INTRODUCTION

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, despite the fact that knowledge about its etiology, diagnostics, systemic chemotherapy and surgical techniques have significantly developed and improved during the last three decades[1-4]. The most problematic issue concerning the clinical management of GC is diagnosis at an advanced,and often metastasized, stage[5]. This circumstance is explained by the fact that local symptoms occur only at an advanced stage. Apart from extensive local tumor growth rendering the patient ineligible for curative resection, peritoneal carcinomatosis, which is synchronous in approximately 10% of patients, limits therapeutic options in this subset of patients[6-11].

Another metastatic site, other than the peritoneum,is the ovaries; tumors at these sites are referred to as Krukenberg tumors (KTs). These tumors are very often misdiagnosed as primary ovarian cancer and may be occasionally diagnosed during a clinical work-up for abdominal tenderness in the lower abdomen[12,13]. The KT is described mainly as a rare metastatic tumor of the ovary that originates from the gastrointestinal tract(stomach - 76%; colorectum - 4%, biliary system -3%; appendix - 3%) but can also originate from breast(4%) and from other miscellaneous sites such as the pancreas, uterus, cervix, or urinary bladder[14,15]. KT is considered a late-stage disease, and despite growing clinical knowledge, there are still many controversies regarding standardized treatment protocols for this subset of patients[16]. To date, there are no universally accepted and recommended prognostic factors for KT treatment that indicate the superiority of one particular surgical algorithm or chemotherapeutic regimen over another[17,18].

We report the first case in the recent and past literature of the application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as neoadjuvant therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a patient who was with primarily diagnosed and underwent surgery for a KT.

Table 1 Coexisting diseases - data from the patient’s medical history report

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CASE REPORT

A 49-year-old woman with several co-morbidities(Table 1) was admitted in February 2017 to another hospital with ascites and abdominal masses. Abdominal ultrasound showed bilateral ovarian tumors, ascites and suspicion of peritoneal metastases, suggesting locally advanced ovarian cancer. An exploratory laparotomy was performed by the gynecology team, con firming the presence of two ovarian masses (left: 8 cm × 6 cm, right 12 cm × 8 cm), diffuse peritoneal metastasis (peritoneal carcinomatosis index - PCI = 19) and ascites (volume= 120 mL). Bilateral hysterectomy was performed in combination with bilateral adnexectomy, omentectomy,appendectomy and pelvic lymphadenectomy. The intraoperative situs was evaluated by the gastrointestinal surgeon who con firmed that complete cytoreduction was not possible.

二是开展民营经济筑基工程。夯实民营经济发展基础，壮大民营经济规模，提升民营经济竞争力。引导同行业民营经济抱团合作发展，充分发挥行业协会、商会作用，加大民营企业合作，组织开展项目洽谈、集体招商引才、共享研发攻关、融资担保等活动。建议政府设立年度民营企业奖励计划，形成鼓励民营经济创新发展的预期，重点鼓励支持创业型、创新型、高成长性民营企业。

Recovery was uneventful. Histology revealed signet ring tumor cells arranged singly, in cords or in nests within cellular ovarian stroma (Figure 1A and B). Additional staining revealed CK7(+), CK20(-), CDX2(+) and CA125(-) status, suggesting a primary tumor originating from the upper gastrointestinal (GI-) tract. Postoperative upper GI endoscopy showed a mucin-positive, poorly differentiated adenocarcinoma located in the antral mucosa (Figure 1C and D). Staging was completed with an abdominal CT scan that showed a super ficially located metastasis in liver segment 5 (Figure 2).

The patient was referred in April 2017 to our tertiary center for further therapy.

At admission, the patient had reduced general condition (ECOG - 2) and in reduced nutritional status(BMI of 18.37 and weight loss identified in the nutritional anamnesis). Laboratory tests were within normal limits.The patient was presented to the multidisciplinary tumor board, and a systemic combination chemotherapy combined with intraperitoneal chemotherapy with cisplatin and doxorubicin (as a pressurized aerosol, PIPAC C/D)was recommended, with palliative intent. The patient gave voluntary and informed consent to the planned treatment, and the study was performed in accordance with the precepts established by the declaration of Helsinki.

The PIPAC procedure was first performed in May 2017, according to standard protocols described by Hubner et al[19]. Shortly thereafter, after a 12 mmHg capnoperitoneum has been established, two trocars were inserted, and a staging laparoscopy was performed. After con firmation of the tightness of the abdomen, a solution of low-dose cisplatin (7.5 mg/m2 BSA) and doxorubicin(1.5 mg/m2 BSA) diluted in 200 mL of saline solution was aerosolized at a pressure of 12 mmHg and a temperature of 37 ℃ into the abdomen using a CE-certified nebulizer(Capnopen®, Capnomed, Villingendorf, Germany).After 30 min of application, the toxic aerosol was safely removed via a closed aerosol waste system (CAWS). The diagram displaying the PIPAC procedure is presented in Figure 3. The PIPAC procedure was tolerated very well,and no postoperative complications were noted.

Figure 1 Histological ovary assay. A: Signet ring of tumor cell in filtration within the ovarian stroma (10 ×, HE); B: Mucicarmine staining highlights the presence of mucin in the cytoplasm (10 ×). Histopathologic evaluation of antral mucosa showing (C) poorly differentiated carcinoma in filtration with signet ring cells (20 ×, HE) and(D) mucicarmine staining of mucin-positive cells in the gastric mucosa (10 ×).

Figure 2 Abdominal computed tomography and abdominopelvic magnetic resonance scans. A: Post-contrast computed tomography image in the portal venous phase showing a hyperintense enhancing lesion in segment V (isodense in the native phase) of the liver, which was diagnosed as a super ficially located suspicious metastatic lesion; B-E: Abdominopelvic magnetic resonance scans with evident masses and suspicious nodules.

During the clinical work-up, we encountered another problematic clinical issue regarding the patients metastatic lesion in the liver, which would normally render a patient ineligible for PIPAC treatment[33]. Fortunately, the metastatic lesion in our patient was located super ficially,and after PIPAC was performed, no complications were reported.

Figure 3 Schematic presentation of the pressurized intraperitoneal aerosol chemotherapy procedure. The procedure is performed under general anesthesia and based on standard diagnostic laparoscopy procedures. Two small incisions are always made to obtain surgical access using two double-balloon secured trocars(D-B＊ - double-balloon secured trocars). The first one is used for the laparoscopic camera and is connected to a closed aerosol waste system (CAWS＊). The second one connected to the CO2 insuf flator is for the micropump nebulizer used for delivering chemotherapy under pressure via a high-pressure line.

Figure 4 Palliative open D2 gastrectomy combined with liver metastasectomy. A: Liver metastasectomy procedure involving removal of the metastatic lesion combined with parenchyma coagulation; B: Open gastrectomy procedure showing the staple line after resection; C: Creation of a Roux-en-Y anastomosis (RNY) using sutures.

DISCUSSION

24 McGill F, Ritter DB, Rickard C, Kaleya RN, Wadler S, Greston WM. Management of Krukenberg tumors: an 11-year experience and review of the literature. Prim Care Update Ob Gyns 1998; 5:157-158 [PMID: 10838292]

In this paper, we present the case of 49-year-old PC patient with a high PCI index who was diagnosed primarily with KT due to an intrapathology assay in which bilateral hysterectomy combined with removal of the uterine appendages, omentectomy, appendectomy and pelvic lymphadenectomy was performed. The optimal treatment in such cases has still not been fully described in schematic recommendations and guidelines regarding the role of gastrectomy[25]. In recent and past literature,the beneficial outcomes of palliative gastrectomy have been presented[26]. Thus, because of the young age and good performance status of our patient along with the nonacceptance of standard intravenous forms of therapies with a parallel allowance for an intraperitoneal form of drug delivery, we elected the aforementioned treatment protocol consisting of “neoadjuvant” PIPAC followed by D2 gastrectomy. During our literature review we found information about some cases in which cytoreductive surgeries were performed in combination with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) procedures with good clinical effects that improved the survival of GC patients[27-29]. In our case, such an intervention was not possible due to the very aggressive CRS surgery and the patient’s disqualification by medical oncologists. We also found interesting data about a novel and promising intraoperative drug delivery technique - pressurized intraperitoneal aerosol chemotherapy - that has also been used as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in different clinical cases[30]. In the recent and past literature,the effectiveness of repetitive PIPAC has also been documented for irresectable PC originating from pancreatic or ovarian cancer with a median histologically proven regression rate of up to 50%[20,30-32]. In this case, our MDT recommended PIPAC as a bridge (sandwich) therapy before a possible more de finitive CRS+HIPEC procedure with palliative D2 gastrectomy without other cytoreduction and final qualification for standard chemotherapy protocols, according to the current international guidelines,until these therapies are personally acceptable to the patient.

由此，我国当下通过“一带一路”倡议推行国际经贸合作，需要转变理念和方式，重视法律合作，适时跟上世界发展趋势，借着法律自发趋同的世界法律合作潮流开展国际经贸活动，实现“一带一路”所涉国家长久的互利共赢。该理念和方式的转变也是我国的必然选择。

Eight weeks after the PIPAC procedure, an exploratory laparotomy was performed. This time period has been suggested in the literature as the optimal time period between the next surgical intervention and each PIPAC surgery[20]. Macroscopically, a 3-cm tumor was palpated in the gastric body, in filtrating the gastric serosa, and no diffuse peritoneal metastasis were found anymore during a detailed standard surgical intraoperative PC lesion assessment, so complete cytoreduction (CC-0 according to Sugarbaker) appeared feasible. Therefore, curative gastrectomy, D2 lymphadenectomy and atypical liver resection were performed (Figure 4). Histopathologic evaluation demonstrated a poorly differentiated carcinoma of the stomach, which was ypT3N2 (4/40)and high grade (G3) (Figure 5). The liver metastasis had a diameter of 2.5 cm. All the resection margins were tumor-free, so the procedure was considered (potentially)curative. The postoperative course was uneventful.Four months after surgery, the patient was completely recovered and had returned to her daily activities (ECOG =1; BMI = 20.23). Postoperative adjuvant chemotherapy with Xeloda was recommended. Narrow follow-up examinations (abdominal CT scan) will be performed.

Figure 5 Histopathologic evaluation performed after open D2 gastrectomy combined with liver metastasectomy. A: Tumor microfocus in filtrations in the peritoneal adipose tissue in the vicinity of the distal surgical margin (obj. 20 ×, HE); B: Metastatic foci in the subcapsular region of the lymph node (obj. 20 ×, HE); C, D:Liver metastasis of gastric carcinoma (obj. 10 ×, 20 ×, HE).

18 Lu W, Yuan L, Liu X, Guo SW. Identification of prognostic factors for Krukenberg tumor. GMIT 2013; 2: 52-56 [DOI: 10.1016/j.gmit.2013.02.006]

ARTICLE HIGHLIGHTS

Case characteristics

A 49-year-old female patient with reduced general condition and nutritional status (low BMI and weight loss in the nutritional anamnesis) was admitted after bilateral hysterectomy with a diagnosis of diffuse peritoneal carcinomatosis and several co-morbidities.

既然皇帝与储君都要学习青齐学术，那么宗室贵戚自然也要跟风仿效。史书中不乏宗王为子弟延请青齐学者为师之例。任城王元澄之子元顺，“九岁师事乐安陈丰，初书王羲之《小学篇》数千言”，“〔年〕十六，通《杜氏春秋》，恒集门生，讨论同异”。北魏青州、沧州皆有乐安郡，陈丰既然讲授《杜氏春秋》，显然是青州乐安人。据《元顺墓志》，元顺生于太和十一年，师事陈丰则在太和十九年。此外，元澄对曾“受业齐土”的张普惠另眼相看，“重其学业，为其声价，仆射李冲曾至澄处，见普惠言论，亦善之”。孝明帝时，仆射元钦“曾托青州人高僧寿为子求师”，所求自是青州学者。

Clinical diagnosis

The final clinical diagnosis was made by upper gastrointestinal (GI) endoscopy combined with a pathological assay that showed a mucin-positive, poorly differentiated adenocarcinoma located in the gastric antral mucosa.

Differential diagnosis

The differential diagnosis included severe peritoneal carcinomatosis and primary origin cancer with a particular emphasis on ovarian cancer.

2.2 LncRNA-8439 在 2 种肿瘤悬浮球中呈一致的上调表达 采用实时荧光定量 PCR 检测上述9 个 lncRNA 在人肝癌细胞系 Huh7 和 Hep3B 及其相应的肿瘤悬浮球中的表达量。结果（图2）显示 9 个与肿瘤干细胞多能因子相关的 lncRNA中，仅有 lncRNA-8439 在 2 种肿瘤细胞悬浮球中呈一致上调表达，与对应的贴壁细胞系表达量相比差异均有统计学意义（P 均＜0.01），故选择lncRNA-8439 作进一步研究。

Laboratory diagnosis

The CT scan performed during hospitalization in our department showed an additional super ficially located metastasis in liver segment 5.

Imaging diagnosis

Despite the patient’s reduced general condition and nutritional status, all of the performed laboratory tests were within normal limits.

Pathological diagnosis

In this case, staining revealed CK7(+), CK20(-), CDX2(+) and CA125(-) status,suggesting a primary tumor originating from the upper GI- tract. A postoperative upper GI endoscopy showed a mucin-positive, poorly differentiated adenocarcinoma located in the gastric antral mucosa.

Treatment

The PIPAC procedure was based on the administration of a solution of lowdose cisplatin (7.5 mg/m2 BSA) and doxorubicin (1.5 mg/m2) BSA diluted in 200 mL of saline solution aerosolized at a pressure of 12 mmHg and a temperature of 37 ℃ into the abdomen using a CE-certified nebulizer as neoadjuvant therapy before palliative D2 gastrectomy combined with liver metastasectomy.

Related reports

Very few cases of spontaneous regression of an intra-abdominal inflammatory myofibroblastic tumor have been reported in the literature. The clinical and pathological characteristics of inflammatory myofibroblastic tumors remain unclear, and the treatment is controversial.

Term explanation

The acronym PIPAC describes pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Experiences and lessons

This case might contribute to future con firmation of the usefulness of PIPAC as a rescue or neoadjuvant, supportive form of therapy in a very select group of patients. This clinical development might be particularly important for patients with a KT presentation of gastric cancer who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

REFERENCES

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藤尾不喜欢在父亲指定婚姻对象。她认为宗近是游手好闲粗俗之人。在文中的几处表现了藤尾的厌恶情绪。比如，夏目漱石在文中说“真讨厌…那样乏去的人”，厌恶之情溢于言表。总之，宗近无法满足藤尾的愿望。要说为什么，两个人的性格和处理事情的方法完全不一致。即使两人结婚，也只会加快藤尾的死亡。

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本研究还发现，两组患者中TNM分期Ⅳ期的患者均在10%以上，由于ERAS是外科、麻醉、护理、营养等多学科协作采取的系统性综合措施，因而制定患者入组和排除标准比较宽泛，目的是让更多的患者从中受益，因而未将肿瘤分期作为排除标准。因此，本研究无差异化地实施了ERAS方案，统计发现这部分患者对ERAS方案依从率和并发症率与Ⅰ～Ⅲ期患者差异无统计学意义。因此，笔者认为无论临床分期还是病理分期的Ⅳ期患者，如果病情允许，都可以尽量实施ERAS方案。

10 Hosseini SN, Mousavinasab SN, Moghimi MH, Fallah R. Delay in diagnosis and treatment of gastric cancer: from the beginning of symptoms to surgery--an Iranian study. Turk J Gastroenterol 2007;18: 77-81 [PMID: 17602354]

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30 Girshally R, Demtröder C, Albayrak N, Zieren J, Tempfer C,Reymond MA. Pressurized intraperitoneal aerosol chemotherapy(PIPAC) as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 2016; 14: 253 [PMID: 27678344 DOI: 10.1186/s12957-016-1008-0]

13 Kubeček O, Laco J, Špaček J, Petera J, Kopecký J, Kubečková A, Filip S. The pathogenesis, diagnosis, and management of metastatic tumors to the ovary: a comprehensive review. Clin Exp Metastasis 2017; 34: 295-307 [PMID: 28730323 DOI: 10.1007/s10585-017-9856-8]

Andrew Nachis将融媒体定义为印刷、音频、视频、数字之间的战略性联盟。可见，融媒体时代中，信息传播的技术以及资源内容都需要实现交互与融合，这对于大众媒体县级广播电视台来讲是一种全新的发展理念，县级广播电视台要借助融媒体时代的东风，迎难而上，积极探索融媒体格局下的发展路径。

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17 Nakamura Y, Hiramatsu A, Koyama T, Oyama Y, Tanaka A,Honma K. A Krukenberg Tumor from an Occult Intramucosal Gastric Carcinoma Identified during an Autopsy. Case Rep Oncol Med 2014; 2014: 797429 [PMID: 25386374 DOI:10.1155/2014/797429]

In our opinion, in the future, additional clinical studies should be performed in multiple centers to confirm the usefulness of PIPAC as a rescue or neoadjuvant, supportive form of therapy in a very select group of patients. This case might contribute to future con firmation of the usefulness of PIPAC as a rescue or neoadjuvant, supportive form of therapy in a very select group of patients. This clinical development might be particularly important for patients with a KT presentation of gastric cancer who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

对于一款电视节目来讲，要想获得较好的效果，在对其进行编制之前必须明确其定位，然后围绕该定位塑造与之相匹配的风格与内涵，这样才能够使制作出来的电视节目更加具有吸引力。但是，从当前电视节目实际制作现状来看，许多节目存在定位不够明确的问题，以

19 Hübner M, Grass F, Teixeira-Farinha H, Pache B, Mathevet P,Demartines N. Pressurized IntraPeritoneal Aerosol Chemotherapy- Practical aspects. Eur J Surg Oncol 2017; 43: 1102-1109 [PMID:28431896 DOI: 10.1016/j.ejso.2017.03.019]

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The diagnosis of a Krukenberg tumor of gastric cancer origin is associated with a poorer prognosis than other types of primary origin KTs and is significantly more clinically problematic[21]. Several papers focus on different treatment options in patients with KT and mainly report on two specific issues: (1) The role of gastrectomy and metastasectomy under different clinical conditions; and(2) the assessment of the effectiveness and superiority of surgical and chemotherapy interventions[22,23]. The main problem in such descriptions is related to the fact that in large number of papers, the analyzed material concerned data only until the time of KT diagnosis[24].

25 Khosla M, Imran A, Fidias P. Diffuse gastric cancer with Krukenberg tumor: A case report. Int J Case Rep Images 2016; 7:733-737 [DOI: 10.5348/ijcri-2016128-CR-10716]

26 Hsu JT, Liao JA, Chuang HC, Chen TD, Chen TH, Kuo CJ, Lin CJ, Chou WC, Yeh TS, Jan YY. Palliative gastrectomy is bene ficial in selected cases of metastatic gastric cancer. BMC Palliat Care 2017; 16: 19 [PMID: 28288593 DOI: 10.1186/s12904-017-0192-1]

27 Wu XJ, Yuan P, Li ZY, Bu ZD, Zhang LH, Wu AW, Zong XL,Li SX, Shan F, Ji X, Ren H, Ji JF. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination. Tumour Biol 2013; 34: 463-469 [PMID: 23108893 DOI: 10.1007/s13277-012-0571-4]

28 Li-Yung C, Chun-Yu F, Huai-En L, De-Chua C. Treatment of Krukenberg tumor with hyperthermic intraperitoneal chemotherapy: A report of three cases. JMS-NDMC 2016; 36:197-201 [DOI: 10.4103/1011-4564.192838]

29 Nowacki M, Wisniewski M, Werengowska-Ciecwierz K, Roszek K, Czarnecka J, Łakomska I, Kloskowski T, Tyloch D, Debski R,Pietkun K, Pokrywczynska M, Grzanka D, Czajkowski R, Drewa G,Jundziłł A, Agyin JK, Habib SL, Terzyk AP, Drewa T. Nanovehicles as a novel target strategy for hyperthermic intraperitoneal chemotherapy: a multidisciplinary study of peritoneal carcinomatosis.Oncotarget 2015; 6: 22776-22798 [PMID: 26254295]

为了使高校思想政治理论课能有序的开展实践教学，就要求高校应在实践教学方面加大资金的投入，拨出专款用于思想政治理论课的实践教学活动的组织开展上。此外，思想政治理论课教学部门还要与高校学生处、团委以及各院系积极的沟通，在高校经费申请的同时，也要联合广泛的社会力量争取到更多的资金支持，募集更多的经费用于实践教学，为顺利开展教学活动提供基本的物质保障。思想政治理论课实践教学直接关系到学生的成长与成才，更与高校提高思想政治理论教学质量有密切关系。从长远发展来看，还将关系到我国有效落实素质教育以及最终能否实现人才兴国战略计划。

12 Matar HE, Elmetwally AS, Salu I, Borgstein R, Oluwajobi O.Krukenberg tumour arising from adenocarcinoma of the gastrooesophageal junction in a 28-year-old female presenting as lower abdominal swelling mimicking an inguinal hernia. BMJ Case Rep 2011; 2011: [PMID: 22700347 DOI: 10.1136/bcr.12.2010.3597]

31 Graversen M, Detlefsen S, Bjerregaard JK, Pfeiffer P, Mortensen MB. Peritoneal metastasis from pancreatic cancer treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Clin Exp Metastasis 2017; 34: 309-314 [PMID: 28516306 DOI:10.1007/s10585-017-9849-7]

投标供应商为了中标获取利益，各个供应商之间彼此达成协议：一致抬高或压低投标报价，藉以形成垄断报价；或者相互陪标，轮流中标，串通一气，操纵中标结果。由于高校科研设备的专业性及一些科研项目的特殊要求，能够做到的供应商本来就比较少，更加增加了串标围标的几率。另外，一些供应商虚假应标，在投标文件中承诺实现招标文件中的所有需求，在履行合同的过程中，偷工减料，以次充好或者一些在投标文件中承诺的功能在实际实施时无法兑现，严重损害采购人的利益，最终采购人只能解除合同重新采购，而中标供应商一般就是被没收履约保证金，使用部门的科研进度被耽搁，造成不可估量的损失。

32 Khosrawipour T, Khosrawipour V, Giger-Pabst U. Pressurized Intra Peritoneal Aerosol Chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma. PLoS One 2017; 12: e0186709 [PMID: 29049340 DOI: 10.1371/journal.pone.0186709]

在上市公司股东与经理人的委托-代理关系中，股东是委托人，经理是代理人，如果股东信任，经理人诚信，股东与经理人彼此的收益分别是y1,y2；若经理人欺骗，股东不起诉，股东与经理人的收益分别是y3,y4；若经理人欺骗，股东起诉，法院判决欺骗的经理人赔偿rx，这里，r是判决赔偿的概率，x是股东要求赔偿的金额，起诉所产生的司法成本C，不失一般性，y4>y2,y1>y3,y1,y2,y4均大于0 。

33 Hilal Z, Rezniczek GA, Klenke R, Dogan A, Tempfer CB.Nutritional status, cachexia, and anorexia in women with peritoneal metastasis and intraperitoneal chemotherapy: a longitudinal analysis. J Gynecol Oncol 2017; 28: e80 [PMID: 29027398 DOI:10.3802/jgo.2017.28.e80]