Impact of chemotherapy on collagen metabolism: a study of serum PIIINP (aminoterminal propeptide of type III procollagen) in advanced sarcomas

We have previously shown that the serum aminoterminal propeptide of type III procollagen (PIIINP) is a prognostic factor for survival in localised soft-tissue sarcomas, and that elevated values are frequent in metastatic discase. In the present study PIIINP is analysed during chemotherapy in 26 patients with advanced sarcomas. Non-responders had a significantly higher pretreatment level of PIIINP than responders (P=0.05), when only patients with no recent therapeutic interventions were studied. However, during chemotherapy PIIINP followed the clinical course of the malignant disease in only a minority of patients. Patients with recent surgery or recently completed chemotherapy had an increased pretreatment PIIINP value (P=0.03). In these patients PIIINP declined during chemotherapy irrespective of tumour response. A pretreatment PIIINP level within the reference range tended to increase with time irrespective of response. Moreover, the values taken during a chemotherapy infusion were significantly higher than those immediately preceding the corresponding cycle (P=0.001). Our results suggest that pretreatment PIIINP is of value as a prognostic factor for chemotherapy response in patients with advanced sarcomas. During chemotherapy PIINP is of minor importance in monitoring response because of the influence of chemotherapy and other therapeutic interventions on the level of PIIINP.This study was supported in part by grants from the Finnish Cancer Foundations, the Medical Research Council of the Academy of Finland and Finska Läkaresällskapet (Finnish Medical Society)     

ShcC proteins: Brain aging and beyond

To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.     

The impact of lymph node disease in extremity soft-tissue sarcomas: a population-based analysis

Background

Because of the low incidence of regional lymph node metastasis, node-positive soft-tissue sarcoma patients remain poorly characterized. Our objective was to assess regional lymph node metastasis in extremity sarcoma patients using a large population database.

Methods

The Surveillance, Epidemiology, and End Results database was queried for extremity sarcoma patients. Clinicopathologic data and outcomes were examined to evaluate the significance of regional lymph node metastasis.

Results

Of 7,159 patients without distant metastasis, 64 patients had identified regional lymph node metastasis (.9%). Regional lymph node metastasis was associated with younger age, tumor grade, size, invasion, and tumor subtype. Excluding distant metastasis, lymph node status was the strongest prognostic factor (hazards ratio = 5.1, P < .001).

Conclusions

Isolated regional lymph node metastasis is rare in extremity sarcoma patients. However, in the absence of distant metastasis, lymph node status is the most important prognostic factor. The management of positive lymph nodes remains uncertain although diagnosing lymph node metastasis may identify early biologically aggressive disease.     

Treatment of undifferentiated embryonal sarcoma of the liver in children—single center experience

Background

Undifferentiated embryonal sarcoma of the liver (UESL) represents less than 5% of all malignant hepatic tumors in childhood. It is considered an aggressive neoplasm with an unfavorable prognosis. The aim of this paper is to present a single center experience in the treatment of children with UESL.

Materials and methods

Ten children with UESL were treated between 1981 and 2012. Age at diagnosis ranged from 4 months to 17 years (median age, 6 years and 9 months). Surgery after neoadjuvant chemotherapy (CHT) was performed in 7 patients, and in 3 patients primary surgery was done. Adjuvant chemotherapy was administered in all 10 patients (CYVADIC, CAV, CAV/ETIF/IF + ADM, CDDP/PLADO). Right hemihepatectomy was performed in 1 patient, extended right hemihepatectomy in 6, and partial resection of the right lobe (segments V-VI, segment V) in 2 patients. One patient with unresectable tumor affecting both lobes was listed for liver transplantation (LTx).

Results

Follow-up from diagnosis ranged from 50 to 222 months (mean 138 months). Among 9 patients treated with partial liver resection, distant metastases/local recurrence was not observed in any, and disease-free survival in this group is 100% (9 patients alive). The patient that underwent liver transplantation died of multiorgan failure 4 months postoperatively.However, this patient was misdiagnosed as having hepatoblastoma (HBL) and received PLADO chemotherapy. The overall survival rate is 90%.

Conclusion

Excellent results with long-term survival can be achieved in children with UESL with conventional therapy, including a combination of neoadjuvant and adjuvant chemotherapy and surgery, even in large extensively growing tumors.     

Intraoperative electron radiation therapy as an important treatment modality in retroperitoneal sarcoma

Background

Local recurrence (LR) rates in patients with retroperitoneal sarcoma (RPS) are high, ranging from 40% to 80%, with no definitive studies describing the best way to administer radiation. Intraoperative electron beam radiation therapy (IOERT) provides a theoretical advantage for access to the tumor bed with reduced toxicity to surrounding structures. The goal of this study was to evaluate the role of IOERT in high-risk patients.

Methods

An institutional review board approved, single institution sarcoma database was queried to identify patients who received IOERT for treatment of RPS from 2/2001 to 1/2009. Data were analyzed using the Kaplan–Meier method, Cox regression, and Fisher Exact tests.

Results

Eighteen patients (median age 51 y, 25–76 y) underwent tumor resection with IOERT (median dose 1250 cGy) for primary (n = 13) and recurrent (n = 5) RPS. Seventeen patients received neoadjuvant radiotherapy. Eight high-grade and 10 low-grade tumors were identified. Median tumor size was 15 cm. Four patients died and two in the perioperative period. Median follow-up of survivors was 3.6 y. Five patients (31%) developed an LR in the irradiated field. Three patients with primary disease (25%) and two (50%) with recurrent disease developed an LR (P = 0.5). Four patients with high-grade tumors (57%) and one with a low-grade tumor (11%) developed an LR (P = 0.1). The 2- and 5-y OS rates were 100% and 72%. Two- and 5-y LR rates were 13% and 36%.

Conclusions

Using a multidisciplinary approach, we have achieved low LR rates in our high-risk patient population indicating that IOERT may play an important role in managing these patients.     

手指软组织肉瘤的创面修复与重建

目的 回顾性分析手指原发软组织肉瘤病例,判断在根治肿瘤的同时是否能实施保指以满足手指外观功能的需要.方法 收集2007年4月至2009年11月期间11例手指软组织肉瘤保指的患者,采取肿瘤广泛切除后,对创面覆盖选用第一掌背动脉皮瓣7例,第二掌背动脉皮瓣修复4例;其中5例合并肌腱缺损患者同期行肌腱移植修复,1例骨质缺损行髂骨移植术.结果 术后6例接受新辅助化学治疗,1例接受辅助放射治疗.术后随访时间14个月至5年,9例肿瘤无复发,1例术后14个月肺转移死亡,1例肺转移带瘤生存.术后皮瓣全部存活,1例局部复发行截指.术后1年手指外观满意度为81％,功能评分为8～15分,平均12.6分,优或良10例,占91％.结论 建议对手指软组织肉瘤有保指可能时应尽可能实施保指,并同期进行功能重建.     

Mesenchymal Tumors of the Gastrointestinal Tract Other than GIST

Mesenchymal tumors involve the gastrointestinal (GI) tract more frequently than other visceral organs. Many such tumors are small, and are benign and increasingly being detected incidentally during colonoscopic screening. Some tumors show distinctive features at this site, such as schwannoma and clear cell sarcoma–like tumor of the GI tract. Without knowledge of these features, recognition of these tumor types can be difficult. This reviews addresses recent developments and diagnostic features of mesenchymal tumors of the GI tract other than gastrointestinal stromal tumor (GIST).     

Cellular Receptors Involved in KSHV Infection

The process of Kaposi’s Sarcoma Herpes Virus’ (KSHV) entry into target cells is complex and engages several viral glycoproteins which bind to a large range of host cell surface molecules. Receptors for KSHV include heparan sulphate proteoglycans (HSPGs), several integrins and Eph receptors, cystine/glutamate antiporter (xCT) and Dendritic Cell-Specific Intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This diverse range of potential binding and entry sites allows KSHV to have a broad cell tropism, and entry into specific cells is dependent on the available receptor repertoire. Several molecules involved in KSHV entry have been well characterized, particularly those postulated to be associated with KSHV-associated pathologies such as Kaposi’s Sarcoma (KS). In this review, KSHV infection of specific cell types pertinent to its pathogenesis will be comprehensively summarized with a focus on the specific cell surface binding and entry receptors KSHV exploits to gain access to a variety of cell types. Gaps in the current literature regarding understanding interactions between KSHV glycoproteins and cellular receptors in virus infection are identified which will lead to the development of virus infection intervention strategies.