阴茎癌腹股沟淋巴结转移行术前新辅助化疗的临床疗效分析

目的探讨阴茎癌腹股沟淋巴结转移行术前新辅助化疗的临床疗效。方法回顾性分析2001年至2008年收治的13例接受术前新辅助化疗及手术治疗的阴茎癌腹股沟淋巴结转移病例的临床及随访资料,并进行生存分析。结果阴茎癌淋巴结转移13例,均行以顺铂、博来霉素、甲氨蝶呤为主要方案的术前新辅助化疗,其后11例行阴茎部分切除术+单侧或双侧腹股沟淋巴结清扫术,2例行局部放射治疗。从阴茎癌腹股沟淋巴结转移治疗后开始计算生存率,1例失随访。1、2、5年生存率分别为75.0%(9/12)、66.7%(8/12)和41.7%(5/12)。结论对阴茎癌腹股沟淋巴结转移患者采用新辅助化疗结合手术治疗是一种有效的治疗手段。     

Sentinel lymph node biopsy for staging penile cancer

Eighteen sentinel lymph node biopsies were performed in 10 patients with invasive squamous carcinoma of the penis. Five of 15 biopsies associated with inguinal lymphadenopathy and 2 of 3 biopsies associated with palpably normal inguinal nodes were positive. Among 7 ipsilateral regional lymphadenectomies undertaken because of a positive biopsy, additional lymph node metastases were uncovered in only 1 instance. Among 5 patients with negative biopsies bilaterally, none had other superficial inguinal lymph node metastases and all but one have remained free of tumor (mean follow-up 26 months). These data support the possibility that the sentinel lymph node is often the first site of regional lymphatic metastasis in penile cancer.     

Multimodality therapy in penile cancer: when and which treatments?

Objectives  Metastatic penile cancer typically comes to attention while the clinical extent of disease is limited to the inguinal or pelvic lymph nodes. Primary surgical management of lymph node metastases achieves tumor control and long-term survival for only a small percentage of these patients. To determine the optimal use of multimodality treatment in locally advanced penile cancer, we conducted a literature review. Methods  Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search were also reviewed. Results  There is an emerging strategy of preoperative (neoadjuvant) combination chemotherapy to improve the progression-free survival of penile cancer patients with bulky regional lymph node metastases. Radiotherapy for inguinal metastases and postoperative (adjuvant) radiation for selected patients has also been effective in this setting. Conclusions  In patients with lymph node metastases, the benefit of ilioinguinal lymphadenectomy may be extended by the addition of neoadjuvant chemotherapy. Postoperative radiotherapy can be offered depending on the amount of residual disease after chemotherapy. Chemo-radiotherapy has been successful in squamous cell cancers from other sites (vulva and anal canal) and may be considered for unresectable penile cancer.     

腹股沟淋巴结清扫在阴茎癌治疗中的应用

［摘要］ 阴茎癌是一种比较少见的恶性肿瘤。其发病率具有显著的地域差异性,其中,在欧美等发达国家具有较低的发病率,然而,在非洲、南美洲以及亚洲的部分发展中国家或地区,阴茎癌的发病率较高。目前,阴茎癌的主要治疗方法包括：保留阴茎的治疗（微小病灶切除术）;阴茎部分切除术;阴茎根治性切除术。区域淋巴结有无转移、转移程度、能否根治切除是影响阴茎癌患者生存率的决定性因素。阴茎癌最早和最常见的区域淋巴结转移部位为腹股沟淋巴结,本文主要阐述了传统开放手术、改良的腹股沟淋巴结清扫术、腹腔镜与机器人辅助腹股沟淋巴结清扫手术在阴茎癌治疗中的应用及各手术方式常见并发症及防治措施。     

Conservative excision of penile melanoma

Penile melanoma is a rare disease, especially in younger men. Most authorities advocate aggressive surgical management by partial or radical phallectomy and in some cases inguinal lymph node dissection. A 27-year old man with a clinical stage I, Clark's level II, microinvasive (less than 0.76 mm) superficial spreading penile melanoma underwent conservative resection and skin grafting without inguinal node dissection. He has normal penile function and is disease free 5 years following surgery. We believe that in clinical stage I, microinvasive penile melanoma, local excision without inguinal node dissection should be the treatment of choice.     

Functional imaging in penile cancer: PET/computed tomography, MRI, and sentinel lymph node biopsy

PURPOSE OF REVIEW: The presence and extent of lymph node metastasis and primary tumor are among the most important prognostic factors in penile cancer. While inguinal lymphadenectomy is currently the most accurate means of staging, it is associated with severe morbidity and even mortality. Recent literature was reviewed for alternative means of staging. RECENT FINDINGS: Functional imaging modalities distinguish between inguinal lymph nodes with and without metastasis. The false-negative rate of dynamic sentinel lymph node biopsy has recently improved from approximately 20 to 5% in one study. In 13 patients with penile cancer, (18)F-fluorodeoxyglucose-PET/computed tomography was 80% sensitive and 100% specific for lymph node metastasis, but missed micro-metastasis. In seven patients with penile cancer, MRI with lymphotrophic nanoparticles was 100% sensitive and 97% specific for lymph node metastasis. SUMMARY: Combined PET/computed tomography and sentinel lymph node biopsy may help to detect both inguinal micrometastasis and pelvic and abdominal metastasis. Since MRI is highly accurate for staging of both primary penile cancer and its lymph node metastasis, however, it may turn out to be a powerful tool for a one-stop modality in the staging of penile cancer.     

Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging penile cancer: results with pathological correlation

PURPOSE: We assessed the sensitivity of preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging the inguinal region of patients with penile cancer and no palpable inguinal adenopathy. MATERIALS AND METHODS: The records of 31 patients with invasive penile cancer and nonpalpable (29) or nonsuspicious (2) inguinal lymph nodes were reviewed. Preoperatively lymphoscintigraphy plus dynamic sentinel node biopsy with (99m)technetium labeled sulfur colloid and isosulfan blue dye was performed in 21 patients and dynamic sentinel node biopsy alone with blue dye only was done in 10. All patients underwent superficial lymph node dissection regardless of preoperative lymphoscintigraphy or dynamic sentinel node biopsy findings to establish pathological nodal status. RESULTS: Six of 32 groins that showed drainage on preoperative lymphoscintigraphy had inguinal node metastasis, as did 1 of 10 that was drainage negative. The sensitivity of preoperative lymphoscintigraphy drainage for cancer detection was 86%. Using dynamic sentinel node biopsy with blue dye plus radiotracer 5 sentinel lymph nodes were positive for cancer, although 2 false-negative results were obtained. Thus, the sensitivity of dynamic sentinel node biopsy per groin for cancer detection was 71%. CONCLUSIONS: In our experience preoperative lymphoscintigraphy and dynamic sentinel node biopsy as currently performed remain insufficient for detecting occult inguinal disease. Superficial lymph node dissection remains the gold standard for detecting inguinal microscopic metastasis in select patients.     

Intra-arterial infusion chemotherapy for penile carcinoma with deep inguinal lymph node metastasis

From July 1994 to January 1999, three patients with penile squamous cell carcinoma with deep inguinal lymph node metastases without distant metastases were treated with multimodality treatment including intra-arterial infusion chemotherapy mainly with monthly courses of cisplatin, methotrexate and bleomycin. One patient achieved a complete response and 2 achieved a partial response. It appears to be reasonable to presume that intra-arterial chemotherapy has a beneficial effect in the management of penile cancer with fixed metastatic inguinal lymph nodes, but a larger number of patients and longer follow-up are required to confirm these results.     

Lymphadenectomy in the Surgical Management of Penile Cancer

Context

Uncertainty remains about the extent and indications for inguinal lymphadenectomy in penile cancer, a procedure known for relatively high morbidity. Several attempts have been made to develop strategies which can improve the diagnostic quality and reduce the morbidity of the management of inguinal lymph nodes in penile cancer.

Objective

To analyse the existing published data on the surgical management of inguinal nodes in penile cancer regarding morbidity and survival.

Evidence acquisition

A Medline search was performed of the English-language literature (1966–September 2008) using the MeSH terms penile carcinoma, lymph node dissection, lymphadenectomy, and complications.

Evidence synthesis

Lymph node metastases are frequent in penile cancer, even in early pT1G2 stages. Since the results of systemic treatment of advanced penile cancer are disappointing, complete dissection of all involved lymph nodes is highly recommended. The extent of lymph node dissection should be adapted to clinical stage, as this corresponds to metastatic spread. For low-risk patients (pTis, pTa, and pT1G1) without palpable lymph nodes and with good compliance, a surveillance strategy may be chosen. For all other patients without palpable lymph nodes (including intermediate risk pT1G2 disease), a modified bilateral lymphadenectomy is recommended. An alternative to this is a dynamic sentinel lymph node biopsy in specialised centres. All patients with histologically proven lymph node metastases should undergo radical inguinal lymphadenectomy. Pelvic lymph node dissection should be done in all patients with more than two metastatic inguinal lymph nodes. In case of fixed inguinal lymph nodes, neoadjuvant chemotherapy is recommended, followed by node resection.

Conclusions

Lymphadenectomy is an integral part of the management of penile cancer, since early dissection of involved lymph nodes improves survival.     

Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer

PURPOSE: We determine if histopathological factors of the primary penile tumor can stratify the risk of the development of inguinal lymph node metastases. MATERIALS AND METHODS: Clinical records of 48 consecutive patients with squamous cell carcinoma of the penis who underwent resection of the primary lesion and either inguinal lymph node dissection or were observed for signs of recurrence (median followup 59 months) were reviewed. Parameters examined included pathological tumor stage, quantified depth of invasion and tumor thickness, histological and nuclear grade, percentage of poorly differentiated cancer in the primary tumor, number of mitoses and presence or absence of vascular invasion. Variables were compared in 18 lymph node positive and 30 lymph node negative cases. RESULTS: Pathological tumor stage, vascular invasion and presence of greater than 50% poorly differentiated cancer were the strongest predictors of nodal metastasis on univariate and multivariate regression analyses. None of 15 pT1 tumors exhibited vascular invasion or lymph node metastases. Of 33 patients with pT2 or greater tumors 21 (64%) had vascular invasion and 18 (55%) had metastases. Only 4 of 25 patients (15%) with 50% or less poorly differentiated cancer in the penile tumor had metastases compared with 14 of 23 patients (61%) with greater than 50% poorly differentiated cancer (p = 0.001). No other variables tested were significantly different among the patient cohorts. CONCLUSIONS: Pathological stage of the penile tumor, vascular invasion and greater than 50% poorly differentiated cancer were independent prognostic factors for inguinal lymph node metastasis. Prophylactic lymphadenectomy in compliant patients with pT1 lesions without vascular invasion and 50% or less poorly differentiated cancer does not appear warranted.     

Staging laparotomy in the treatment of metastatic melanoma of the lower extremities.

Twenty-six consecutive patients with melanoma of the lower extremities metastatic to the superficial inguinal lymph nodes were subjected to laparotomy. No patient had preoperative evidence of tumor dissemination past the superficial inguinal nodes. However three patients (12%) had metastases to the liver or para-aortic lymph nodes documented at laparotomy and were not subjected to iliac and obturator lymph node dissection. One of these patients had concomitant local recurrence of melanoma at the ankle. The other two patients had superficial inguinal lymph nodes at least 5 cm in diameter, although two other such patients with similar 5 cm lymph nodes did not have positive intra-abdominal findings. The remaining 23 of the 26 patients underwent ipsilateral iliac and obturator lymph node dissection, which proved positive in 3/23 patients (13%). Of these 23 patients undergoing iliac and obturator node dissection, 18 had clinically positive (and microscopically positive) superficial inguinal nodes prior to their dissection, while the remaining 5 patients had clinically negative (but microscopically positive) superficial inguinal nodes. The three cases of positive dissected iliac and obturator nodes occurred among the 18 patients with clinically positive superficial inguinal nodes (17%). Among the 5 patients with clinically negative, microscopically positive superficial groin nodes, there was no detectable deep inguinal nodal spread (or hepatic or para-aortic involvement).     

腔镜下阴茎癌双侧腹股沟淋巴结清扫术14例报告

目的探讨腔镜下阴茎癌双侧腹股沟淋巴结清扫术的效果。方法2009年9月～2011年11月对14例阴茎癌行腔镜下双侧腹股沟淋巴结清扫术。术前对腹股沟淋巴结和隐静脉进行多普勒超声扫描和盆腔淋巴CT检查,术中建立人工手术腔隙,置人腔镜以及操作器械,先用超声刀扩大皮下腔隙,向上至腹股沟韧带上方的腹外斜肌腱膜,外侧至缝匠肌外缘,内侧为长收肌内侧,下界为股三角顶端,解剖出股动静脉、大隐静脉及其分支,并切除该范围内的淋巴结和脂肪组织,从穿刺孔取出清扫的淋巴结和脂肪组织,术后置引流管引流。结果14例均顺利完成腔镜下腹股沟淋巴清扫术,术中未发生并发症。手术时间平均103min（95～112min）,术中出血量平均85ml（20～130m1）。双侧切除淋巴结共5—14枚,平均9枚,淋巴结均阴性。术后留置引流管平均5d（3～7d）。术后住院5～8d,平均6d。1例出现淋巴囊肿,2个月后消退,其余患者未发生股血管损伤、皮缘坏死、愈合延迟、皮下积液和淋巴漏等切口相关的并发症。14例术后随访6—20个月,平均9个月,患者无明显双下肢肿胀及活动障碍。结论腔镜下阴茎癌双侧腹股沟淋巴结清扫术可以保证清扫范围并减少标准开放手术带来的切口相关并发症。     

Early versus delayed lymph-node dissection versus no lymph-node dissection in carcinoma of the penis

Assessment of the inguinal lymph nodes for metastases in patients with penile cancer is inaccurate. About 50 per cent of patients with node enlargement have no tumor on histologic examination, and 20 per cent of patients with clinically negative nodes have micrometastases. Lymph-node biopsies, including sentinel-node biopsy, are of limited staging value. Patients with lesions that do not invade the corpora and who have no palpable nodes should be followed carefully after excision of the primary tumor at 2- to 3-month intervals. If compliance with such a follow-up is doubtful, bilateral superficial groin-node dissection seems appropriate. Those with persistent adenopathy should undergo superficial lymph-node dissection first, and if positive nodes are found, bilateral deep-node dissection should then be performed. Bilateral inguinal and pelvic lymphadenectomy is recommended for patients with lesions invading the corpora with clinically negative or positive nodes because of the high incidence of lymph-node metastases in such cases. Where adenopathy persists after excision of the primary tumor, we advocate first limited pelvic dissection. If the pelvic nodes are negative or are not extensively involved, bilateral groin dissection should be performed, preferably in two stages. Percutaneous fine-needle aspiration of palpable or nonpalpable nodes can improve preoperative staging in patients with penile cancer.     

Lymphoscintigraphy in penile cancer: limited value of sentinel node biopsy in patients with clinically suspicious lymph nodes

The staging lymph node dissection in patients with penile carcinoma is accompanied with a high morbidity. As many patients are free of nodal metastases the lymphoscintigraphic sentinel node biopsy is supposed to minimize perioperative morbidity in these patients. In the current study the accuracy of the lymphoscintigraphic sentinel node biopsy was verified against the gold standard of radical inguinal dissection. In particular, patients with enlarged lymph nodes have also been included since one half of these patients is known to have histologically negative lymph nodes. Between 2000 and 2004 fifteen patients with penile carcinoma were elected to undergo bilateral groin dissection, thus 30 inguinal areas have been dissected. Nine patients have had clinically palpable nodes. All patients underwent lymphoscintigraphy after injection of Tc99-nanocolloid subcutaneously into the peritumoral area. Intraoperatively the sentinel nodes were identified with the aid of a gamma ray detection probe and excised. Afterwards a standard groin dissection was performed and the different lymph nodes were histopathologically assessed separately. In all patients lymph nodes with high radioactivity uptake were detected bilaterally. In 10 out of 30 inguinal areas histopathologically positive lymph nodes were present. In four of them the sentinel node was positive for tumor but in six dissection areas lymph node metastases were found despite a negative sentinel node. These patients had clinically palpable lymph nodes in their histologically positive inguinal regions. If no palpable nodes were present dynamic sentinel biopsy detected the positive nodes. The current study showed that dynamic sentinel node biopsy in patients with clinically suspicious lymph nodes is of low value for detection of lymphatic spread in penile cancer. Therefore the gold standard in these patients remains the radical groin dissection. However, dynamic sentinel node biospy is still a promising strategy to identify lymphatic spreading in clinically N0 patients and therefore to prevent unnecessary groin dissection.     

Cancer of the penis. Experience at the Norwegian Radium Hospital 1974-1985

The cancer-related 5-year survival was 80% in 79 patients with penile cancer treated at the Norwegian Radium Hospital from 1974 to 1985 (N0 = 61, N1-2 = 12, N3 = 6). Sentinel node biopsy (SLN) of the inguinal lymph nodes medial to the saphenous vein helps to identify patients with early regional spread. The survival for these N+ patients is favourable if radical lymph node dissection is performed immediately. A tumour-negative SLN biopsy does, however, not exclude the subsequent development of inguinal lymph node metastases. These were found equally often during follow-up in patients with or without primary performance of SLN biopsy. Five of 6 patients, relapsing with groin metastases, were cured by secondary lymph node dissection. Most of the small primary tumours (T1/T2) can be treated radically by primary radiotherapy, but frequent follow-up is necessary to detect surgically curable penile recurrences (3 of 11 patients). Combination treatment of chemotherapy, radiotherapy and surgery represents a good palliation treatment in advanced cases.     

Controversies in ilioinguinal lymphadenectomy for cancer of the penis.

One of the most important aspects in oncology is the definition of clinically relevant subgroups of patients whose disease wil have different behavior to enable decision making about therapeutic methods. The appropriate management of regional adenopathy in patients with penile cancer has generated a number of controversies. Generally, clinical determination of the extent of local disease is difficult. About 50% of patients with node enlargement have no tumor on histologic examination, and 20% of patients with clinically negative nodes have micrometastases. Lymph node biopsies, including sentinel node biopsy, are of limited staging value. Patients with lesions that do not invade the corpora and who have no palpable nodes should be followed carefully at 2- to 3-month intervals after excision of the primary tumor. Those with persistent adenopathy should undergo superficial lymph node dissection first, and if positive nodes are found, bilateral deep node dissection should be performed. Bilateral inguinal and pelvic lymphadenectomy is recommended for patients with lesions invading the corpora with clinically negative or positive nodes because of the high incidence of lymph node metastases in such cases (Table 1). When adenopathy persists after excision of the primary tumor, we advocate first a limited pelvic dissection. If the pelvic nodes are negative or not extensively involved, bilateral groin dissection should be performed, preferably in two stages. Percutaneous fine-needle aspiration of palpable or nonpalpable nodes can be helpful in preoperative staging in patients with penile cancer. Potential areas of study include identification of better risk factors and improvement of preoperative staging methods. This goal is hampered by the fact that penile cancer is a rare finding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pelvic lymph node dissection for penile carcinoma: extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival

PURPOSE: We identified pathological parameters of inguinal lymph node involvement with the aim of predicting pelvic lymph node involvement and survival. MATERIALS AND METHODS: A total of 308 patients with penile carcinoma and adequate followup were included in this study. The outcome of 102 patients who underwent lymphadenectomy for lymph node metastases was analyzed further. Histopathological characteristics of the regional lymph nodes were reviewed including unilateral or bilateral involvement, the number of involved nodes, pathological tumor grade of the involved nodes, and the presence of extracapsular growth. RESULTS: Tumor grade of the involved inguinal lymph nodes (OR 6.0, 95% CI 1.2-30.3) and the number of involved nodes (2 or less vs more than 2) (OR 12.1, 95% CI 3.0-48.1) were independent prognostic factors for pelvic lymph node involvement. Extracapsular growth (OR 2.3, 95% CI 1.1-4.8), bilateral inguinal involvement OR 3.4, 95% CI 1.2-9.4) and pelvic lymph node involvement (OR 3.1, 95% CI 1.4-6.6) were independent prognostic factors for disease specific survival. CONCLUSIONS: Patients with only 1 or 2 inguinal lymph nodes involved without extracapsular growth and no poorly differentiated tumor within these nodes are at low risk of pelvic lymph node involvement and have a good prognosis with a 5-year survival rate of approximately 90%. Pelvic lymph node dissection seems to be unnecessary in these cases.     

Current controversies and developments on the role of lymphadenectomy for penile cancer

Penile squamous cell carcinoma is a rare cancer in men. The main prognosticators of survival for penile cancer patients remain the presence and the extent of lymph node metastasis. While radical inguinal lymphadenectomy has been the cornerstone of regional lymph node management for many years, it is still associated with significant morbidity and psychological distress. Recent developments in penile squamous cell carcinoma management have been met with some controversy in the urologic oncology community. Herein, we review the current controversies and developments on the role of inguinal lymphadenectomy for penile cancer.     

Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases

PURPOSE: In this retrospective study we compared the clinical outcome of early vs delayed excision of lymph node metastases in patients with penile squamous cell carcinoma. MATERIALS AND METHODS: A total of 40 patients with a T2-3 penile carcinoma with lymph node metastases were included in this study. All patients initially presented with bilateral impalpable lymph nodes. In 20 patients (50%) metastases were removed when they became clinically apparent during meticulous followup (median interval 6 months, range 1 to 24). There were 20 patients (50%) who underwent resection of inguinal metastases detected on dynamic sentinel node biopsy before they became palpable. The histopathological characteristics of the tumors and lymph nodes were reevaluated. RESULTS: The 2 populations were similar in terms of patient age, T-stage, pathological tumor grade, vascular invasion and infiltration depth. Disease specific 3-year survival of patients with positive lymph nodes detected during surveillance was 35% and in those who underwent early resection, 84% (log rank p = 0.0017). In multivariate analysis early resection of occult inguinal metastases detected on dynamic sentinel node biopsy was an independent prognostic factor for disease specific survival (p = 0.006). CONCLUSIONS: Early resection of lymph node metastases in patients with penile carcinoma improves survival.     

Size of metastasis in the sentinel node predicts additional nodal involvement in penile carcinoma

PURPOSE: The majority of patients with penile cancer with a tumor positive sentinel node do not benefit from complementary lymph node dissection because of absent additional involved nodes. We analyzed factors that may determine the involvement of additional nodes. MATERIALS AND METHODS: A total of 158 patients with clinically node negative penile carcinoma underwent sentinel node biopsy. Complementary inguinal lymph node dissection was performed when the sentinel node was tumor positive. The size of the sentinel node metastasis was measured and classified as micrometastasis--2 mm or less, or macrometastasis--more than 2 mm. Sentinel and dissection specimen nodes were step-sectioned. Factors were analyzed for their association with additional nodal involvement, including stage, diameter, grade, absence or presence of vascular invasion of the primary tumor, and sentinel node metastasis size. RESULTS: Tumor positive sentinel nodes were found in 46 groins and complementary lymph node dissection was performed. Nine of these 46 groins (20%) contained additional involved lymph nodes. On univariate and multivariate analyses the size of the sentinel node metastasis proved to be the only significant prognostic variable for additional lymph node involvement (each p = 0.02). None of the 15 groins with only micrometastasis in the sentinel node contained additional involved nodes. CONCLUSIONS: In penile carcinoma additional nodal involvement was related to the size of the metastasis in the sentinel node. Sentinel node micrometastasis was not associated with other involved lymph nodes. This finding suggests that these patients can be spared complementary lymph node dissection.