Can we triumph over locally advanced cervical cancer with colossal para-aortic lymph nodes? A case report

BACKGROUND Para-aortic lymph nodes(PALNs)are common sites for the regional spread of cervical squamous cell carcinoma(SCC).CASE SUMMARY We report the case of a 36-year-old woman who presented with cervical SCC with multiple bulky PALNs,largest measured 4.5 cm×5 cm×10 cm.The patient was treated with radical intent with definitive chemoradiation using sequential doseescalated adaptive radiotherapy,followed by maintenance chemotherapy.The patient achieved a complete response;she has been doing well since the completion of treatment with no evidence of the disease for 2 years.CONCLUSION Regardless of the size of PALN metastases of cervical carcinoma origin,it is still treatable(with radical intent)via concurrent chemoradiation.Adaptive radiotherapy allows dose escalation with minimal toxicity.

Role of D2 gastrectomy in gastric cancer with clinical para-aortic lymph node metastasis

BACKGROUND Owing to the technical difficulty of pathological diagnosis, imaging is still the most commonly used method for clinical diagnosis of para-aortic lymph node metastasis(PALM) and evaluation of therapeutic effects in gastric cancer, which leads to inevitable false-positive findings in imaging. Patients with clinical PALM may have entirely different pathological stages(stage IV or not), which require completely different treatment strategies. There is no consensus on whether surgical intervention should be implemented for this group of patients. In particular, the value of D2 gastrectomy in a multidisciplinary treatment(MDT)approach for advanced gastric cancer with clinical PALM remains unknown.AIM To investigate the value of D2 gastrectomy in a MDT approach for gastric cancer patients with clinical PALM.METHODS In this real-world study, clinico-pathological data of all gastric cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2011 and 2016 were reviewed to identify those with clinically enlarged PALM. All the clinico-pathological data were prospectively documented in the patient medical record. For all the gastric cancer patients with advanced stage disease,especially those with suspicious distant metastasis, the treatment methods were determined by a multidisciplinary team.RESULTS In total, 48 of 7077 primary gastric cancer patients were diagnosed as having clinical PALM without other distant metastases. All 48 patients received chemotherapy as the initial treatment. Complete or partial response was observed in 39.6%(19/48) of patients in overall and 52.1%(25/48) of patients in the primary tumor. Complete response of PALM was observed in 50.0%(24/48)of patients. After chemotherapy, 45.8%(22/48) of patients received D2 gastrectomy, and 12.5%(6/48) of patients received additional radiotherapy. The postoperative major complication rate and mortality were 27.3%(6/22) and 4.5%(1/22), respectively. The median overall survival and progression-free survival of all the patients were 18.9 and 12.1 mo, respectively. The median overall survival of patients who underwent surgical resection or not was 50.7 and 12.8 mo,respectively. The 3-year and 5-year survival rates were 56.8% and 47.3%,respectively, for patients who underwent D2 resection. Limited PALM and complete response of PALM after chemotherapy were identified as favorable factors for D2 gastrectomy.CONCLUSION For gastric cancer patients with radiologically suspicious PALM that responds well to chemotherapy, D2 gastrectomy could be a safe and effective treatment and should be adopted in a MDT approach for gastric cancer with clinical PALM.

CA19-9 level determines therapeutic modality in pancreatic cancer patients with para-aortic lymph node metastasis

Background: In general, para-aortic lymph node(LN16) metastasis has been considered as a contraindication for pancreatic resection. However, some pancreatic cancer patients with LN16 metastasis have been reported to survive for longer than expected after pancreatectomy. The purpose of this study was to determine whether pancreatic cancer patients with LN16 metastasis might benefit from surgery.Methods: We retrospectively reviewed 201 consecutive patients with invasive pancreatic ductal adenocarcinoma who underwent surgery at Osaka National Hospital between April 2003 and December 2012.These patients included 22 patients with LN16 metastasis who underwent an extended lymphadenectomy and 25 patients who underwent a palliative surgical biliary and gastric bypass. The clinicopathological data and outcomes were evaluated using univariate and multivariate analyses.Results: The overall survival of the patients with LN16 metastasis was poorer than that of the LN16-negative patients(P = 0.0014). An overall survival analysis of the LN16-positive patients stratified according to the preoperative CA19-9 level showed a significant difference between patients with a low preoperative CA19-9 level(≤360 U/mL) and those with a high preoperative CA19-9 level(>360 U/mL)(P = 0.0301). No significant difference in overall survival of patients was observed between those with LN16 positivity and those who underwent bypass surgery. However, the overall survival of the LN16-positive patients with a CA19-9 level ≤360 U/mL(n = 11) was significantly higher than that of those who underwent bypass surgery(P = 0.0452).Conclusion: Surgical resection and extended lymphadenectomy remains an option for pancreatic cancer patients with LN16-positivity whose CA19-9 level is ≤360 U/mL.

Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma

BACKGROUND Para-aortic lymph nodes(PALN)are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma(PDAC).The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis,while others not sharing the same results.PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases.AIM To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC.METHODS This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020.Statistical comparison of the data between PALN+and PALN-subgroups,survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed,specifically assessing oncological outcomes such as median overall survival(OS)and disease-free survival(DFS).RESULTS 81 cases had PALN sampling and 17(21%)were positive.Pathological N stage was significantly different between PALN+and PALN-patients(P=0.005),while no difference was observed in any of the other characteristics.Preoperative imaging diagnosed PALN positivity in one case.OS and DFS were comparable between PALN+and PALN-patients with lymph node positive disease(OS:13.2 mo vs 18.8 mo,P=0.161;DFS:13 mo vs 16.4 mo,P=0.179).No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting(OS:23.4 mo vs 20.6 mo,P=0.192;DFS:23.9 mo vs 20.5 mo,P=0.718).On the contrary,when patients did not receive chemotherapy,PALN disease had substantially shorter OS(5.5 mo vs 14.2 mo;P=0.015)and DFS(4.4 mo vs 9.8 mo;P<0.001).PALN involvement was not identified as an independent predictor for OS after multivariable analysis,while it was for DFS doubling the risk of recurrence.CONCLUSION PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC,surgery and chemotherapy,and should not be considered as a contraindication to resection.

Thoracic para-aortic lymph node recurrence in patients with esophageal squamous cell carcinoma:A propensity score-matching analysis

BACKGROUND Thoracic para-aortic lymph node(TPLN)recurrence in esophageal squamous cell carcinoma(ESCC)is rare and its impact on survival is unknown.We studied survival in patients with ESCC who developed TPLN recurrence.AIM To study the survival in patients with ESCC who developed TPLNs recurrence.METHODS Data were collected retrospectively for 219 patients who had undergone curative surgery for ESCC during January 2012 to November 2017 and who developed recurrences(36.29%of 604 patients who had undergone curative surgeries for ESCC).The patients were classified into positive(+)and negative(-)TPLN metastasis subgroups.We also investigated TPLN recurrence in 223 patients with ESCC following definitive chemoradiotherapy during 2012-2013.Following propensity score matching(PSM)and survival estimation,factors predictive of overall survival(OS)were explored using a Cox proportional hazards model.RESULTS Among the patients with confirmed recurrence,18 were TPLN(+)and 13 developed synchronous distant metastases.Before PSM,TPLN(+)was associated with worse recurrence-free(P=0.00049)and OS[vs TPLN(-);P=0.0027],whereas only the intergroup difference in recurrence-free survival remained significant after PSM(P=0.013).The Cox analysis yielded similar results.Among the patients who had received definitive chemoradiotherapy,3(1.35%)had preoperative TPLN enlargement and none had developed recurrences.CONCLUSION TPLN metastasis is rare but may be associated with poor survival.

Effectiveness of intraoperative ultrasonography for para-aortic lymph nodes in preventing unnecessary lymphadenectomy in ovarian carcinoma

Objective: To evaluate the usefulness of intraoperative ultrasonography (IU) for para-aortic nodes to identify women who do not require pelvic and paraaortic lymphadenectomy in ovarian carcinoma. Methods: Computed tomography (CT) was used for assessing both pelvic and para-aortic lymph nodes, and IU only for para-aortic nodes in 87 women with ovarian carcinoma. All women underwent surgery with routine systematic pelvic and para-aortic lymphadenectomy. We assumed that no lymphadenectomy had been performed when no enlarged node was detected by either CT or IU or when the woman was in T1 stage. Under these assumptions, the numbers of women who would have had missed metastases and who could have avoided lymphadenectomy were counted. These figures were recounted on the combination of T stage and IU. Results: A total of 22 women had pathological node metastases. The numbers of women with missed metastases on the basis of CT, IU, and T stage were 12, 2, 5, and these who could have avoided lymphadenectomy were 72, 39, and 49, respectively. There were more women avoiding lymphadenectomy by CT than IU and T stage;however, more women with missed node metastases. Both numbers were not significantly different between IU and T stage. On the combination of T stage and IU, 29 of 49 women in T1 stage could have avoided lymphadenectomy without missed metastases. Conclusions: IU for the para-aortic node is a useful method for identifying women who do not require lymphadenectomy for T1 stage ovarian carcinoma.

Para-aortic node involvement is not an independent predictor of survival after resection for pancreatic cancer

To analyze the importance of para-aortic node status in a series of patients who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODSBetween January 2000 and December 2012, 151 patients underwent PD with para-aortic node dissection for pancreatic adenocarcinoma in our Institution. Patients were divided into two groups: patients with negative PALNs (PALNs-), and patients with metastatic PALNs (PALNs+). Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of para-aortic nodes, tumor’s grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as P < 0.05. RESULTSA total of 107 patients (74%) had nodal metastases. Median number of pathologically assessed lymph nodes was 26 (range 14-63). Twenty-five patients (16.5%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred forty-one patients recurred and died for tumor recurrence, one is alive with recurrence, and 9 are alive and free of disease. Overall survival was significantly influenced by grading (P = 0.0001), radicality of resection (P = 0.001), stage (P = 0.03), lymph node status (P = 0.04), para-aortic nodes metastases (P = 0.02). Multivariate analysis showed that grading was an independent prognostic factor for overall survival (P = 0.0001), while grading (P = 0.0001) and radicality of resection (P = 0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. CONCLUSIONIn this experience, lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, but they were not independent prognostic factors.

Advances in para-aortic nodal dissection in gastric cancer surgery: A review of research progress over the last decade

Approximately 17%-40%of para-aortic lymph node(PAN)metastasis occurs in patients with advanced gastric cancer.As the third tier of lymphatic drainage of the stomach and the final station in front of the systemic circulation,PAN infiltration is defined as distant metastasis and plays a key role in the evaluation of the prognosis of advanced gastric cancer.Many clinical factors including tumor size≥5 cm,pT3 or pT4 depth of tumor invasion,pN2 and pN3 stages,the macroscopic type of Borrmann Ⅲ/Ⅳ,and the diffuse/mixed Lauren classification are indicators of PAN metastasis.Whether PAN dissection(PAND)should be performed on patients with or without the macroscopic PAN invasion remains unascertained,regardless of the numerous retrospective comparative studies reported on the improved prognosis over D2 alone.Another paradoxical result from many other studies showed no significant difference in the overall survival between these two lymphadenectomies.A phase Ⅱ trial launched by the Japan Clinical Oncology Group indicated that two or three courses of S-1 and cisplatin preoperatively followed by radical surgery with D2+PAND and postoperative S-1 is the current standard strategy for the treatment of patients with extensive lymph node metastasis,and this regimen could be substituted by a promising strategy with effective combination chemotherapy or suitable chemotherapy duration.This review focuses on the advances in radical gastrectomy plus PAND with or without chemotherapy for patients with advanced gastric cancer.

Prognostic value of para-aortic lymph node metastasis and dissection for pancreatic head ductal adenocarcinoma: a retrospective cohort study

Background:Para-aortic lymph node(PALN)metastasis affects approximately 20%of patients with pancreatic ductal adenocarcinoma(PDAC).However,the prognostic significance of PALN metastases and dissection remains unclear.Methods:This retrospective cohort study included patients with PDAC of the pancreatic head who had undergone pancreaticoduodenectomy(PD)at our center between January 2017 and December 2020.Results:A total of 234 patients were included in the study.PALN dissection improved the median overall survival(OS)without statistical significance(24.1 vs 18.1 months,P=.156).The median recurrence-free survival was significantly longer in the PALN-dissection group than the group without PALN dissection(18.2 vs 11.6 months,P=.040).Conversely,there were no significant differences in the long-term prognosis between the PALN-positive and PALN-negative subgroups in the PALN-dissection group.Multivariate analysis showed that PALN metastasis was not an independent risk factor for OS(hazard ratio:0.831,95%confidence interval:0.538–1.285,P=.406).Conclusions:For patients with pancreatic head ductal adenocarcinoma,PD with PALN dissection may achieve survival prolongation and bridge the survival gap between patients with and without PALN metastasis without significantly increasing the perioperative risks.

Clinical significance of para-aortic lymph node dissection and prognosis in ovarian cancer

Lymph node metastasis has an important effect on prognosis of patients with ovarian cancer. Moreover, the impact of para-aortic lymph node （PAN） removal on patient prognosis is still unclear. In this study, 80 patients were divided into groups A and B. Group A consisted of 30 patients who underwent PAN ＋ pelvic lymph node （PLN） dissection, whereas group B consisted of 50 patients who only underwent PLN dissection. Analysis of the correlation between PAN clearance and prognosis in epithelial ovarian cancer was conducted. Nineteen cases of lymph node metastasis were found in group A, among whom seven cases were positive for PAN, three cases for PLN, and nine cases for both PAN and PLN. In group B, 13 cases were positive for lymph node metastasis. Our study suggested that the metastatic rate of lymph node is 40.0%. Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type both in groups A and B （P 〈 0.05）. In groups A and B, the three-year survival rates were 77.9% and 69.0%, and the five-year survival rates were 46.7% and 39.2%, respectively. However, the difference was not statistically significant （P 〉 0.05）. The three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively. Furthermore, PLN-positive patients who cleared PAN had significantly higher survival rate （P = 0.044）. In group A, the three-year survival rates of positive and negative lymph nodes were 43.5% and 72.7%, and the five-year survival rates were 27.2% and 58.5%, respectively. The difference was statistically significant （P= 0.048）. Cox model analysis of single factor suggested that lymph node status affected the survival rate （P 〈 0.01）, which was the death risk factor. Consequently, in ovarian carcinoma cytoreductive surgery, resection of the para-aortic lymph node, which has an important function in clinical treatment and prognosis of patients with ovarian cancer, is necessary.

不同模式治疗食管癌术后颈部淋巴结寡转移患者预后分析的真实世界研究

目的探讨不同模式治疗食管癌术后颈部淋巴结寡转移患者的预后情况.方法采用回顾性队列研究方法.收集2007年5月至2023年6月中山大学肿瘤防治中心收治的5692例食管癌患者的临床病理资料;男4473例,女1219例;年龄为61(55~66)岁.5692例患者中,127例发生颈部淋巴结寡转移,其中23例行单纯手术治疗,设为单纯手术组;74例行放疗、化疗或放化疗,设为放化疗组;30例行手术联合放疗、化疗或放化疗,设为联合治疗组.偏态分布的计量资料以M(范围)表示.计数资料以绝对数或百分比表示,组间比较采用χ^(2)检验或Fisher确切概率法.基线资料差异采用逆概率加权法(IPTW)进行校正.采用X-tile软件(v3.6.1)确定预后最佳截断值.中位随访时间采用逆Kaplan-Meier法计算,数据缺失值采用多重插补法处理.采用Kaplan-Meier法绘制生存曲线,Log-rank检验进行生存分析.单因素和多因素分析采用COX比例风险回归模型,将单因素分析中P<0.2的临床病理因素纳入多因素分析.结果(1)生存情况.127例患者的中位随访时间为47个月,中位无进展生存时间为31个月,中位总生存时间为53个月;1、3、5年无进展生存率分别为61.5%、43.0%、36.5%,1、3、5年总生存率分别为85.6%、60.2%、45.7%.IPTW校正后,单纯手术组、放化疗组、联合治疗组患者中位无进展生存时间分别为55、23、61个月;单纯手术组患者1、3、5年无进展生存率分别为72.9%、69.7%、43.6%,放化疗组患者分别为61.1%、37.3%、32.6%,联合治疗组患者分别为60.9%、52.9%、52.9%,3组患者无进展生存率比较,差异无统计学意义(χ^(2)=0.34,P>0.05).单纯手术组、放化疗组、联合治疗组患者中位总生存时间分别为未达到、60、45个月;单纯手术组患者1、3、5年总生存率分别为87.6%、82.0%、55.1%,放化疗组患者分别为91.3%、57.4%、46.8%,联合治疗组患者分别为87.1%、64.3%、32.2%,3组患者总生存率比较,差异无统计学意义(χ^(2)=0.10,P>0.05).(2)预后分析.IPTW校正后,多因素分析结果显示:有合并症、行新辅助治疗是影响颈部淋巴结寡转移患者无进展生存时间的独立危险因素(风险比=2.25,2.74,95%可信区间为1.08~5.65,1.49~5.06,P<0.05),行新辅助治疗、寡转移时间≤24个月是影响颈部淋巴结寡转移患者总生存时间的独立危险因素(风险比=2.85,2.08,95%可信区间为1.52~5.34,1.04~4.17,P<0.05).进一步分析,行新辅助治疗与未行新辅助治疗患者1、3、5年总生存率分别为83.7%、35.3%、16.4%和91.6%、72.6%、56.2%,两者比较,差异有统计学意义(χ^(2)=9.26,P<0.05);寡转移时间≤24个月和>24个月患者1、3、5年总生存率分别为84.9%、53.9%、40.1%和97.8%、80.5%、59.9%,两者比较,差异有统计学意义(χ^(2)=9.20,P<0.05).结论单纯手术治疗、放化疗、联合治疗食管癌术后颈部淋巴结寡转移患者预后无差异;有合并症是影响颈部淋巴结寡转移患者无进展生存时间的独立危险因素,寡转移时间≤24个月是影响颈部淋巴结寡转移患者总生存时间的独立危险因素,行新辅助治疗是影响颈部淋巴结寡转移患者无进展生存时间和总生存时间的独立危险因素;未行新辅助治疗、寡转移时间>24个月患者预后更佳.

结直肠癌肝脏、腹主动脉旁淋巴结寡转移的MDT策略

结直肠癌是最常见的恶性肿瘤之一,发病率和死亡率均居所有肿瘤前列。转移是结直肠癌预后不佳的主要因素之一,其常见转移部位为肝、肺及淋巴结系统等,其中肝脏是结直肠癌血行转移最主要的靶器官之一。针对结直肠癌转移病灶,多学科综合诊疗(MDT),是治疗的最佳选择。而随着多学科诊疗的进展,结直肠癌"寡转移"逐渐被提出,寡转移是指肿瘤生物侵袭性较温和的一段时期,存在于局限性原发灶与广泛性转移之间的过渡阶段,转移瘤的数量有限且转移器官具有特异性。本文通过对2例结直肠癌同时性肝脏寡转移患者(其中一例伴同时性腹主动脉旁淋巴结转移)MDT治疗策略的分析与文献复习,就结直肠癌肝脏及孤立的腹主动脉旁淋巴结(PALN)寡转移的概念及诊治进展做一综述。

Recent trends from the results of clinical trials on gastric cancer surgery

The Japan Clinical Oncology Group has recently conducted large scale clinical trials with findings that have revealed pivotal strategies for the treatment of resectable gastric cancer surgery.These findings include the fact that D3 lymphadenectomy does not improve survival rates when compared to D2 lymphadenectomy,and it is not recommended for resectable gastric cancer.Also,a transhiatal approach is recommended,instead of the left thoraco-abdominal approach,for the treatment of adenocarcinoma of the esophago-gastric junction or gastric cardia which has invaded≤3 cm of the esophagus.Gastrectomy with splenectomy and bursectomy had been recommended as a part of the D2 lymphadenectomy.However,the results of the recent clinical trials revealed that splenectomy should be avoided in total gastrectomy with D2 lymphadenectomy for proximal gastric cancer and that bursectomy should be avoided in gastrectomy with D2 lymphadenectomy for resectable gastric cancer.Both splenectomy and bursec-tomy were found to be unable to improve survival,but instead increased operative morbidity.These trials revealed that the above-mentioned invasive and aggressive procedures did not provide sufficient survival benefits and that gastric cancer surgery may be trending from an“invasive to less invasive”and“aggressive to more conservative”approach.

Treatment strategy for metastatic gastric cancer in Japan

Despite recent progress in diagnostic imaging,gastric cancer(GC)is occasionally found at an advanced stage with distant metastasis.As metastatic GC is difficult to cure,the treatment strategy should be considered individually based on the physical and socioeconomic status of patients as well as on the GC symptoms.The first choice of treatment for metastatic GC is chemotherapy,and several chemotherapeutic regimens for metastatic or recurrent GC have been developed through randomized controlled trials.Ongoing clinical trials will provide novel therapeutic options for patients with metastatic GC in the near future,while individualization of treatment based on detailed molecular information,so-called precision medicine,is eagerly anticipated.In this article,we review recent publications and guidelines focusing on recent progress in the treatment of metastatic GC in Japan.