scholarly journals Results of surgical treatment of localized and locally advanced adrenocortical cancer in children

2021 ◽  
Vol 8 (2) ◽  
pp. 42-49
Author(s):  
A. S. Temniy ◽  
A. P. Kazantsev ◽  
P. A. Kerimov ◽  
N. Yu. Kalinchenko ◽  
M. V. Rubanskaya ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Surgical Excision ◽  
Stage I ◽  
Adrenocortical Cancer ◽  
Ki 67 ◽  
Results Of Treatment ◽  
Low Incidence ◽  
Radical Surgical Resection

Introduction. Adrenal cortical carcinoma (ACC) is a rare cancer but is the most common primary cancer in the adrenal gland. Despite the low incidence of ACC the mortality rate ranges from 0.04 to 0.2 %, in the overall structure of cancer mortality. Treatment of ACC is mainly surgical and radical surgical excision is the treatment of choice for local disease stages.Aim of the study — to present our results of surgical treatment of localized and locally advanced ACC in children and to determine the risk factors of relapse.Materials and methods. Twenty-eight patients (median age of 47.8 (06—216) mo.) with localized and locally advanced ACC underwent a retrospectively analysis. Stage I, II, and III revealed in 12 (45 %), 7 (25 %), and 9 (30 %), respectively. In 19 (68 %) cases the secretion of one or more hormone observed. Macroscopically and microscopically complete resection were performed in 26 (93 %) and 23 (82 %) patients, respectively. The median tumor volume was 183 (3.6—1608) cm3 and the median tumor weight was 207.9 (48—710) g.Results. Five-year overall (OS) and relapse-free (RFS) survival were 71 % and 69 %, respectively. OS and RFS according to stage I, II, and III were 100 % vs. 71 % vs. 17 % and 100 % vs. 71 % vs. 14 % respectively. The radical surgical resection and the level of Ki-67 expression influenced significantly the rates of OS and RFS (p < 0.001).Conclusion. The main factor affecting the survival rate of ACC in children with stages I—III is the radical surgical resection. It should be taken into account when planning postoperative therapy. Some of biological characteristics of the tumor could also significantly affect the results of treatment.

Different Therapeutic Approaches and Outcome in the Treatment of Pterygium

1998 ◽  
Vol 8 (3) ◽  
pp. 148-152 ◽  
Author(s):  
C. H. Karabatsas ◽  
G. W. Marsh ◽  
A. M. Cook ◽  
S. D. Cook
Keyword(s):  
Surgical Treatment ◽  
Surgical Techniques ◽  
Surgical Excision ◽  
Lamellar Keratoplasty ◽  
Therapeutic Approaches ◽  
Therapeutic Modalities ◽  
Results Of Treatment ◽  
One Year

Purpose This study was initiated to investigate the role of different therapeutic modalities in the outcome of the surgical treatment of pterygium. Methods The results of treatment of pterygia with a variety of surgical techniques were studied in 56 eyes (49 patients) operated on at Bristol Eye Hospital during a period of five years. The surgical techniques included simple excision; bare sclera; conjunctival autograft; sliding conjunctival flap; lamellar keratoplasty and penetrating keratoplasty. Twelve eyes received additional beta irradiation in a fractionated total dose of 40 Gys. Results The incidence of recurrence was 23.2% for the 43 treated primary pterygia, and 23% for the 13 recurrent pterygia. All recurrences occurred between 2.5 and 11 months postoperatively. None of the 11 cases where additional beta irradiation was used showed any recurrence or other complication within the study period. In the recurrent pterygia group, the cases treated with a combination of surgical excision and beta irradiation, showed significantly lower recurrence rate (p<0.001) compared to those cases treated with surgical excision alone. Conclusions Beta irradiation as a complement to surgical treatment of pterygium, is successful in treating high risk cases such as reoperations, whereas for the majority of primary pterygia surgical excision alone is adequate. Additionally, follow up of one year will reveal any recurrences.

Preoperative gemcitabine based chemoradiotherapy in locally advanced nonmetastatic pancreatic adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15677-e15677
Author(s):  
D. Maximous ◽  
M. E. Abdel-Wanis ◽  
M. A. Aboziada ◽  
M. I. El-Sayed ◽  
A. A. Abd-Elsayed
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Tumour Response ◽  
Metastatic Pancreatic Cancer ◽  
Surgical Reconstruction ◽  
Biliary Leakage ◽  
Dismal Prognosis ◽  
Radical Surgical Resection

e15677 Background: Almost 30% of patients with pancreatic cancer present with locally advanced tumours in absence of distant metastasis. Because surgical resection is often contraindicated by vascular invasion, this disease has a dismal prognosis. The combination of gemcitabine with concurrent radiation therapy is a promising approach that is being investigated in patients’ unresectable pancreatic cancer. Aim of the work: The efficacy of preoperative gemcitabine based chemo-radiotherapy in increasing the resectability rate for patients locally advanced, non metastatic pancreatic cancer was assessed. Methods: 25 patients were treated by preoperative gemcitabine based chemo-radiotherapy. Approximately 6 weeks after completion of chemo radiation, evaluation was performed regarding tumour response and resectability. Pancreatico-duodenectomy was done for operable patients with surgical reconstruction. Results: Patients who achieved complete remission (CR) were 2 out of 25 patients while those achieved partial remission (PR) were 11 out of 25, 6 of them were considered operable. Thus Pancreatico- duodenectomy was done for 8 patients with surgical reconstruction. The postoperative 30 day mortality occurred only in one patient. The postoperative morbidity occurred in the form of minor biliary leakage occurred only in 1 patient & leakage from gastrointestinal anaestomosis in 1 patient. Out of 8 patients who underwent radical surgical resection, only one patient developed local recurrence and simultaneous liver metastasis during the follow up period. The median survival was 12 months. Conclusions: preoperative gemcitabine based chemoradiation might benefit patients with locally advanced non metastatic pancreatic cancer by increasing the resectability without significant acute toxicity. No significant financial relationships to disclose.

Room for improvement? The adoption of multimodal esophageal cancer care in the United States.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 78-78
Author(s):  
R. P. Merkow ◽  
K. Y. Bilimoria ◽  
M. McCarter ◽  
A. Stewart ◽  
W. B. Chow ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Tumor Size ◽  
Locally Advanced ◽  
The United States ◽  
Stage I ◽  
Stage Ii ◽  
Cancer Data ◽  
Factors Associated

78 Background: Consensus guidelines recommend neoadjuvant chemo- or chemoradiation therapy as the preferred treatment for locally advanced esophageal adenocarcinoma; however, it is unknown if this recommendation has been widely adopted in the U.S. Our objective was to examine esophageal cancer multimodal therapy and identify factors associated with the use of neoadjuvant therapy. Methods: From the National Cancer Data Base, patients with middle third, lower third and GE junction (GEJ) adenocarcinomas were identified. Patients who were clinical stage I-III and underwent surgical resection were included. Separate logistic regression models were developed to identify predictors of neoadjuvant therapy utilization and outcomes. Results: From 1998 to 2007, 8,051 patients underwent surgical resection for esophageal cancer: 16.3% stage I, 45.0% stage II and 38.7% stage III. For stage II/III tumors, neoadjuvant use increased (49.0% to 77.8%, p<0.001). After adjustment, factors associated with underuse of neoadjuvant therapy in stage II/III patients were older age, Black or Hispanic ethnicity, more severe comorbidities, tumor location (GEJ and middle vs. lower third), tumor size ≥ 2cm, stage II (vs. III) and geographic region. Stage II/III patients not receiving neoadjuvant had an over two fold increased risk of positive lymph nodes (OR 2.14. 95% CI 1.79 – 2.55, p<0.001). In addition, the positive surgical margin rate increased almost three fold (OR 2.80 95% CI 2.17-3.62, p<0.001) but 30-day postoperative mortality risk was not significantly affected (OR 1.50 95% CI 0.94-2.39; p=0.090). For stage I patients, neoadjuvant therapy decreased over time (38.0% to 11.4%, p<0.001). The overuse of neoadjuvant therapy was associated with higher tumor grade, larger tumor size, and low surgical case volume (all p<0.05). Conclusions: The adoption of neoadjuvant therapy has increased in the past decade; however, opportunity exists to improve guideline treatment for locally advanced esophageal cancer. Registry-based feedback to individual hospitals, such as benchmark comparison tools, could help institutions provide care in concordance with national guidelines. No significant financial relationships to disclose.

The role of neoadjuvant imatinib therapy of patients with primary locally advanced GIST.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11037-11037
Author(s):  
Peter Arkhiri ◽  
Irina Poddubnaya ◽  
Sergey N. Nered ◽  
Ivan N. Peregorodiev ◽  
Maxim P. Nikulin ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Surgical Resection ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Percutaneous Biopsy ◽  
Imatinib Therapy ◽  
Maximal Response ◽  
Optimal Timing ◽  
Adjuvant Imatinib ◽  
Advanced Gist

11037 Background: percutaneous biopsy of gastrointestinal tumors is contraindicated, that is why prospective randomized trials of efficiency of preoperative imatinib therapy weren't conducted. According to the results of theRTOG S-0132/ACRIN 6665, CST1571-BDE43 and other studies, neoadjuvant imatinib therapy increase tumor resectability and improve progression-free and disease-specific survival. The optimal timing of surgical intervention is likely during the maximal response on treatment (6 to 12 months as a rule). Methods: We have analyzed the treatment results of 86 patients with locally advanced GIST which were treated since January 1st 2002 till 20 January 2016 at N.N. Blokhin Russian Cancer Centre. The primary tumor was located in the stomach - 32 pts (37,2%), duodenum and small bowel - 37 (43,1%), other (colon, rectum and extraorgan) – 17 pts ( 19,7%). The median follow-up time was 4.9 years. There are 4 groups in the trail: group 1 - 29 patients received only surgical treatment, group 2 - 12 pts– surgical resection with adjuvant imatinib therapy for 1 year; group 3 - 25 pts – adjuvant imatinib therapy for 3 years and group 4 - 17 pts– surgical resection with neoadjuvant and adjuvant imatinib therapy (1 - 3 years). The remained 3 patients received surgical resection with adjuvant imatinib therapy for 5 years. Results: Survival analyses showed a significant improvement of RFS and OS in patients who received combined treatment with neoadjuvant and adjuvant imatinib therapy. The five-year RFS in first group of patients was 10,8%, in 2 group - 16,7%, in 3 group - 68,4%, and 4 group - 79,8% (p = 0.0001). The 5-year overall survival in these groups was 42,6%, 66,7%, 76,1% and 91.6% ( p = 0,0072) respectively. In the patients with 5-years adjuvant therapy, diseases progression was not noted. During neoadjuvant therapy disease progression has been registered in two patients. The median time of preoperative imatinib therapy was 11 month (from 3 to 24 month). Neoadjuvant imatinib therapy increased the rate of R0 (14 pts – 82,4%) and organ-sparing (12 pts – 70,6%) resections. Conclusions: The optimal approach in patients with locally advanced GIST is combined surgical treatment with neoadjuvant and adjuvant (at least for 3 years) imatinib therapy.

Phase II study of neoadjuvant chemotherapy with modified FOLFOXIRI in borderline resectable or unresectable stage III pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4062-4062 ◽  
Author(s):  
Enrico Vasile ◽  
Nelide De Lio ◽  
Carla Cappelli ◽  
Luca Pollina ◽  
Niccola Funel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Phase Ii ◽  
Locally Advanced ◽  
Local Treatment ◽  
Stage Iii ◽  
Borderline Resectable ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Radical Surgical Resection

4062 Background: FOLFIRINOX has shown high activity in metastatic pancreatic cancer (PC) patients and could be an interesting regimen also for patients with inoperable locally advanced disease. Our group had developed a similar schedule in metastatic colorectal cancer named FOLFOXIRI with good tolerance and activity. Therefore, we have decided to perform a phase II trial to prospectively evaluate the activity of modified FOLFOXIRI in borderline resectable or unresectable PC. Methods: Modified FOLFOXIRI consisted of a lower dose of irinotecan (150 mg/sqm) and of infusional 5-fluorouracil (2800 mg/sqm as a 48-hour continuous infusion on days 1 to 3) with no bolus 5-fluorouracil. Folinic acid and oxaliplatin (85 mg/sqm) remained unchanged. The study enrolled patients with diagnosis of pancreatic adenocarcinoma, stage III borderline resectable or unresectable disease (cT4,cN0-1,cM0), ECOG PS 0-1, age 18-75. The primary end-point of the study was the percent of patients who undergo radical surgical resection after chemotherapy. Results: Thirty-two patients have been enrolled; M/F=12/20; PS 0/1=16/16. Median age was 60 years (range 44-75). Median number of FOLFOXIRI cycles was 6 (range 2-14). Grade 3-4 toxicities was experienced by 20 patients during chemotherapy. Twelve partial responses (37%) and 14 stable diseases (45%) have been observed; 2 patients had progressive diseases (6%). The remaining 4 patients (12%) have not been yet evaluated because are still in the first months of treatment. A local treatment was received after chemotherapy by 18 patients until now: 13 (41%) received radical surgical resection and 5 received concomitant chemo-radiotherapy. Three explorative laparotomy showed occult metastases. In other 7 cases surgery is planned while 2 patients refused surgery. Median progression-free survival is 14.0 months and median overall survival is 24.2 months with a two-year survival rate of 54%. Conclusions: Chemotherapy with FOLFOXIRI seems active in locally advanced PC and may allow to obtain a downstaging of disease leading to achieve a curative surgical resection in some cases. Longer follow up is needed to better evaluate long-term outcome of this strategy.

scholarly journals Results of surgical treatment of patients of elderly and senile age with complicated forms of locally advanced colon cancer

2019 ◽  
Vol 11 (2) ◽  
pp. 35-42
Author(s):  
N. I. Glushkov ◽  
T. L. Gorshenin ◽  
M. Ya. Belikova ◽  
S. K. Dulaeva ◽  
I. K. Borovik
Keyword(s):  
Colon Cancer ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Locally Advanced ◽  
Results Of Treatment ◽  
Advanced Colon Cancer

The paper analyzes the results of treatment of 74 elderly and senile patients with complicated forms of locally advanced colon cancer. The article demonstrates the prevalence of symptomatic operations due to the severity of the condition advanced oncological process. The use of endovideosurgical technologies in treating patients with complications of locally advanced colon cancer reduces the number of postoperative complications.

scholarly journals A Novel Steroidogenic Factor-1 Antagonist, OR-449, as a Targeted Therapy for Adrenocortical Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1010-A1010
Author(s):  
Paul Crowe ◽  
Ray Fox ◽  
Haiyan Tao ◽  
Emily Eastwood ◽  
Neil Raheja ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Unmet Need ◽  
Primary Treatment ◽  
Tumor Xenograft ◽  
Orphan Nuclear Receptor ◽  
Adrenocortical Cancer ◽  
Steroidogenic Factor 1 ◽  
Immunocompromised Mice

Abstract Adrenocortical carcinoma (ACC) is a rare cancer with an annual incidence of 0.7-2.0 cases per million in the US and EU. Surgical resection combined with adjuvant chemotherapy remains the primary treatment for patients with advanced disease. Although surgery is an option for most patients, oftentimes cases presenting with locally advanced or metastatic disease are not candidates for surgical resection. Furthermore, the non-specific adrenolytic and highly toxic FDA-approved chemotherapy drug, mitotane, is only marginally effective in adult and pediatric ACC. Steroidogenic factor-1 (SF-1 or NR5A1), an orphan nuclear receptor that is essential for the growth and development of the adrenal gland, is highly expressed in adult and pediatric ACC. Moreover, SF- is the major, active transcription factor in ACC (1,2). To address the unmet need for a targeted therapy in ACC, we identified potent small molecule SF-1 antagonists that block SF-1 transcriptional activity through the SF-1 ligand-binding domain (IC50 = 15-20 nM in a CHO cell reporter assay). In short-term dissociated cell cultures established from SJ-ACC3 (3), a pediatric ACC patient-derived tumor xenograft (PDX), OR-449 and a related SF-1 antagonist, OR-907S, blocked DNA synthesis as measured by inhibition of EdU incorporation in SF-1+ cells (IC50 = 500-600 nM, &gt;80% efficacy at 10 μM) whereas OR-907R, the 100-fold less potent enantiomer of OR-907S, is nearly inactive. OR-449, which has &gt;20% oral bioavailability and a long plasma half-life (&gt; 9 h) in mouse, rat and dog, inhibited growth of SJ-ACC3 tumors grown in immunocompromised mice following daily oral dosing (30 mg/kg) for 4 weeks. SF-1-responsive genes, both down- and up-regulated, identified by RNAseq (by comparison of OR-907S and OR-907R in SJ-ACC3 dissociated cell culture), also responded to OR-449 in SJ-ACC3 xenografts following 7 days of dosing, indicating transcriptional regulation of SF-1 by OR-449. Importantly, in an exploratory 2-week mouse safety study, OR-449 showed no adverse effects when dosed up to 100 mg/kg. Taken together, these findings suggest that SF-1 antagonists could provide a safe and effective targeted therapy for ACC. References: (1) Mohan, et al., Curr. Opin. Endocrinol. Metab. Res., 2019; 8:72; (2) Corces, et al., Science, 2018; 362:eaav1898; (3) Pinto, et al., Clin. Cancer. Res., 2013; 19:1740.

scholarly journals PCSK9 Inhibitors for the Management of Mitotane-Induced Hypercholesterolemia in Adrenocortical Carcinoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A310-A311
Author(s):  
John A Aurora ◽  
Feyza Erenler ◽  
Stephany Matta ◽  
Ronald M Lechan
Keyword(s):  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Mitotic Rate ◽  
Adrenocortical Cancer ◽  
Pcsk9 Inhibitors ◽  
Ki 67 ◽  
Pcsk9 Inhibitor ◽  
Cyp3a4 Inducer ◽  
Coa Reductase

Abstract Background: After surgical resection in adrenocortical carcinoma (ACC), mitotane is often used as adjuvant therapy. However, mitotane can cause adverse effects, such as inducing hypercholesterolemia by stimulating HMG-CoA reductase. In addition, mitotane is a strong CYP3A4 inducer which presents a challenge with statins, such as lovastatin, simvastatin, and atorvastatin. We present a case using a PCSK9 inhibitor in mitotane-induced hypercholesterolemia which was refractory to the maximum dose of rosuvastatin. Clinical Case: A laparoscopic left adrenalectomy was performed on a 45-year old female with Stage 3 (T3, NX, M0) ACC (4.5 x 3.4 x 3.2 cm). Her ACC was determined to be high grade with a mitotic rate 20/50 HPF and Ki-67 of 18.7% with lymphovascular invasion and tumor invasion of periadrenal adipose tissue. Following surgical resection, she started adjuvant therapy mitotane and oral hydrocortisone replacement, as well as 6 weeks of radiation therapy. Prior to starting mitotane, her LDL-C was 133 mg/dL (normal range &lt;130 mg/dL) and treated with simvastatin 40 mg daily. A drug interaction was identified between simvastatin and mitotane, with mitotane reducing effects of simvastatin via CYP3A4 induction, so rosuvastatin 10 mg daily was started instead. A trial of combination rosuvastatin and ezetimibe was used; however, patient discontinued ezetimibe due to reported side effects. As the dose of mitotane increased to achieve a blood concentration of 14–20 mcg/mL, LDL-C simultaneously increased along with a corresponding dose increase of rosuvastatin. While being on mitotane 2 g daily and rosuvastatin 40 mg daily, her lipids peaked with LDL-C 219 mg/dL. The decision was made to start evolocumab administered as 140 mg subcutaneously every 2 weeks in addition to rosuvastatin 40 mg daily. After 4 months of therapy with combination evolocumab and rosuvastatin, her LDL-C decreased to 111 mg/dL, a 49% reduction, while achieving a mitotane concentration of 13 mcg/mL using 4 g daily. Conclusion: Utilizing a PCSK9 inhibitor, such as evolocumab, allows the dose of mitotane to be increased to achieve a therapeutic level while maintaining adequate control of cholesterol. With options for management of mitotane-induced hypercholesterolemia being limited, off-label use of a PCSK9 inhibitor can be justified clinically as moderate LDL-C reduction has also been shown in a prior published case report (1). Evolocumab is a well-tolerated subcutaneous injection, and should be considered for patients with resistant hypercholesterolemia while on mitotane. References: (1) Tsakiridou ED, Liberopoulos E, Giotaki Z, et al. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor use in the management of resistant hypercholesterolemia induced by mitotane treatment for adrenocortical cancer. J Clin Lipidol. 2018;12(3):826–829.

Nongastrointestinal Stromal Tumor Spindle Cell Sarcomas of the Colon or Rectum

2018 ◽  
Vol 84 (4) ◽  
pp. 570-575
Author(s):  
Naruhiko Ikoma ◽  
Christina L. Roland ◽  
Janice N. Cormier ◽  
Yi-Ju Chiang ◽  
Keila E. Torres ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Surgical Resection ◽  
Local Excision ◽  
Spindle Cell ◽  
Stromal Tumor ◽  
Rectal Tumors ◽  
Colon Tumors ◽  
Included Patient ◽  
Low Incidence ◽  
Tumor Spindle Cell

Because of the low incidence of nongastrointestinal stromal tumor (non-GIST) spindle cell sarcomas of the colon or rectum, the clinical behavior and ideal surgical treatment of these tumors and patient outcomes are poorly defined. The purpose of this study was to characterize these tumors and to determine the best surgical approach. We identified 1056 patients with non-GIST spindle cell sarcomas of the colon or rectum (1998–2010) in the National Cancer Database and collected data for each patient that included patient and tumor characteristics, tumor site (colon vs rectum), surgery type, and outcomes. The median overall survival was significantly longer in patients with rectal tumors than in those with colon tumors ( P < 0.01). Patients with colon tumors who underwent anatomic surgical resection showed a trend toward longer median survival than those with no surgical treatment [hazard ratio (HR), 1.94; P = 0.09] or who underwent local excision (HR, 1.74; P = 0.09). Patients with rectal tumors did not benefit from anatomic surgical resection, but there was a trend favoring local excision (HR, 0.55; P = 0.06). Local sphincter-sparing procedures should be considered for rectal non-GIST tumors whenever technically feasible.

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