韧带样瘤的诊治进展及热点问题

韧带样瘤是一种深部筋膜或肌腱膜结构来源的低度恶性的纤维性肿瘤,发病率较低.腹壁外和腹壁韧带样瘤的治疗以外科手术为主.首选切缘2 cm以上的广泛根治性切除,确保切缘阴性;无法达广泛切除或切缘阴性时,首选保全功能性手术.切缘阳性、复发性患者或无法手术者可考虑辅助放疗.腹腔内韧带样瘤多见于家族结肠腺瘤息肉病患者,手术切除复发率高,目前推荐首选大剂量的三苯氧胺和舒林酸治疗.由于韧带样瘤自然病程多变,药物治疗等疗效多不确切,包含观察等待的个体化治疗方案有望成为韧带样瘤的一种新的治疗模式.     

Abdominal desmoid tumors

Desmoid tumors are rare, benign, fibromatous lesions that are the result of abnormal proliferation of myofibroblasts. Desmoid tumors can be classified as extra-abdominal and abdominal. Abdominal desmoid tumors are either superficial or intraabdominal. These tumors are associated with a high recurrence rates, even if their microscopic characters indicate a benign disease; their biologic behavior often indicates rather a "malignant" disease, which can cause even the death. Intraabdominal desmoid tumors can engulf surrounding viscera and vessels, thereby greatly complicating their surgical treatment. Management is multidisciplinary. Simple observation is a reasonable management option for asymptomatic patients; spontaneous regression of these tumors may be observed. Complete excision is the treatment of choice for tumors causing symptoms or complications. Surgery should be minimized as much as feasible, while at the same time achieving free margins. Adjuvant therapy should be considered in selected cases; the role of other management options (including gene transfer therapy) is currently under intensive investigation.     

151例韧带样瘤的疗效及预后分析

背景与目的:韧带样瘤的预后影响因素仍存在争论.既往大样本预后分析往往混杂有腹腔内韧带样瘤和手术不完整切除的情况.本文着重分析外科手术完整切除(R0,R1)的腹壁及腹壁外韧带样瘤的预后影响因素.方法:收集1987年1月-2007年12月经本院外科收治的198例韧带样瘤患者的资料,回顾性分析其中手术完整切除无肉眼残留的151例患者临床资料、随访其生存及复发情况.结果:中位随访时间为102个月,随访期间无患者死亡,总体生存率为100%.31例患者局部复发,复发率为20%.其中5年无复发生存率(recurrence free survival,RFS)为79%,10年RFS为78%.单因素分析表明,入院情况、性别、肿瘤部位及大小、病变数目、切缘情况是影响RFS的主要因素(P＜0.05).多因素分析表明,肿瘤大小与切缘情况是影响RFS的独立预后因素.辅助放疗并不能显著提高患者的局部控制率,但切缘阳性患者可能从中受益.结论:无论是原发还是复发腹壁及腹壁外韧带样瘤患者,都应在保全肢体功能的情况下,争取做到R0切除,腹壁外韧带瘤患者较易复发,若切缘阳性,治疗应该更加积极.病变数目是局部复发的独立预后因素,多发性韧带样瘤更易复发,诊治较棘手,临床应注意多中心发病的可能性.     

Extra-abdominal desmoid tumor--analysis of 26 patients

Twenty-six patients with extra-abdominal desmoid tumor are reported. The tumor was located in the head and neck (6 cases), chest wall (3 cases), arm and leg (9 cases), paravertebral tissue (6 cases) and in the abdomen (2 cases). Of the 26 patients, 17 were treated for the first time and 9 had recurrent lesions. This tumor, showing aggressive growth, involved peripheral nerves (7 cases), blood vessels (4 cases), bones (11 cases) or viscera (2 cases). Surgery is the treatment of choice. The recurrence rate was 11% in those who received their first treatment. Wide dissection led to lower recurrence than simple excision (23% vs 72%). The authors stress the importance of excising at least 2-3 cm beyond the tumor margin and extra-abdominal desmoid tumor should be treated as a soft tissue tumor with low malignancy.     

Extremity and trunk desmoid tumors: a multifactorial analysis of outcome

BACKGROUND: The natural history of desmoid tumors remains an enigma. Previous reports attempting to identify their biology have included recurrent and primary tumors as well as tumors from both intra- and extra-abdominal sites. The purpose of this study was to analyze patients with primary extremity and trunk desmoid tumors treated and followed at a single institution and to determine factors influencing disease free survival. METHODS: Between July 1982 and June 1997, 189 patients with extremity and superficial trunk desmoid tumors were treated and followed prospectively. Of these, 105 presented with primary disease and formed the basis of this study. RESULTS: The median follow-up for the entire group of patients was 49 months; it was 46 months for patients who did not develop a local recurrence. During this time, 24 patients (23%) had a local recurrence. No patients died of disease. The 2-year and 5-year local recurrence free survival rates were 80% and 75%, respectively. None of the prognostic factors analyzed, including age, gender, depth of tumor, size of tumor, or tumor site, were significant for predicting local recurrence. Moreover, positive resection margins were not predictive of recurrence. The selective use of adjuvant radiation therapy did not influence the rate of local recurrence regardless of the margin status. CONCLUSIONS: Attempts to achieve negative resection margins may result in unnecessary morbidity and may not prevent local recurrence. Operations that preserve function and structure should be the primary goal, because the presence of residual disease cannot be clearly shown to impact adversely on 5-year disease free or overall survival.     

硬纤维瘤的临床特点--附100例病例报告

目的：探讨硬纤维瘤的临床特点和治疗方法。方法：回顾分析我院１９６４－１９９７年间外科收的１００例硬纤维瘤,包括腹壁硬纤维瘤５３例,腹壁外硬纤维瘤４７例。结果：全组１００例硬纤维瘤行广泛切除术６８例,根治切除术２７例,术后合并放疗１２例,全组病例复发率３６％,本院治疗复发率１０．８％,１例病人死于肿瘤肺转移。结论：硬纤维瘤呈侵袭性生长,复发率高,治疗应按低度恶性软组织肿瘤处理。外科手术是主要的治疗方     

The surgical management of sacrococcygeal chordoma

BACKGROUND: Complete excision of sacrococcygeal chordoma is necessary at initial surgery due to its poor sensitivity to radiotherapy and chemotherapy. However, due to the anatomic characteristics of this tumor, intralesional excision tends to be employed, resulting in local recurrences in many patients. METHODS: The clinical features and results of surgical treatment of 13 patients with sacrococcygeal chordoma who were treated at the Chiba Cancer Center and Chiba University beginning in 1972 were analyzed. RESULTS: Intralesional excision was performed in eight patients, marginal excision in two patients, and wide excision in three patients. Local recurrence was observed in six patients, with a high proportion occurring in the gluteal muscles attached to the sacrum (the gluteus maximus muscle and piriform muscle). Seven patients died of their disease and six patients were alive with no evidence of disease. The 5-year survival rate was 81.8% and the 10-year survival rate was 29.1%. CONCLUSIONS: It is highly possible that residual chordoma infiltrating the gluteal muscles accounts mainly for the local recurrences. Therefore, a precise preoperative assessment of the tumor infiltration into the gluteal muscles by magnetic resonance imaging is important for the prevention of local recurrence. For complete tumor removal, a radical wide posterior surgical margin of the gluteal muscles should be employed. A less radical anterior surgical margin is sufficient because there is a firm presacral fascia anterior to the sacrum. The appropriate surgical margin for the complete removal of the chordoma differs according to the location of the tumor and tissues involved.     

Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution.

PURPOSE: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). PATIENTS AND METHODS: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. RESULTS: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). CONCLUSION: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.     

Desmoid tumors: Local control and patterns of relapse following radiation therapy

Desmoid tumors are benign neoplasms, arising from musculoaponeurotic tissues, which tend to be locally infiltrative, resulting in a high rate of local recurrence following surgical resection. Nineteen patients with desmoid tumors underwent radiation therapy at the University of California, San Francisco, between 1970 and 1980. Fifteen patients were referred with local recurrence following one or more surgical resections. Three patients were referred for initial radiation therapy with unresectable tumors, and one patient received planned postoperative irradiation following subtotal tumor resection. At the time of treatment, 8 patients had nonresectable disease measuring greater than 10 cm. Five patients had residual tumor masses measuring 4 to 6 cm, and six had only microscopic disease following resection. The majority of patients were treated to a tumor dose of 50–55 Gy at 1.6 to 1.8 Gy per fraction. With a median follow-up of 8 years, 13 patients remained free of recurrent disease following radiation therapy. The 5 year relapse free survival was 72% with 10 patients continuing to be free of disease 5 to 11 years following therapy. Local control was not related to the amount of disease present at the time of treatment. Of the 6 patients who developed recurrent disease, only 1 patient had a true in-field recurrence. Four patients recurred at the margin of the radiation field 1 to 5 years following therapy. Of these four patients, 3 were successfully salvaged while 1 died as a result of tumor extension into a major vessel. One patient with an extensive mesenteric mass did not respond to therapy and died 1 month post irradiation. The patient with the in-field recurrence and 1 patient with a marginal recurrence were successfully treated with combination chemotherapy. Moderate dose radiation therapy to desmoid tumors can result in lasting local control when surgical resection is not possible. Post operative radiation can improve the rate of local control for patients with a high risk of recurrence. As desmoid tumors tend to be locally infiltrative, fields must be very generous to prevent marginal recurrence. Systemic chemotherapy offers an alternative to ablative surgery in the event of local failure following radiation therapy.     

Desmoid tumor--review and follow-up of ten cases

Ten cases of desmoid tumor, diagnosed, treated, and followed during the past 11 years, were reviewed and the patients reexamined. Two were up to 3 years, two up to 5 years, and four up to 11 years after excision. The remaining two patients were lost to follow-up. The 10 patients included one male and nine females; six females were of childbearing age and three were postmenopausal. In four females the desmoid tumor was located near various surgical scars. In the one recurrent desmoid it was most probably related to both repeated traumatization of the abdominal wall due to pregnancies and hyperestrogenism. All the surgical margins of resection were microscopically involved by the process. An open liver biopsy, performed simultaneously with the excision of the recurrent desmoid, showed benign nodular hyperplasia compatible with hyperestrogenism. Estrogen and progesterone receptors of this desmoid were negative. In the present series follow-up revealed, in contrast to general agreement, that in spite of incomplete excision, the recurrence rate was low. We suggest that the surgical approach to desmoid tumors could be less radical, except possibly for lesions in patients with multiple causative factors.     

Analysis of phyllodes tumor recurrence according to the histologic grade

Local recurrence of phyllodes tumor (PT) of the breast is an adverse outcome that can result in sarcomatous degeneration. The aim of this study was to investigate the histologic and surgical factors associated with local recurrence. A total of 193 PT cases were studied: 145 (75.1 %) benign cases, 33 (17.1 %) borderline cases, and 15 (7.8 %) malignant cases. Stratifying our analysis according to histologic grade, we investigated the relationship between disease-free survival (DFS) and both histologic and surgical factors, including histologic grade, stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, type of surgical procedure (local excision, wide excision, and mastectomy), surgical margin status, and radiation therapy. In the case of benign PT, all patients with local recurrences (3.4 %) had been treated with local excision, and all recurrent tumors were also benign. The local recurrence rate for locally excised benign PTs was not associated with surgical margin status or radiation therapy. In the case of borderline PT, local excision was associated with an increased local recurrence rate (P = 0.046). In malignant PT, small tumor size (≤4.0 cm) was associated with an increased local recurrence rate (P = 0.041). Univariate analyses indicated that surgical procedure (mastectomy < local excision < wide excision; P < 0.001) was significantly associated with shorter DFS in borderline PT. A positive surgical resection margin (P < 0.001) was associated with DFS in malignant PT. The factors associated with local recurrence differed with the histologic grade of PT, as did the features of local recurrence itself. In particular, benign PT had very low rate of local recurrence regardless of surgical margin status or radiation therapy, even when treated with local excision. In the case of benign PT, no recurrent tumors had worse histologic grades than the initial tumors.     

Curative limb saving operation (curative wide resection)

The recent results of surgical treatment of soft tissue sarcomas have dramatically improved. The result of the group study of soft tissue sarcomas, which was supported by the Ministry of Health and Welfare (1962-1976) showed that the local recurrence rate was 50%, and the metastatic rate was 60%. In contrast with this result, the recent results of our curative wide resection showed the local recurrence rate of 10%, and the metastatic rate of 30%. These procedures are based on the clinico-pathological findings which we studied. Curative wide resection is a method of radical wide resection, similar to radical local resection (reported by Enneking) and radical local excision (reported by Stenar). Our procedures are the least aggressive of the three radical wide resections, but our results are the same as the other wide resection methods. To obtain good results with these procedures, accurate preoperative diagnosis and skillful surgery are necessary.     

The role of imatinib mesylate in adjuvant therapy of extra-abdominal desmoid tumors

BACKGROUND: Extra-abdominal desmoid tumors are rare neoplasms with variable biological behavior. The mainstay of treatment is surgery. Complementary treatment with tyrosine-kinase receptor inhibitor drugs, particularly imatinib mesylate, has been reported in the literature. The purpose of this study was to determine the possible presence of tyrosine-kinase receptors in extra-abdominal desmoid tumors as a marker for imatinib mesylate therapy. PATIENTS AND METHODS: From 1999 to 2004, immunohistochemical methods were carried-out in 14 patients with histologically confirmed extra-abdominal desmoid tumors to determine c-KIT positivity (existence of tyrosine-kinase receptors and PDGFRA and PDGFRB). RESULTS: All desmoid tumors were c-KIT negative, which demonstrates absence of tyrosine-kinase receptors. CONCLUSION: The histological c-KIT markup is an easy and reliable method that can detect whether a desmoid tumor is sensitive to additional treatment with a tyrosine-kinase receptor inhibitor. Molecular biological analysis for the identification of KIT and PDGFR mutation should be performed before imatinib mesylate is included in any treatment protocol.     

The role of postoperative irradiation in the treatment of locally recurrent incompletely resected extra-abdominal desmoid tumors

Background: To define the efficacy of postoperative irradiation in patients with recurrent extra-abdominal desmoid tumors in whom surgical intervention has resulted in microscopically or grossly positive surgical margins.Methods: A retrospective analysis was performed on all patients referred to the department of radiation oncology at the Detroit Medical Center with a diagnosis of recurrent extra-abdominal desmoid tumor. This analysis includes all patients seen from 1 January 1990 through 31 December 1999. A total of 11 patients were treated to 13 sites. Ten had microscopically positive margins and three had gross residual disease. Three patients were noted to have multifocal disease at the time of initial representation. Local control, survival, follow-up, and subsequent development of new tumors are measured from the last day of treatment with irradiation.Results: Thirteen sites were treated. Seven patients had received chemotherapy/hormonal therapy prior to surgery and/or irradiation. The most commonly used drug was tamoxifen (n=6). The type of radiation delivered included external beam irradiation alone (n=3), combined external beam irradiation and brachytherapy (n=4), brachytherapy alone (n=3) and 252-Cf neutron brachytherapy alone (n=3). Follow-up has ranged from 29 to 115 months (median=76 months). Three patients have failed locally at 17, 24 and 29 months. One of these was treated for gross residual disease. No patient has died of tumor-related causes. Salvage at the failed sites was possible in twom of three with re-irradiation using external neutrons and/or aggressive surgical intervention and systemic therapy. Complications were most often noted to include decrease range in motion, especially in joint areas, and skin reactions which were normal in presentation. In one site there was development soft tissue necrosis.Conclusion: Based on our experience we recommend postoperative irradiation for all recurrent extra-abdominal desmoid lesions with microscopically or grossly positive surgical margins. Furthermore, patients with recurrent desmoid tumors involving the bony structures of the hand or feet are poor candidates for brachytherapy alone. For patients with extremity lesions, brachytherapy may be a reasonable treatment option provided adequate margins around the tumor bed are covered. The continued recommended use of irradiation in this group of patients is warranted.     

小儿臀部侵袭性纤维瘤病的诊断和治疗(附15例)

目的 探讨小儿臀部侵袭性纤维瘤病的临床特点和手术治疗。方法 15例小儿臀部侵袭性纤维瘤病全部行手术切除。结果 15例全部完整切除，13例随访1.6～8年，平均4年2个月，复发4例，其中1例二次复发。结论 小儿臀部侵袭性纤维瘤病具有浸润性生长的特点，没有完整的包膜，容易复发，应早期诊断，完整广泛切除肿瘤及周围组织，是减少术后复发的有效方法。     

Treatment of extra-abdominal desmoid tumors with interferon-alpha with or without tretinoin

BACKGROUND AND OBJECTIVES: Surgery is the main treatment for extra-abdominal desmoid tumors, but the results of further management remain uncertain. Therefore, a retrospective analysis was undertaken to evaluate the toxicity and efficacy of treatment with interferon-alpha (IFN-alpha) +/- tretinoin in this setting. METHODS: Thirteen patients with extra-abdominal desmoid tumors and a median age of 32 years (range, 15-73) received IFN-alpha. Seven of these patients received a combination of IFN-alpha and tretinoin in order to test further enhancement. RESULTS: After a mean observation period of 27 +/- 15 months (mean +/- standard deviation) under treatment with IFN-alpha +/- tretinoin, local control was seen in 11 of 13 patients (85%). Seven patients had no evidence of disease at a mean disease-free interval of 22 +/- 18 months; in two patients progressive disease occurred after only 7 and 9 months, respectively, of observation. In another four patients, progression of the desmoid tumor was stabilized. CONCLUSIONS: The data of this retrospective, nonrandomized study on therapy with IFN-alpha +/- tretinoin suggest that such treatment may be effective in prolonging the disease-free interval of patients after intralesional or marginal surgery. Because of the encouraging response rate, this regimen appears to be another nonsurgical treatment alternative.     

Surgical treatment of rectal cancer: local resection

Local treatment of rectal cancer aims to decrease the morbidity and the functional sequela associated with radical surgery without compromising local tumor control and long-term survival. Local excision is associated with a higher rate of local recurrence compared with radical surgery, and salvage radical surgery cannot guarantee equivalent long-term survival compared with radical surgery as the primary form of therapy. Therefore, strict criteria for patient selection are critical for local excision to be successful. Selecting the optimal therapy for an individual patient with rectal cancer is crucial and requires consideration of both tumor and patient characteristics. Endorectal ultrasonography is essential for the accurate assessment of rectal wall invasion and nodal metastasis. Only patients with well- or moderately differentiated T1 tumors without blood vessel or lymphatic vessel invasion are candidates for curative local excision as the only form of treatment. Tumors penetrating the muscularis propria should not be treated by local excision alone. These patients can be asked to participate in a trial of chemoradiation followed by local excision. Otherwise, they should undergo radical surgery. The tumor should be removed by full-thickness local excision with an adequate normal margin for pathologic evaluation. Final decisions regarding the treatment strategy should be based on the pathology of the surgical specimen. Intense, close follow-up is critical for early diagnosis of local recurrences as many of them may be surgically salvaged by radical resection. Local treatment can also be used for palliation of patients with histological unfavorable or advanced tumors, and those who are medically unfit for radical surgery.     

Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin

BACKGROUND: The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases. METHODS: The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed. RESULTS: Median age was 45 years old (range 28-75) and tumor size was 1-17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1-273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P = 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01-0.743, P = 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P = 0.0139). CONCLUSION: Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.     

韧带样纤维瘤术后复发的临床及病理学研究

目的分析韧带样纤维瘤的临床特点,并通过检测韧带样纤维瘤周边病理学改变以了解其生物学行为特点及复发的相关因素。方法收集2003年至2008年我科切除的56例韧带样纤维瘤患者的临床资料及标本,对其可能与术后复发相关的临床因素如：性别、年龄、肿瘤部位、体积、侵犯主要血管神经、侵犯骨、切缘质量、是否接受放疗及药物治疗等进行统计学分析,并对病灶周边组织进行组织病理学研究。结果本组患者均获得完整随访,随访时间33—108个月,总体复发率为39．3％,平均复发时间初治组为17．3个月（5—23个月）,复发组为14．8个月（3—26个月）。患者的性别、年龄、肿瘤部位、体积、侵犯骨、是否接受放疗、药物治疗与肿瘤复发无统计学相关性,而侵犯主要血管神经、切缘质量与肿瘤复发有统计学相关性。切缘阴性、肿瘤未侵犯重要血管神经的患者术后复发率较低沪〈0．05）。韧带样纤维瘤在病理学为良性,但可广泛浸润病变周边肌肉、脂肪、韧带、血管、神经、骨等组织,可突破骨皮质侵入髓腔内,但不能侵入血管及神经内部。结论韧带样纤维瘤术后复发率较高,侵犯主要血管神经、切缘质量是影响术后复发率的主要因素。病理学上,此病具有很强的局部侵袭能力,但无远处转移,术中达到满意的外科边界较为困难。所以当切缘阳性或单纯手术治疗效果不满意时可采用放疗、药物治疗等多种手段进行综合治疗,以降低局部复发率。     

Desmoid tumours of the anterior abdominal wall.

AIMS: To review the surgical management and outcomes for large desmoid tumours of the abdominal wall. METHODS: Seven patients with large desmoid tumours of the anterior abdominal wall were treated by wide local excision and reconstruction with two layers of Marlex V mesh (Bard, Galway, Ireland). RESULTS: No patient having initial surgery at this hospital has either a significant residual functional deficit or developed a recurrence. CONCLUSIONS: Large desmoid tumours of the abdominal wall are safely and adequately managed with abdominal wall resection followed by mesh reconstruction.