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1.  Risk of Thromboembolic Events after Perioperative Chemotherapy Versus Surgery Alone for Esophageal Adenocarcinoma 
Annals of Surgical Oncology  2011;19(2):684-692.
Background
Major oncologic surgery is associated with a high incidence of thromboembolic events (TEE). Addition of perioperative chemotherapy in esophageal cancer surgery may increase the risk of TEE.
Methods
The thromboembolic toxicity profile was analyzed in patients with esophageal adenocarcinoma (EAC). Two groups were identified: patients who underwent esophagectomy and received perioperative chemotherapy with epirubicin, cisplatin, and capecitabine (ECC; n = 52), and patients who were treated with surgery alone (n = 35).
Results
A total of 22 TEEs was observed in 17 patients (32.7%) in the chemotherapy group and 3 patients (7.5%) in the surgery-alone group (P < .01). The relative risk of developing a TEE for patients receiving perioperative chemotherapy during the whole treatment period was 3.8 (95% confidence interval 1.2–12.0). A preoperatively occurring TEE did not increase the risk of postoperative TEE, nor did it increase postoperative hospital stay (P = .325). Median postoperative hospital stay was 23 days (range 14–78) for patients with a postoperative TEE and 15 days (range 10–105) for patients without TEE (P = .126). Perioperative chemotherapy with the epirubicin, cisplatin, and capecitabine regimen was independently associated with the development of TEE in the combined preoperative and postoperative period (P = .034).
Conclusions
Perioperative chemotherapy improves survival for operable esophageal cancer but comes at the price of toxicity. Perioperative chemotherapy for EAC increases the risk of TEE. However, chemotherapy-related preoperative TEE did not increase the risk of postoperative TEE, nor did it increase postoperative hospital stay, justifying its use in clinical practice.
doi:10.1245/s10434-011-2005-8
PMCID: PMC3264865  PMID: 21837523
2.  Responses and adverse effects of carboplatin-based chemotherapy for pediatric intracranial germ cell tumors 
Korean Journal of Pediatrics  2011;54(3):128-132.
Purpose
Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs). However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy.
Methods
We examined 35 patients (27 men and 8 women) diagnosed with IC-GCTs between August 2004 and April 2008 and received risk-adapted carboplatin-based chemotherapy at the Samsung Medical Center. Patients were divided into either low-risk (LR) or high-risk (HR) groups and a retrospective analysis was performed using information from the medical records.
Results
Although hematological complications were common, hearing difficulties or grade 3 or 4 creatinine level elevation were not observed in patients who underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia did not differ between the risk groups. The overall survival was 100% and event-free survival (EFS) was 95.7%. The EFS rate was 100% in the LR group and 90% in the HR group, respectively.
Conclusion
Despite their common occurrence in high-risk patients, no lethal hematological complications were associated with carboplatin-based treatment. The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs.
doi:10.3345/kjp.2011.54.3.128
PMCID: PMC3120999  PMID: 21738543
Intracranial germ cell tumor; Carboplatin; Adverse effects
3.  Tallness is associated with risk of testicular cancer: evidence for the nutrition hypothesis 
British Journal of Cancer  2008;99(9):1517-1521.
The pathogenesis of testicular germ cell tumours (GCTs) is potentially influenced by high-energy nutrition during infancy. As adult height is a proxy for childhood nutrition, we investigated the role of nutrition in GCT pathogenesis by comparing stature of patients with healthy men. In a matched case–control study, 6415 patients with GCT were compared with healthy army conscripts (1:6 matching modus) with regard to height (cm) and body mass index (BMI; kg/m2). Statistical analysis involved tabulation of descriptive height measures and BMI. Conditional logistic regression models were used to quantify the association of GCT with height, with odds ratios (OR) adjusted for BMI. The literature was searched for studies on stature in GCT patients. Body size is significantly associated with risk of GCT, very tall men (>195 cm) having a GCT risk of OR=3.35 (95% confidence intervals (CI): 2.88–3.90; adjusted). Short stature is protective (OR=0.798; 95% CI: 0.68–0.93). Both histologic subgroups are associated with tallness. Of 16 previous reports, 7 were confirmative, 5 had null and 4 equivocal results. The association of stature with GCT risk accords with the nutrition hypothesis of GCT. This study expands the current view of GCT tumorigenesis by suggesting that high-calorie intake in childhood promotes GCT precursors originating in utero.
doi:10.1038/sj.bjc.6604695
PMCID: PMC2579680  PMID: 18827809
testicular cancer; body size; childhood nutrition; seminoma; non-seminoma; BMI
4.  Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours 
British Journal of Cancer  2005;93(4):412-417.
We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1–20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31–173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients.
doi:10.1038/sj.bjc.6602724
PMCID: PMC2361583  PMID: 16106248
extragonadal germ cell tumour; high-dose chemotherapy; salvage therapy; children
5.  Predictors of viable germ cell tumor in postchemotherapeutic residual retroperitoneal masses 
Urology Annals  2014;6(1):27-30.
Objective:
The aim of this study was to identify predictors of viable germ cell tumor (GCT) in postchemotherapeutic residual retroperitoneal masses.
Materials and Methods:
The pertinent clinical and pathologic data of 16 male patients who underwent postchemotherapeutic retroperitoneal lymph node dissection (PC-RPLND) at King Faisal Specialist Hospital and Research Centre between 1994 and 2005 were reviewed retrospectively. It was found that all patients received cisplatin-based chemotherapy for advanced testicular GCT.
Results:
Out of the 16 male patients, 2 (13%), 8 (50%), and 6 (37%) had viable GCT, fibrosis, and teratoma, respectively. Ten (10) of the patients with prechemotherapeutic S1 tumor markers did not have viable GCT, and two of the six patients who had prechemotherapeutic S2 tumor markers have viable GCT. All tumor marker levels normalized after chemotherapy even in patients with viable GCT. Four patients had vascular invasion without viable GCT. Furthermore, four patients had more than 60% embryonal elements in the original pathology, but only 1 had viable GCT at PC-RPLND. Four of the five patients with immature teratoma had teratoma at PC-RPLND but no viable GCT; however, out of the four patients with mature teratoma, one had viable GCT and two had teratoma at PC-RPLND. Of the two patients with viable GCT, one had 100% embryonal cancer in the original pathology, prechemotherapeutic S2 tumor markers, history of orchiopexy, and no vascular invasion; the other patient had yolk sac tumor with 25% embryonal elements and 40% teratoma in the original pathology, and prechemotherapeutic S2 tumor markers.
Conclusion:
None of the clinical or pathological parameters showed a strong correlation with the presence of viable GCT in PC-RPLND. However, patients with ≥S2 may be at higher risk to have viable GCT. Further studies are needed to clarify this.
doi:10.4103/0974-7796.127017
PMCID: PMC3963339  PMID: 24669118
Chemotherapy; germ cell tumor; predictor; retroperitoneal lymph node dissection
6.  Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy 
BMC Oral Health  2006;6:13.
Background
We describe the risk indicators for oral mucositis (OM) in paediatric oncology patients hospitalised in the Institut Gustave Roussy (Villejuif-Paris) and treated with alkylant chemotherapy with autologous peripheral blood progenitor cells.
Methods
The sample was selected using PIGAS software. Three groups of subjects received different chemotherapy regimens: A. Melphalan, B. Busulfan and C. other alkylant protocols. The degree of mucositis was recorded by CTC version 2.0 (Common Toxicity Criteria). Descriptive statistics were performed. The association between mucositis and risk indicator variables was tested using a χ2 test. The association between case status and covariates was tested using unconditional logistic regression analysis.
Results
Of the 337 children enrolled, 241 showed mucositis (group 1) and 96 did not show mucositis (group 2) during alkylant chemotherapy. There was a higher prevalence of male patients in both groups. The three different chemotherapy regimen groups are correlated with the appearance of oral mucositis (χ2 = 22.42, p < 0.01). Weight loss was higher in group 1 (χ2 = 6.31, p = 0.01). The duration of aplasia was lower in the Busulfan protocol (7.5 days) than in the Melphalan group (9.3 days) or the other regimens (8.6 days). The use of Bufulfan® was directly associated with case status (presence of oral mucositis): odds ratio [OR] = 2.1 and confidence interval [95%CI] = 1.3–3.0. Also, occurrences of germinal tumours and secondary bacterial infections were directly linked with case status: [OR] = 1.4 and 1.8, confidence interval [95%CI] = 1.2 – 1.7 and 1.1 – 2.5, respectively.
Conclusion
The presence of OM was associated with the three different chemotherapy regimens considered; in particularly patients treated with Busulfan had the highest prevalence.
doi:10.1186/1472-6831-6-13
PMCID: PMC1629008  PMID: 17049085
7.  Improved Outcome of Central Nervous System Germ Cell Tumors: Implications for the Role of Risk-adapted Intensive Chemotherapy 
Journal of Korean Medical Science  2010;25(3):458-465.
To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, P=0.06; group 2 vs. 3, P=0.29; group 1 vs. 3, P=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.
doi:10.3346/jkms.2010.25.3.458
PMCID: PMC2826748  PMID: 20191048
Neoplasms, Germ Cell and Embryonal; Central Nervous System; Drug Therapy; Survival
8.  Testicular Germ Cell Tumors with Sarcomatous Components: An Analysis of 33 Cases 
The American journal of surgical pathology  2009;33(8):10.1097/PAS.0b013e3181adb9d7.
The development of sarcomatous component (SC) in testicular germ cell tumor (GCT) is an uncommon phenomenon. We searched our surgical pathology files from 1985 to 2007 and identified 33 cases of testicular GCTs with SC. The average age of patients was 31 years. All patients underwent radical orchiectomy, which demonstrated a GCT in all patients except for 3 patients who had received neoadjuvant chemotherapy. All testicular GCTs contained a teratomatous component. The GCTs were pure teratomas in 3 cases, and were mixed GCTs in the other cases. The SC was observed in primary testicular tumor (n = 19), in metastasis (n = 11), or in both primary testicular tumor and metastasis (n=3). The average percentage of the SC in the primary testicular GCT was 32% (range, 5% to 99%). The most common histologic type of SC was rhabdomyosarcoma (n = 24), followed by high-grade unclassified sarcoma (n = 5), rhabdomyosarcoma admixed with high-grade unclassified sarcoma (n = 2), angiosarcoma (n = 1), and low-grade myxoid sarcoma (n = 1). Clinical follow-up information was available for 27 patients. Of the 13 patients whose SC was limited to the testicular GCT, 2 died of GCT not otherwise specified (NOS) at 37 and 68 months, respectively; and 11 patients were free of disease at a mean of 46 months. Of the 14 patients with a SC in the metastasis, 7 patients died of GCT NOS at a mean of 95 months, and 7 patients were free of disease at a mean of 104 months. These results suggest that patients with a SC confined to the primary testicular GCT may not have a higher risk of mortality than those at a comparable stage without a SC. However, patients with a SC in the metastasis have an increased risk of mortality.
doi:10.1097/PAS.0b013e3181adb9d7
PMCID: PMC3812063  PMID: 19561445
testicular germ cell tumor; sarcomatous component; rhabdomyosarcoma
9.  Extensive arterial and venous thrombo-embolism with chemotherapy for testicular cancer: a case report 
Cases Journal  2009;2:9082.
Germ cell tumours tend to affect young adults and with advanced treatments achieve more than 90% cure rates. Over the years cisplatin has significantly improved the relapse free survival in these patients, hence forming an essential component of chemotherapy regimes. But, the thrombo-embolic complications suffered with cisplatin significantly affect the quality of life in these young patients.
We describe a young adult who suffered a potentially fatal cerebral and pulmonary vascular insult on completing first cycle of cisplatin-based chemotherapy for a non-seminomatous germ cell tumour. Venous and arterial thrombo-embolism was the mechanism of injury and was promptly managed surgically and medically including neuro-rehabilitation.
doi:10.1186/1757-1626-2-9082
PMCID: PMC2803879  PMID: 20062719
10.  Application of the International Germ Cell Consensus Classification to the Nova Scotia population of patients with germ cell tumours 
Background
The International Germ Cell Consensus Classification (IGCCC) is the internationally accepted, clinically based prognostic classification used to assist in the management and research of metastatic germ cell tumours (GCTs). The goal of this study was to determine whether the IGCCC is applicable to a population-based cohort.
Methods
We completed a retrospective chart review of patients who received diagnoses of GCT in Nova Scotia between 1984 and 2004 and who received treatment with platin-based chemotherapy for metastatic disease. We assigned the IGCCC to each patient based on the site of the primary lesion, the presence or absence of nonpulmonary visceral metastases and prechemotherapy tumour marker values. We calculated Kaplan–Meier estimates of 5-year progression-free survival (PFS) and overall survival for each IGCCC group.
Results
The study cohort comprised 129 patients. The distribution and outcomes in each group of patients in Nova Scotia was similar to that published in the IGCCC. Among patients with nonseminoma GCTs (NSGCT) 61% had good, 22% had intermediate and 17% had poor prognoses. Among those with seminomas, 85% had good and 15% had intermediate prognoses. Among patients with NSGCTs, the 5-year PFS was 90%, 69% and 55%, and the 5-year overall survival was 94%, 84%, 61% in the good, intermediate, and poor prognostic categories respectively. Among patients with seminomas, the 5-year PFS was 95% and 50% and the 5-year overall survival was 94% and 50% in the good and intermediate prognostic categories, respectively.
Conclusion
The IGCCC seems applicable to a population-based cohort, with similar distribution of categories and clear prognostic ability.
PMCID: PMC2666903  PMID: 19424465
11.  Transoesophageal echocardiography in selecting patients for anticoagulation after ischaemic stroke or transient ischaemic attack 
Objectives: To investigate prospectively the role of transoesophageal echocardiography (TEE) in selecting patients for anticoagulation in an unselected stroke population.
Methods: Transthoracic echocardiography (TTE) and TEE were done in all clinically suitable hospitalised patients (n = 457) with transient ischaemic attack or ischaemic stroke in the acute phase during a two year period in Turku University Hospital. 441 patients were successfully evaluated for cardiac sources of embolism using TEE within 31 days of the event.
Results: A major risk factor for a cardiac source of embolism excluding atrial fibrillation, acute myocardial infarction, and prosthetic valve was detected in 10% of patients and a minor risk factor for a cardiac source of embolism in 46%. When a major risk factor of a cardiac source of embolism was detected using TTE or TEE and no contraindications were present, the patient was given anticoagulation drugs. If a minor risk factor for a cardiac source of embolism was detected, anticoagulation treatment was started after clinical assessment, if no contraindications were present. In 62 (14%) cases, the patient was given oral anticoagulation drugs or the necessity of ongoing anticoagulation treatment was confirmed on the basis of TEE. When these anticoagulation treated patients were evaluated using logistic regression analysis, they were found to have significantly more atrial fibrillation and histories of myocardial infarctions. Moreover, the patients were mainly men. When patients in sinus rhythm and without any history of cardiac disease were analysed, 8% of patients were found to have been given anticoagulation drugs on the basis of TEE data.
Conclusion: This study suggests that TEE should be used in patients with stroke even without any clinical evidence of cardiac disease when the patients are candidates for anticoagulation.
doi:10.1136/jnnp.73.1.29
PMCID: PMC1757302  PMID: 12082041
12.  Results of combined treatment of anaplastic thyroid carcinoma (ATC) 
BMC Cancer  2011;11:469.
Background
Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis.
Methods
We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin.
Results
Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months.
Conclusion
Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging.
doi:10.1186/1471-2407-11-469
PMCID: PMC3219746  PMID: 22044775
13.  Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK11 
Neoplasia (New York, N.Y.)  2004;6(4):297-301.
Abstract
Male germ cell tumors (GCTs) are extremely sensitive to platinum-containing chemotherapy, with only 10% of patients showing therapy resistance. However, the biological basis of the high curability of disseminated GCTs by chemotherapy is still unknown. Recently, we demonstrated that the mammalian serine/arginine-rich protein-specific kinase 1 (SRPK1) is a cisplatin-sensitive gene, inactivation of which leads to cisplatin resistance. Because, in mammalians, the expression of SRPK1 is preferentially high in testicular tissues, cisplatin responsiveness of male GCTs might be associated with SRPK1 levels. In the present study, we monitored SRPK1 protein expression in a unique series of nonseminomatous GCTs by immunohistochemistry. Randomly selected GCTs (n = 70) and tumors from patients responding to standard chemotherapy (n = 20) generally showed strong SRPK1 staining. In contrast, expression in refractory GCTs (n = 20) as well as in GCTs from poor-prognosis patients responding to high-dose chemotherapy only (n = 11) was significantly lower (two-sided Wilcoxon rank sum test: P < .001). In conclusion, our data suggest that SRPK1 expression might be an important prognostic indicator for the chemoresponsiveness of nonseminomatous GCTs.
PMCID: PMC1502111  PMID: 15256051
Chemotherapy resistance; germ cell tumors; chemotherapy sensitivity; protein kinase SRPK1; immunohistochemistry
14.  Role of chemotherapy prior to orchiectomy in metastatic testicular cancer—is testis really a sanctuary site? 
ecancermedicalscience  2014;8:407.
A germ-cell tumour (GCT) of the testis is a chemosensitive tumour with high cure rates even in advanced disease. Radical inguinal orchiectomy is the initial procedure used to diagnose it which helps to risk-stratify these patients. However, in patients with life-threatening metastases, primary chemotherapy was attempted in a few studies, followed by delayed orchiectomy. The aim of this review is to study the histopathological findings of delayed orchiectomy and the retroperitoneal lymph node dissection (RPLND) specimens, to assess difference and concordance in response rates in histological types of GCTs in pathological specimens. Overall, 352 patients received initial chemotherapy followed by orchiectomy, and 235 of them had undergone RPLND. Delayed orchiectomy specimens had viable tumour in 74 (21%) patients, scarring/necrosis in 171 patients (48.5%), and teratoma in 107 (30.3%) patients. RPLND specimens had residual disease in 36 (15.3%) patients, scarring/necrosis in 100 patients (42.5%), and teratoma in 99 patients (42.3%). Patients with seminoma who underwent delayed orchiectomy had complete disappearance of tumour in 81.3% of cases, and in non-seminomatous GCT, it was 43.4%. These results raise the question of the existence of a blood–testis barrier in patients with advanced GCT and argue against the testis as a sanctuary site.
doi:10.3332/ecancer.2014.407
PMCID: PMC3936913  PMID: 24624227
primary chemotherapy; delayed orchiectomy; advanced germ-cell tumours; germ-cell tumours
15.  Role of radiotherapy and chemotherapy in the risk of second malignant neoplasms after cancer in childhood. 
British Journal of Cancer  1989;59(5):792-796.
Of a cohort of 634 children treated from 1942 to 1969 at the Gustave Roussy Institute for a first cancer and alive 5 years after treatment, 32 later developed second malignant neoplasms (SMN). A case-control study was performed to determine the relationship between the dose of radiotherapy received on a given anatomical site for the treatment of a first cancer, and the risk of SMN development at the same anatomical site. Another aim of the study was to analyse the effects of the association of radiotherapy with chemotherapy on the risk of SMN. The 32 cases of second malignant neoplasms were individually matched with one to nine patients of the cohort (a total of 162) who did not develop a SMN after a first cancer, matching on age, sex, type of first cancer and follow-up duration. The doses of radiotherapy delivered for the treatment of the first cancer were retrospectively estimated at the 26 anatomical sites of SMN. When the SMN was a leukaemia, the mean active bone-marrow dose was estimated as a weighted mean of the doses received by 20 bone sites. As compared to anatomical sites in children who had not received radiotherapy, the sites which had received 50 Gy or more had a relative risk of SMN of 5.8 (P less than 0.05). When taking into account the dose received at the site of the SMN, neither the number of fractions nor the type of radiations were related to the risk of SMN. Children who had received chemotherapy had a relative risk of SMN of 2.7 (95% CI: 1.2-6.4), adjusted for the dose of radiotherapy, as compared to those who had not. The relative risk of SMN did not vary with the dose nor the duration of the chemotherapy. Dactinomycin was found to increase the relative risk of second soft tissue and bone sarcomas. Cyclophosphamide was found to be less carcinogenic than the other alkylants. The relative risk of SMN was equal to 2.0 (n.s.) after radiotherapy of more than 25 Gy, to 4.4 (n.s.) after chemotherapy, and to 21.4 (P less than 0.01) after the combination of these two treatments modalities, as compared to patients treated by surgery alone. This study suggests that the oncogenic effect of radiations might be increased by chemotherapy, and that the combination of the two treatment modalities might be one of the major factors responsible for overall risk of SMN.
PMCID: PMC2247246  PMID: 2736215
16.  Highlights from the Third International Central Nervous System Germ Cell Tumour symposium: laying the foundations for future consensus 
ecancermedicalscience  2013;7:333.
The Third International Central Nervous System (CNS) Germ Cell Tumour (GCT) Symposium brought together over 100 delegates from all over the world to learn about the latest developments in these tumours and discuss future strategies for their management. Some areas of consensus were agreed upon, and controversies were discussed. Among these, the classification of GCTs and the surgical approach to their management were among the greatest areas of difference between different parts of the world. The need for radiotherapy (RT) as a part of standard first-line management for all malignant CNS GCTs was agreed, as well as the need for additional chemotherapy to maximise the cure in nongerminomatous malignant GCTs; the benefit of the addition of chemotherapy in localised germinoma to reduce the RT burden was also accepted as a good practice. The potential of biological parameters to assist the future diagnosis, treatment stratification, and disease monitoring for CNS GCTs was discussed. Such biological parameters may also represent targets for the development of novel therapies. The need for further collaboration between groups engaged in biological studies was agreed. The merits of proton beam RT were debated, and the importance of mitigating the long-term side effects of the treatment was underlined by a session on late effects.
doi:10.3332/ecancer.2013.333
PMCID: PMC3709531  PMID: 23861728
Third International CNS GCT Symposium; central nervous system; germ cell tumour; germinoma; nongerminoma
17.  Late Recurrence and Second Primary Malignancy among 139 Patients with Germ Cell Tumors: Long-term Outcome of the Disease in a Single-center Experience 
Objective
We retrospectively evaluated long-term oncological outcomes in patients with germ cell tumors (GCTs) primarily treated at our institution and assessed late recurrence and second primary malignancies.
Methods
This study included a total of 139 males with newly diagnosed GCTs of the testis or extragonadal origin who received treatment, including surgery, chemotherapy and radiation therapy, at our hospital between 1980 and 2005. We reviewed late recurrence that occurred at least 2 years after the initial disease-free status and secondary malignancies as well as oncological outcomes.
Results
In patients with seminoma, 5-year progression-free survival and cause-specific survival rates were 87.2% and 100% for Stage I, 88.9% and 100% for Stage II, and 50.0% and 50.0% for Stage III, respectively, whereas in those with non-seminomatous GCTs, they were 79.1% and 96.3% for Stage I, 89.5% and 89.4% for Stage II, and 85.7% and 78.4% for Stage III, respectively. Late recurrence was found in five (3.6%) patients and all of them responded to salvage treatment and achieved disease-free status. Second primary hematological neoplasms occurred in three (2.2%), although they had a long-term free of the primary disease. All died of the second primary disease.
Conclusions
Late recurrence was successfully managed with appropriate treatments, although its incidence was not negligible. Periodic follow-up may be necessary for >5 years in patients with GCTs for early detection of late recurrence. In addition, care should be taken to watch for the development of life-threatening second primary malignant disease during long-term follow-up.
doi:10.1093/jjco/hyp142
PMCID: PMC2813544  PMID: 19906660
urology; urologic-med; urologic-radOncol
18.  Malignant giant-cell tumours of bone  
International Orthopaedics  1998;22(1):19-26.
Summary.
Twenty-nine patients with malignant giant-cell tumours of bone (GCT) were followed- up for between 6 months and 18 years. Seventeen of the tumours were primary and 12 were due to malignant degeneration of initially benign lesions. The clinical features did not differ from those of benign GCT, except for a higher incidence in the distal tibia and sacrum. Anaplastic GCTs were included in the study because their clinical and radiographic features and prognosis were no different from those of the GCT grade III of Jaffe. Eighteen of the tumours were grade III, and 11 were anaplastic. This retrospective study was intended to assess the effects of chemotherapy and surgery for malignant GCT. Three treatment groups were selected, in which treatment was either by surgery alone, surgery plus chemotherapy, or radiotherapy alone. – The prognosis was poor and the 5 year tumour-free survival rate in the series was 50%. The prognosis was the same for primary as for secondarily malignant tumours. There was no statistical difference in survival between malignant grade III and anaplastic malignant tumours. The one-year survival rate for patients treated by chemotherapy and surgery was statistically higher (chi 2 test) than for persons treated by surgery alone. However, the five-year survival rate and the actuarial survival curves were not statistically different in the two groups (log rank test). – Chemotherapy appears to be of some value in the treatment of these malignant tumours but a larger series is required to confirm the efficacy of this approach.
doi:10.1007/s002640050201
PMCID: PMC3619644  PMID: 9549577
19.  Malignant Clinical Presentation of a Benign Granular Cell Tumor of Breast in a Patient with Previously Treated Contralateral Invasive Ductal Carcinoma 
GCT is a rare neoplasm and usually shows the benign character. GCT can occur in any body site and may be multifocal. The most common involved site is tongue which accounts for nearly 30% of all cases but skin and subcutaneous tissue are also affected frequently. Breast is an unusually involved site and accounts for 6% of all GCTs. The histiogenesis of GCT is still controversial but further investigations and immunohistochemical examinations were exposed to neural origin and the tumor is thought to be derived from Schwann cells of peripheral nerves. Generally used technique to diagnose GCT is the positivity of S-100 immunohistochemical staining. Despite its benign nature, GCT may mimic breast carsinoma clinically and radiologically and easily be misdiagnosed for breast cancer. We herein report a case of granular cell tumor that arose in a 56 year-old female patient who previously had been treated from an invasive ductal carcinoma in contralateral breast.
doi:10.1155/2012/974740
PMCID: PMC3517838  PMID: 23243536
20.  Current Update of Management of Clinical Stage I Non Seminomatous Germ Cell Tumors of Testis 
The management of patients with testicular germ cell tumors (GCT) has evolved significantly over the past 30 years with cure rates approaching nearly 100% for low-stage disease and more than 80% for advanced disease. Controversy surrounds about ideal management of clinical stage I non seminomatous germ cell tumors (CS I NSGCT) of the testis due to multiple treatment options available with more or less equal efficacy. Nerve-sparing retroperitoneal lymph node dissection (RPLND), adjuvant chemotherapy with two cycles of bleomycin, etoposide, and cisplatin , or surveillance have all achieved long-term survival in nearly 100% of patients with clinical stage I NSGCT. Retroperitoneal lymph node dissection is still favoured as the therapy of choice for clinical stage I non-seminomatous germ cell tumors in many centres, but as risk factors for the primary tumor have become better understood, surveillance and risk-adapted therapy, including surveillance for low-risk patients and adjuvant chemotherapy for the high-risk group, is now being considered a therapeutic option. The objective of this study is to review current developments in the management of CS I NSGCT testis with emphasis on risk stratification and treatment recommendations.
doi:10.1007/s13193-012-0124-8
PMCID: PMC3392487  PMID: 23730098
Testis cancer; NSGCT stage 1; Surveillance; Chemotherapy; RPLND
21.  Family history of cancer and malignant germ cell tumors in children: A report from the Children's Oncology Group 
Cancer causes & control : CCC  2009;21(2):181-189.
Family history of testicular cancer is an established risk factor for adult testicular germ cell tumors (GCT). We evaluated the association between family history of cancer and pediatric GCT in a Children's Oncology Group case–control study that included 274 GCT cases (195 female and 79 male) diagnosed
doi:10.1007/s10552-009-9448-2
PMCID: PMC2861351  PMID: 19842050
Germ cell tumor; Family history; Children
Background:
Atherosclerotic aortic arch plaques (AAP) have been linked to an increased risk of thrombo-embolic events as a cause of acute ischemic stroke of undetermined etiology.
Objectives:
To find out the presence of atherosclerotic plaques in aortic arch and their potential role as a source of embolism in cerebral infarction of undetermined etiology.
Methods:
We performed trans-esophageal echocardiography (TEE) and multislice computerized tomography (MSCT) of the aortic arch on 30 patients with acute ischemic stroke of undetermined cause from a total series of 150 non-selected patients with acute ischemic stroke studied prospectively by clinical evaluation, laboratory investigations, cranial computed tomography, color coded duplex ultrasonography of the carotid arteries and transcranial Doppler (TCD).
Results:
Using trans-esophageal echocardiography eight patients (29.6%) had atherosclerotic aortic arch plaques, while using multislice computerized tomography atherosclerotic aortic arch plaques were revealed in twelve patients (40%). Atherosclerotic aortic arch plaques were significantly related to older age, male gender, hypertension, ischemic heart disease and low-grade atherosclerotic carotid lesions. Multislice computerized tomography of the aortic arch was more sensitive than trans-esophageal echocardiography in detecting the site, size and characters of atherosclerotic aortic arch plaques.
Conclusion:
Atherosclerotic aortic arch plaques are a frequent finding in patients with acute ischemic stroke of undetermined cause supporting the hypothesis that aortic plaques have embolic potential. In addition, multislice computerized tomography is more sensitive than trans-esophageal echocardiography in detecting atherosclerotic aortic arch plaques and better characterization of these plaques especially relevant one.
PMCID: PMC3317276  PMID: 22518260
Aorta; Atherosclerotic plaques; Echocardiography; Multislice Computerized Tomography; Stroke
Recognition of the therapeutic role of retroperitoneal lymph node dissection (RPLND) in the setting of testicular germ cell tumors (GCTs) is of utmost importance. Although the histologic findings of RPLND provide diagnostic and prognostic information, the adequacy of initial RPLND is an independent predictor of clinical outcome. Despite the advent of effective cisplatin-based chemotherapy for testicular GCTs, patients who have undergone suboptimal surgery at the time of initial RPLND are compromised. Despite the initial enthusiasm surrounding anatomic mapping studies, the use of modified RPLND templates has the potential to leave a significant number of patients with unresected retroperitoneal disease. Teratomatous elements are particularly common. Patients with retroperitoneal relapse following initial RPLND should be treated with reoperative RPLND and chemotherapy and can expect long term survival rates nearing 70% when treated in tertiary centers by experienced surgeons.
doi:10.4103/0970-1591.60452
PMCID: PMC2878419  PMID: 20535295
Recurrence; relapse; reoperative; retroperitoneal lymph node dissection; testicular cancer
Aims
Transesophageal echocardiography (TEE) is the gold standard for the detection of thrombi in patients with atrial fibrillation (AF) before undergoing early electrical cardioversion (CV). However, TEE generates inconclusive results in a considerable number of patients. This study investigated the influence of contrast enhancement on interpretability of TEE for the detection of left atrial (LA) thrombi compared to conventional TEE and assessed, whether there are differences in the rate of thromboembolic events after electrical cardioversion.
Methods
Of 180 patients with AF (51 females, 65.2±13 years) who were referred to CV, 90 were examined with native imaging and contrast enhancement within the same examination (group 1), and 90 were examined with native TEE alone and served as control (group 2). Cineloops of the multiplane examination of the LA and LA appendage (LAA) were stored digitally before and, in group 1, after intravenous bolus application of a transpulmonary contrast agent. Images of group 1 were assessed offline and the diagnosis of LA thrombi was made semi-quantitatively: 1= thrombus present; 2=inconclusive result; 3=no thrombus. The presence of spontaneous echocontrast (SEC) was registered and flow velocity in the LA appendage (LAA-flow) was measured. All patients in whom CV was performed were followed up for 1 year or until relapse of AF. CV related adverse events were defined as any thromboembolic event within 1 week after CV.
Results
No serious adverse events occurred during TEE and contrast enhanced imaging. In group 1 atrial thrombi were diagnosed in 14 (15.6%) during native and in 10 (11.1%) patients during contrast enhanced imaging (p<0.001). Of the 10 patients with thrombi in the contrast TEE group, 7 revealed a decreased LAA-flow (≤0,3m/s) and 8 showed moderate or marked SEC. Uncertain results were significantly more common during native imaging than with contrast enhanced TEE (16 vs. 5 patients, p<0.01). Thrombi could definitely be excluded in 60 (66.7%) during conventional and in 75 patients (83.3%) during contrast enhanced TEE (p<0.01). CV was performed subsequently after exclusion of thrombi and at the discretion of the investigator. In group 1, 74 patients (82.2%) were cardioverted and no patient suffered a CV related complication (p=0.084). In group 2, 76 patients (84.4%) underwent CV, of whom 3 suffered a thromboembolic complication after CV (2 strokes, 1 peripheral embolism).
Conclusion
In patients with AF planned for CV contrast enhancement renders TEE images more interpretable, facilitates the exclusion of atrial thrombi and may reduce the rate of embolic adverse events.
doi:10.1186/1476-7120-11-1
PMCID: PMC3554518  PMID: 23295101
Atrial fibrillation; Atrial thrombus; Contrast echocardiography; Transesophageal echocardiography; Cardioversion; Thromboembolic events
Maternal vitamin supplementation has been linked to a reduced risk of several pediatric malignancies. We examined this relationship in a study of childhood germ cell tumors (GCTs). Subjects included 278 GCT cases diagnosed <15 years during 1993-2001 at a United States or Canadian Children's Oncology Group Institution and 423 controls that were ascertained through random digit dialing matched to cases on sex, and age within one year. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% Confidence Intervals (CIs) for the association between GCTs and maternal vitamin use at several time points during and around pregnancy. In models controlling for the child's age, sex, household income, and maternal education, any maternal vitamin use during the 6 months prior to conception through nursing was associated with a non-significant reduced risk of GCTs (OR=0.7; 95% CI 0.0.4-1.2). Inverse associations were observed for both extragonadal (OR=0.8; 95% CI 0.4-1.6) and gonadal (OR=0.6; 95% CI 0.3-1.1) tumors and for dysgerminoma/seminoma (OR=0.6; 95% CI 0.2-1.3) and teratoma (OR=0.5; 95% CI 0.2-0.9) but not yolk sac tumors (OR=1.1; 95% CI 0.5-2.3). No consistent patterns were found with respect to vitamin use during the periconceptional period (6 months before pregnancy and first trimester) or first trimester specifically. In conclusion, while our study suggests that maternal vitamin supplementation may reduce the risk or pediatric GCTs in the offspring, the small study size and limitations inherent to observational studies must be considered when interpreting these results.
doi:10.1158/1055-9965.EPI-09-0462
PMCID: PMC2759848  PMID: 19755653
germ cell tumors; pediatrics; prenatal vitamins; folic acid; risk factors

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