Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group

Purpose: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T₃ primary tumors, or the need for pelvic exenteration for patients with T₄ primary tumors, not amenable to resection by standard radical vulvectomy.Methods and Materials: Seventy-three evaluable patients with clinical Stage III–IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal–femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior–posterior-anterior (AP–PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal–femoral and lower pelvic lymph nodes.Results: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects.Conclusion: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.     

Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: a multicenter study.

BACKGROUND: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue V was injected intradermally shortly before surgery. Routine groin lymph node dissection and radical vulvectomy were performed. During the surgery, blue lymph vessels and lymph nodes were identified, and the blue lymph nodes were sent separately for histologic examination. The negative predictive value of the blue lymph nodes for the absence of metastases was assessed by histologic examination of the groin lymph node specimens. RESULTS: Fifty-one patients in whom 93 groin lymph node dissections were performed were entered. One or more blue lymph nodes were detected in only 52 groins (56%). Nine (17%) of these were tumor positive, and 6 blue lymph nodes were the only tumor positive lymph nodes in the specimen in which they were found. There were two false-negative blue lymph nodes. The negative predictive value was 0.953. CONCLUSIONS: It was shown in this multicenter study that sentinel lymph node detection in vulvar carcinoma patients with blue dye only is not feasible because its negative predictive value is too low. Further studies involving the use of a combination of radioactive labeled technetium and blue dye are warranted.     

Irradiation in carcinoma of the vulva: factors affecting outcome

Purpose: This report reviews the increasing role of radiation therapy in the management of patients with histologically confirmed vulvar carcinoma, based on a retrospective analysis of 68 patients with primary disease (2 in situ and 66 invasive) and 18 patients with recurrent tumor treated with irradiation alone or combined with surgery.Methods and Materials: Of the patients with primary tumors, 14 were treated with wide local excision plus irradiation, 19 received irradiation alone after biopsy, 24 were treated with radical vulvectomy followed by irradiation to the operative fields and inguinal–femoral/pelvic lymph nodes, and 11 received postoperative irradiation after partial or simple vulvectomy. The 18 patients with recurrent tumors were treated with irradiation alone. Indications and techniques of irradiation are discussed in detail.Results: In patients treated with biopsy/local excision and irradiation, local tumor control was 92% to 100% in Stages T1-3N0, 40% in similar stages with N1-3, and 27% in recurrent tumors. In patients treated with partial/radical vulvectomy and irradiation, primary tumor control was 90% in patients with T1-3 tumors and any nodal stage, 33% in patients with any T stage and N3 lymph nodes, and 66% with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for T1N0, 62% for T2-3N0, 30% for T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 tumors. Four of 18 patients (22%) treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and irradiation. In patients with T1-2 tumors treated with biopsy/wide tumor excision and irradiation with doses under 50 Gy, local tumor control was 75% (3 of 4), in contrast to 100% (13 of 13) with 50.1 to 65 Gy. In patients with T3-4 tumors treated with local wide excision and irradiation, tumor control was 0% with doses below 50 Gy (3 patients) and 63% (7 of 11) with 50.1 to 65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and irradiation, local tumor control was 83% (14 of 17), regardless of dose level, and in T3-4 tumors, it was 62% (5 of 8) with 50 to 60 Gy and 80% (8 of 10) with doses higher than 60 Gy. The differences are not statistically significant. There was no significant dose response for tumor control in the inguinal–femoral lymph nodes; doses of 50 Gy were adequate for elective treatment of nonpalpable lymph nodes, and 60 to 70 Gy controlled tumor growth in 75% to 80% of patients with N2-3 nodes when administered postoperatively after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess.Conclusions: Irradiation is playing a greater role in the management of patients with carcinoma of the vulva; combined with wide local tumor excision or used alone in T1-2 tumors, it is an alternative treatment to radical vulvectomy, with significantly less morbidity. Postradical vulvectomy irradiation in locally advanced tumors improves tumor control at the primary site and the regional lymphatics in comparison with reports of surgery alone.     

Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO I/II

PURPOSE: Between 1953 and 1978, postoperative radiotherapy was used as an adjuvant therapy for carcinoma of the vulva that had not been treated with radical vulvectomy. We evaluated long-term results and possible prognostic factors. METHODS AND MATERIALS: Ninety-two patients were treated. Surgical procedures were simple vulvectomy, electrocoagulation, or local excision. Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year retrospective follow-up was done evaluating the records and statistical survival rates. RESULTS: Five-year actuarial survival rates in T1 patients were 71% (77% cause-specific survival rate), for T2 patients 43% (48% cause-specific survival rate). The difference between T1 and T2 patients was significant (p < 0.05). Patients with tumors of the labia minora had a significantly higher survival rate than those with different sites affected. Doses of 45 Gy or more to the vulva were sufficient to increase the 5-year cause-specific survival rate from 55% to 88%. The results in three subgroups were analyzed, group 1 having received electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the vulva. There was a significant effect on 10-year cause-specific survival rates: 48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the significant independent factors were T classification, tumor sites and-with only marginal significance-radiation doses to the vulva. CONCLUSIONS: The prognosis in early vulva carcinoma after nonradical surgery primarily depends on T classification and the site of the primary tumor. With univariate analyses, the dose has a significant effect on survival. In multivariate analyses the dose is a marginal independent factor in the whole group of patients. After nonradical surgery of early vulva carcinoma, the vulva should be irradiated resulting in better long-term survival.     

Management of vulvar cancer]

In the treatment of vulvar malignancy surgery, chemotherapy, irradiation therapy and so on can be used. Actually, it was rarely performed only by a single method. For treatment by the stage of cancer progression, the superficial cancer was treated by wide local resection for the patients except old women who were done simple vulvectomy. For the invasive cancer, stage 1 or 2, the pre-operative bleomycin (BLM) was administered to reduce the tumor mass, thereafter, radical vulvectomy with inguinal lymph node resection was performed. If inguinal lymph nodes metastasis was found, area of resection was extended to pelvic lymph nodes. Recently, micro-invasive carcinoma was defined that the foci was below 2 cm and interstitial invasion below 1 mm. In this condition, it was needless to remove the lymph nodes. For the stage of 3 or 4 which was inoperable, chemotherapy (mainly BLM) combined with irradiation therapy was done. In the cases of good general condition, it was chosen by super-radical vulvectomy.     

Lymph node metastasis in intrahepatic cholangiocarcinoma

BACKGROUND: Lymph node metastasis is a significant prognostic factor in intrahepatic cholangiocarcinoma. This study was aimed at investigating lymph node metastasis in intrahepatic cholangiocarcinoma and to examine whether the extent of metastasis affects outcomes after surgery. METHODS: From 1980 through 1996, 70 patients with intrahepatic cholangiocarcinoma underwent hepatectomy, with a 50% curative resection rate. Lymph node dissection was performed in 51 patients, and the presence of lymph node metastasis was examined microscopically. The metastatic nodes were divided into groups N1, N2 or N3 using the classification proposed by the Liver Cancer Study Group of Japan. RESULTS: Twenty-three patients had lymph node metastasis. Metastasis was to N1 nodes in 10 patients, to N2 nodes in nine patients and to N3 nodes in four patients. Nineteen patients had metastatic nodes in the hepatoduodenal ligament, which was the most common metastatic site regardless of tumor location. The five-year survival rate in patients with lymph node metastasis (0%) was significantly lower (p < 0.0001) than that in patients without lymph node metastasis (51 %); however, five-year survival rates did not differ between patients with metastases to N1, N2 and N3 nodes. CONCLUSIONS: Lymph nodes in the hepatoduodenal ligament may be sentinel nodes for intrahepatic cholangiocarcinoma, and outcomes after surgery for patients with lymph node metastasis are poor regardless of the sites of nodal metastasis.     

A case of vulva cancer responding to the recombinant human tumor necrosis factor (PT-950)--local injection therapy

A case of vulva cancer responding to the recombinant human tumor necrosis factor (rHu-TNF: PT-050), which had been administered to double inguinal lymph nodes, is herein reported. A 60-year-old female underwent resection of a vulva cancer following a diagnosis of condyloma acuminatum. After surgery, however, exacerbation of a residual tumor, sited on the right of the vulva, and metastasis of the double inguinal lymph nodes were uncovered. For treatment, rHu-TNF was injected in the inguinal lymph nodes at a dose of 1 x 10(6)U per injection, 2 times a week. After 8 therapeutic sessions for 4 weeks, a marked response was observed not only in swelling of the lymph nodes, into which rHu-TNF had been injected, but also in the tumor of primary focus, which received no injections. On the 32 nd day after the final injection of rHu-TNF, the tumor of primary focus completely disappeared and the swelling of lymph nodes had diminished to 25% of the initial volume.     

Progression of intraepithelial Paget's disease of the vulva to invasive carcinoma.

Sequential progression from intraepithelial Paget's disease of the vulva to invasive carcinoma after an interval of 10.8 years is documented in this report. Infiltration of the dermis with permeation of lymphatics and metastasis to regional lymph nodes are believed to have resulted directly from foci of intraepidermal Paget's cells that persisted after a simple vulvectomy. No underlying primary sweat gland carcinoma was present. Hence, this case establishes the invasive potential of intraepithelial vulvar Paget's disease and substantiates the notion that it is indeed a type of carcinoma in situ.     

Skip metastasis in nonsmall cell lung carcinoma: predictive markers and isolated tumor cells in N1 lymph nodes

BACKGROUND: Skip metastasis to mediastinal lymph nodes is a prognostic factor for patients with nonsmall cell lung carcinoma (NSCLC). Little is known about the biologic behavior of tumors with noncontinuous spread to the mediastinal lymph nodes. In patients with pN2 skip metastases, micrometastases to N1 lymph nodes, which only mimic skip metastases, have not been investigated. METHODS: In a retrospective study, the authors analyzed the primary tumor specimens from 45 patients with pN2 NSCLC (18 patients had squamous cell carcinomas, 23 had adenocarcinomas, and 4 had large cell carcinomas). They immunohistochemically evaluated the expression of p21, p53, MUC-1, Bcl-2, c-ErbB-2, and E-cadherin. Survival rates and biomarker expression levels were compared between patients with pN2 disease and infiltration of N1 lymph nodes (without skip metastasis [n = 28]) and patients with pN2 disease without N1 infiltration (with skip metastasis [n = 17]). To evaluate micrometastasis in the pN1 lymph nodes of 17 patients with skip metastases, lymph nodes were stained using the anticytokeratin antibody, AE1/AE3. RESULTS: The 5-year survival rate of patients with skip metastases was 41%, compared with 14% for patients without skip metastases (P = 0.019). In a multivariate analysis, the incidence of skip metastases did not vary significantly according to gender, age, histology, pT status, or cM status. Three skip-positive patients (17.6%) had micrometastatic tumor involvement of pN1 lymph nodes. After adding these patients to the group of patients without skip metastases, there was still a significant difference in survival between the two groups. p53, MUC-1, c-ErbB-2, and E-cadherin expression levels in primary tumor specimens were not significantly different in patients with continuous metastasis and patients with skip metastases. Patients with skip metastases expressed lower levels of p21 (P = 0.026), whereas Bcl-2 expression levels were considerably higher (P = 0.019) compared with the corresponding levels in patients without skip metastases. CONCLUSIONS: Patients with NSCLC and pN2 skip metastases have a more favorable prognosis than do patients with pN2 disease without skip metastases. Tumor specimens from these patients exhibit elevated expression of the antiapoptosis gene BCL2 and lower expression levels of p21 relative to patients with pN2 disease without skip metastases. Micrometastases occurred in 3 of 17 (17.6%) patients with pN2 disease and skip metastases diagnosed by routine histopathology.     

非小细胞肺癌纵隔淋巴结转移(N2)的外科治疗选择

目的 探讨有纵隔淋巴结转移（N2）的非小细胞肺癌（NSCLC）的外科治疗选择。方法 回顾性分析总结325例N2 NSCLC的外科治疗效果和经验。结果 全组5年生存率为19．6％,其中根治性切除者高于姑息性切除者,鳞癌高于腺癌,行袖式肺叶切除和全肺切除者高于常规肺叶切除者,纵隔淋巴结转移1～3枚者高于〉3枚者,术后综合治疗者高于单一外科治疗者,上述差异均有统计学意义。所有T3、T4以及M1患者均无5年生存者。结论 对于N2 NSCLC肿瘤为Tl或T2、病理类型为非腺癌以及纵隔转移淋巴结〈4枚者,外科治疗是最好的选择。对于肿瘤为T3的患者,外科治疗可能并非良策,肿瘤的根治性切除以及肺门和纵隔的系统淋巴结清扫,是病变分期和生存率提高的关键所在,术后综合治疗有助于患者的远期生存,尤其适用于有肿瘤残留和（或）纵隔转移淋巴结〉3枚的患者。     

巴氏腺腺样囊性癌临床病理分析

目的 探讨巴氏腺腺样囊性癌的临床病理特征和治疗方法.方法 回顾性分析6例巴氏腺腺样囊性癌患者的临床及病理资料.6例患者的中位年龄为40.5岁(30～54岁).主要治疗方式为手术切除,其中单纯外阴肿物剥除术1例,外阴根治性切除术加双侧腹股沟淋巴结清扫或活检术4例,外阴局部扩大切除术加双侧腹股沟淋巴结活检术1例.有2例患者术后补充放疗.6例患者均随访至2009年4月1日,中位随访时间124.5个月(8～241个月).结果 6例巴氏腺腺样囊性癌均经病理确诊,肿瘤细胞呈筛状排列及侵犯神经是其典型的病理特点.术后病理显示,切缘阳性2例,阴性1例,邻近肿瘤1例,不详2例.腹股沟淋巴结阴性5例,不详1例.有4例患者复发,其中3例局部复发,后出现肺转移;1例仅出现肺转移.在复发患者中,死亡1例,生存时间为135个月;另3例患者分别带瘤生存120、30和36个月,总生存时间分别为241、128和103个月.2例无复发患者无瘤生存8个月和121个月.结论 巴氏腺腺样囊性癌生长缓慢,患者长期预后较好,但容易局部复发和肺转移.首选治疗方法为手术切除,对于术后切缘阳性、局部浸润较深或侵犯神经者以及复发无法手术者可行辅助放疗或姑息性放疗.     

非小细胞肺癌叶支气管及段支气管淋巴结转移对疾病病理分期的影响和淋巴结转移规律的研究

目的探讨IIA^IIIA期非小细胞肺癌叶支气管及段支气管淋巴结转移对患者病理分期的影响和淋巴结转移规律的研究。方法选取2013年1月至2013年6月间接受标准肺癌根治手术及系统性胸内淋巴结清扫术患者48例,进行手术标本肺门(10组)、叶间(1l组)、肺叶(12组)及肺段(13组)淋巴结分站病理检测,结合临床资料进行统计学分析。结果 48例患者共切除淋巴结935枚,(19.1±7.2)枚/例。N1淋巴结417枚,转移356枚,转移率为85.4%;N2淋巴结518枚,转移356枚,转移率为68.7%。其中发现跳跃转移4例,其N2淋巴结42枚,14枚阳性,(4±5.78)枚/例,转移率为33.3%;非跳跃转移23例,其N2淋巴结476枚,342枚阳性,(20±3.15)枚/例,转移率为71.8%。N2跳跃转移与非跳跃性转移在不同性别、年龄、吸烟与否、分检淋巴结数量之间差异无统计学意义(P>0.05),而与肿瘤大小、病理类型有关(P<0.05)。N1淋巴结阳性患者中,第10组、11组、12组、13组淋巴结转移阳性率分别为33.3%、52.1%、25.0%和16.7%;同时当淋巴结清扫只进行至第11组淋巴结,N1期漏诊率达44.4%(12/27)。结论 N1淋巴结中,肺叶12组和肺段13组淋巴结在肺癌转移过程中占据相当的比例,需要进行这两组淋巴结的分检以提高分期诊断的准确性。     

Ten years of progress in radiation oncology

Background

We previously demonstrated that extracapsular invasion (ECI) at a metastatic sentinel node was significantly associated with the presence of positive non-sentinel nodes in patients with breast cancer. However, the mechanism of metastatic spreading of tumor cells to distant lymph nodes in patients with colorectal carcinoma is not fully understood. In this study, we investigated the factors that may determine the likelihood of additional regional lymph node metastasis when metastasis is found in nodes at the N1 site in colorectal cancer, especially focusing on the presence of ECI.

Methods

Two hundred and twenty-eight consecutive patients who underwent colorectal resection were identified for inclusion in this study, of which 37 (16.2%) had positive lymph nodes at the N1 site. Six of these 37 cases had additional metastasis in N2 site lymph nodes. We reviewed the clinicopathological features of these cases and performed statistical analysis of the data.

Results

In the univariate analysis ECI at the N1 site was the only factor significantly associated with the presence of cancer cells in the N2 site. Other factors, including number of positive lymph nodes, lymphovascular invasion of the primary tumor, tumor size and tumor depth of invasion, were not associated with metastatic involvement at the N2 site.

Conclusions

Our results suggest that the presence of ECI at metastatic lymph nodes at the N1 site is correlated with further metastasis at the N2 site. These findings imply the possibility that ECI might indicate the ability of colorectal tumor cells to disseminate to distant lymph nodes.     

Serum squamous cell carcinoma antigen levels in invasive squamous vulvar cancer.

Squamous cell carcinoma (SCC) antigen levels were studied in 34 patients with primary (N = 27) or recurrent (N = 7) SCC of the vulva. In primary disease, the SCC antigen level was greater than 2.5 ng/ml in only four patients (15%). Elevated antigen levels ranged from 2.7-18.0 ng/ml. All of these patients had advanced disease by either clinical or surgical staging systems. Four of twelve patients with inguinal metastasis had elevated SCC antigen levels. In two of these patients the inguinal nodes were abnormal to palpation. No association of the SCC level and the degree of tumor differentiation was observed. SCC antigen levels were increased slightly (2.7-4.5 ng/ml) in three of six patients with locally recurrent disease. In one patient with distant recurrence the SCC antigen was 15.3 ng/ml. In both primary and recurrent disease all elevated SCC antigen levels decreased with effective therapy. Vulvar cancer is primarily a local disease that is easily assessed by physical examination. An effective tumor marker in vulvar cancer would benefit only the rare patient with distant but not local disease.     

Enhancement of lymph node metastasis and distant metastasis of thyroid carcinoma

BACKGROUND: The mechanisms of local and distant metastases are imperfectly understood. The goal of the current study was to add to the body of knowledge regarding local and distant metastases of thyroid malignancies. METHODS: The authors performed multivariate analysis of 573 patients who underwent surgery between November 1994 and May 2002 for follicular (FTC; n = 100), papillary (PTC; n = 236), or medullary thyroid carcinoma (MTC; n = 237) at a university hospital. RESULTS: In multivariate analysis, extrathyroidal extension consistently evolved as the key risk factor for both lymph node metastasis and distant metastasis. This correlation was most pronounced in MTC and least pronounced in FTC. The risk of lymph node metastasis also increased with reoperative status in patients with MTC and with primary tumor diameter in patients with MTC (tumor diameter > 10 mm) and patients with PTC (tumor diameter > 20 mm). In the PTC group, lymph node metastasis was more common among patients younger than age 45. In the MTC group, extrathyroidal growth and distant metastasis were associated exclusively with lymph node metastasis. Lymph node metastasis was the only secondary risk factor for distant metastasis. In the analysis of risk factors for distant metastasis in the FTC and PTC groups, no interaction was found between extrathyroidal growth and lymph node metastasis. This finding suggests that extrathyroidal growth and lymph node metastasis of FTC and PTC, and presumably also MTC, represent separate mechanisms and routes of distant metastasis. CONCLUSIONS: Screening for both local residual disease and distant metastases should be intensified in the high-risk population of patients whose primary tumors exhibit large diameters, extrathyroidal growth, or lymph node metastasis.     

Induction chemotherapy with cisplatin, vinorelbine, and mitomycin-C followed by surgery for patients with pathologic N2 non-small-cell lung cancer

PURPOSE: The treatment strategy for patients with non-small-cell lung cancer (NSCLC) involving ipsilateral mediastinal lymph nodes is still controversial. We performed a phase II feasibility study of induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC. PATIENTS AND METHODS: Patients with mediastinoscopy- positive stage IIIA N2 NSCLC received 2 cycles of cisplatin 80 mg/m2, vinorelbine 25 mg/m2, and mitomycin-C 8 mg/m2. Patients without progressive disease underwent thoracotomy and lobectomy with lymph node dissections 2-4 weeks later. RESULTS: From January 2000 to July 2004, 24 eligible patients (15 men, 9 women) were enrolled. Induction chemotherapy was completed as planned in 23 patients (95.8%). Hematological toxicity was the primary grade 3/4 toxicity. Twelve (50%) patients achieved a partial response. Twenty-three patients underwent surgical resection, and complete resection was achieved in 22 patients (95.7%). There were no surgery-related deaths. Pathologic complete response in metastatic lymph nodes was achieved in 5 patients. With a median follow-up of 5.4 years (range, 2.88-7.7 years), the estimated 5-year survival was 51.8% (95% CI, 41.3-62.3) and progression-free survival was 46.6% (95% CI, 36-57.2). CONCLUSION: Induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC was feasible and associated with high response to lymph node metastasis and good survival.     

非小细胞肺癌Ｎ３ 组淋巴结行纵隔镜探查活检指征的探讨

目的：探讨和筛选出对非小细胞肺癌（ＮＳＣＬＣ）Ｎ_３组淋巴结需行纵隔镜探查活检的临床指征。方法：８９例Ⅰ～ⅢＡ期ＮＳＣＬＣ患者开胸术前行经颈纵隔镜检查,其中１２例联合右斜角肌活检术、１０例联合前纵隔切开术检查Ｎ３组淋巴结的病理状况。结果：纵隔镜检查后共发现９例为不宜再行开胸手术患者,其中３例为右斜角肌淋巴结转移,６例为病灶对侧纵隔淋巴结转移。统计学分析显示,肺腺癌组的Ｎ３发生率高于非腺癌组（Ｐ＜０.０５）,血清ＣＥＡ水平升高组的Ｎ_３发生率高于正常组（Ｐ＜０.０５）,同侧纵隔淋巴结多站转移组的Ｎ_３发生率高于同侧单站转移组（Ｐ＜０.０５）。结论：肺腺癌、血清ＣＥＡ升高和病灶同侧纵隔淋巴结多站转移的ＮＳＣＬＣ,推荐行病灶对侧或斜角肌前淋巴结活检,以排除Ｎ_３病变,为最优化的多学科治疗提供依据。     

基于IMRT和RTOG颈部淋巴结分区标准的鼻咽癌N分期研究

目的 建立一个基于IMRT和RTOG颈部淋巴结分区标准的鼻咽癌新N分期。 方法 回顾分析广西医科大学第一附属医院2010—2011年经病理学证实、无DM并接受IMRT的初治鼻咽癌患者324例,根据鼻咽癌UICC/AJCC分期标准(第7版)进行重新分期。Kaplan-Meier法计算生存率,Logrank法单因素预后分析,Cox模型多因素预后分析。 结果 324例患者中269例(83.0%)出现转移淋巴结,中位随访58个月(6~77个月),全组5年OS率为84.8%,DFS率为77.1%,RFS率为92.7%,DMFS率为80.5%。对其中颈部淋巴结阳性患者预后因素分析显示咽后淋巴结、颈部淋巴结水平、侧数是影响鼻咽癌患者预后因素(P值均<0.05)。根据风险比差异确定鼻咽癌新N分期: N₀期为无淋巴结转移;N₁期为Ⅶ_a区或/和单侧上颈(Ⅰ、Ⅱ、Ⅲ、V_a区)淋巴结转移;N₂期为双侧上颈(Ⅰ、Ⅱ、Ⅲ、Ⅴ_aa区)淋巴结转移;N₃期为Ⅳ _a、Ⅴ_b区及以下区域淋巴结转移。 结论 基于IMRT和RTOG颈部淋巴结分区标准的鼻咽癌新N分期更符合现状,并能更客观预测预后、指导治疗。     

From tumor lymphangiogenesis to lymphvascular niche

Metastasis in sentinel lymph nodes indicates the initial spread of tumors from a primary site. The recent discovery of tumor-associated growth of lymphatic vessels clarified that tumor lymphangiogenesis actively promotes enhanced draining/sentinel lymph node metastasis. Studies of experimental carcinogenesis have further established that tumors continue to induce lymphangiogenesis in metastatic foci such as draining lymph nodes. Lymphangiogenesis within draining lymph nodes probably contributes to enhanced distant lymph node and distant organ metastases. Lymph node lymphangiogenesis has recently been identified in several human malignancies, such as cutaneous malignant melanoma. Tumor-associated lymphangiogenesis thus has potential significance not only at the primary site, but also in lymph nodes. Primary tumors induce new lymphatic vessel growth in draining lymph nodes before metastasis. The remarkable enlargement of sinusoidal lymphatic endothelium might facilitate tumor cell transport to the lymph nodes, and potentially contribute to the migration, residence, and/or survival of metastatic tumor cancer stem cells by inducing a specific tumor microenvironment. Therefore, the novel concept of 'lymphvascular niche' is proposed herein to explain lymphatic network expansion. This concept might help to improve understanding of the molecular mechanism of lymph node metastasis, and change therapeutic approaches to treating cancer metastasis. ( Cancer Sci 2009; 100: 983–989)     

Prognostic evaluation of preoperative thermochemoradiotherapy for N(3) cervical lymph node metastases of oral cancer

OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy, histopathological efficacy, and response to preoperative thermochemoradiotherapy for N(3) cervical lymph node metastases of oral cancer. METHODS: Preoperative thermochemoradiotherapy was performed in 8 patients with oral cancer and N(3) cervical lymph node metastasis. These patients underwent four-weekly sessions of hyperthermia, combined with radiotherapy (40 Gy) as well as chemotherapy with cisplatin (CDDP; 100 mg/m2), all prior to surgery. Radical neck dissection was performed 4 weeks after completion of preoperative thermochemoradiotherapy. RESULTS: The preoperative treatment of cervical lymph node metastases yielded a partial response in 6 patients, while 2 patients demonstrated no change. Histopathologically, grade III was detected in 1, grade IIb in 4 and grade IIa in 3 patients after surgery, according to the criteria of Shimosato. The follow-up period ranged from 13 to 64 months (mean 34). Of the 8 patients, 2 died (1 of lymph node metastasis and 1 had metastasis to a distant site), and 6 patients were alive at the last follow-up, with the longest postoperative disease-free survival being 63 months. The 5-year cumulative survival rate was 70.0%. CONCLUSION: These results indicate that preoperative thermochemoradiotherapy is a promising modality for patients with N(3) cervical lymph node metastasis of oral cancer.