Different sequential approaches of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treating ovarian cancer with malignant ascites

Background and objectives

Treatment for malignant ascites in advanced ovarian cancer (OC) patients remains controversial. The objective of this study was to investigate the efficacy of combined continuous circulatory hyperthermic intraperitoneal chemotherapy (HIPEC) preceded or followed by cytoreductive surgery (CRS) for malignant ascites in OC patients.

Methods

Female OC patients (n = 32) with malignant ascites were divided based on stable (n = 17) or unstable (n = 15) vital signs. Stable patients were treated with CRS immediately followed by HIPEC (CRS + HIPEC). Unstable patients were treated using B-mode ultrasound-guided HIPEC followed by delayed CRS upon vital sign stability (HIPEC + dCRS). All patients were followed up until death or until December 2012.

Results

Median follow-up was 29 months. All patients showed ascite regression [objective remission rates (ORR) = 100 %]. Among stable patients, CRS + HIPEC was successful in 14/17 (83.4 %). Among unstable patients, HIPEC + dCRS was successful in 13/15 (86.7 %). Median survival times were 19 and 17 months in the stable and unstable groups, respectively. No significant differences in CRS rates, ascites ORR, Karnofsky performance status scores, or survival rates were observed between groups (P > 0.05).

Conclusion

Cytoreductive surgery with immediate HIPEC and HIPEC with dCRS, determined by vital sign stability, may lead to similar outcomes in OC patients with malignant ascites.     

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.     

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases Ⅰ, Ⅱ and Ⅲ clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.     

Intraperitoneal hyperthermic chemotherapy in the management of recurrent peritoneal carcinomatosis. Preliminary results in 5 patients

Peritoneal carcinomatosis has been treated by extensive cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). We report here our experience of 5 patients treated twice or three times by recurrent procedure of HIPEC and cytoreduction. The mortality rate was 0% and morbidity one 30%. Three patients have died at 6, 10, 18 months respectively after the second cytoreduction surgery and HIPEC, and two patients are still alive at 40 and 67 months. Our results might suggest that recurrent peritoneal carcinomatosis after cytoreduction and HIPEC, could be usefully treated by another cytoreduction and HIPEC procedure in a curative approach superior to more conventional treatments.     

Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer

PurposeSeveral studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to provide a comprehensive overview of chemotherapeutic agents used for HIPEC in gastric cancer.MethodsA literature search was conducted using the PubMed database to identify studies on chemotherapy used for HIPEC in gastric cancer patients.Results and conclusionThe chemotherapeutic regime of choice in HIPEC for gastric cancer has yet to be determined. The wide variety in studies and study parameters, such as chemotherapeutic agents, dosage, patient characteristics, temperature of perfusate, duration of perfusion, carrier solutions, intraperitoneal pressure and open or closed perfusion techniques, warrant more experimental and clinical studies to determine the optimal treatment schedule. A combination of drugs probably results in a more effective treatment.     

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.     

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.     

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.     

Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from pseudomixoma peritonei

AIM： To investigate the most important aspects of hyperthermic intraperitoneal chemotherapy （HIPEC） that has been accepted as the standard treatment for pseudomyxoma peritonei （PMP）, with special regard to morbidity, overall survival （OS） and disease free survival （DFS） over 10 years. METHODS： Fifty-three patients affected by PMP underwent cytoreduction （CCR） and HIPEC with a ＂semi-closed＂ abdomen technique in our institution. The peritonectomy procedure and completeness of CCR were classified according to Sugarbaker criteria. Preoperative evaluation always included thoracic and abdominal CT scan to stage peritoneal disease and exclude distant metastases. Fifty-one patients in our series were treated with a protocol based on administration of cisplatinum 100 mg/m^2 plus mitomycin C 16 mg/m^2, at a temperature of 41.5℃ for 60 min. Anastomoses were always performed at the end of HIPEC. The mean duration of surgery was 12 h including HIPEC. Continuous monitoring of hepatic and renal functions and hydroelectrolytic balance was performed in the postoperative period. RESULTS： Twenty-four patients presented with postoperative complications： surgical morbidity was observed in 16 patients and 6 patients were reoperated. All complications were successfully treated and no postoperative deaths were observed. Risk factors for postoperative morbidity were considered to be gender, age, body surface, duration of surgery,Peritoneal Cancer Index （PCI） and tumor residual value （CC score）. No statistically significant correlation was found during the multivariate analysis： only the CC score was statistically significant. The OS in our experience was 81.8%, with a DFS of 80% at 5 years and of 70% at 10 years. CONCLUSION： In our experience, even if HIPEC combined with cytoreductive surgery involves a high risk of morbidity, postoperative complications can be resolved favorably in most cases with correct patient selection and adequate postoperative care, thus minimizing mortality. The assoc     

替吉奥联合腹腔热灌注顺铂、甘露聚糖肽对晚期胃癌合并腹腔积液患者的疗效观察

目的研究替吉奥联合腹腔热灌注顺铂、甘露聚糖肽对晚期胃癌合并腹腔积液患者的疗效。方法选取2012年2月至2015年3月在深圳市第四人民医院接受治疗的晚期胃癌合并腹腔积液患者84例,以数字法随机分为A、B、C组,每组各28例。A组予替吉奥口服联合腹腔热灌注顺铂+甘露聚糖肽,B组予腹腔热灌注顺铂+甘露聚糖肽,C组予腹腔热灌注顺铂化学治疗,对比3组的疗效。结果 A组治疗有效率、生活质量总改善率显著高于B组和C组,A组患者6个月生存率显著高于B组(P均0.05)。结论替吉奥联合腹腔热灌注顺铂、甘露聚糖肽对晚期胃癌合并腹腔积液患者的疗效显著,且预后较好。     

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.     

Preventive intraperitoneal hyperthermic perfusion chemotherapy for patients with T4 stage colon adenocarcinoma

Techniques in Coloproctology - Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be an effective treatment for peritoneal tumors; whether preventive HIPEC after radical resection...     

Comparison of serial debulking and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei of appendiceal origin

Purpose

Patients with pseudomyxoma peritonei (PMP) benefit from cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reports on this modality usually have included only patients with successful HIPEC treatment, which can potentially cause biased results. We report the survival of a PMP population treated by CRS and HIPEC, including patients who were not eligible for HIPEC.

Methods

The outcome of the whole population of 87 patients with PMP treated by CRS and HIPEC in Helsinki University Central Hospital between 2008 and 2011 was evaluated. The results of treatment were compared with 33 patients treated by serial debulking in our unit between 1984 and 2008.

Results

Of the 87 patients in the HIPEC-era group, 56 received HIPEC, 12 were treated non-radically in an attempt at HIPEC, 9 were debulked and 10 were referred back or transferred to palliative care without surgery. The 5-year overall survival for the debulking-era group and the HIPEC-era group were 67 and 69 %, respectively. The number of patients with no evidence of disease was higher in the HIPEC-era group (47/87) than that in the debulking-era group (8/33) at the end of the follow-up. Overall survival for patients who underwent successful CRS and HIPEC at 2 and 5 years was 95 and 93 %, respectively.

Conclusions

The improved survival from using the CRS and HIPEC was not apparent after 5-year follow-up, when the whole patient population was included in the analysis. Even so, patients successfully treated by CRS and HIPEC manage well.     

重组人血管内皮抑制素联合顺铂腹腔热灌注化疗对肝胆胰恶性肿瘤腹腔积液的疗效观察

目的探讨对肝胆胰恶性肿瘤腹腔积液患者采用重组人血管内皮抑制素联合顺铂腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy, HIPEC)的效果和安全性。方法将70例肝胆胰恶性肿瘤腹腔积液患者分成对照组和观察组,对照组给予顺铂行HIPEC,观察组加用重组人血管内皮抑制素行HIPEC;观察两组的肿瘤、细胞免疫和肝功能指标的变化,以及疗效和化疗毒副反应。结果 3周后两组的AFP、CEA、CA125和CD8;水平低于治疗前,CD4;和CD4;/CD8;水平升高,观察组的改善幅度高于对照组(P<0.05)。两组的ALT和TBA水平低于治疗前,ALB和Fg水平升高(P<0.05);组间差异无统计学意义(P>0.05)。观察组的ORR和DCR高于对照组(P<0.05);毒副反应率组间差异无统计学意义(P>0.05)。结论对肝胆胰恶性肿瘤腹腔积液患者采用重组人血管内皮抑制素联合顺铂行HIPEC,能控制肿瘤发展,提高细胞免疫功能,改善肝功能和疾病预后,安全性较高。     

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.     

&ldquo;En bloc&rdquo; 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.     

“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 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 ...     

Multimodality treatment of peritoneal carcinomatosis from colorectal cancer: first results of a new German centre for peritoneal surface malignancies

Background The presence of peritoneal carcinomatosis arising from colorectal cancer is associated with a poor prognosis. It was the purpose of this study to analyze morbidity, mortality, and survival after major cytoreductive surgery and intraperitoneal chemotherapy. Materials and methods Thirty-two patients with peritoneal carcinomatosis were operated between April 2004 and June 2006 with the aim of complete macroscopical cytoreduction. All had a primary colorectal carcinoma. Surgery in these patients was followed by hyperthermic intraperitoneal chemotherapy (HIPEC) consisting of mitomycin C and doxorubicin. Data were analyzed retrospectively. Results Of all patients, 16 had appendix and 16 non-appendiceal colorectal carcinoma. A macroscopically complete cytoreduction was achieved in 24 patients by parietal and visceral peritonectomy procedures. All resections were combined with HIPEC. Overall morbidity was 34%. Most frequent surgical complications were intestinal obstruction (4/32), enteric fistula (2/32), pancreatitis (2/32), and bile leakage (2/32). One patient presented grade 4 renal toxicity. There was no hospital mortality. The median follow-up was 12 months. The 1-year overall survival rate is 96%. All patients after complete cytoreduction are still alive. Conclusions Cytoreductive surgery combined with HIPEC is associated with an acceptable morbidity and low mortality. Complete cytoreduction may improve survival, particularly in well-selected patients having a low tumor volume and no extra-abdominal metastases.     

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.