阑尾黏液性肿瘤的诊断及治疗进展

摘 要：阑尾黏液性肿瘤（appendiceal mucinous neoplasm,AMN）临床罕见,对于局限于阑尾管腔的AMN临床表现倾向良性,手术完整切除后预后良好。如处理不当发生破裂或肿瘤进展发生腹膜假黏液瘤（pesudomyxomaperitonei,PMP）,临床重视不够未及时处理将会导致预后不良的结局且严重影响生活质量。术前彩超及CT检查对诊断AMN有一定的临床价值,但总体术前诊断较为局限,多数病例为术中意外发现,约40%的病例手术后才能确诊。对于AMN,外科手术完整切除肿瘤避免囊壁破裂是基本处理原则,可以最大限度的降低未来复发风险,延长患者远期生存。术后应密切随访警惕PMP发生及合并异时的结直肠肿瘤可能。如术中一旦发现肿瘤破裂必须充分探查腹腔评价并记录腹腔内肿瘤负荷情况,对于发生PMP的患者应及时转往腹膜肿瘤治疗经验丰富的中心进行治疗,以免错过最佳的根治手术治疗时机。     

原发性阑尾肿瘤临床误诊原因分析

目的 探讨原发性阑尾肿瘤的误诊原因，提高阑尾肿瘤的急诊水平。方法 回顾性分析27例住院手术并经病理确诊为阑尾肿瘤患者的临床资料。结果 27例阑尾肿瘤仅2例术前获确诊。误诊为急性阑尾炎和慢性阑尾炎急性发作16例，误诊为妇科肿瘤3例，肠梗阻4例，消化道出血2例，误诊率92.6％(25/27)。二次手术率为29.6％(8/27)。病理诊断黏液腺癌9例，类癌7例，腺癌3例，印戒细胞癌2例，腺瘤6例(其中2例发生恶变)。术中可疑为肿瘤者行快速冷冻切片，病理检查确诊为恶性者行右半结肠切除术者22例；良性肿瘤和肿瘤直径小于1cm的类癌行阑尾单纯切除术者5例。结论 阑尾肿瘤最易误诊为阑尾炎和慢性阑尾炎急性发作，对急诊患者应重视阑尾肿块的手术中探查及处理；对不能判定性质的肿块，术中应常规做冷冻切片行病理检查，以提高阑尾肿瘤诊断率和疗效。     

Appendiceal neuroendocrine tumors: Recent insights and clinical implications

New insights emerged last decade that enriched our knowledge regarding the biological behavior of appendiceal neuroendocrine tumors (NETs), which range from totally benign tumors less than 1cm to goblet cell carcinomas which behave similarly to colorectal adenocarcinoma. The clinical implication of that knowledge reflected to surgical strategies which also vary from simple appendicectomy to radical abdominal procedures based on specific clinical and histological characteristics. Since the diagnosis is usually established post-appendicectomy, current recommendations focus on the early detection of: (1) the subgroup of patients who require further therapy; (2) the recurrence based on the chromogranin a plasma levels; and (3) other malignancies which are commonly developed in patients with appendiceal NETs.     

Appendiceal Mucocele. A retrospective Analysis of 19 Cases

Background

Appendiceal mucocele is an infrequent well-recognized entity that can present in a variety of clinical syndromes or can be asymptomatic and discovered incidentally.

Patients and Methods

Nineteen patients with a diagnosis of primary appendiceal mucocele treated in our institution between January 1, 1987 and December 31, 2006 were included in this retrospective analysis.

Results

The histological examination of the specimens revealed simple and hyperplastic appendiceal mucocele in nine cases (47%), mucinous appendiceal cystadenoma in eight cases (42%), and mucinous appendiceal cystadenocarcinoma in two cases (11%). Thirteen patients (68%) underwent appendectomy, five patients (26%) right colectomy, and two patients (6%) underwent right colectomy for invasive appendiceal cystadenocarcinoma and at the same time right nephrectomy and sigmoidectomy, respectively, for concomitant malignancy.

Conclusion

Mucocele of the appendix may be related to a benign or malignant appendiceal process, leading to individualized diagnosis and treatment.     

阑尾类癌6例临床分析

[目的]探讨阑尾类癌的临床诊断和治疗.[方法]6例均以急性阑尾炎就诊.行单纯阑尾切除5例,其中2例术后1～3个月再次手术行右半结肠切除.[结果]术中冰冻病检诊断2例.肿瘤直径8～20mm,5例位于头部.2例再次手术行右半结肠切除者无肿瘤残留和远处转移.全组术后随访1.5～22年,无肿瘤复发.[结论]阑尾类癌术前诊断困难.肿瘤直径≤20mm阑尾类癌远处转移少见,无局部浸润和远处转移结合术中冰冻病检无肿瘤残留行单纯阑尾切除即可.     

Risk Factors for Appendiceal Metastasis with Epithelial Ovarian Cancer

Purpose: To investigate the risk factors for appendiceal metastasis of epithelial ovarian cancer and comparefindings with the previous studies. Materials and Methods: One hundred and thirty-four patients withepithelial ovarian cancer were assessed in this study. All of them had undergone a surgical procedure includingappendectomy. Of these, 21 (15.7%) patients who had appendiceal metastasis were analyzed as the case groupand the patients with no metastasis were the controls, compared according to stage, grade, histology of tumor,preoperative Ca125 levels, presence of ascites, peritoneal cytology, diameter and site of tumor considered asrisk factors. Results: We found statistically significant differences between the groups in terms of stage, grade,right-sided tumor location, presence of ascites, diameter of tumor≥10 cm and positive peritoneal cytology(p<0.05). In the logistic regression model, stage, grade, presence of ascites, right-sided location and diameter oftumor were independent risk factors. ROC curve analysis showed that stage, grade and diameter of the tumorwere discriminative factors for appendiceal metastasis. Conclusions: In epithelial ovarian cancer, stage, grade,presence of ascites, right-sided location and large tumor size have importance for estimation of risk of appendicealmetastasis. As we compare our findings with previous studies, there is no definite recommendation for the riskfactors of appendiceal metastasis in epithelial ovarian cancer and more studies are needed.     

Hematological malignancies

The same progress in the recent therapeutic strategy for older adults with hematological malignancies has also been seen in younger adults. The standard initial therapy for elderly acute promylocytic leukemia is the combination with all-trans retinoic acid and anthracyclines. For other acute myeloid leukemias (AML), many trials of combination chemotherapy have not improved the outcome of elderly patients. Gemtuzumab ozogamicin,which is an immunoconjugate binding to CD 33 on the surface of AML blasts, has produced good results for elderly patients in either monotherapy or in combination with conventional chemotherapeutic drugs. One of the BCR-ABL tyrosine kinase inhibitors, imatinib mesylate, is active for elderly Philadelphia-positive leukemia including acute lymphoblastic leukemia and chronic myeloid leukemia. In the treatment of elderly diffuse large B cell lymphoma, combination of rituximab and cyclophosphamide+doxorubicin+vincristine+prednisone (CHOP) has become the therapy of choice based upon a Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial even though there are some other trials for elderly patients such as dose-dense CHOP therapy. For follicular lymphoma, combination therapies of rituximab and cytotoxic drugs such as R-CHOP and R-CVP are also considered as promising therapies. For the management of multiple myeloma, high-dose chemotherapy, mainly melphalan with autologous stem cell transplantation, has become the standard treatment even for elderly patients less than 65 years of age.     

Hematologic malignancies

This article reviews highlights in the field of hematologic malignancies presented at the 2001 annual meeting of the American Society of Clinical Oncology. Targeted therapies continue to proceed from the laboratory to the clinic. Monoclonal antibody-based therapies predominate, and further data on radioimmunoconjugates (RICs) (tositumomab and Iodine 131 tositumomab [Bexxar] and ibritumomab tiuxetan [Zevalin]) are presented. Both agents have high response rates in relapsed B-cell non-Hodgkin's lymphoma (NHL). Results from the first trial directly comparing an RIC (Zevalin) to an unconjugated antibody (rituximab) are presented. A novel application of RIC therapy as part of high-dose therapy for mantle cell NHL is described. A new fusion toxin, BL22, targets the CD22 antigen and shows marked activity in the treatment of hairy cell leukemia. Similarly, the Hu1D10 monoclonal antibody has activity in B-cell NHL and might have a relatively unique mechanism of action. Finally, advances in the treatment of mucositis are described. These abstracts all describe therapies derived from our enhanced understanding of tumor immunology and molecular biology.     

Second malignancies

The secondary development of malignant tumors after the treatment of Hodgkin's disease has been termed the price of success, but is relevant also to other types of cancer and gives an opportunity to study mechanisms of carcinogenesis and tumor induction. The authors review here their experience with second malignant neoplasms (SMN) as well as the result of an extensive search of the recent literature. The primary malignancies discussed in this article include Hodgkin's disease, pediatric cancer, breast cancer, lung cancer and other types of tumors. The international literature was searched (Medline 1989-1995) for reports of SMN with special emphasis on risk factors and the molecular mechanisms of tumor induction. In Hodgkin's disease, a 3 to 5-fold elevated risk for SMN was recognized, with a 15-year cumulative incidence in the range of 11-18%. All types of malignancies have a statistically increased risk (leukemias, non-Hodgkin's lymphomas, solid tumors). The risk for leukemia is related to the intensity of treatment with alkylating agents. Some solid tumors like lung cancer or breast cancer are related to radiation therapy. Present-day treatments may carry a lower risk of inducing secondary malignancies than treatments in the past. For non-Hodgkin's lymphoma as primary malignancy, fewer data exist on SMN. In pediatric cancer, no general risk estimate can be given and the genetic influence is greater as a cause of SMN. The improved prognosis for acute lymphoblastic leukemia has led to a changing pattern of pediatric SMN. In head and neck- and in lung cancer, the same etiologic factors which cause the primary tumor may also cause SMN. SMN occur as part of familial cancer syndromes. Two types of treatment related leukemias (mostly AMLs) exist and can be recognized by cytogenetic and molecular analysis. A complete follow-up is necessary to fully appreciate the risk of second malignancy. The goal to prevent SMN must be reached without decreasing the cure rates of the primary tumor. New treatment approaches need to be carefully monitored for SMN. Improved tests of mutagenesis and molecular screening may help to recognize patients prone to develop SMN and permit to estimate certain types of risk. Screening and prevention strategies are useful in high-risk situations.     

AIDS-related malignancies

Cancer remains a significant burden for human immunodeficiency virus (HIV)-infected individuals. Most cancers that are associated with HIV infection are driven by oncogenic viruses, such as Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus and human papillomavirus. Gaining insight into the epidemiology and mechanisms that underlie AIDS-related cancers has provided us with a better understanding of cancer immunity and viral oncogenesis.     

Impact of Molecular Alterations and Targeted Therapy in Appendiceal Adenocarcinomas

Background.

Appendiceal adenocarcinomas (AAs) are rare and this has limited their molecular understanding. The purpose of our study was to characterize the molecular profile of AA and explore the role of targeted therapy against cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR).

Patients and Methods.

We performed a retrospective review of 607 patients with AA at a single institution. A total of 149 patients underwent molecular testing for at least one of the following: activating mutations in KRAS, BRAF, cKIT, EGFR, or PI3K; protein expression of c-KIT or COX-2; or microsatellite instability (MSI) status by immunohistochemistry. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS) and to determine associations among OS, COX-2 expression, KRAS mutations, and other characteristics.

Results.

Age, grade, stage, signet ring cells, mucinous histology, and completeness of cytoreduction score correlated with survival outcomes. COX-2 expression, KRAS, PI3K, and BRAF mutations were seen in 61%, 55%, 17%, and 4% of patients, respectively. High MSI was seen in 6% of patients. KRAS mutation was strongly associated with well differentiated or moderately differentiated AA (p < .01). COX-2 expression (p = .33) and the presence of KRAS mutation (p = .91) had no impact on OS. The use of celecoxib in patients whose tumors expressed COX-2 (p = .84) and the use of cetuximab or panitumumab in patients with KRAS wild-type tumors (p = .83) also had no impact on OS.

Conclusion.

In this cohort, we demonstrated that COX-2 expression and KRAS mutations were frequently seen in AA, although neither exhibited any prognostic significance. MSI was infrequent in AA. Targeted therapy against COX-2 and EGFR appeared to provide no clinical benefit. Well and moderately differentiated AA were molecularly distinct from poorly differentiated AA.