S-classification of sentinel lymph node biopsy predicts the results of complete regional lymph node dissection

The purpose of this study was to identify melanoma patients with positive sentinel lymph nodes (SLNs) at increased risk for further metastases in this specific lymph node basin. A series of consecutive patients with primary malignant melanoma stage I and II were evaluated retrospectively. The results of SLN biopsy in 26 patients with positive SLNs were compared with those of complete regional lymph node dissection (RLND) using the recently published S-classification of SLNs. The results of S-classification of SLNs were correlated with the outcome of complete RLND. There was a significant correlation between the S stage of positive SLNs and the results of complete RLND (P=0.02). Only patients with SIII stage (n=4) SLNs were found to have further metastases in the residual lymph node basin. The present study indicates that patients with SI stage and SII stage SLNs rarely have further metastases in the specific lymph node basin.     

Multiparametric in situ mRNA hybridization analysis of gastric biopsies predicts lymph node metastasis in patients with gastric carcinoma.

We examined the expression level of several genes that regulate different steps in metastasis formation in formalin-fixed, paraffin-embedded biopsies of 189 primary human gastric carcinomas prior to surgical resection in patients in whom lymph node metastasis was not evident by endoscopic ultrasound or computed tomography (CT) scan. The expressions of epidermal growth factor receptor (EGF-R), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and E-cadherin were examined by a colorimetric in situ mRNA hybridization technique. The integrity of the mRNAs was verified, leaving 161 (85.2%) patients for study. After gastrectomy, 82 patients had positive lymph nodes and 79 patients had negative lymph nodes. The concurrent expression levels of MMP-2 and E-cadherin mRNAs were significantly higher and lower, respectively, in the metastatic tumors than the non-metastatic tumors. Expression of EGF-R and VEGF was not different between the metastatic and non-metastatic tumors. However, when only the intestinal-type of gastric cancer was evaluated, the level of VEGF mRNA was significantly higher in tumors associated with lymph node metastasis than in those without metastasis. However, a high MMP-2:E-cadherin ratio significantly correlated with lymph node metastasis in both types of gastric cancer. These results suggest that multiparametric in situ hybridization analysis for several metastasis-related genes may allow the preoperative prediction of lymph node metastasis from gastric cancer.     

Surgical outcome of laparoscopy-assisted gastrectomy with extraperigastric lymph node dissection for gastric cancer.

AIM: The aim of this study was to determine the feasibility of laparoscopy-assisted gastrectomy (LAG) with extraperigastric lymph node dissection for gastric cancer. METHODS: The authors attempted LAG with extraperigastric lymph node dissection in 117 consecutive gastric cancer patients between May 1998 and January 2004. The clinico-pathologic characteristics, operative outcomes, post-operative morbidities and mortalities, and follow-up findings of patients with advanced gastric cancer were evaluated. RESULTS: LAG with extraperigastric lymph node dissection were successfully performed in 114 of 117 patients (success rate, 97%). Of these 114 successful cases, 100 cases were early gastric cancers and 14 cases were advanced gastric cancers. The mean operation time for the 114 cases was 259 (range 150-415) min, and the mean number of retrieved lymph nodes was 23 (range 6-66). Operative mortality, hospital death, and overall post-operative complication rates were 0, 1.7 and 14.7%, respectively. Follow-up was available in 110 of the 112 patients (two post-operative hospital deaths were excluded from the 114). Follow-up ranged from 6 to 74 months (median: 19). 108 patients remain alive without recurrence or port-site metastasis. CONCLUSIONS: LAG with extraperigastric lymph node dissection is a technically feasible and acceptable method for the surgical treatment of gastric cancer.     

Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma

BACKGROUND: Axillary lymph node dissection for staging the axilla in breast carcinoma patients is associated with considerable morbidity, such as edema of the arm, pain, sensory disturbances, impairment of arm mobility, and shoulder stiffness. Sentinel lymph node biopsy electively removes the first lymph node, which gets the drainage from the tumor and should therefore be associated with nearly zero morbidity. METHODS: Postoperative morbidity (increase in arm circumference, subjective lymphedema, pain, numbness, effect on arm strength and mobility, and stiffness) of the operated arm was prospectively compared in 35 breast carcinoma patients after axillary lymph node dissection (ALND) of Level I and II and 35 patients following sentinel lymph node (SN) biopsy. RESULTS: Patient characteristics were comparable between the two groups. Postoperative follow-up was 15.4 months (range, 4-28 months) in the SN group and 17.0 months (range, 4-28 months) in the ALND group. Following axillary dissection, patients showed a significant increase in upper and forearm circumference of the operated arm compared with the SN patients, as well as a significantly higher rate of subjective lymphedema, pain, numbness, and motion restriction. No difference between the two groups was found regarding arm stiffness or arm strength, nor did the type of surgery affect daily living. CONCLUSIONS: SN biopsy is associated with negligible morbidity compared with complete axillary lymph node dissection.     

Impact of axillary lymph node dissection on breast cancer outcome in clinically node negative patients

BACKGROUND:

The regional lymph node control and survival impact of axillary dissection in breast cancer has been the subject of multiple randomized trials, with various results. This study reviews and conducts a meta‐analysis of contemporary trials of axillary dissection in patients with early stage breast cancer.

METHODS:

A systematic MEDLINE review identified 3 randomized trials published between January 2000 and January 2007 of axillary dissection versus no dissection in clinically lymph node negative early stage breast cancer patients. A fourth trial of axillary radiotherapy versus no axillary treatment was also identified and included in this review. Meta‐analyses were performed for survival, axillary recurrence, metastatic disease, and ipsilateral breast recurrence.

RESULTS:

All trials reported a higher rate of axillary recurrence (1.5%‐3%, median follow‐up 5‐15 years) in the absence of axillary dissection or radiotherapy. Overall survival was similar with and without definitive axillary treatment in 3 of the 4 trials, with an increased rate of nonbreast cancer‐related death in the observation arm of the fourth trial. Meta‐analyses found no significant difference in overall survival (odds ratio [OR] 1.55; 95% confidence interval [CI], 0.74‐3.24), metastases (OR 0.91; 95% CI, 0.65‐1.29), or ipsilateral breast recurrence (OR 1.11; 95% CI, 0.68‐1.83) associated with axillary treatment. A significantly lower rate of axillary recurrence was seen after lymphadenectomy (OR 0.28; 95% CI, 0.11‐0.73, P<.01).

CONCLUSIONS:

Axillary dissection does not confer a survival benefit in the setting of early stage clinically lymph node negative breast cancer. Although the rate of axillary failure was increased in the absence of dissection, the absolute risk was found to be extremely low. Cancer 2009. © 2009 American Cancer Society.     

Extent of lymph node dissection in rectal carcinoma

Basing on 170 specimens of advanced rectal cancers radically resected, metastatic rule and extent of lymph node dissection were studied in order to guide future surgical treatment. In 170 cases, 77 had lymph node metastases. The lymph node metastatic rate was 45.3% and metastatic degree was 8.9% (527/5 912). Metastasis of the rectal cancer, according to the lymphatic anatomy, can be divided into upward, lateral and downward drain. Because the rectal cancer at any site can lead to the upward metastasis, the upward lymph node dissection, up to the base of inferior mesenteric artery (the third line of lymph nodes), must be done in all rectal cases, otherwise, 10% of patients would have residual cancer. In view of the lateral metastasis occurring only in rectal cancers under the peritoneal reflection, for which lateral lymph node dissection is necessary or one eighth of patients would have residual lesion. Generally, no lateral lymph node dissection is needed in cancers above the peritoneal reflection. Pathologic factor influencing the lymphatic metastasis is the form of tumor growth, such as poorly differentiated and mucoid adenocarcinomas aggressively growing deeply and extensively resulting in a higher lymph node metastatic rate, for which lymph node dissection must be performed.     

Current status of lymph node dissection in gastric cancer

Gastrectomy with lymph node (LN) dissection has been regarded as the standard surgery for gastric cancer (GC), however, the rational extent of lymphadenectomy remains controversial. Though gastrectomy with extended lymphadenectomy beyond D2 is classified as a non-standard gastrectomy, its clinical significance has been evaluated in many studies. Although hard evidence is lacking, D2 plus superior mesenteric vein (No. 14v) LN dissection is recommended when harbor metastasis to No. 6 nodes is suspected in the lower stomach, and dissection of splenic hilar (No. 10) LN can be performed for advanced GC invading the greater curvature of the upper stomach, and D2 plus posterior surface of the pancreatic head (No. 13) LN dissection may be an option in a potentially curative gastrectomy for cancer invading the duodenum. Prophylactic D2+ para-aortic nodal dissection (PAND) was not routinely recommended for advanced GC patients, but therapeutic D2 plus PAND may offer a chance of cure in selected patients, preoperative chemotherapy was considered as the standard treatment for GC with para-aortic node metastasis. There has been no consensus on the extent of lymphadenectomy for the adenocarcinoma of the esophagogastric junction (AEG) so far. The length of esophageal invasion can be used as a reference point for mediastinal LN metastases, and the distance from the esophagogastric junction to the distal end of the tumor is essential for determining the optimal extent of resection. The quality of lymphadenectomy may influence prognosis in GC patients. Both hospital volume and surgeon volume were important factors for the quality of radical gastrectomy. Centralization of GC surgery may be needed to improve prognosis.     

Laparoscopic gastrectomy with lymph node dissection for gastric cancer

Since 1991, laparoscopic surgery has been adopted for the treatment of gastric cancer, and it has been performed worldwide, especially in Japan and Korea. We reviewed the English-language literature to clarify the current status of and problems associated with laparoscopic gastrectomy with lymph node dissection as treatment for gastric cancer. In Japan, early-stage gastric cancer (T1/T2, N0) is considered the only indication for laparoscopic gastrectomy. As yet, there is little high-level evidence based on long-term outcome supporting laparoscopic gastrectomy for cancer, but reports have provided level 3 evidence that the procedure is technically safe, and that it yields better short-term outcomes than open surgery; that is, recovery is faster, hospital stay is shorter, there is less pain, and cosmesis is better. However, investigation into the oncological outcome of laparoscopic gastrectomy as treatment for cancer is lacking. To establish laparoscopic surgery as a standard treatment for gastric cancer, multicenter randomized controlled trials to compare the short- and long-term outcomes of laparoscopic surgery versus open surgery are necessary.     

Body mass index predicts the incidence of radiation pneumonitis in breast cancer patients

In patients receiving breast radiotherapy, the risk of radiation pneumonitis has been associated with the volume of irradiated lung, and concomitant methotrexate, paclitaxel, and tamoxifen therapy. Many of the studies of radiation pneumonitis are based on estimates of pulmonary risk using central lung distance that is calculated using two-dimensional techniques. With the treatment of internal mammary nodes and three-dimensional treatment planning for breast cancer becoming increasingly more common, there is a need to further consider the impact of dose-volume metrics in assessing radiation pneumonitis risk. We herein present a case control study assessing the impact of clinical and dose-volume metrics on the development of radiation pneumonitis in patients receiving sequential chemotherapy and local-regional radiotherapy.     

Genomic profiling of gastric cancer predicts lymph node status and survival

Gastric carcinogenesis is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. We analysed the patterns of chromosomal instability in 35 gastric carcinomas and their clinical correlations. With microarray competitive genomic hybridization, genomewide chromosomal copy number changes can be studied with high resolution and sensitivity. A genomewide scanning array with 2275 BAC and P1 clones spotted in triplicate was used. This array provided an average resolution of 1.4 Mb across the genome. Patterns of chromosomal aberrations were analysed by hierarchical cluster analysis of the normalized log(2) tumour to normal fluorescence ratios of all clones, and cluster membership was correlated to clinicopathological data including survival. Hierarchical cluster analysis revealed three groups with different genomic profiles that correlated significantly with lymph node status (P=0.02). Moreover, gastric cancer cases from cluster 3 showed a significantly better prognosis than those from clusters 1 and 2 (P=0.02). Genomic profiling of gastric adenocarcinomas based on microarray analysis of chromosomal copy number changes predicted lymph node status and survival. The possibility to discriminate between patients with a high risk of lymph node metastasis could clinically be helpful for selecting patients for extended lymph node resection.     

胃癌淋巴结转移枚数与手术后放射治疗效果的相关性

目的探讨分析胃癌淋巴结转移枚数与术后放疗疗效及相应病理检查结果的相关性。方法 2006年5月至2008年5月收治的胃癌患者,均行胃癌根治性手术治疗,术后诊断为胃癌伴淋巴结转移的患者214例。所有组内淋巴结转移行D2或D3式清扫,且治疗前后均予以放射治疗。结果胃癌患者淋巴结转移枚数与性别、年龄等一般因素无关系,而与肿瘤大小、浸润深度及分期呈正相关。淋巴结转移1⁵个、65个、6⁹个及>9个的胃癌患者,其术后及放疗后5年生存率分别为50%、30%和<10%,三者之间差异有统计学意义(P<0.05)。结论胃癌患者胃周阳性淋巴结转移数与预后有关,结合肿瘤大小及生长浸润方式可以简便而准确地判断胃癌术后患者的预后情况。     

Sentinel lymph node biopsy and axillary lymph node dissection

Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. A combination of dye- and gamma probe-guided methods can identify SLN more accurately and easily than either of these techniques alone. On the other hand, SLN biopsy is highly accurate and sensitive in patients with small tumors, and no false-negative SLN biopsy has been reported for a breast cancer < 1.0-1.5 cm. Moreover, extensive intraoperative examination of SLNs using frozen sections can attain a sensitivity comparable to that obtained by histologic examination on the permanent sections. In practice, therefore, axillary dissection can be avoided in patients with small tumors in whom the SLNs are negative.     

Quality control of lymph node dissection in the Dutch randomized trial of D1 and D2 lymph node dissection for gastric cancer

Background. Variability among surgeons and reduced protocol adherence threaten the conduct and outcome of surgical multicenter trials. We introduced, in the Dutch Gastric Cancer Trial of D1 and D2 (extended) lymph node dissection for gastric cancer, a novel way of managing instruction, quality control, and evaluation of protocol adherence. Methods. Of 1078 patients entered in the Dutch trial, 711 patients with potentially curative resections were evaluated. Numbers and locations of lymph nodes detected at pathological investigation were compared according to the guidelines of the Japanese Research Society for the Study of Gastric Carcer. Non-compliance indicated inadequate removal of lymph node stations, whereas contamination indicated that lymph nodes were detected outside the intended level of dissection. Protocol adherence during the course of the trial, and the impact on complications, hospital mortality, and survival were evaluated. Results. Major non-compliance was noted in 15.3% of D1 and 25.9% of D2 patients. Contamination was present in 22.9% of D1 and 23.5% of D2 patients, and was limited to one or two lymph node stations only. Intensification of quality control resulted in only a marginal improvement in protocol adherence and in the number of lymph nodes detected. There was no association between protocol adherence and the occurrence of complications or long term survival. Conclusions. Contamination proved an important parameter to substantiate protocol adherence by the surgeon, whereas non-compliance had a multifactorial cause. Non-adherence to the protocol did not lead to increased hospital morbidity and mortality, but also had no impact on long term survival. Received for publication on Aug. 17, 1998; accepted on Nov. 12, 1998     

甲状腺乳头状癌颈部淋巴结转移特点及清扫策略

背景与目的：目前,在甲状腺癌颈淋巴结清扫方面存有较大分歧。该研究总结甲状腺乳头状癌淋巴结转移的特点,为择区淋巴结清扫提供理论依据。方法：回顾性分析2006年7月—2014年8月收治的462例甲状腺乳头状癌患者病历资料,分析其淋巴结转移规律及其影响因素,评判cN0标准的准确性。结果：全组患者均行患侧中央区(Ⅵ区)淋巴结清扫,320例行侧颈区淋巴结清扫术(Ⅱ～Ⅴ区)或择区淋巴结清扫(Ⅱ～Ⅳ区中的部分或全部),90例行对侧中央区淋巴结活检。73.2%(338/462)符合cN0标准,病理证实其中有184例淋巴结转移,cN0标准误诊率达60.9%。颈部淋巴结总转移率为65.4%(302/462),侧颈区淋巴结转移率为42.6%(197/462),“跳跃转移”率为13.1%(42/320),对侧中央区淋巴结转移率为50%(45/90)。男性、肿瘤累及腺叶上1/3、肿瘤T3或T4、多中心病灶是淋巴结转移的危险因素。肿瘤累及腺叶上1/3是喉前淋巴结转移及“跳跃转移”的危险因素。喉前淋巴结转移及中央区淋巴结2个以上转移者侧颈区淋巴结转移率显著增加(分别为85.7%和83.3%, P＜0.05)。结论：现行cN0标准不能作为确定淋巴结清扫范围的依据;甲状腺乳头状癌易发生淋巴结转移,其中Ⅵ区淋巴结转移率最高,依次为Ⅲ区、Ⅱ区、Ⅳ区、Ⅴ区;初次手术应常规清扫患侧中央区淋巴结,建议将Ⅵ区淋巴结送冰冻病理;当喉前淋巴结有转移或Ⅵ区2个以上淋巴结转移时,或肿瘤累及腺叶上1/3者,有必要行侧颈区(或择区)淋巴结清扫;对侧中央区淋巴结转移率较高,需予以重视;中央区淋巴结再分亚区具有重要意义,应深入研究。     

胃癌行腹主动脉旁淋巴结清扫的研究进展

手术治疗是治疗胃癌的主要方式之一,标准的术中淋巴结清扫尤为重要。关于胃癌患者是否行腹主动脉旁淋巴结清扫（para-aortic lymph node dissection,PAND）仍存在争议。预防性PAND的意义被否定,但治疗性PAND的效果还有待进一步的研究去证实。术前化疗联合规范的手术治疗可能是未来进展期胃癌伴腹主动脉旁淋巴结转移的标准治疗模式。本文就胃癌行PAND的研究进行综述,以期为临床实践提供指导。      

Predictors of outcome in patients undergoing postchemotherapy retroperitoneal lymph node dissection for testicular cancer

BACKGROUND: The management of metastatic nonseminomatous germ cell tumors (NSGCT) frequently consists of systemic chemotherapy followed by retroperitoneal lymph node dissection (PC-RPLND). The aim of the present study was to evaluate the authors' PC-RPLND experience and identify predictors of outcome in these patients. METHODS: Between 1980 and 2003, 236 patients with clinical Stage IIA-III NSGCT underwent PC-RPLND. Their medical records were retrospectively reviewed for pertinent clinical and treatment-related outcomes. The 5-year disease-specific and recurrence-free survival was 85% and 75%, respectively, with the median length of follow-up after RPLND 45 months (6-250 months). RESULTS: The median age of patients at diagnosis was 28 years, with all patients receiving systemic chemotherapy (median of 5 cycles) before RPLND. On multivariate analysis, predictors of poorer disease-specific survival (DSS) included systemic symptoms at presentation (P = .05), elevated pre-RPLND serum alpha fetoprotein (AFP, P = .006) and beta-human chorionic gonadotropin (HCG, P = .004), postoperative complications (P = .03), and recurrence (P < .0001). Predictors of poorer recurrence-free survival (RFS) included advanced clinical stage (IIC-III, P = .001) and presence of viable tumor in the RPLND specimen (P = .03). A pre-RPLND serum AFP > 9 ng/mL and HCG > 4.1 mIU/mL were found to predict a worse DSS (P = .03 and .03, respectively). CONCLUSIONS: In patients undergoing PC-RPLND, preoperative tumor markers and the occurrence of postoperative complications or recurrence are predictive of poorer DSS. Advanced clinical stage and viable tumor in the surgical specimen predict worse RFS.     

Radiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications

Adjuvant radiation treatment following lymph node dissection in the melanoma patient has been suggested and investigated in an attempt to gain regional control and improve survival. In this review we discussed the treatment, the loco-regional control, disease-free and survival rates and complications. Historically melanoma has been thought of as a relatively radioresistant tumour. Nowadays, radiation delivered according to the hypofractionated schedule is the most used, although there are no data to confirm that this schedule improves the therapeutic impact. Almost all the reviewed studies were retrospective, which could have led to an underestimation of the true incidence of the treatment toxicity and morbidity. Adjuvant radiotherapy after lymph node dissection for metastases of melanoma seems to improve loco-regional control without improving overall survival. The available data indicate the need for improved regional control rates in patients with extranodal extension, multiple involved nodes (more than three) and patients with large involved nodes (larger than 3 cm). The complications seem manageable and consist mainly of fibrosis and edema.