论我国胃肠道癌腹膜转移诊治的难点和痛点

经过一个半世纪的发展, 近现代临床肿瘤学研究取得了巨大成就。作为三大常见转移途径之一, 直到20世纪末, 胃肠道癌腹膜种植转移, 才开始被重新认识, 至今日才逐渐开始形成规范性诊断治疗体系。本文回顾腹膜转移癌诊治研究的发展历史, 反思临床实践中的教训与经验, 阐述腹膜转移癌在疾病再认识、机制深入理解和临床诊治策略上的难点, 以及在理论建设、技术培训和学科建设中的痛点, 并提出了认清客观现实、夯实技术培训和推进协同研究的解决方案, 为腹膜肿瘤学稳步发展提供参考。     

腹腔热灌注化疗在胃肠道恶性肿瘤腹膜转移中的应用

腹膜癌(peritoneal carcinomatosis,PC)是腹膜表面播散性生长的一类局部区域性肿瘤,常见于胃肠道恶性肿瘤腹膜转移,它被认为是一种终末期疾病,既往常采用姑息性治疗。细胞减灭术(cytoreductive surgery,CRS)加术中、术后早期腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC),联合围手术期系统化疗的综合治疗策略是目前治疗PC的标准方案,可降低腹膜肿瘤复发率、延长患者生存时间,并取得了一定的临床疗效。本文就腹腔热灌注化疗在胃肠道恶性肿瘤腹膜转移中的应用进行概述。     

腹腔内恶性肿瘤腹膜转移的治疗进展

腹膜转移癌多由进展期胃肠道癌肿和卵巢癌等恶性肿瘤的腹腔内播散和转移所致,属于癌肿演进过程中的终末阶段。临床上这些患者往往伴有不同程度的恶性腹水和胃肠道并发症等,病情发展快,预后差,治疗相当困难。近年来对腹膜癌转移的外科治疗有了一些新的认识和发展,对于一些恶性程度低、肿瘤分化较好的患者仍可进行以减瘤性腹膜切除术为主的综合性治疗,并可取得较好的临床疗效,现就其主要有关的内容作一综合分析。     

肿瘤细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移的现状与前景

淋巴、血液和种植转移是恶性肿瘤的基本特性.针对胃肠道肿瘤转移的治疗,可清晰看到3个阶段,即针对淋巴结转移的诊断分期和治疗体系,针对血液包括肝、肺转移的诊断评估和治疗体系,针对腹膜种植转移的诊断评估和治疗体系.我国腹膜转移诊治相关研究起步晚,目前仍是临床肿瘤治疗的难题之一[1].     

胃肠道癌术中腹腔内温热化疗临床适应证的探讨

目的:探讨胃肠道癌术中腹腔内温热化疗(IPHC)防治腹膜转移的临床适应证.方法:78例胃癌,5例结肠癌,剖腹后先收集腹水或腹腔冲洗液行细胞学或病理学检查,寻找游离癌细胞,并与肿瘤生物学特性进行单因素和多因素判别分析.结果:腹腔内游离癌细胞阳性率同腹膜转移、浆膜侵犯、TNM分期、浆膜侵犯面积、淋巴转移、腹水、Borrmann分型等因素有关(P<0.05),其中前两者为独立影响因素(P<0.0001).结论:IPHC的临床适应证为:①肉眼可见腹膜转移灶或癌性腹水;②术后腹膜转移;③腹腔冲洗液中发现游离癌细胞;④肿瘤侵及浆膜.     

术前针形腹腔镜检查评估中晚期胃肠道癌的治疗方案

目的 探讨针形腹腔镜检查对中晚期胃肠道癌治疗方案的术前评估。方法 25例老年中晚期胃肠道癌在术前局麻下接受 2 mm针形腹腔镜检查。结果 胃癌淋巴转移和腹膜转移与剖腹手术比较,符合率分别为 61. 5％（ 8/13例）和 3/5例。结直肠癌淋巴转移和腹膜转移符合率分别为 5/6例和 1/2例。结论 局麻下针形腹腔镜检查作为补充和完善影像学和临床诊断,在肿瘤的临床分期、治疗方案制定、合理术式选择等方面均具一定价值,值得进一步探讨。     

胃肠道癌腹膜转移的化疗策略

腹膜转移是严重影响胃肠道癌患者预后的独立不良因素,"种子-土壤"学说被认为是解释腹膜转移的主要理论。由于腹膜转移结节初发时体积小,早期诊断尤为困难,因此,腹膜转移的风险评估就显得尤为重要。目前诊断方法已由临床病理因素逐渐向细胞学、乃至分子层面纵深发展,而包括影像组学在内的多组学整合评估,也进一步丰富了腹膜转移的精准诊断...     

经自然腔道内镜手术腹腔内镜探查对腹膜恶性肿瘤的诊断价值

目的探讨经自然腔道内镜手术（NOTES）腹腔内镜探查对腹膜恶性肿瘤的诊断价值。方法回顾性分析腹膜恶性肿瘤患者NOTES腹腔内镜探查的内镜表现、肿瘤病理学诊断及肿瘤来源。结果53例腹膜恶性肿瘤患者中,腹膜结节型32．2％,腹膜溃疡型22．6％,腹腔肿块型22．6％,腹膜浸润型13．2％,网膜包裹型9．4％。腹膜恶性肿瘤肿瘤病理学诊断结果：淋巴瘤17．0％,间质瘤15．1％,腹膜粘液细胞癌11．32％,腹膜间皮瘤11．32％,腹膜转移癌45．3％。24例腹腔转移癌的组织来源：卵巢癌腹腔转移29．2％,胃癌腹腔转移16．6％,结肠癌腹腔转移12．5％,原发性肝癌腹腔转移12．5％,胰腺癌腹腔转移8．3％,十二指肠乳头癌腹腔转移4．2％、胆管细胞癌腹腔转移4．2％,原发病灶不明者12．5％。结论NOTES腹腔内镜探查对腹膜病变检查直观性强,获取病理标本靶向性好,是诊断腹膜恶性肿瘤的安全有前方法。     

胃上三分之一部的腺癌(英)

胃贲门癌易侵犯食管并发生淋巴结转移,故患者预后较差.癌生长的部位给手术增加了难度,常不能完全切除干净.贲门腺癌文献已有介绍,但食管浸润,尤其是胃上部腺癌引起食管浸润的临床病理学资料却少有报道.本文分析胃上1/3部腺癌的临床病理学资料.研究对象是1964～1978年经手术治疗的223例胃上1/3部腺癌患者.全部病例均经病理诊断,以确定癌浸润的深度和方式、有无淋巴转移、组织学类型以及累及食管情况.治愈性切除术是指对没有腹膜种植和远处转移的病人实行周围淋巴结全部清扫,切除断端没有细胞浸润.根据临床病理学资料确定食管     

结直肠癌腹膜转移的分子机制和治疗策略

腹膜是结直肠癌的常见转移部位, 腹膜转移被认为是结直肠癌的晚期阶段。"种子-土壤"学说和"寡转移"学说是腹膜转移发生发展机制的主要假设。近年来, 结直肠癌腹膜转移相关的机制研究逐渐深入, 我们更加清晰地认识到腹膜转移灶的形成依赖于多种分子的协同作用, 以完成肿瘤细胞脱离原发灶至定植于腹膜并形成转移灶的全过程, 而肿瘤微环境的各组成部分也在其中发挥了重要的调控作用。在治疗方面, 肿瘤细胞减灭术及腹腔热灌注化疗在临床上得到了更为广泛的应用。而随着分子机制研究的进展, 除全身化疗外, 靶向治疗和免疫治疗也越来越多地应用于腹膜转移的治疗中, 有助于改善结直肠癌腹膜转移患者的预后。     

图像处理和人工神经网络在肺癌细胞病理诊断中的应用

目的探求基于计算机图像处理和人工神经网络的“肺癌早期细胞病理电脑诊断系统”（lung cancer diagnosing system，LCDS）在肺癌临床细胞病理诊断中的应用价值。方法运用LCDS对512例经皮肺穿刺标本的细胞学涂片进行检测评判和综合分析，并对其中手术治疗的362例进行LCDS细胞病理诊断与术后组织病理诊断对比分析研究。结果LCDS能运用图像处理和专家系统完成对肺部病灶癌细胞和非癌细胞的识别诊断，进而运用人工神经网络能完成肺鳞癌、腺癌、小细胞癌等主要病理类型的细胞病理诊断，与临床组织病理或细胞病理诊断结果对比，总符合率为91．80％。其中362例接受外科手术者以术后组织病理诊断结果为标准，LCDS检测诊断的敏感性为94．79％（291／307例），特异性为90．91％（50／55例），准确性为94．20％（341／362例）。结论LCDS所采用的诊断模型是实用而有效的，具有诊断准确率高、易于操作培训等优势，有可能为肺癌早期细胞病理诊断提供又一实用有效的手段。     

Are "micrometastases" of the peritoneum equivalent to distant metastases?

Tumor progression after curative resection of gastrointestinal cancer is probably caused by disseminated tumor cells that can be detected in different body compartments, e.g. the peritoneum. The clinical importance and prognostic significance of gross peritoneal metastasis is well known whereas the prognostic relevance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer is still unclear. Disseminated tumor cells in the peritoneal cavity are generally detected by cytology, immunohistochemistry or polymerase chain reaction-based molecular methods. A consensus on the most adequate detection method has not yet been found making the comparison of different data difficult. The prognostic relevance of tumor cell dissemination has, at least in part, been shown for gastric, pancreatic and colon cancer, and the prognostic data regarding gastric cancer are most convincing. Peritoneal "micrometastases" are obviously not equivalent to distant metastases as the evidence for their prognostic significance is clearly less than that for gross peritoneal metastases. This article gives a critical review of the detection and prognostic significance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer.     

Better preservation of peritoneal morphologic features and defense in rats after long-term exposure to a bicarbonate/lactate-buffered solution.

The long-term effects of a standard lactate-buffered dialysis fluid and a new, two-chamber, bicarbonate/lactate-buffered dialysis fluid (with fewer glucose degradation products and a neutral pH) were compared in an in vivo peritoneal exposure model. Rats were given daily injections, via an access port, of 10 ml of standard solution or bicarbonate/lactate-buffered solution for 9 to 10 wk. The omentum, peritoneum, and mesothelial cell layer were screened for morphologic changes. In addition, the bacterial clearing capacity of the peritoneal cells was studied. Significantly more milky spots and blood vessels were observed in the omenta of animals treated with standard solution (P < 0.03 for both parameters). Electron-microscopic analysis demonstrated dramatic changes in the appearance of the vascular endothelial cells of the milky spots and a severely damaged or even absent mesothelium on the peritoneal membrane of the standard solution-treated animals. In contrast, the mesothelium was still present in the bicarbonate/lactate-buffered solution group, although the cells lost microvilli. Both peritoneal dialysis fluids significantly increased the density of mesothelial cells (per square millimeter) on the surface of the liver and the thickness of the submesothelial extracellular matrix of the peritoneum (both P < 0.04 for both fluids versus control). A significantly better ex vivo bacterial clearing capacity was observed with peritoneal cells from the bicarbonate/lactate-buffered solution group, compared with the standard solution group (P < 0.05 in both experiments). These results demonstrate that instillation of bicarbonate/lactate-buffered solution into rats for 9 to 10 wk preserves both morphologic and immune parameters much more effectively, compared with standard solution. These findings may be of considerable clinical importance.     

Laparoscopic Narrow-Band Imaging for the Diagnosis of Peritoneal Metastasis in Gastric Cancer

Background

Staging laparoscopy (SL) is often used to diagnose peritoneal metastasis in patients with advanced gastric cancer, but accurate detection of metastasis can be difficult. We evaluated the usefulness of laparoscopic narrow-band imaging (NBI) versus conventional laparoscopic white-light imaging (WLI) for the diagnosis of peritoneal metastasis.

Methods

We excised 37 white nodules from the parietal peritoneum of 26 patients with gastric cancer and suspected peritoneal metastasis. The WLI and NBI findings were compared with the pathological findings. All the peritoneal lesions examined were observed as white nodules on WLI. Intranodular vessels were evaluated by WLI and NBI for (1) vessel dilatation, (2) vessel tortuousness, (3) vessel heterogeneity, and (4) brown spots.

Results

Each individual abnormal finding had a diagnostic accuracy of less than 79 % with or without NBI. Detection of any one abnormal finding had a sensitivity, specificity, and accuracy of 47.8, 85.7, and 62.2 %, respectively, on WLI and 91.3, 71.4, and 83.8 %, respectively, on NBI, for detection of peritoneal metastasis. Detection of any one abnormal finding on NBI plus clear demarcation of the nodule on WLI had a sensitivity of 91.3 %, specificity of 92.9 %, and accuracy of 91.9 % for detection of peritoneal metastasis. Pathological examination showed that a brown spot detected on NBI correlated with dilated vessels around cancer cells. Vascular endothelial growth factor was expressed in 76.2 % of peritoneal metastases.

Conclusions

NBI was more sensitive for the detection of dilated vessels than WLI. NBI could be a useful tool for the diagnosis of peritoneal metastasis during SL.     

Anti-beta1 integrin antibody reduces surgery-induced adhesion of colon carcinoma cells to traumatized peritoneal surfaces

OBJECTIVE: To study the mechanisms behind surgery-induced augmentation of tumor outgrowth. SUMMARY BACKGROUND DATA: Surgery provides the best chance of cure for most primary intra-abdominal carcinomas. Effective treatment is however relatively frequent complicated by peritoneal recurrences, which often originate from free-floating intraperitoneal tumor cells that implant on peritoneal surfaces. We previously reported that surgical trauma promotes development of peritoneal metastases. METHODS: Evaluation of adhesion of CC531s rat colon carcinoma cell line intraperitoneally after laparotomy using in vivo, ex vivo, and in vitro models. Also, human ex vivo models were used to study peritoneal tumor cell adhesion. RESULTS: Peritoneal imprints of operated rats showed that direct damaging of the peritoneum resulted in enhanced adhesion of rat CC531 colon carcinoma cells to submesothelial extracellular matrix (ECM) proteins in vivo, which was confirmed by electron microscopy. Additionally, the inflammatory reaction of the peritoneal cavity led to retraction of mesothelial cells, hereby also exposing ECM at peritoneal surfaces that had not been traumatized directly. Furthermore, we demonstrated that beta1 integrin subunits represented the primary mediators involved in adherence to either isolated ECM components or excised traumatized rat and human peritoneum. Importantly, incubation of CC531s cells with anti-beta1 integrin antibodies resulted in a significant decrease of tumor cell adhesion in vivo. CONCLUSIONS: Surgical trauma results in exposure of ECM at directly and nondirectly damaged peritoneal surfaces, leading to increased beta1 integrin-dependent tumor cell adhesion. Perioperative therapies, which aim to block beta1 integrin subunits, might therefore serve as new clinical tools for the prevention of peritoneal recurrences.     

结直肠癌腹膜转移的诊治策略与挑战

腹膜是结直肠癌常见的转移部位,与其他转移部位相比预后较差。早期的观点认为,腹膜转移是疾病的终末状态,全身化疗为主的姑息性治疗是其主要治疗手段。随着肿瘤细胞减灭术(CRS)+腹腔热灌注化疗(HIPEC)的治疗模式逐渐得到外科医生的认可,以及靶向治疗和免疫药物的应用,结直肠癌腹膜转移患者的预后得到了很大改善。然而,结直肠癌腹膜转移的诊治仍面临很多挑战和争议。本文从对结直肠癌腹膜转移的认识演变出发,讨论了腹膜转移可能的机制,包括"寡转移"学说和"种子-土壤"学说;进一步探讨了结直肠癌腹膜转移的诊治策略及面临的挑战,包括影像学检查的局限性、腹腔镜探查的争议、腹膜转移负荷评估困难、术后复发监测和疗效评估手段有限以及中国不同地区间诊治水平差异较大等问题。同时强调了CRS+HIPEC围手术期多学科管理的重要性,并提出应加强腹膜转移的基础与临床转化研究,推广腹膜转移的规范化诊治是提高结直肠癌腹膜转移患者预后的根本。     

数字化肺癌细胞病理诊断系统的研制和临床应用

目的探讨数字化肺癌细胞病理诊断系统在临床肺癌细胞病理诊断中的应用效果。方法自动提取涂片上的细胞图像,运用B样条和改进deBoor-Cox方法对重叠细胞区域进行分离和可视化重构;运用基于强化学习技术的图像分割法将细胞区域从背景中分离出来,实现对目标图像的正确提取分割预处理;将细胞病理专家知识数字化用以提取较精确的细胞特征信息;运用决策树、支持向量机、贝叶斯等先进的分类算法,使系统拥有高精度和强分类能力,能同时进行癌与非癌的判断、肺癌细胞的分类（鳞癌、腺癌、小细胞癌及未分类癌）及核异型细胞评估。结果初步研制的数字化肺癌细胞病理诊断系统运行顺利,判断较为快速准确,随机应用于临床120例肺部病灶穿刺所得224幅细胞学涂片,肺癌识别诊断准确率92．3％,肺癌细胞的分类诊断符合率82．5％,核异型细胞判断识别率71．6％。结论数字化肺癌细胞病理诊断系统操作可行、对肺癌细胞学涂片判断准确率高,克服了重叠细胞识别率低、涂片染色差异和不良以及背景杂质等干扰因素,提供了相对客观统一的肺癌细胞病理学诊断策略,可用于肺部病灶穿刺细胞学识别分类诊断,为肺癌的早诊早治提供了一个重要的科学手段。     

5-aminolevulinic acid-induced (ALA) fluorescence for the laparoscopic diagnosis of peritoneal metastasis

Background: We performed a randomized experimental study in a rat model to evaluate the use of 5-aminolevulinic acid-induced (ALA) fluorescence in the laparoscopic diagnosis of peritoneal metastases of ovarian cancer. Methods: We injected 103 ovarian adenocarcinoma cells in the peritoneum of 31 rats. One week later, 5-aminolevulinic acid was injected in the peritoneum (100 mg/kg). After 3 h, we examined the rats using a 10-mm endoscope with a mono CCD camera and a light source developed for photodynamic diagnosis. Metastases on the parietal peritoneum were evaluated independently by two surgeons randomly assigned to use either a conventional light mode or the fluorescence mode. Results: The mean number of metastases detected was 2.84 with conventional laparoscopic light and 5.74 with ALA-induced fluorescence (p <0.0008). Metastases diagnosed by fluorescence were confirmed by pathologic examination. random peritoneal biopsy specimens taken from nonfluorescent areas were negative. conclusion: in this experiment, ala-induced fluorescence improved the detection of peritoneal metastases of ovarian cancer.     

Pleural multicystic mesothelial proliferation. The so-called multicystic mesothelioma

We report on the clinical and pathological features of a hitherto unrecognized multicystic and multifocal mesothelial lesion arising in the pleural cavity of a 37-year-old Caucasian woman. The lesions consisted of clusters of thin-walled cysts separated by connective tissue and lined by a single layer of flattened and cuboidal mesothelium. Mucin stains, immunohistochemistry, and electron microscopy were consistent with a mesothelial origin. The pathological features are identical to those of the previously reported multicystic mesotheliomas of the peritoneum. Although these multicystic peritoneal mesothelial lesions have been regarded as neoplasms, absent stromal extension, lack of mitotic activity, and (in this case) continuity with morphologically normal surrounding mesothelium are suggestive of a reactive process. The term "multicystic mesothelial proliferation" may therefore be more appropriate. Because these lesions may be detected as discrete pleural based masses on chest radiograph and CT scan, they may be submitted for frozen section during operative resection. It is therefore important to be aware of their existence, morphology, and differential diagnosis.     

Evaluation of povidone abdominal washing for prevention of peritoneal cancer cell seeding: experimental study in the rat

GOAL: The aim of the study was to evaluate the in vitro cytototoxicity of diluted povidone iodine on colon cancer cells and its in vivo antitumoral effect in a model of peritoneal carcinomatosis in the rat. METHODS: Cell cytotoxicity of a povidone iodine diluted solution was assessed, in vitro, on rat colon cancer cells (DHD/K12/PROb) and human colon cancer cells (HT29). The antitumoral effect of diluted povidone iodine washing was measured in BDIX rats after the intraperitoneal inoculation of 10(6) DHD/K12/PROb cells. Results were compared to an abdominal washing within a 9 g/l salinel solution. In one experiment, peritoneal scars and a colocolic anastomosis were performed after the injection of cancer cells. RESULTS: A short 10 min incubation of human and rat colon cancer cells with diluted povidone iodine resulted in a complete cell killing. In animals, a peritoneal washing with 1% diluted povidone iodine completely inhibited the tumor growth in parietal peritoneum. However, development of peritoneal tumor nodules was not inhibited in the omentum, in scarified peritoneum or in intestinal anastomosis. CONCLUSIONS: Despite its high in vitro efficacy, diluted povidone iodine has an incomplete effect in the prevention of peritoneal carcinomatosis, with only a partial inhibition in scarred peritoneum epiplo?c area and intestinal anastomosis. In contrary, it procures a complete inhibition of tumor growth in normal peritoneum.