conversion rate to open procedure was 8% (2of 25) in the laparoscopic-assisted group and 2% (1/50) in the robotic-assisted group. The average post operative hospital stay was 7.4, 7.36 and 6 days in the open, laparoscopic - and robotic-assisted group (p = 0.01) respectively. Robotic rectal resections show a trend towards better surgical results in the form of improved circumferential resection margins, completeness of TME and lower conversion rates.

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Operative Challenges with Minimally Invasive McKeown Esophagostomy with Two-Field Lymphadenectomy in a Case of Situs Inversus Totalis with Carcinoma Esophagus: A Case Report with Review of the Literature

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Abstract

Situs inversus totalis is an uncommon anatomical congenital anomaly characterized by complete transposition of viscera with right-to-left reversal across the sagittal plane. Consequently, surgery in such cases is more technically challenging and requires a complete reorientation of visual-motor coordination skills. We describe a case of a 50-year-old gentleman with locally advanced lower esophagus carcinoma post-neoadjuvant chemoradiotherapy with situs inversus totalis and treated with minimally invasive McKeown esophagectomy using a left thoracoscopic, laparoscopic-assisted and right cervical approach. The operative procedure and difficulties during surgery are highlighted. Minimal invasive esophagectomy is safe and feasible in situs inversus totalis. Recognition of the anatomy with a meticulous preoperative planning is advocated for an uneventful operative intervention.

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QOL-06. QUALITY OF LIFE IN MEDULLOBLASTOMA SURVIVORS IN WESTERN MEXICO

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Abstract
BACKGROUND
Treatment of children with medulloblastoma (MB) can lead survivors to lidiate with long term sequelae and affect their quality of life (QoL). This study evaluates QoL in long term MB survivors. DESIGN/
METHODS
Clinical files of MB survivors from 1997 to 2016 were retrospectively analyzed. QoL was defined by Schipper Criteria in a five dimensional evaluation: clinical data, physic effects of treatment, academic develop, functional state and self welfare report.
RESULTS
Clinical data: Twenty eight survivors were identified, mean age at review was 18 years, median follow up was 106 months. Functional state: Last visit Karfnosky/lansky were 90 to 80% in 25% of patients. Physic effects of treatment: Cerebellar Mutism or ataxia were present in 25% of cases. Two patients required external dispositives. Audiometry detected an auditive tonal decrease in 25% of cases. An endocrine disfunction was present in 46% of cases, 32% required hormone replacement and 28% having short size. Renal damage without dialysis was detected in 7% and 10% had a transient tubulopaty. One case had bilateral amaurosis and 14% uses glasses. Three patients had a life partner. One female has offspring and two males had azoospermia. Academic development: While 90% attends to school, 35.7% complained of learning difficulties and 18% needed special education. Self welfare report: Difficulties in social environment were described in 21% and 14% still feeling sick during years.
CONCLUSIONS
Survivors of MB had adverse physical effects, followed by academic development, functional state and self welfare report and all this has a negative impact in their QoL.
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