Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery( CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in longterm survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.     

Colorectal peritoneal metastases: Optimal management review

The peritoneum is a common site of dissemination for colorrectal cancer, with a poorer prognosis than other sites of metastases. In the last two decades, it has been considered as a locoregional disease progression and treated as such with curative intention treatments. Cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) is the actual reference treatment for these patients as better survival results have been reached as compared to systemic chemotherapy alone, but its therapeutic efficacy is still under debate. Actual guidelines recommend that the management of colorectal cancer with peritoneal metastases should be led by a multidisciplinary team carried out in experienced centers and consider CRS + HIPEC for selected patients. Accumulative evidence in the last three years suggests that this is a curative treatment that may improve patients disease-free survival, decrease the risk of recurrence, and does not increase the risk of treatment-related mortality. In this review we aim to gather the latest results from referral centers and opinions from experts about the effectiveness and feasibility of CRS + HIPEC for treating peritoneal disease from colorectal malignancies.     

Hyperthermic intraperitoneal chemotherapy for gastric and colorectal cancer in Mainland China

AIM:To investigate the current status of peritoneal carcinomatosis(PC) management,as well as the usage of cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) in mainland China.METHODS:A potentially curative therapeutic strategy for selecting patients with PC,known as Techniques,consists of CRS in combination with HIPEC.A systemic search of published works and clinical trials was performed.Additional papers were retrieved by crosschecking references and obtaining information from ...     

Therapeutic options for peritoneal metastasis arising from colorectal cancer

Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer(pm CRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standar-dization of oncologic treatment regimens for pm CRC. The addition of further therapeutic options such as neo-adjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investig-ated to optimize therapeutic regimens and further improve the oncological outcome.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Where are we?

Peritoneal surface malignancies are generally associated with poor prognosis. In daily clinical routine, systemic chemotherapy is still considered the only reasonable therapy despite of encouraging results of cytoreductive surgery (CRS) along with intraperitoneal hyperthermic chemotherapy (HIPEC). The Achilles heel of CRS and HIPEC is appropriate patient selection and precise surgical technique preventing patients from excessive morbidity and mortality. Given these findings, new concepts of second look surgery for high risk patients allow detection of peritoneal spread ahead of clinical symptoms or presence of peritoneal masses reducing perioperative morbidity. In addition, personalized intraperitoneal chemotherapy might further improve outcome by appreciating individual tumor biology. These days, every physician should be aware of CRS and HIPEC for treatment of peritoneal surface malignancies. Since there is now sufficient data for the superiority of CRS and HIPEC to systemic chemotherapy in selected patients, our next goal should be providing this strategy with minimal morbidity and mortality even in the presence of higher tumor load.     

Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

This article is to offer a concise review on the use of cytoreductive surgery （CRS） plus intraperitoneal hyperthermic chemotherapy （IPHC） for the treatment of peritoneal carcinomatosis （PC）. Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 too. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases

AIM: To systematically review the available evidence regarding cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for colorectal peritoneal metastases (CPM).METHODS: An electronic literature search was carried out to identify publications reporting oncological outcome data (overall survival and/or disease free survival and/or recurrence rates) following CRS and IPC for treatment of CPM. Studies reporting outcomes following CRS and IPC for cancer subtypes other than colorectal were only included if data were reported independently for colorectal cancer-associated cases; in addition studies reporting outcomes for peritoneal carcinomatosis of appendiceal origin were excluded.RESULTS: Twenty seven studies, published between 1999 and 2013 with a combined population of 2838 patients met the predefined inclusion criteria. Included studies comprised 21 case series, 5 case-control studies and 1 randomised controlled trial. Four studies provided comparative oncological outcome data for patients undergoing CRS in combination with IPC vs systemic chemotherapy alone. The primary indication for treatment was CPM in 96% of cases (2714/2838) and recurrent CPM (rCPM) in the remaining 4% (124/2838). In the majority of included studies (20/27) CRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC). In 3 studies HIPEC was used in combination with early post-operative intraperitoneal chemotherapy (EPIC), and 2 studies used EPIC only, following CRS. Two studies evaluated comparative outcomes with CRS + HIPEC vs CRS + EPIC for treatment of CPM. The delivery of IPC was performed using an “open” or “closed” abdomen approach in the included studies.CONCLUSION: The available evidence presented in this review indicates that enhanced survival times can be achieved for CPM after combined treatment with CRS and IPC.     

肿瘤细胞减灭术加腹腔热灌注化疗治疗结直肠癌腹膜转移癌的临床研究

目的：探讨肿瘤细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）治疗结直肠癌腹膜转移癌（ CRC PC）的疗效及安全性。方法选取结直肠癌腹膜转移癌（ CRC PC）患者67例,随机分为治疗组（ CRS＋HIPEC）38例,对照组（CRS＋静脉辅助化疗）29例,比较两组的生存期、生存率、术后并发症及化疗毒副作用。结果治疗组中位生存期23.0个月,显著长于对照组的11.0个月（ P＜0.01）,治疗组1、2、3年生存率分别为70.9％、45.7％、8.2％,分别优于对照组的68.8％、21.2％、0％。术后并发症发生率两组相似（ P＞0.05）。化疗毒副作用：对照组恶心呕吐、白细胞减少、血小板减少发生率较治疗组高（P＜0.01）,而治疗组腹胀、腹泻发生率较对照组高（ P＜0.01或P＜0.05）;两组其他毒副作用相似（ P＞0.05）。结论 CRS＋HIPEC治疗CRC PC能明显延长患者生存期,并发症和化疗毒副作用并没有明显增加。     

腹膜转移癌诊疗决策中评分系统的研究进展

腹膜转移是肿瘤的晚期阶段，预后较差。肿瘤细胞减灭术联合腹腔热灌注化疗（CRS+HIPEC）可以显著改善患者预后。患者的预后往往和腹膜疾病的严重程度和CRS肿瘤细胞减灭的程度相关。在术前和术中有各种评分系统合理评估患者腹膜肿瘤负荷，本文对腹膜转移癌诊疗决策中评分系统展开综述。     

Second-look surgery plus hyperthermic intraperitoneal chemotherapy for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Does it really save lives?

The treatment of peritoneal carcinomatosis (PC) of colorectal origin with cytoreductive surgery(CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%, so it is no longer labeled as a fatal disease, and offers prolonged survival for patients with a low peritoneal carcinomatosis index. Metachronous PC of colorectal origin is so predictable that there is a model which has been used to successfully determine the individual risk of each patient. Patients at risk are clearly identified; those with the highest risk have small peritoneal nodules present in the first surgery (70% probability of developing PC), ovarian metastases(60%), perforated tumor onset or intraoperative tumor rupture(50%). Current clinical, biological and imaging techniques still lack sufficient sensitivity to diagnose PC in its initial stages, when CRS plus HIPEC has a greater impact and a higher cure rate. Second-look surgery with HIPEC or prophylactic HIPEC at the time of the first intervention have been proposed as means of preventing and/or anticipating clinical or radiological relapse in at-risk patients. Both techniques have shown a significant decrease in peritoneal relapses and should be considered essential weapons in the management of colorectal cancer.     

Management of peritoneal carcinomatosis from colorectal cancer: review of the literature

Background

Today, we do not have a universally accepted evidence on how to treat peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international guidelines.

Methods

The present study is a review of the literature investigating current strategies to treat CRC PC.

Results

Despite the progresses of systemic chemotherapy, the presence of PC among patients with metastatic CRC reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC treated are alive for 5 years. Many trials evaluate the combined treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC PC, suggesting a survival benefit in highly selected patients. Only one trial is randomized and presents some biases. The two main prognostic factors are Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score). There is no universal agreement on how to approach the synchronous presence of PC and liver metastasis with a curative intent during the same procedure. A growing interest among the scientific community has arisen about systematic second-look surgery and HIPEC treatment in high-risk patients.

Conclusion

Current evidences suggest that CRS and HIPEC might be beneficial in highly selected patients affected with PC from CRC. Anyway, today, there is a shortage of well-designed phase 3 trials.     

“En bloc” caudate lobe and inferior vena cava resection following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal and liver metastasis of colorectal cancer

There are diverse protocols to manage patients with recurrent disease after primary cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. We describe a case of metachronous liver metastasis after CRS and HIPEC for colorectal cancer, successfully treated with a selective metastectomy and partial graft of the inferior vena cava. A 35-year-old female presented with a large tumour in the cecum and consequent colonic stenosis. After an emergency right colectomy, the patient received adjuvant chemotherapy. One year later she was diagnosed with peritoneal carcinomatosis, and it was decided to carry out a CRS/HIPEC. After 2 years of total remission, an isolated metachronous liver metastasis was detected by magnetic resonance imaging surveillance. The patient underwent a third procedure including a caudate lobe and partial inferior vena cava resection with a prosthetic graft interposition, achieving an R0 situation. The postoperative course was uneventful and the patient was discharged on postoperative day 17 after the liver resection. At 18-mo follow-up after the liver resection the patient remained free of recurrence. In selected patients, the option of re-operation due to recurrent disease should be discussed. Even liver resection of a metachronous metastasis and an extended vascular resection are acceptable after CRS/HIPEC and can be considered as a potential treatment option to remove all macroscopic lesions.     

肿瘤细胞减灭术及腹腔热灌注化疗联合肝切除治疗结直肠癌腹膜转移合并肝转移的临床疗效

目的探讨肿瘤细胞减灭术（CRS）及腹腔热灌注化疗（HIPEC）联合肝切除治疗结直肠癌腹膜转移（CRPM）合并肝转移（LM）的安全性及有效性。 方法回顾性收集中国医学科学院肿瘤医院结直肠外科自2017年6月至2019年6月采用CRS+HIPEC联合肝切除治疗的16例CRPM合并孤立LM患者的临床病理资料。 结果男性6例,女性10例,中位年龄62岁。全组患者接受CRS+HIPEC联合同步肝切除,肝脏转移瘤均获得完整切除。中位总生存期25个月,中位无病生存期9个月。1年及3年总生存率分别为75.0%及37.0%,1年及3年无病生存率分别为50.0%及9.4%。6例（37.5%）出现轻度并发症（Clavien-Dindo Ⅰ~Ⅱ）,4例（25.0%）出现严重并发症（Ⅲ~Ⅳ）。 结论CRPM合并孤立的、能完整切除的LM的患者接受CRS+HIPEC联合同期肝切除是安全可行的,同时可为患者带来一定生存获益。     

Advances in the management of peritoneal mesothelioma

Malignant peritoneal mesothelioma (PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Accordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1 (SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease.     

肿瘤细胞减灭术联合腹腔热灌注化疗（CRS/HIPEC）治疗结直肠癌腹膜转移的现状和进展

腹膜是结直肠癌转移的好发部位。结直肠癌发生腹膜转移长期以来被认为预后很差,主要采用姑息性手段治疗。尽管化疗及靶向治疗在结直肠癌治疗上有很大进展,但对于腹膜转移的结直肠癌疗效并不理想。最近越来越多的证据表明,肿瘤细胞减灭术(CRS)联合腹腔内热灌注化疗(HIPEC)的治疗方法能给这部分患者带来较大的生存获益。本文综述了结直肠癌腹膜转移的诊治现状和相关进展。目前认为CRS联合HIPEC对选择的结直肠癌腹膜转移患者是一种安全有效的治疗模式,但HIPEC能否预防进展期结直肠癌发生腹膜转移,还有待进一步的临床试验研究。     

Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options

Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the historical prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients with CRC. Risk factors for developing PC have been identified: right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemotherapeutical and surgical treatments have achieved promising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hyperthermic intraperitoneal chemotherapy. This editorial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.     

“En bloc ” caudate lobe and inferior vena cava resection following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal and liver metastasis of colorectal cancer

There are diverse protocols to manage patients with recurrent disease after primary cytoreductive surgery(CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) for peritoneal carcinomatosis. We describe a case of metachronous liver metastasis after CRS and HIPEC for colorectal cancer, successfully treated with a selective metastectomy and partial graft of the inferior vena cava. A 35-year-old female presented with a large tumour in the cecum and consequent colonic stenosis. After an emergency right colectomy, the patient received adjuvant chemotherapy. One year later she was diagnosed with peritoneal carcinomatosis, and it was decided to carry out a CRS/HIPEC. After 2 years of total remission, an isolated metachronous liver metastasis was detected by magnetic resonance imaging surveillance. The patient underwent a third procedure including a caudate lobe and partial inferior vena cava resection with a prosthetic graft interposition, achieving an R0 situation. The postoperative course was uneventful and the patient was discharged on postoperative day 17 after the liver resection. At 18-mo follow-up after the liver resection the patient remained free of recurrence. In selected patients, the option of re-operation due to recurrent disease should be discussed. Even liver resection of a metachronous metastasis and an extended vascular resection are acceptable after CRS/HIPEC and can be considered as a potential treatment option to remove all macroscopic lesions.     

Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results

Ovarian cancer (OC) is the sixth most common neoplasm in women. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with maximal regional chemotherapy, has been proposed to treat OC. At present, less randomized trials has determined HIPEC real impact on patients with OC. In this brief report, we reported results of selected studies of treatment with HIPEC for patients with OC. Future prospects are conclusively discussed.     

Experience after 100 patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

AIM: To investigate perioperative patient morbidity/mortality and outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).METHODS: Of 150 patients 100 were treated with cytoreductive surgery and HIPEC and retrospectively analyzed. Clinical and postoperative follow-up data were evaluated. Body mass index (BMI), age and peritoneal carcinomatosis index (PCI) were chosen as selection criteria with regard to tumor-free survival and perioperative morbidity for this multimodal therapy.RESULTS: CRS with HIPEC was successfully performed in 100 out of 150 patients. Fifty patients were excluded because of intraoperative contraindication. Median PCI was 17 (1-39). In 89% a radical resection (CC0/CC1) was achieved. One patient died postoperatively due to multiorgan failure. Neither PCI, age nor BMI was a risk factor for postoperative complications/outcome according to the DINDO classification. In 9% Re-CRS with HIPEC was performed during the follow-up period.CONCLUSION: Patient selection remains the most important issue. Neither PCI, age nor BMI alone should be an exclusion criterion for this multimodal therapy.