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1.  Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence 
Annals of surgical oncology  2015;23(1):126-133.
Background
Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC.
Methods
Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence.
Results
A total of 180 patients with a median age of 52 years (interquartile range 43–61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last followup, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06–6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19–7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01–1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70–16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01).
Conclusions
Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.
doi:10.1245/s10434-015-4810-y
PMCID: PMC4962540  PMID: 26282907
2.  Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group 
BACKGROUND
Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines.
STUDY DESIGN
Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS).
RESULTS
Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS.
CONCLUSIONS
When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.
doi:10.1016/j.jamcollsurg.2015.12.013
PMCID: PMC4957938  PMID: 26775162
3.  Incidence of Perioperative Complications Following Resection of Adrenocortical Carcinoma and Its Association with Long-Term Survival 
World journal of surgery  2016;40(3):706-714.
Background
The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival.
Methods
Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed.
Results
A total of 265 patients with median age of 52 years (IQR 44–63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8 %). A postoperative complication occurred in 99 patients for a morbidity of 37.4 %; five patients (1.9 %) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95 % CI 1.00–8.18), and a hormonally functional tumor (OR 3.56, 95 % CI 1.65–7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95 % CI 2.24–13.80; P < 0.001).
Conclusion
Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.
doi:10.1007/s00268-015-3307-y
PMCID: PMC4957940  PMID: 26546184
4.  Outcomes after resection of cortisol-secreting adrenocortical carcinoma 
American journal of surgery  2015;211(6):1106-1113.
BACKGROUND
We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC).
METHODS
The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed.
RESULTS
The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01).
CONCLUSIONS
Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.
doi:10.1016/j.amjsurg.2015.09.020
PMCID: PMC4957943  PMID: 26810939
Adrenocortical; Carcinoma; Cortisol; Outcomes
5.  Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes 
Annals of surgical oncology  2015;23(1):134-141.
Background
The influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC.
Methods
A total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1.
Results
R0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03–4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04–6.99; p = 0.04).
Conclusions
A positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.
doi:10.1245/s10434-015-4803-x
PMCID: PMC4955567  PMID: 26286195
6.  Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma 
Background
Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Given the lack of data on readmission after resection of ACC, the objective of the current study was to define the incidence of readmission, as well as identify risk factors associated with readmission among patients with ACC who underwent surgical resection.
Methods
Two hundred nine patients who underwent resection of ACC between January 1993 and December 2014 at 1 of 13 major centers in the USA were identified. Demographic and clinicopathological data were collected and analyzed relative to readmission.
Results
Median patient age was 52 years, and 62 % of the patients were female. Median tumor size was 12 cm, and the majority of patients had an American Society of Anesthesiologists (ASA) class of 3–4 (n=85, 56 %). The overall incidence of readmission within 90 days from surgery was 18 % (n=38). Factors associated with readmission included high ASA class (odds ratio (OR), 4.88 (95 % confidence interval (CI), 1.75–13.61); P=0.002), metastatic disease on presentation (OR, 2.98 (95 % CI, 1.37–6.46); P=0.006), EBL (>700 mL: OR, 2.75 (95 % CI, 1.16–6.51); P=0.02), complication (OR, 1.91 (95 % CI, 1.20–3.05); P=0.007), and prolonged length of stay (LOS; ≥9 days: OR, 4.12 (95 % CI, 1.88–9.01); P<0.001). On multivariate logistic regression, a high ASA class (OR, 4.01 (95 % CI, 1.44–11.17); P=0.008) and metastatic disease on presentation (OR, 3.44 (95 % CI, 1.34–8.84); P=0.01) remained independently associated with higher odds of readmission.
Conclusion
Readmission following surgery for ACC was common as one in five patients experienced a readmission. Patients with a high ASA class and metastatic disease on presentation were over four and three times more likely to be readmitted after surgical treatment for ACC, respectively.
doi:10.1007/s11605-015-2917-x
PMCID: PMC4951184  PMID: 26286367
Adrenocortical carcinoma; Surgery; Readmission
7.  The q-Laguerre matrix polynomials 
SpringerPlus  2016;5:550.
The Laguerre polynomials have been extended to Laguerre matrix polynomials by means of studying certain second-order matrix differential equation. In this paper, certain second-order matrix q-difference equation is investigated and solved. Its solution gives a generalized of the q-Laguerre polynomials in matrix variable. Four generating functions of this matrix polynomials are investigated. Two slightly different explicit forms are introduced. Three-term recurrence relation, Rodrigues-type formula and the q-orthogonality property are given.
doi:10.1186/s40064-016-2178-5
PMCID: PMC4851681  PMID: 27190749
q-Laguerre matrix polynomials; q-Gamma matrix function; Matrix functional calculus; Three terms recurrence relation; Rodrigues-type formula; 33D05; 33D45; 15A16
8.  Primary Synovial Sarcomas of the Mediastinum: A Systematic Review and Pooled Analysis of the Published Literature 
ISRN Oncology  2014;2014:412527.
Background. The aim of this systematic review is to attempt to provide a descriptive analysis for cases of synovial sarcoma (SS) arising in the mediastinum and to analyze prognostic factors. Methods. We performed PubMed database search in July 2013. Twenty-two studies, which included 40 patients, form the basis of this review. Demographic and disease-related factors were analyzed for possible influence on survival. Findings were compared with extremity SS studies reported in literature. Results. Sixteen cases (40%) presented with locally advanced unresectable disease, 2 (5%) with metastatic disease, and 22 (55%) with localized resectable disease. Median tumor size was 11 cm (range: 5–20 cm). Thirty patients were assessable for survival and had a 5-year OS of 36%. Completeness of resection was the only factor associated with significant improvement in OS (5-year survival of 63% and 0% in favor of complete resection, P = 0.003). Conclusion. Mediastinal SS is associated with poor prognosis as more cases are diagnosed at an advanced stage and with larger tumor size compared to extremity SS. Complete surgical resection is the only identified factor associated with better prognosis and may result in survival outcomes that are comparable with those for localized SS of the extremity.
doi:10.1155/2014/412527
PMCID: PMC3916017  PMID: 24563786
9.  Bladder preservation by concurrent chemoradiation for muscle-invasive bladder cancer: Applicability in low-income countries 
Background
Radical cystectomy is the standard treatment for patients with muscle-invasive urinary bladder cancer; however, is associated with major treatment – related morbidity. Furthermore, a significant proportion of patients are deemed unsuitable for surgery due to inoperability, advanced age, and/or comorbid conditions. As such, several groups have explored effectiveness of less radical therapeutic strategies that aim at bladder preservation. Nonetheless, there is scarcity of reports assessing the applicability of urinary bladder-sparing outside developed countries.
Aim
Determine the achievable outcomes for patients with muscle-invasive urinary bladder cancer treated via bladder-sparing techniques in a low income country.
Materials and methods
Fourteen consecutive patients with a diagnosis of muscle-invasive urinary bladder cancer (clinical stage; T2-3N0M0) were treated via a bladder-sparing approach at King Hussein Cancer Center (Amman, Jordan) between 2005 and 2009. Records were electronically retrieved and retrospectively analyzed and included 11 males and 3 females from 41 to 74 years of age (median age, 61). Initial therapy consisted of trans-urethral resection of bladder tumor (TURBT) followed by induction chemotherapy then irradiation (4500cGy) with concurrent platinum-based chemotherapy. Urological evaluation directed additional therapy in a proportion of patients with irradiation (up to 6400 cGy) in patients who achieved CR.
Results
Eleven patients were evaluable for pathological response at time of re-staging; of whom 8 (73%) achieved CR and 3 (27%) achieved partial response (PR). In all but one patient; combined-modality treatment was well tolerated. After a median follow-up of 18.5 months (range, 3–48 months); 5 of 8 (62.5%) patients with CR were alive.
Conclusions
Bladder-sparing strategies via concurrent chemoradiation for muscle-invasive bladder cancer results in an acceptable rate of complete pathological response with adequate short-term outcomes. This approach appears applicable in low-income countries.
doi:10.1016/j.rpor.2011.04.003
PMCID: PMC3863137  PMID: 24376977
Urinary bladder; Cancer; TURBT; Low-income; Bladder-preservation; CR, complete response; PR, partial response; TURBT, transurethral resection of bladder tumor; TCCB, transitional cell carcinoma of the bladder; cCRT, concurrent chemoradiation
10.  Stage I seminoma: treatment outcome at King Hussein Cancer Center in Jordan 
BMC Urology  2012;12:10.
Background
The aim of this report is to address treatment outcomes of patients with early-stage seminoma in a single institution with special reference to patients with history of surgical violation of the scrotum.
Methods
Seventy four patients with pure seminoma were treated at King Hussein Cancer Center (Amman, Jordan) between 2003 and 2010. All patients underwent orchiectomy. All but 3 patients received adjuvant radiotherapy. Patients who underwent surgical violation of the scrotum prior to referral were managed by further excision or irradiation of the scrotal scar. The follow-up ranged from 1 to 200 months (mean, 33 months).
Results
At the time of follow-up; all but one patient remain alive. The 3-year relapse-free survival for the entire cohort was 95.9%. Three patients developed relapse, all of whom received adjuvant irradiation following inguinal orchiectomy and initially harbored tumors larger than 4 cm upon pathological examination. Median time to relapse was 14 months (range, 8–25 months). None were associated with elevated tumor markers prior to detection of relapse. All but one patient were successfully salvaged by chemotherapy.
Conclusions
Our results confirm the excellent prognosis of patients with early-stage seminoma treated by orchiectomy and adjuvant radiotherapy in a developing country. Although all patients who developed relapse demonstrated adverse pathological findings upon initial assessment, no consistent predictor of relapse was found. Scrotal scar re-excision or irradiation in patients with prior history of surgical violation of the scrotum are effective measures in preventing local failure.
doi:10.1186/1471-2490-12-10
PMCID: PMC3419628  PMID: 22531005
11.  The optimal sequence of radiotherapy and chemotherapy in adjuvant treatment of breast cancer 
Background
The optimal time sequences for chemotherapy and radiation therapy after breast surgery for patients with breast cancer remains unknown. Most of published studies were done for early breast cancer patients. However, in Egypt advanced stages were the common presentation. This retrospective analysis aimed to assess the optimum sequence for our population.
Methods
267 eligible patients planned to receive adjuvant chemotherapy [FAC] and radiotherapy. Majority of patients (87.6%) underwent modified radical mastectomy while, 12.4% had conservative surgery.
We divided the patients into 3 groups according to the sequence of chemotherapy and radiotherapy. Sixty-seven patients (25.1%) received postoperative radiotherapy before chemotherapy [group A]. One hundred and fifty patients (56.2%) were treated in a sandwich scheme (group B), which means that 3 chemotherapy cycles were given prior to radiotherapy followed by 3 further chemotherapy cycles. A group of 50 patients (18.7%) was treated sequentially (group C), which means that radiotherapy was supplied after finishing the last chemotherapy cycle. Patients' characteristics are balanced between different groups.
Results
Disease free survival was estimated at 2.5 years, and it was 83.5%, 82.3% and 80% for patient receiving radiation before chemotherapy [group A], sandwich [group B] and after finishing chemotherapy [group C] respectively (p > 0.5). Grade 2 pneumonitis, which necessitates treatment with steroid, was detected in 3.4% of our patients, while grade 2 radiation dermatitis was 17.6%. There are no clinical significant differences between different groups regarded pulmonary or skin toxicities.
Conclusion
Regarding disease free survival and treatment toxicities, in our study, we did not find any significant difference between the different radiotherapy and chemotherapy sequences.
doi:10.1186/1755-7682-4-35
PMCID: PMC3206410  PMID: 21999819
breast cancer; chemotherapy; radiotherapy; sequence

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