Results of Treatment of 385 Patients With Peritoneal Surface Spread of Appendiceal Malignancy

Introduction: In the past, peritoneal carcinomatosis, regardless of primary tumor type, has always been a lethal condition. Recently, special treatments using cytoreductive surgery with peritonectomy procedures combined with perioperative intraperitoneal chemotherapy have resulted in long-term survival. Appendiceal malignancy with a low incidence of liver and lymph node metastases may be especially appropriate for these aggressive local regional treatments.Methods: All patients treated with surgery before January 1999 are included. Patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy. The intraperitoneal chemotherapy was given in the perioperative period, starting with mitomycin C at 12.5 mg/m² for males and 10 mg/m² for females. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theater with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, five consecutive days of intraperitoneal 5-fluorouracil at 650 mg/m2 instilled in 1–1.5 liters of 1.5% dextrose peritoneal dialysis solution. A complete cytoreduction was defined as tumor nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as having adenomucinosis, adenomucinosis/carcinomatosis hybrid, or mucinous carcinomatosis. A previous surgical score was used to estimate the extent of previous surgical procedures.Results: The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P < .0001), the histopathological character of the appendix malignancy (P < .0001), and the extent of previous surgical interventions (P = .001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; with hybrid pathology, survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years.Conclusions: Cytoreductive surgery and perioperative intraperitoneal chemotherapy can be used to salvage selected patients with peritoneal surface spread of appendiceal primary tumors. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999     

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.     

腹膜假黏液瘤的临床病理特征和预后分析

目的 探讨腹膜假黏液瘤的临床病理特点和预后。方法 回顾我院33例腹膜假黏液瘤患者的临床资料,对病理组织重新阅片和分型,对随访资料进行生存分析。结果 33例患者中男女之比为1：2,平均年龄50岁,发病至确诊中位间期为12个月,误诊率高达84．8％。腹胀、腹部包块、腹围增大为主要临床表现。肠道肿瘤标志物、影像学和腹腔穿刺等辅助检查常有阳性发现。减瘤手术为主要的治疗方法,化疗是主要的辅助疗法。病理分型中良性66．7％,交界性21．2％,恶性12．1％。中位生存期为70个月。病理类型和化疗对生存时间具有影响。结论 腹膜假黏液瘤具有独特的临床病理特点,肠道肿瘤标志物、影像学和腹腔穿刺对诊断具有提示意义,目前的治疗方法有待于完善,病理类型和化疗是预后的影响因素,应对其加强认识以降低误诊率。     

Mucocele of Appendiceal Stump – an Atypical Presentation and a Diagnostic Dilemma

Background: Appendiceal mucocele is a well-recognised entity that can present in a variety of clinical syndromes or can occur as an incidental surgical finding. The term mucocele is inherently imprecise and inclusive of both benign and malignant lesions. Mucocele of the appendiceal stump is a rare entity.

Aim: We present a case of an appendiceal stump mucocele caused by a mucinous cystadenoma clinically presented as a giant retroperitoneal mass. Diagnosis was made postoperatively, after pathological study of the surgical sample.

Case report: The case of a 54-year-old woman, with a previous appendectomy, suffering from a painful mass in the right lower quadrant of the abdomen, is reported. Imaging showed a large cystic structure at the base of the caecum. Surgery revealed a 13 x 5.5 cm retroperitoneal cystic mass, which was excised together with the appendiceal remnant. Pathological diagnosis was that of a mucocele arising from the appendiceal stump due to the development of a benign mucinous cystadenoma. The patient was discharged on the fourth post-operative day after an uneventful recovery.

Conclusion: Mucocele of the appendiceal stump is a rare entity. In spite of extensive pre-operative investigations, preoperative diagnosis may still remain elusive and may only be made at the time of surgery.     

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。