Timing of Resection of Liver Metastases Synchronous to Colorectal Tumor: Proposal of Prognosis-Based Decisional Model

Background Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy. Methods The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B). Results Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064) Conclusions Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.     

非小细胞肺癌中CD44v6的表达及与其脑转移的关系

目的:研究非小细胞肺癌中CD44v6的表达及与其分型、颅内转移的关系。方法:应用免疫组化法检测30例非小细胞肺癌组织标本中CD44v6的表达,并分析其临床意义。结果:CD44v6高表达与非小细胞肺癌的淋巴结转移及颅内转移有关(P<0.05),是非小细胞肺癌颅内转移的主要风险因子。结论:检测CD44v6蛋白的表达,有可能为判断非小细胞肺癌淋巴结转移、颅内转移的发展以及评估预后提供依据。     

Cannabinoid agonist WIN55,212-2 induces apoptosis in cerebellar granule cells via activation of the CB1 receptor and downregulation of bcl-xL gene expression

The endogenous cannabinoid system is involved in the regulation of a number of physiologic effects in both the central and peripheral nervous systems. Its role in the control of neuronal cell proliferation has attracted major attention because of its potential implications for new therapeutic strategies. In the present study, we demonstrated that treatment of cultured cerebellar granule cells with the synthetic cannabinoid WIN55,212-2, causes cell-body and nuclear shrinkage, which are hallmarks of neuronal apoptosis, as well as concentration-dependent decrease in cell viability. Staining with the fluorescent nuclear dye, Hoechst 33258, revealed apoptosis in 27.1% and 58.5% of cells exposed to 1 and 10 microM of WIN55,212-2, respectively (P < 0.01 and P < 0.001 vs. control respectively) after 36 hr. After 24 hr of exposure to WIN55,212-2, mRNA levels for the anti-apoptotic gene bcl-xL were reduced to 45.6% of those found in control (P < 0.01). These effects were completely reverted when cells were exposed to the synthetic cannabinoid in the presence of the specific CB1-receptor antagonist, SR141716A (1 microM). Moreover, the pro-apoptotic effect of 10 microM WIN55,212-2 could be reduced by the addition to the incubation medium of a cell-permeant inhibitor of caspase-1 (50 nM). Finally, WIN55,212-2 significantly increased caspase-1 activity after 24 hr. These findings show that the activation of CB1 receptors on cerebellar granule cells induces apoptotic cell death, which is associated with downregulation of the anti-apoptotic gene, bcl-xL, and at least in part, activation of caspase-1.     

脊柱肿瘤患者流行病学及术后生存状况分析

[目的]总结分析2000年1月～2007年1月于上海长征医院脊柱外科行手术治疗的原发或转移性脊柱肿瘤患者流行病学特征和术后生存状况.[方法]选取所有符合条件患者的病历及随访资料作为研究对象.收集的资料包括性别、年龄、肿瘤类型/原发肿瘤类型、肿瘤部位、术后生存时间.分为原发脊柱肿瘤和转移性脊柱肿瘤两组.[结果]入选371例患者,其中原发组170例(45.8％),转移组201例(54.2％).原发脊柱肿瘤组中,男性101例(59.4％),女性69例(40.6％);年龄范围(10～81)岁,平均年龄(43.6±16.5)岁.转移性脊柱肿瘤组中,男性126例(62.7％),女性75例(37.3％);年龄范围21～87岁,平均年龄(53.6±10.5)岁.原发组中骨巨细胞瘤和脊索瘤最多,各35例,各占20.6％.转移组患者中肺癌、肝癌和甲状腺癌例数占前三位,分别为66例(32.8％)、42例(20.9％)、23例(11.4％).两组患者肿瘤侵犯部位及频率大体相近,但原发组肿瘤侵犯骶骨和寰枢椎的较转移组多.截止到2010年6月30日,原发组最短术后生存时间为14个月,最长为121个月,中位生存时间为71.7个月,5年期生存率为50％;转移组最短生存时间为3个月,最长生存时间为67个月,中位生存时间为28.4个月,3年期生存率为37％.[结论]两组患者的年龄差异有统计学意义,原发脊柱肿瘤组患者的年龄分布更广,且平均年龄更小.原发组患者术后生存时间远长于转移性组患者.手术治疗原发性脊柱肿瘤效果显著.对于转移性脊柱肿瘤患者来说,外科手术是一种对症的姑息治疗,延长转移癌患者的生存时间、改善其生命质量的关键在于针对原发肿瘤的综合治疗.     

Effects of the bone morphogenetic protein binding protein spp24 (secreted phosphoprotein 24 kD) on the growth of human lung cancer cells

Bone morphogenetic proteins (BMPs) and transforming growth factor‐beta (TGF‐β) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP‐2 and TGF‐β and to markedly inhibit the osteogenic properties of rhBMP‐2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP‐2) and reduce tumor growth in a system (A549 human non‐small cell lung cancer cell line) where autocrine stimulation by BMP‐2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co‐injection of BMP‐2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP‐2 and reduced the tumor growth when added to tumor cells that were not treated with BMP‐2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP‐2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1712–1718, 2011     

Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases

Background

Colorectal liver metastases with hepatic vein (HV) involvement may require combined resection of the liver and HV. However, the short- and long-term outcomes of such a procedure remain unclear.

Methods

We reviewed 16 cases of liver resection with major HV resection and reconstruction.

Results

The patients had a median age of 58.5 years (range, 50–74 y). In total, 18 HVs were reconstructed using a customized great saphenous vein graft (n = 10), direct anastomosis (n = 1), external iliac vein (n = 2), portal vein (n = 1), umbilical vein patch graft (n = 3), or ovarian vein patch graft (n = 1). There was no hospital mortality, and the morbidity rate was 50%. With a median follow-up period of 30 months (range, 4–89 mo), 3 patients died of tumor recurrence and 13 were alive with (n = 6) and without (n = 7) disease. Cumulative 1-, 3-, and 5-year survival rates were 93%, 76%, and 76%, respectively.

Conclusions

HV resection and reconstruction combined with liver resection can be performed safely with reasonable long-term results.     

Perioperative Morbidity Affects Long-Term Survival in Patients Following Liver Resection for Colorectal Metastases

Background Hepatic resection is the treatment of choice in patients with colorectal liver metastases. Perioperative morbidity is associated with decreased long-term survival in several cancers. The aim of this study was to assess the impact of perioperative morbidity and other prognostic factors on the outcome of patients undergoing liver resection for colorectal metastases. Methods One hundred ninety seven patients undergoing liver resection with curative intent were investigated. The influence of prognostic factors, such as complications, tumor stage, margins, age, sex, number of lesions, transfusion, portal inflow obstruction, and era and type of resection, was assessed using univariate and multivariate analysis. Complications were graded using an objective surgical complication classification. Results The 5-year survival rate was 38%, with a median follow up of 4.5 years. The disease-free survival rate at 5 years was 23%. The perioperative morbidity and mortality rates were 30 and 2.5%, respectively. The median survival of patients with perioperative complications was 3.2 years, compared to 4.4 years in those patients without complications (p < 0.01). For patients with positive resection margins, the median survival was 2.1 years, compared 4.4 years in patients with a margin (p = 0.019). Conclusion Perioperative morbidity and a positive resection margin had a negative impact on long-term survival in patients following liver resection for colorectal metastases. This paper has been presented at the annual meeting of the Royal Australian College of Surgeons 2006 and was accepted for oral presentation at the IHPBA 2006 meeting in Edinburgh.     

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

Background We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown. Methods Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m² 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen). Results Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively. Conclusions HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.     

Involvement of the cerebellar dorsal vermis in vergence eye movements in monkeys

Frontal-eyed primates use both smooth pursuit in frontoparallel planes (frontal pursuit) and pursuit-in-depth (vergence pursuit) to track objects moving slowly in 3-dimensional (3D) space. To understand how 3D-pursuit signals represented in frontal eye fields are processed further by downstream pathways, monkeys were trained to pursue a spot moving in 3D virtual space. We characterized pursuit signals in Purkinje (P) cells in the cerebellar dorsal vermis and their discharge during vergence pursuit. In 41% of pursuit P-cells, 3D-pursuit signals were observed. However, the majority of vermal-pursuit P-cells (59%) discharged either for vergence pursuit (43%) or for frontal pursuit (16%). Moreover, the majority (74%) of vergence-related P-cells carried convergence signals, displaying both vergence eye position and velocity sensitivity during sinusoidal and step vergence eye movements. Preferred frontal-pursuit directions of vergence + frontal-pursuit P-cells were distributed in all directions. Most pursuit P-cells (73%) discharged before the onset of vergence eye movements; the median lead time was 16 ms. Muscimol infusion into the sites where convergence P-cells were recorded resulted in a reduction of peak convergence eye velocity, of initial convergence eye acceleration, and of frontal-pursuit eye velocity. These results suggest involvement of the dorsal vermis in conversion of 3D-pursuit signals and in convergence eye movements.     

直肠癌合并肝转移时原发肿瘤的手术选择及其疗效评估

目的:回顾性分析本院收治的直肠癌合并肝转移病例,探讨直肠原发灶手术的不同方式。方法：1991年10月～1999年10月,收治直肠癌伴肝转移病例43例,其中男30例,女13例,年龄33～75岁;原发肿瘤位于直肠上段者9例,中段者14例,下段者20例。依据原发肿瘤部位,采取不同的术式,其中直肠前切除者14例,Miles手术者11例,Hartmann手术者7例,结肠造口者11例。结果：全组死亡31例,中位生存时间：直肠前切除者13.8个月,Miles手术者13.7个月,造瘘术者9.2个月;现尚生存者12例(27.9%),均达一年以上,有2例存活8年,仍在继续随访中;肿瘤未切除而作造瘘术者均已死亡。结论：直肠癌合并肝转移时,对原发肿瘤的处理应采用积极治疗手段,以期延长生存期、改善生存质量。