Global gene expression in pseudomyxoma peritonei,with parallel development of two immortalized cell lines

Pseudomyxoma peritonei (PMP) is a rare tumor of appendiceal origin. Treatment is major cytoreductive surgery but morbidity is high. PMP is considered chemo-resistant; its molecular biology is understudied; and presently, there is no platform for pre-clinical drug testing. Here, we performed exon array analysis from laser micro-dissected PMP tissue and normal colonic epithelia. The array analysis identified 27 up-regulated and 34 down-regulated genes: candidate up-regulated genes included SLC16A4, DSC3, Aldolase B, EPHX4, and ARHGAP24; candidate down-regulated genes were MS4A12, TMIGD1 and Caspase-5. We confirmed differential expression of the candidate genes and their protein products using in-situ hybridization and immuno-histochemistry. In parallel, we established two primary PMP cell lines, N14A and N15A, and immortalized with an SV40 T-antigen lentiviral vector. We cross-checked for expression of the candidate genes (from the array analyses) using qPCR in the cell lines and demonstrated that the gene profiles were distinct from those of colorectal tumor libraries and commonly used colon cell lines. N14A and N15A were responsiveness to mitomycin and oxaliplatin. This study characterizes global gene expression in PMP, and the parallel development of the first immortalized PMP cell lines; fit for pre-clinical testing and PMP oncogene discovery.     

Establishment and characterization of a murine xenograft model of appendiceal mucinous adenocarcinoma

We describe the clinical, pathologic and molecular characteristics of a xenograft model of metastatic mucinous appendiceal adenocarcinoma. Tumours from patients with mucinous appendiceal neoplasms were implanted in nude mice and observed for evidence of intraperitoneal tumour growth. Morphologic and immunohistochemical features, temporal growth characteristics relative to controls, and loss of heterozygosity (LOH) at multiple chromosomal alleles were assessed in a successfully engrafted tumour. Two of seventeen implanted tumours successfully engrafted and only one mucinous adenocarcinoma propagated throughout the course of the study. The successful xenograft is morphologically similar to the original tumour, produces abundant extracellular mucin and exhibits non‐invasive growth on peritoneal surfaces. The temporal growth characteristics of the xenograft tumour relative to controls reveal that tumour burden can be followed indirectly by measuring the weight or abdominal girth of engrafted animals. The cytokeratin, mucin core protein, CDX2, Ki‐67 and p53 expression patterns are identical in the xenograft and resected tumour and are consistent with the expected pattern of protein expression for mucinous adenocarcinoma of the appendix. LOH was found in 1 of 10 informative chromosomal loci (chromosome 10p23) in xenograft tumour cells. Although we were unable to engraft a low‐grade appendiceal mucinous neoplasm, the engrafted adenocarcinoma will be useful for future evaluation of novel therapeutic strategies directed at mucinous appendiceal adenocarcinoma and evaluation of strategies for treating widespread, bulky, mucinous peritoneal surface neoplasms. Xenograft tumour enrichment can facilitate molecular studies of appendiceal epithelial neoplasia.     

腹膜假性黏液瘤的 CT、MRI 表现

目的：探讨5例经病理证实的腹膜假性黏液瘤（PM P ）的C T 及M RI表现及病理组织学特征,提高对该病的诊断水平。方法回顾分析5例经腹腔穿刺或手术证实的PMP的CT、MRI资料并结合文献讨论,分析其CT、MRI表现及临床病理特点。结果5例中,1例为阑尾黏液腺癌,1例为急性阑尾炎术后2年,1例为无任何原发肿瘤,1例为十二指肠黏液腺癌,1例为双侧卵巢癌,C T、M RI表现为腹腔内分隔样囊性病变或／和腹膜弥漫性饼状“胶冻腹”改变,并1例肝、脾周围多发结节样、扇贝样压迹。结论腹部CT、MRI平扫＋增强可以显示PMP病灶部位、形态,有一定的特殊影像学表现。     

腹膜假性粘液瘤的CT诊断与鉴别诊断

目的 探讨腹膜假性粘液瘤的CT表现,提高对本病的诊断与鉴别诊断水平。方法 选取经手术及病理证实的腹膜假性粘液瘤8例,全部病例术前均行腹部CT平扫和增强检查;回顾分析其CT影像表现。结果 （1）典型CT表现：8例均出现腹、盆腔脏器扇贝形压迹;7例表现为腹腔、盆腔脏器周边的分房粘液团块,可多发或单发;单发/多发者其内密度均匀,CT值略高于水,增强后边缘性强化;囊壁厚度一致或不均。（2）不典型CT表现：3例可显示原发病灶及腹膜后淋巴结肿大。5例合并有网膜、肠系膜浸润性改变。7例合并有腹水;2例合并钙化。对于不典型CT表现,在CT征象上与其它非粘液癌性腹膜炎相仿,也较难鉴别。结论 CT检查对腹膜假性粘液瘤有重要的诊断和鉴别诊断价值。     

腹膜假性粘液瘤7例的诊治体会

目的:探讨腹膜假性粘液瘤的诊断和治疗方法。方法:对2003~2007年我科收治的7例患者的临床治疗进行回顾性分析,总结诊治经验,并复习相关文献。结果:7例患者均经手术治疗,病理证实。术后4例辅以化疗,3例未行特殊治疗。随访,2例1年内死亡,最长存活者已达4年。结论:腹膜假性粘液瘤是一种少见病,术前诊断较为困难,腹腔穿刺抽出胶样液应首先考虑该病的可能性,B超和CEA检查对诊断可能有帮助。外科手术治疗仍是目前有效的治疗手段。     

A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis

Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse collection of intraperitoneal gelatinous fluid is associated with gelatinous implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic metastasis is extremely rare. In addition, an inguinal mass as an initial presentation is also relatively rare. This is a case report of a PMP patient who had splenic metastasis and showed an inguinal tumor as an initial presentation. A 59-year-old female patient, who had undergone bilateral oophorectomy because of a ruptured ovarian mucinous tumor of boderline malignancy 12 years previously, presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed tomography revealed a low density mass in the pelvic cavity and in the inguinal lesion, as well as in the spleen without any diseases around the organ. The preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and appendectomy, as well as left inguinal herniorrhaphy. Histological examinations revealed a splenic metastasis of PMP originating from the ovarian low-grade mucinous tumor. She received postoperative intraperitoneal lavage as well as chemotherapy, and has survived for over 7 years postoperatively without any evidence of recurrence, as confirmed by repeated follow-up CT examinations and CEA determination. Splenic metastasis of PMP is extremely rare; this represents only the third reported case of its kind in the literature. Furthermore, it should be noted that an inguinal tumor can sometimes be an initial presentation of PMP.     

腹膜假性粘液瘤的超声诊断

报告１２例腹膜假性粘液瘤的超声检查结果。文中阐述了腹膜假性粘液瘤超声诊断的临床意义，描述其声像图表现并与腹腔和手术所见对照，腹腔内大小等的光团，内部呈细小蜂窝祥回声为其特征性声像。作者认为超声在本病的诊断方面具有重要的临床意义。     

A new standard of care for the management of peritoneal surface malignancy

Cancer dissemination to peritoneal surfaces was, in the past, a lethal condition with a limited survival. Clinical and pharmacologic research have shown that options for both treatment and prevention are now reality. The diseases most commonly treated include peritoneal dissemination from appendiceal malignancy, colorectal malignancy, and peritoneal mesothelioma. Selection factors are important to minimize the number of treated patients who will experience short-term benefit. Treatments involve cytoreductive surgery and perioperative chemotherapy. The intraperitoneal chemotherapy in the operating room is used with heat. Although this combined approach has been criticized, the informed oncologist will seek to identify those patients that may benefit from this more optimistic concept of peritoneal dissemination of cancer.