卵巢癌术后腹腔和静脉联合化疗的可行性

目的:探讨手术后用腹腔联合静脉化疗对卵巢癌治疗的可行性。方法:将卵巢上皮性癌88例分为两组:①联合化疗组:腹腔用药及静脉联合用药组,45例,Ⅰ/Ⅱ期21例(23.86%),Ⅲ/Ⅳ期24例(27.27%),在术中置入腹腔化疗管,术后每周1次腹腔化疗,用顺铂(DDP)与氟尿嘧啶(5-FU)为主加丝裂霉素C(MMC)或消瘤芥(AT-1258)的一种,共用3次。以后用静脉化疗,同静脉化疗组方案;②静脉化疗组(静脉用药组):43例,化疗方案为CAP,每3周一次,Ⅰ/Ⅱ期24例(27.27%),Ⅲ/Ⅳ期19例(21.59%)。结果:联合化疗组与静脉化疗组的患者在第3及6疗程结束后CA125下降程度Ⅰ/Ⅱ期与Ⅲ/Ⅳ期分别比较,差异有显著性(P值均<0.05)。第3疗程治疗后CA125>35u/ml的患者与CA125<35u/ml的患者3年生存率用Log Rank检验,差异有显著性(P<0.05)。联合化疗组与静脉化疗组的Ⅰ/Ⅱ期平均生存期分别为(35.05±0.54)、(32.38±1.19)个月,联合化疗组与静脉化疗组的Ⅲ/Ⅳ期平均生存期分别为(31.33±1.41)、(28.26±1.88)个月。联合化疗组与静脉化疗组Ⅰ/Ⅱ期3年生存率用Log Rank检验,两组差异无显著性(P值为0.156);联合化疗组与静脉化疗组Ⅲ/Ⅳ期3年生存率用LogRank检验,两组差异无显著性(P值为0.08)。有腹水70例的患者中联合化疗组3年生存率与静脉化疗组相比较,差异有显著性(P<0.05)。结论:术后用腹腔联合静脉化疗对卵巢癌治疗,可使血清CA125下降较明显,差异有显著性。3个疗程治疗后血清CA125<35u/ml与CA125>35u/ml的患者3年生存率差异有显著性。虽然术后联合化疗组与静脉化疗组相比较3年生存率差异无显著性,但是腹腔联合静脉化疗平均生存期较长。有腹水的患者经腹腔联合化疗3年生存率与单纯的静脉化疗相比较差异有显著性,故腹腔联合静脉化疗适用于有腹水及腹腔有转移灶的卵巢癌患者。     

中医药治疗肺癌对患者血清CA-125的影响

背景与目的:CA-125已经是公认的卵巢癌标志物,在长期的临床观察中发现血清CA-125在肺癌诊治中具有一定的诊断及判定预后的价值.本研究探讨中医药治疗术后与不能切除肿瘤的肺癌患者时对血清CA-125的影响;同时探讨血清CA-125与肺癌临床分期及病理学类型相关性.方法:用微粒学酶免分析法检测30例健康人及60例肺癌患者中医综合治疗方案治疗前后血清CA-125水平,并作对比分析.结果:血清CA-125在肺癌患者的值(91±45)与健康人(18±5)相比,差异有非常显著性,(P＜0.001),血清CA-125在ⅢA/ⅢB及Ⅳ期肺癌患者中值分别为85±21及142±25,与Ⅰ/Ⅱ期患者的35±11相比,差异有非常显著性(P＜0.001)肺腺癌患者CA-125水平(127±31)与鳞癌(58±27)及小细胞癌(56±26)相比,差异有非常显著性(P＜0.001).ⅢA/ⅢB及Ⅳ期肺癌患者中医药综合治疗方案治疗后CA-125值分别为(36±11;87±15)于治疗前(85±21;142±25)相比,差异有非常显著性.(P＜0.001).但对于Ⅰ/Ⅱ期患者治疗后(33±10)与治疗前(35±11)相比,差异无显著性(P＞0.05).结论:中医药治疗肺癌,在Ⅲ/Ⅳ期的肺癌患者可显著的降低血清CA-125水平,在Ⅰ/Ⅱ期的肺癌患者也有明显的降低血清CA-125水平的趋势.血清CA-125水平与肺癌患者临床分期、病理类型有关.     

卵巢透明细胞癌血液学检验的临床意义

目的探讨卵巢透明细胞癌（OCCA）血液学检验结果的临床意义及其与预后的关系。方法回顾性分析1999年2月至2009年9月间我院收治的121例卵巢透明细胞癌患者的临床资料。结果中位发病年龄48岁（24～73岁）。FIGO分期：Ⅰ期57.0%（69/121）,Ⅱ期9.9%（12/121）,Ⅲ期30.6%（37/121）,Ⅳ期2.6%（3/121）。总的5年生存率（49.8%）：Ⅰ期68.7%,Ⅱ期76.4%,Ⅲ期13.9%,Ⅳ期0。初次治疗前、术后1周、化疗3程后及复发时CA125均值分别为（433.9±1051.3）U/ml、（162.9±327.0）U/ml、（20.3±40.5）U/ml和（317.0±1023.8）U/ml。初次治疗前CA125水平高于正常参考值者占87.2%（75/86）。初次治疗前CA19-9均值为（90.6±152.8）U/ml,高于正常参考值者占50.7%（34/67）;CEA均值为（3.6±9.4）ng/ml,高于正常参考值者占6.9%（2/29）;乳酸脱氢酶（LDH）均值（259.3±168.8）U/L,高于正常参考值者占35.9%（14/39）;血清钙均值（2.4±0.2）mmol/L,高于正常参考值者占9.8%（4/41）;血清铁均值（10.3±6.4）μmol/L,低于正常参考值者占35.1%（13/37）;血红蛋白（HGB）均值（123.7±17.4）g/L,低于正常参考值者占17.4%（4/23）。初次治疗前CA125水平≤1000U/ml组和〉1000U/ml组中位生存时间比较,差异有显著性（P=0.019）。化疗3程后CA125水平≤20U/ml组和〉20U/ml组中位生存时间比较,差异有显著性（P=0.002）。结论 OCCA血液学检验特点包括CA125及CA19-9升高、乳酸脱氢酶（LDH）升高、血钙升高、血清铁降低和血红蛋白（HGB）降低,初次治疗前和化疗3程后CA125水平可能与OC-CA的预后相关。     

88例卵巢透明细胞癌临床及预后分析

目的分析卵巢透明细胞癌的临床病理特点,探讨更有效的治疗方法和影响预后的因素。方法回顾性分析1984年1月至2005年5月收治的88例卵巢透明细胞癌患者的临床及随访资料。结果(1)43例患者术后给予以铂类为主的联合化疗,有效率为35.0%,复发率为67.4%,3、5年生存率分别为43.9%和29.3%;33例患者给予紫杉醇(PTX)联合铂类化疗,有效率为73.9%,复发率为45.5%,3、5年生存率分别为57.3%和40.5%;12例患者给予开普拓(CPT-11) 丝裂霉素(MMC)联合化疗,有效率为71.4%,复发率为25.0%,3年生存率为70.7%。(2)88例患者中,复发47例,复发率为53.4%。Ⅰ期患者总的复发率(45.4%)明显低于Ⅱ Ⅲ期患者(75.0%);Ⅰ期行淋巴结清扫术患者的复发率(27.8%)明显低于未行淋巴结清扫术者(51.3%);CA125升高患者的复发率(67.3%)明显高于CA125正常或不详者(38.1%)。(3)88例患者总的3、5年生存率分别为48.7%和40.9%。Ⅰ期患者总的3、5年生存率明显高于Ⅱ Ⅲ期患者(P<0.05);Ⅰ期行淋巴结清扫术患者的3、5年生存率明显高于未行淋巴结清扫术者(P<0.05);Ⅲ期术后残存肿瘤<2cm患者的3、5年生存率明显高于残存肿瘤≥2 cm的患者(P<0.05);CA125升高患者的3、5年生存率与CA125正常或不详者的差异无统计学意义(P>0.05)。结论卵巢透明细胞癌的预后较差,对以铂类为主的联合化疗可能更耐药;临床分期、是否行淋巴结清扫术以及化疗方案的选择等因素可能会影响预后。     

卵巢癌患者TPS与CA125测定

[目的]探讨卵巢上皮性癌患者组织多肽特异抗原(tissue polypeptide specificantigen,TPS)与CA125水平测定及其临床意义.[方法]采用ELISA法和EIA法分别检测96例卵巢上皮性癌患者和33例妇科良性疾病患者血清TPS与CA125水平并进行比较分析.[结果]Ⅲ Ⅳ期卵巢上皮性癌患者血清TPS和CA125平均水平及阳性率均高于Ⅰ Ⅱ期(P<0.05),治疗有效组TPS和CA125水平显著低于初诊未治组,而复发转移组TPS水平明显高于初诊未治组.[结论]TPS与CA125水平的联合检测对卵巢癌诊断、疗效及预后有临床应用价值.     

原发性卵巢透明细胞癌53例

目的:探讨卵巢透明细胞癌(OCCC)的临床特点及预后.方法:回顾性分析我院1995年1月～2005年12月53例原发性卵巢透明细胞癌患者临床资料,对其临床特点与治疗情况进行总结并分析其预后.结果:53例透明细胞癌占同期本院卵巢上皮癌的4.3%,根据FIGO分期,Ⅰ～Ⅱ期38例占71.70%,5年生存率36.84%,复发率30.23%;Ⅲ期患者15例,5年生存率28.67%,复发率46.67%.两者相比较有统计学差异(P=0.01).Ⅰ+Ⅱ期/Ⅲ期患者理想的肿瘤细胞减灭术5年生存率分别为40.00%/20.00%;不理想的肿瘤细胞减灭术5年生存率均为0,有统计学意义,P<0.05.紫杉醇联合铂类/传统铂类为主的化疗治疗有效率分别为33.33%/26.32%,两者相比较无统计学差异,P=0.10.术后联合放疗的患者5年生存率50.00%,与术后单纯化疗的患者相比差异有统计学意义,P=0.02.OCCC术后联合免疫治疗组与非联合组5年生存率比较无统计学意义(P=0.43),但2年及5年无疾病进展生存率(PFS)分别为80.00%/40.00%;25.00%/18.70%,两者相比较有统计学差异(P<0.02;P<0.05).是否合并子宫内膜异位症对生存率无统计学差异.结论:卵巢透明细胞癌以早期患者多见,易合并子宫内膜异位症,易复发,对化疗不敏感,预后差;紫杉醇联合铂类化疗有效率与传统铂类化疗相比较无明显差异;所有OCCC患者应行理想细胞减灭术,尤其对于早期患者尤为重要,术后联合放疗、免疫治疗,可望改善预后.     

卵巢上皮性癌FIGO 2013年分期和1988年分期比较研究

摘 要：［目的］ 探讨卵巢上皮性癌FIGO 2013年分期变化的合理性。［方法］ 选取536例卵巢上皮性癌患者初治病例,整理和分析其临床病理和随访资料,按照FIGO 2013年分期标准进行重新分期,通过比较各期5年生存率以评价2013年分期的合理性。［结果］ （1）2013年分期中,Ⅰ、Ⅱ、Ⅲ、Ⅳ期各期总体数量未发生变化,总体比较Ⅰ、Ⅱ、Ⅲ、Ⅳ期生存率有统计学差异。（2）1988年分期中,5年生存率分别为ⅠA期91.4%、ⅠB期84.2%、ⅠC期77.9%（P＜0.05）,Ⅰ期各亚期5年生存率差异有统计学意义;ⅡC期66.4%（ⅡA期仅4例、ⅡB期仅6例）;ⅢA期48.6%、ⅢB期43.2%、ⅢC期37.9%;Ⅳ期7.4%。（3）2013年分期中,5年生存率分别为ⅠA期91.4%、ⅠB期84.2%、ⅠC1期80.7%、ⅠC2期78.3%、ⅠC3期75.4%(P＜0.05);ⅠC1、ⅠC2、ⅠC3期之间5年生存率差异无统计学意义;ⅡA期74.4%、ⅡB期61.3%（P＜0.05）;ⅢA1期53.6%、ⅢA2期43.6%、ⅢB期38.2%、ⅢC期23.4%,ⅢA1、ⅢA2期5年生存率之间差异有统计学意义;ⅢA1、ⅢA2、ⅢB、ⅢC期之间5年生存率差异有统计学意义;ⅣA期15.6%、ⅣB期11.4%（P＞0.05）。［结论］ 1988年分期和2013年分期各期5年生存率从总体上比较有统计学差异,能够比较有效地区分各期预后的差别。2013年分期中的ⅠC期分为ⅠC1、ⅠC2、ⅠC3亚期并不能更好地评估预后。研究结果支持2013年分期中将ⅢA期分为ⅢA1、ⅢA2亚期。2013年分期将Ⅳ期分为ⅣA、ⅣB期似乎并不合理。     

卵巢透明细胞癌21例临床病理分析

[目的]探讨卵巢透明细胞癌的临床及病理特点。[方法]回顾性分析21例卵巢透明细胞癌患者的临床、病理特点及治疗和预后情况。[结果]术中发现有腹水且多脏器浸润。病理表现特征性的透明细胞和鞋钉细胞。免疫组化14例CK（＋），5例leu M1（＋），2例甲胎蛋白（＋），Vimentin均阴性。Ⅰ～Ⅱ期7例，2年及5年生存率为85．7％及57．1％，Ⅲ～Ⅳ期14例，2年及5年生存率则为57．1％及28．6％（P〈0．05），总的5年生存率为38．1％。[结论]卵巢透明细胞癌预后不良，手术和化疗为主要方式，放疗可以延长生存期。Ⅲ～Ⅳ期患者较Ⅰ～Ⅱ期预后更差。     

卵巢浆液性癌患者血清nidogen-2和糖类抗原125的检测及其临床意义

目的:探讨卵巢浆液性癌患者血清nidogen-2和糖类抗原125(carbohydrate antigen125,CA125)的检测及其临床意义。方法:应用ELISA法和化学发光法分别检测15例卵巢正常者、22例卵巢浆液性囊腺瘤患者和40例卵巢浆液性囊腺癌患者血清nidogen-2和CA125水平。结果:卵巢浆液性囊腺癌患者血清nidogen-2水平明显高于卵巢正常者和卵巢浆液性囊腺瘤患者(P<0.05),卵巢正常者和卵巢浆液性囊腺瘤患者血清nidogen-2水平无明显差异;Ⅲ～Ⅳ期卵巢浆液性囊腺癌患者的血清nidogen-2水平明显高于Ⅰ～Ⅱ期患者(P<0.05)。Nidogen-2和CA125联合检测可提高卵巢浆液性囊腺癌诊断的灵敏度和特异度。结论:Nidogen-2有望成为一种新的卵巢浆液性癌的标志物。     

CA125与TSGF联合检测在宫颈癌诊断中的应用

目的探讨糖类抗原125(CA125)、恶性肿瘤特异性生长因子(TSGF)测定对宫颈癌的诊断应用价值。方法采用CA125酶免试剂盒,TSGF快速诊断试剂盒对56例宫颈癌,其中Ⅰ、Ⅱ期29例,Ⅲ、Ⅳ期27例及52例正常人血清进行CA125及TSGF水平测定。结果宫颈癌CA125及TSGF均增高,与正常对照组比较差异有显著性(P<0.001);宫颈癌Ⅰ+Ⅱ期及Ⅲ+Ⅳ期患者CA125及TSGF均增高,两者之间比较差异有显著性(P<0.001),宫颈癌患者血清CA125、TSGF阳性率分别为71.43%、66.07%,联合测定阳性率为80.36%。结论CA125、TSGF测定对宫颈癌的诊断及临床分期有明显辅助价值,联合检测可明显提高诊断灵敏性。     

Hand-assisted laparoscopic surgery for a large gastrointestinal stromal tumor of the stomach

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach that were successfully treated by hand-assisted laparoscopic surgery (HALS). Two patients, a 56-year-old woman and a 60-year-old man, were admitted to our department for the treatment of a large submucosal tumor of the stomach. After gastrointestinal endoscopy, ultrasonography, computed tomography, and magnetic resonance imaging, we suspected that the masses, measuring 7.0 cm and 8.0 cm in diameter, respectively, were GISTs in the stomach. However, preoperatively, we could not rule out the possibility of malignant neoplasms, because they had been bleeding or gradually growing. Hand-assisted laparoscopic wedge resection was safely performed for the diagnosis and treatment of the submucosal tumor of the stomach. The immunohistochemical diagnosis in both patients was GIST of the stomach with intermediate-grade malignancy. HALS may be a good indication for large GISTs of the stomach that are difficult to diagnose preoperatively, whether they are malignant or benign, because it is safe and minimally invasive, promoting rapid recovery.     

Surgery for gallbladder cancer in the US: a need for greater lymph node clearance

Background

Gallbladder cancer (GBC) is a rare malignancy with a dismal prognosis. Often identified incidentally after laparoscopic cholecystectomy for presumably benign biliary disease, reoperation with partial hepatic resection and periportal lymph node dissection (LND) is frequently performed. The impact of lymph node (LN) clearance for GBC remains unclear.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed with GBC between 1988 and 2009. Survival was calculated using Kaplan-Meier method and compared using log-rank test. Multivariate analysis was performed to identify predictors of survival.

Results

A total of 11,815 patients diagnosed with GBC were identified. Cancer-directed surgery was performed in 8,436 (71.3%) patients. Optimal LN clearance (defined as ≥4 LNs) is associated with young age, advanced T-stage, no radiation therapy, and radical surgery (all <0.001). Greater LND improves survival for all stages (P<0.001). After adjusting for confounding factors, multivariable analysis of patients with node-negative disease demonstrated that early stage, greater LND, and radical surgery were strong independent predictors of survival.

Conclusions

Extensive lymphadenectomy correlates with longer survival even in node negative patients. Extensive LND should be performed in patients with GBC as many patients in the USA are undertreated.     

Validation Study of the International Association for the Study of Lung Cancer Histologic Grading System of Invasive Lung Adenocarcinoma

IntroductionA histologic grading system for invasive lung adenocarcinoma (ADC) has been proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee in June 2020. This study evaluated the prognostic value of the IASLC histologic grading system (the IASLC system) in a large Japanese cohort.MethodsWe performed comprehensive histologic subtyping using the semiquantitative estimation of five major patterns and complex glandular patterns in patients with a completely resected lung ADC and determined the histologic grade using the IASLC system. Concordance index and receiver-operating characteristic curves were used to evaluate the clinical utility of the IASLC system for recurrence and death; the comparison was performed with the architectural-pattern system (the Arch system) and the grading system on the basis of the two most predominant patterns (the Sica’s system).ResultsOf 1002 patients with invasive ADC, 235 had recurrent disease and 166 died of lung cancer. The concordance index and area under the curve of the IASLC system were 0.777 and 0.807 for recurrence and 0.767 and 0.776 for death, respectively. These were similar to those of the Arch system (0.763 and 0.796 for recurrence, 0.743 and 0.755 for death) and the Sica’s system (0.786 and 0.814 for recurrence, 0.762 and 0.773 for death).ConclusionsWe reported that the IASLC system for invasive lung ADC has prognostic significance by evaluating a large Japanese cohort. We believe that the IASLC grading system will provide physicians with better information for postsurgery treatment.     

Influence of the mucosal epithelium microenvironment on Langerhans cells: Implications for the development of squamous intraepithelial lesions of the cervix

We have addressed the notion that the initiation and progression of human papillomavirus associated cancer of the uterine cervix are associated with alterations of Langerhans cells (LC) within the mucosal squamous epithelium. Since the transformation zone (TZ) of the cervix is the site where the majority of squamous intraepithelial lesions (SIL) are initiated, in contrast to the exocervix, we decided to investigate the influence of the local microenvironment within the TZ on the function and density of LC. We show that the TZ is associated with a significant reduction in the density of immature LC (CD1a/LAG) compared to the exocervix. In contrast, the development of SILs is attributed with a relative increased density of immature LC, compared to the TZ. Furthermore, we show that this variability in LC density is correlated with a differential expression of TNFα and MIP3α within the micro‐environment of the TZ and SILs. Both TZ and SIL epithelium‐derived LC, in the presence of allogeneic PBMC, induced lower levels of proliferation and IL2 production and higher levels of the immunosuppressive cytokine IL10 in comparison to the exocervix. Nevertheless, the epithelium‐derived LC in SILs exhibits a reduction in their functional activity, relative to the TZ. Together our studies suggest that the immunosurveillance within the epithelium of the TZ may be intrinsically perturbed due to the altered expression of chemokines/cytokines and the concomitant diminished density of LC. Furthermore, following HPV infection and the development of SILs, the function of LC may be further incapacitated by viral associated mechanisms. © 2001 Wiley‐Liss, Inc.     

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.     

六种分期系统预测AFP阴性肝细胞癌患者术后预后价值的比较

目的 比较巴塞罗那肝癌分期（BCLC）、中国肝癌分期（CNLC）、TNM分期系统、日本整体分期评分系统（JIS）、意大利肝脏肿瘤评分（CLIP）和奥田邦雄分期系统（Okuda）在血清甲胎蛋白（AFP）阴性肝细胞癌（HCC）患者术后预后预测中的价值。方法 回顾性分析2012年1月至2017年12月在广西医科大学附属肿瘤医院肝胆胰脾外科行肝切除术治疗并符合入组标准的AFP阴性HCC患者临床病理资料。患者按照BCLC、CNLC、TNM、JIS、CLIP、Okuda分期系统进行分期,并接受随访。采用时间依赖的受试者工作特征（ROC）曲线、log-rank检验、似然比检验比较6个分期系统的区分度、分层能力及预测价值。结果 CNLC预测HCC患者术后总生存率的ROC曲线下面积（AUC）为0.682,以Ⅱb期为切点,对应的灵敏度为0.655,特异度为0.691;CNLC分期预测1、3、5年生存率的AUC分别为0.670（95%CI：0.603~0.738）、0.575（95%CI：0.441~0.708）、0.689（95%CI：0.407~0.971）,优于其他分期系统（均P<0.05）。Log-rank检验显示,6个分期系统均有较好的危险分层能力。似然比检验显示,CNLC预测总生存率的价值最高（χ2=39.575,P=0.011）。结论 在6个分期系统中,CNLC分期是预测AFP阴性HCC患者术后预后的最佳分期系统。     

Short and long-term outcomes after proximal gastrectomy with double tract reconstruction for Siewert type III adenocarcinoma of the esophagogastric junction: a propensity score matching study from a 10-year experience in a high-volume hospital

BackgroundTotal gastrectomy and proximal gastrectomy (PG) are both surgical options for the treatment of Siewert type III adenocarcinoma of the esophagogastric junction (AEG). Currently there is no consensus on selecting which procedure to perform; in particular, there are few reports of long-term outcomes for patients with local advanced AEG. The aim of this study was to validate the usefulness of PG with double-tract reconstruction in Siewert type III AEG.MethodsThe clinical data of patients with Siewert type III AEG underwent PG with double-tract reconstruction (PG-DT) or total gastrectomy with Roux-en-Y anastomosis (TG-RY) at our hospital between October 2010 and October 2018. According to the defined inclusion and exclusion criteria, 2,146 cases were enrolled in this study. A 1-to-1 propensity score matching (PSM) was performed to compare the short and long-term outcomes between the 2 groups.ResultsThe operation time was longer in the PG-DT group, and the proportion rates of complications and recovery time was similar in the 2 groups. The rates of maintaining bodyweight and free-fat mass index were significantly higher in patients who underwent PG-DT compared to those who underwent TG-RY. While complications, recovery time and survival are similar between two groups.ConclusionsRegarding short-term outcomes, PG-DT seemed to be superior in terms of maintaining body weight and skeletal muscle compared to TG-RY, while both had similar complications. It was found that PG-DT enabled a potentially longer survival of pathological stage II and III Siewert type III AEG, although the finding was statistically insignificant. These results may help surgeons to determine the appropriate surgical approach and strategy for patients with early and locally advanced Siewert type III AEG.     

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. We analyzed 26 MSI-High and 558 non-MSI-High CRC tumors. BRCA2 mutations were highly enriched (50%) in MSI-High CRC. Immunohistochemistry showed that BRCA2-mutated MSI-High CRC had high c-MET (64%) expression compared with BRCA-WT (17%). We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib). We tested CRC cell lines for sensitivity to MMC plus crizotinib or other drug combinations including PARP-inhibitors. Combined treatment of tumor cells with crizotinib and MMC led to increased apoptosis as compared with each drug alone. Additionally, combination treatment with increasing concentrations of both drugs demonstrated a synergistic anti-cancer effect (CI = 0.006–0.74). However, we found no evidence for c-MET upregulation upon effective BRCA2 knockdown in tumor cells ?/+DNA damage. Although we found no mechanistic link between BRCA2 deficiency and c-MET overexpression, c-MET is frequently overexpressed in CRC and BRCA2 is mutated especially in MSI-H CRC. The combination of crizotinib with MMC appeared synergistic regardless of MSI or BRCA2 status. Using an in-vivo CRC xenograft model we found reduced tumor growth with combined crizotinib and MMC therapy (p = 0.0088). Our preclinical results support clinical testing of the combination of MMC and crizotinib in advanced CRC. Targeting cell survival mediated by c-MET in combination with targeting DNA repair may be a reasonable strategy for therapy development in CRC or other cancers.