Pancreaticoduodenectomy in a tertiary referral center in Saudi Arabia: A retrospective case series

ContextPerioperative outcome of pancreaticoduodenectomy is related to work load volume and to whether the procedure is carried out in a tertiary specialized hepato-pancreatico-biliary (HPB) unit.ObjectiveTo evaluate the perioperative outcome associated with pancreaticoduodenectomy in a newly established HPB unit.PatientsAnalysis of 32 patients who underwent pancreaticoduodenectomy (PD) for benign and malignant indications.DesignRetrospective collection of data on preoperative, intraoperative and postoperative care of all patients undergoing PD.ResultsThirty-two patients (16 male and 16 female) with a mean age of 59.5 ± 12.7 years were analyzed. The overall morbidity rate was high at 53%. The most common complication was wound infection (n = 11; 34.4%). Pancreatic and biliary leaks were seen in 5 (15.6%) and 2 (6.2%) cases, respectively, while delayed gastric emptying was recorded in 7 (21.9%). The female sex was not associated with increased morbidity. Presence of co-morbid illness, pylorus-preserving PD, intra-operative blood loss ?1 L, and perioperative blood transfusion were not associated with significantly increased morbidity. The overall hospital mortality was 3.1% and the cumulative overall (OS) and disease free survival (DFS) at 1 year were 80% and 82.3%, respectively. The cumulative overall survival for pancreatic cancer vs ampullary tumor at 1 year were 52% vs 80%, respectively.ConclusionPD is associated with a low risk of operative death when performed by specialized HPB surgeons even in a tertiary referral hospital. However, the postoperative morbidity rate remains high, mostly due to wound infection. Further improvement by reducing postoperative infection may help curtail the high postoperative morbidity.     

骨外黏液样软骨肉瘤一例报道及文献复习

目的结合1例典型病例和文献复习,探讨骨外黏液样软骨肉瘤（EMC）的病理和临床特点。方法报道11例61岁女性左腹股沟EMC的临床表现、诊治经过、组织形态表现,复习近期国内外相关研究报道,包括临床表现、病理学、细胞遗传学、影响预后因素和治疗方法。结果该例术中冰冻病理考虑软骨肉瘤,遂行右髋关节离断术,术后常规病理证实诊断,随访10个月,无复发。结论EMC发病率低易误诊,临床应结合病理检查,目前手术是最主要的治疗方式。     

Skull base chondrosarcoma: a case treated by the CyberKnife system

Skull base chondrosarcomas represent 2% of all chondrosarcomas. They usually have a low grade of malignity and a complete resection may be curative. However, often they are considered irresectable because of the difficult approach and another kind of treatment is needed. We present a 54-year-old male case who, after weeks suffering from diplopia, was diagnosed with skull base chondrosarcoma and treated with the CyberKnife system. A review of radiosurgery techniques for skull base neoplasms is carried out.     

Primary malignant bone neoplasm: a case report of dedifferentiated chondrosarcoma in the rib and review of the literature

Dedifferentiated chondrosarcoma (DDCS) is a rare but highly malignant primary bone neoplasm, which is resistant to radiotherapy and chemotherapy. There remains uncertainly as to the best treatment of this disease and how to improve its prognosis. In this paper we reported a case of DDCS and reviewed the related literatures in order to provide references to throw a light on the histogenesis, diagnosis and therapy of this disease.     

Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population

Background: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas. Methods: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records. Results: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival. Conclusions: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia.     

Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi‐institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre‐operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high‐grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard‐of‐care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.     

3D打印模型辅助肩胛骨软骨肉瘤的地图形外科切除CSCD

目的描述一种地图形切除肩胛骨肿瘤的手术方法,并评估其切除精确性、肿瘤学预后和肩关节功能。方法回顾分析北京积水潭医院2013-2017年6例因肩胛骨肿瘤接受了3D打印模型辅助地图形外科切除手术患者的资料。术前采用CT扫描获得肿瘤数据。将图像数据集导入导航系统(Stryker Navigation),对肿瘤进行标记,术前设计截骨边缘。根据标有肿瘤信息的图像数据打印3D模型。术中按3D打印模型和术前设计截骨线完成手术。将术前计划和实际获得的切缘作比较。对外科边界、肿瘤局部复发、远处转移及肩关节功能进行评估。结果术前计划切缘21.0±8.1 mm,实际手术获得切缘22.0±6.6mm,两者匹配差值为1.0±5.3mm,差异无统计学意义(t=-0.795,P=0.437)。平均随访51.6月,未发现局部复发和远处转移,Neer肩关节功能评分96~100分,平均为98.2分,MSTS功能评分97%~100%,平均99%。结论使用3D打印模型辅助肩胛骨软骨肉瘤的地图形外科切除可以获得精确的肩胛骨部分切除及理想的肿瘤控制效果,术后肩关节功能满意。     

IDH Mutations in AML Patients; A higher Association with Intermediate Risk Cytogenetics

Objective: IDH mutations diversely affect the prognosis of cyogenetically normal acute myeloid leukemia (CN-AML) adult patients. The aim of this study is to assess the frequency of IDH mutations and to evaluate its role in AML prognosis. Methods: We have analyzed IDH1 and 2 mutations using High Resolution Melting curve analysis (HRM) in 70 denovo AML patients. Results: The median age of AML patients is 40 years (16-75). Incidence of IDH mutations is 10/70 (14.3%); 2 (2.9%) IDH1 mutant and 8 (11.4%) IDH2 mutant. Median PB blasts of mutant IDH patients was 67.5% (25-96) vs. 44% (0-98) for wild type (p=0.065). Eight/10 (80%) mutant IDH patients had B.M blasts ≥50% vs. 2/10 (20%) <50% (p<0.001) and were classified as intermediate risk cytogenetics (p=0.020) with wild FLT3-ITD (p=0.001). Ten/10 (100%) mutant IDH patients showed wild NPM1 (p=0.049). Median OS of mutant IDH in the intermediate risk cytogenetics was 1.8 years (0.7-3.1) vs. 3.1 years (1.1-5.5) for wild IDH (p=0.05). Conclusion: IDH mutation is mainly associated with intermediate risk AML and when integrated in this specific subgroup displays a lower survival and can be considered an additional integrated molecular risk marker for AML prognosis.     

Imatinib in advanced chordoma: A retrospective case series analysis

IntroductionImatinib showed activity in 50 chordoma patients treated within a Phase II study. In that study, 70% of patients remained with stable disease (SD), median progression free survival (PFS) was 9 months and median overall survival (OS) was 34 months. We now report on a retrospective series of PDGFB/PDGFRB positive advanced chordoma patients treated with imatinib as a single agent within a compassionate-use programme at Istituto Nazionale Tumori, Milan, Italy (INT) between August 2002 and November 2010, when the programme was closed.Methods48 patients were consecutively treated with imatinib 800 mg/d. All patients had inoperable and progressive disease before starting imatinib. Demographics, treatment duration, toxicity and response rate by Response Evaluation Criteria in Solid Tumors (RECIST) were retrospectively recorded.ResultsThe median duration of therapy was 7 months (1–46.5). No patient is on therapy at present. 46 patients were evaluable for response. No partial responses were detected. Best response was: stable disease 34 (74%), progressive disease 12 (26%). At a median follow-up of 24.5 months (0.5–117), median PFS was 9.9 months (95% confidence interval (CI) 6.7–13). Eight patients (16.5%) remained on therapy >18 months and 10 patients (21%) remained progression-free >18 months. Median OS was 30 months (95% CI 20–40), with 24 (50%) patients dead at the time of the present analysis.ConclusionsWe confirm the activity of imatinib in locally advanced and metastatic chordoma, in terms of >70% tumour growth arrest in previously progressive patients. Median duration of response lasted almost 10 months, with >20% of patients progression-free at 18+ months.     

Clinicopathological Features of Extraskeletal Myxoid Chondrosarcoma： An Analysis of 9 Cases

Objective： To investigate the Clinicopathological （EMC）. Methods： Nine cases of extraskeletal characteristics of extraskeletal myxoid chondrosarcoma myxoid chondrosarcoma were studied. Extensive immunohistochemical analysis was performed in all the cases and ultrastructural studies were done in 2 extraskeletal myxoid chondrosarcomas. Follow-up information was available for seven patients. Results： There were 7 males and 2 females whose ages ranged from 31 to 69 years （median 52.78 years）. Local pain or tenderness and the presence of a palpable mass were the main complaints of the patients. The tumors were located mainly in the lower extremities （66.7%）. Most tumors were deep-seated. They usually had a distinct multinodular configuration delineated by fibrous connective tissue. The tumor cells were arranged in delicate intersecting strands, rings, and garlands for the most part. The myxoid matrix was abundant in most cases. Immunohistochemical analysis was performed in all the cases and ultrastructural studies were done in 2 extraskeletal myxoid chondrosarcomas. EMC expressed vimentin （100%, 9/9）, neuron-specific enolase （77.8%, 7/9）, S-100 protein （66.7%, 6/9）, synaptophysin and chromogranin A （22.2%, 2/9）. None of the tumors expressed EMA and desmin. Ultrastructurally： EMC was characterized by distinct cords of cells immersed in a glycosaminoglycan rich matrix. The cells were rich in mitochondria, had well-developed Golgi apparatus and there were numerous smooth vesicles. In many cells, there were also prominent glycogen deposits and lipid droplets. Some tumor cells had intracisternal microtubules. In one of the 2 extraskeletal myxoid chondrosarcomas there were 140-180 nm diameter membrane-bound dense-core secretory granules in cell bodies. Conclusion： Extraskeletal myxoid chondrosarcoma （EMC） is a rare soft tissue sarcoma characterized by distinctive morphological and cytogenetical features. However, the chondroid nature has been a subject of controversy, and its line     

Prognostic value of IDH1 mutations identified with PCR-RFLP assay in acute myeloid leukemia patients

BackgroundSomatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique.Aim of the workThe aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML.MethodsResidual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations screening.ResultsThe frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p = 0.03). Patients with IDH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p = 0.08).ConclusionIDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDH1 mutations in AML.     

Rectal cancer: situation where a referral center is needed

One of the objectives of the French strategic plan for cancer 2009-2013 is to structure the need for referral surgery, particularly for low rectal carcinoma. However, low rectal cancer is not the only situation in the field of rectal surgery where expert unit are needed for the referral of appropriate patients. We developed the multidisciplinary strategies for low rectal cancer, advanced rectal cancer, recurrent rectal cancer and peritoneal carcinomatosis. Optimal management of these difficult situations can give a chance of long term survival while a non-optimal management could jeopardise the future of patients by changing a potentially curable disease into an incurable one.     

骨外黏液样软骨肉瘤的临床病理分析

背景与目的：骨外黏液样软骨肉瘤(extraskeletal myxoid chondrosarcoma,EMC)是一种好发于四肢深部软组织分化不定的恶性肿瘤,以形成多结节样结构、富含黏液为特点。本研究旨在探讨EMC的临床病理特征、诊断及鉴别诊断。方法：对7例EMC进行病理形态学及免疫组化观察,并复习相关文献。结果：7例EMC患者病理巨检显示,灰白色多结节状半透明肿物,边界清楚。镜下卵圆形或短梭形细胞排列成条索,由纤细的纤维组织分隔,呈分叶状,富含黏液样基质但血管稀少。免疫组化肿瘤细胞表达vimentin,部分患者表达S-100及EMA,但不表达CK。结论：EMC是一种罕见的具有独特病理特点的软组织肿瘤,应与脊索瘤、软骨肉瘤等富含黏液样基质或软骨样分化的肿瘤相鉴别。     

Genome-wide DNA methylation profiling identifies ALDH1A3 promoter methylation as a prognostic predictor in G-CIMP− primary glioblastoma

To date, the aberrations in the DNA methylation patterns that are associated with different prognoses of G-CIMP− primary GBMs remain to be elucidated. Here, DNA methylation profiling of primary GBM tissues from 13 long-term survivors (LTS; overall survival ?18 months) and 20 short-term survivors (STS; overall survival ?9 months) was performed. Then G-CIMP+ samples were excluded. The differentially expressed CpG loci were identified between residual 18 STS and 9 LTS G-CIMP− samples. Methylation levels of 11 CpG loci (10 genes) were statistically significantly lower, and 43 CpG loci (40 genes) were statistically significantly higher in the tumor tissues of LTS than those of STS G-CIMP− samples (P < 0.01). Of the 43 CpG loci that were hypermethylated in LTS G-CIMP− samples, 3 CpG loci localized in the promoter of ALDH1A3. Furthermore, using an independent validation cohort containing 37 primary GBM samples without IDH1 mutation and MGMT promoter methylation, the hypermethylation status of ALDH1A3 promoter predicted a better prognosis with an accompanied low expression of ALDH1A3 protein. Taken together, our results defined prognosis-related methylation signatures systematically for the first time in G-CIMP− primary GBMs. ALDH1A3 promoter methylation conferred a favorable prognosis in G-CIMP− primary GBMs.     

乳腺导管内原位癌治疗趋势和预后单中心分析

目的 分析乳腺导管内原位癌(DCIS)患者治疗模式变化、临床特征、治疗结果及预后因素。方法 回顾性分析2000-2013年收治的 617例女性患者资料。用Kaplan-Meier法计算局部控制率(LC)、无瘤生存率(DFS)及总生存率(OS),并用Logrank检验分析影响生存的预后因素分析。结果 随着DCIS收治病例数逐年增多,保乳手术比例逐渐增加,但全乳切除术仍然为主要手术方式。共 374例患者接受全乳切除术,160例患者接受保乳术及放疗,83例患者仅接受保乳术。术后激素受体阳性者中有 366例(83.6%)接受内分泌治疗。45例(7.3%)患者接受化疗。中位随访时间47个月,全组 5年LC、DFS、OS分别为98.4%、97.5%、98.9%。单因素分析显示 Her-2阳性是OS的不良预后因素(P=0.019)。尽管全乳切除术组较保乳术加或不加放疗组具有更多不良预后因素,三者总生存结果相似。全乳切除术比单纯保乳术有较高的LC及DFS。结论 DCIS具有极好的预后,保乳术组及全乳切术组总体生存结果相仿,但全乳切除术组可获得最佳LC。     

Extraskeletal myxoid chondrosarcoma: a retrospective review from 2 referral centers emphasizing long-term outcomes with surgery and chemotherapy

BACKGROUND.

Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a propensity for local recurrence and metastasis despite an indolent course. To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease.

METHODS.

The clinical behavior and treatment responses of 87 patients with EMC who were seen at 2 institutions between 1975 and 2008 were examined.

RESULTS.

The median age of the patients at the time of diagnosis was 49.5 years, with a male‐to‐female ratio of 2:1. For patients presenting without metastases, 37% developed local recurrence (median time of 3.3 years) and 26% developed distal recurrence (median time of 3.2 years). Approximately 13% of patients presented with metastases. The 5‐year, 10‐year, and 15‐year overall survival rates were 82%, 65%, and 58%, respectively. Twenty‐one patients received 32 evaluable courses of chemotherapy. No significant radiologic or clinical responses were noted. The median time to disease progression while receiving chemotherapy was 5.2 months. The best physician‐assessed response to chemotherapy was stable disease for at least 6 months in 25% of patients, stable disease for <6 months in 41% of patients, and disease progression in 34% of patients. The estimated progression‐free survival rates at 3 months, 4 months, 6 months, and 9 months were 69%, 65%, 40%, and 26%, respectively.

CONCLUSIONS.

This retrospective review highlights the poor response rate to chemotherapy and emphasizes aggressive control of localized disease as the primary approach to management. Although there are biases inherent in retrospective analyses, these data provide a benchmark for time to disease progression for the study of new agents for the treatment of patients with this diagnosis. Cancer 2008. © 2008 American Cancer Society.     

Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute

PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.