Iacono Calogero, Verlato Giuseppe, Zamboni Giuseppe, Scarpa Aldo, Montresor Ettore, Capelli Paola, Bortolasi Luca, Serio Giovanni
Department of Surgery and Gastroenterology, University of Verona Medical School, Verona, Italy.
J Gastrointest Surg. 2007 May;11(5):578-88. doi: 10.1007/s11605-007-0136-9.
To evaluate the prognostic significance of different clinico-pathological and molecular factors, and to compare survival after standard and extended pancreaticoduodenectomy (PD) in ampulla of Vater adenocarcinoma (AVAC). There are discordant data on factors affecting prognosis, and hence therapeutic choices, in AVAC.
Clinical-pathological factors were evaluated in 59 patients, subjected to PD for AVAC; in 42 subjects information on chromosome 17p and 18q allelic losses (LOH) and microsatellite instability (MSI) was also available. The association between survival and type of PD was investigated in the 25 patients operated between 1990 and 2001 (16 standard and nine extended).
The overall 5- and 10-year tumor-related survival rates were 46% and 33%, respectively. Sixteen patients had T-stages 1-2, 14 T-stage 3, and 29 T-stage 4 cancers. Chromosome 17p and 18q LOH were detected in 23 (55%) and 15 cases (36%), respectively, and in 12 cases (29%) coexisted. Five cases were MSI-positive (12%). At univariate analysis, poor survival was associated with cancer ulceration (P = 0.051), poor differentiation (P = 0.008), T-stage 4 (P < 0.001), nodal metastases (P = 0.004), chromosome 17p (P < 0.001) and 18q LOH (P = 0.002), and absence of MSI (P = 0.009). At multivariate analysis, only T-stage (P = 0.002) and 17p LOH (P = 0.001) were independent predictors of survival. All patients with MSI-positive cancers were long-survivors (>12 yrs), whereas only 30% of MSI-negative cancer patients survived at 5 years. Extended pancreaticoduodenectomy was associated with a 3-year disease-related survival higher than standard resection (83% vs 31%; P = 0.018).
MSI and chromosome 17p status allow to better define prognosis within ampullary cancers at the same stage. Surgery alone resulted curative in MSI-positive cancer patients, whereas it was inadequate in patients showing allelic losses, who might benefit from adjuvant therapy. In this observational study, extended PD was associated with increased survival compared to standard procedures.
评估不同临床病理和分子因素对预后的意义，并比较标准胰十二指肠切除术（PD）和扩大胰十二指肠切除术治疗 Vater 壶腹腺癌（AVAC）后的生存率。关于影响 AVAC 预后及治疗选择的因素，目前的数据存在分歧。
对 59 例行 PD 治疗 AVAC 的患者的临床病理因素进行评估；42 例患者还可获得 17 号染色体 p 臂和 18 号染色体 q 臂等位基因缺失（LOH）及微卫星不稳定性（MSI）的信息。对 1990 年至 2001 年间手术的 25 例患者（16 例行标准手术，9 例行扩大手术），研究 PD 类型与生存率之间的关系。
总体 5 年和 10 年肿瘤相关生存率分别为 46%和 33%。16 例患者为 T1 - 2 期癌症，14 例为 T3 期，29 例为 T4 期癌症。分别在 23 例（55%）和 15 例（36%）中检测到 17 号染色体 p 臂和 18 号染色体 q 臂 LOH，12 例（29%）两者共存。5 例为 MSI 阳性（12%）。单因素分析显示，生存不良与癌溃疡（P = 0.051）、低分化（P = 0.008）、T4 期（P < 0.001）、淋巴结转移（P = 0.004）、17 号染色体 p 臂（P < 0.001）和 18 号染色体 q 臂 LOH（P = 0.002）以及 MSI 缺失（P = 0.009）相关。多因素分析显示，只有 T 分期（P = 0.002）和 17 号染色体 p 臂 LOH（P = 0.001）是生存的独立预测因素。所有 MSI 阳性癌症患者均为长期生存者（>12 年），而 MSI 阴性癌症患者 5 年生存率仅为 30%。扩大胰十二指肠切除术的 3 年疾病相关生存率高于标准切除术（83%对 31%；P = 0.018）。
MSI 和 17 号染色体 p 臂状态有助于更好地界定同一分期壶腹癌的预后。单纯手术对 MSI 阳性癌症患者可治愈，而对等位基因缺失患者则不足，后者可能从辅助治疗中获益。在本观察性研究中，与标准手术相比，扩大 PD 可提高生存率。
