Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis:A multicenter propensity scorematched cohort study

Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis

Although gastric cancer with peritoneal carcinomatosis is associated with poor prognosis and is generally treated with palliative systemic therapy, recent studies have shown that cytoreductive surgery（CRS） and hyperthermic intraperitoneal chemotherapy（HIPEC） may prove to be an efficacious treatment option. In addition to reviewing the natural history of gastric cancer with peritoneal carcinomatosis, this mini-review examines literature on the efficacy of CRS and HIPEC as compared to chemotherapy and surgical options. Both randomized and nonrandomized studies were summarized with the emphasis focused on overall survival. In summary, CRS and HIPEC are indeed a promising treatment option for gastric cancer with peritoneal carcinomatosis and large randomized clinical trials are warranted.

Role of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer

BACKGROUND Gastric cancer is the second most common malignant tumor in China,ranking third among all malignant tumor mortality rates.Hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase significantly the effectiveness of intraperitoneal chemotherapeutic drugs,prolong the action time of these drugs on intraperitoneal tumor cells,and enhance their diffusion in tumor tissues.HIPEC may be one of the best choices for the eradication of residual cancer cells in the abdominal cavity.AIM The aim of this study was to study the role of preventive HIPEC after radical gastrectomy.METHODS A prospective analysis was performed with patients with c T4 N0-3 M0 gastric cancer to compare the effects of postoperative prophylactic HIPEC plus intravenous chemotherapy with those of routine adjuvant chemotherapy.Patients’medical records were analyzed,and differences in the peritoneal recurrence rate,diseasefree survival time,and total survival time between groups were examined.RESULTS The first site of tumor recurrence was the peritoneum in 11 cases in the conventional adjuvant chemotherapy group and in 2 cases in the HIPEC group(P=0.020).The 1-year and 3-year disease-free survival rates were 91.9%and 60.4%,respectively,in the conventional adjuvant chemotherapy group and 92.1%and 63.0%,respectively,in the HIPEC group.The 1-year and 3-year overall survival rates were 95.2%and 66.3%,respectively,in the conventional adjuvant chemotherapy group and 96.1%and 68.6%,respectively,in the HIPEC group.No significant difference in postoperative or chemotherapy complications was observed between groups.CONCLUSION In patients with c T4 N0-3 M0 gastric cancer,prophylactic HIPEC after radical tumor surgery is beneficial to reduce peritoneal tumor recurrence and prolong survival.

Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer

BACKGROUND Cytoreductive surgery(CRS)in combination with hyperthermic intraperitoneal chemotherapy(HIPEC)improves patient survival in colorectal cancer(CRC)with peritoneal carcinomatosis(PC).Commonly used cytotoxic agents include mitomycin C(MMC)and oxaliplatin.Studies have reported varying results,and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited.AIM To evaluate therapeutic benefits and complications of CRS+MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors.METHODS One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed.Oxaliplatin and MMC were used in 68 and 34 patients,respectively.Each patient’s demographics and tumour characteristics,operative details,postoperative complications and survival were noted.Complications were stratified and graded using Clavien/Dindo analysis.Prognostic outcome factors were identified using univariate and multivariate analysis of survival.RESULTS The two groups did not differ significantly regarding baseline characteristics.We found no difference in median overall survival between MMC and oxaliplatin HIPEC.Regarding postoperative complications,patients treated with oxaliplatin HIPEC suffered increased complications(66.2%vs 35.3%;P=0.003),particularly intestinal atony,intraabdominal infections and urinary tract infection,and had a prolonged intensive care unit stay compared to the MMC group(7.2 d vs 4.4 d;P=0.035).Regarding univariate analysis of survival,we found primary tumour factors,nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index(PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis.Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis.CONCLUSION In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC,overall survival was not different,though oxaliplatin was associated with a higher postoperative complication rate,indicating treatment favourably with MMC.Further studies comparing HIPEC regimens would improve evidence-based decision-making.

Elemene-containing hyperthermic intraperitoneal chemotherapy combined with chemotherapy for elderly patients with peritoneal metastatic advanced gastric cancer

BACKGROUND Almost all elderly patients with peritoneal metastatic gastric cancer(PGC)are unlikely to tolerate cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy(HIPEC)and adjuvant chemotherapy.However,determining how to optimize the treatment strategy for such patients has always been a clinical problem.Both HIPEC and palliative adjuvant chemotherapy can benefit patients with PGC.Therefore,optimizing HIPEC and chemotherapy regimens has potential clinical value in reducing side effects,and improving treatment tolerance and clinical effectiveness.AIM To explore the effect of HIPEC containing elemene,which is an anti-cancer component extracted in traditional Chinese herbal medicine,combined with reduced capecitabine and oxaliplatin(CapeOx)chemotherapy regimens,in elderly patients with PGC.METHODS In the present study,39 of 52 elderly PGC patients were included and assigned to different HIPEC treatment groups[lobaplatin group(group L)and mixed group(group M)]for analysis.Lobaplatin was used for all three HIPECs in group L.In group M,lobaplatin was used in the middle of the three HIPECs,and elemene was used for the first and third HIPEC.After HIPEC,patients received CapeOx chemotherapy.The incidence of complications(abdominal infection,lung infection,and urinary tract infection),myelosuppression,immune function(CD4/CD8 ratio),average length of hospital stay,and prognosis were compared between these two groups.RESULTS There was no significant difference in the incidence of complications between the two groups during hospitalization(P>0.05).Compared to patients in group M,patients in group L exhibited severe myelosuppression(P=0.027)and increased length of hospital stay(P=0.045).However,no overall survival benefit was observed in group M.Furthermore,the immune function of patients in group M was less affected(P<0.001),when compared to that of patients in group L.The multivariate analysis suggested that the cycles of chemotherapy after perfusion significantly affected the prognosis of patients in both groups.CONCLUSION Compared to the lobaplatin-based HIPEC regimen,the administration of elemene reduced the myelosuppression incidence in elderly PGC patients.The present study sheds light on the implementation of this therapeutic strategy for this set of patients.

Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study

BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(HIPEC)treatment have never been investigated.AIM To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival.METHODS All patients with colorectal peritoneal metastases(1996-2015)completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a biinstitutional database(Uppsala and Sydney)were included in the study.Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs nonneutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered.Univariate and multivariable Cox regression models for diseasefree survival were implemented.RESULTS Two hundred and forty-six patients were identified–32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients.The neutropenia group had more combination oxaliplatin+irinotecan treatment than the nonneutropenia group(66%vs 13%,P=0.0001).The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity.Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group,P=0.07.Median disease-free survival was 16 mo vs 11 mo,respectively,P=0.02.Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio:0.58,95%confidence interval:0.36-0.95,P=0.03.CONCLUSION 13%of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity.Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment.This is in direct contrast to the current paradigm of decreasing the treatment intensity.

Risk factors for postoperative delayed gastric emptying in ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(CRSHIPEC)has shown promising results in improving the survival of ovarian cancer patients.Although the safety profiles of CRS-HIPEC exist,more attention should be paid to gastrointestinal complications,as the procedure involves a considerable proportion of bowel resection and anastomosis.AIM To identify the risk factors for delayed gastric emptying in ovarian cancer treated with CRS-HIPEC.METHODS A cross-sectional study was conducted.According to the inclusion and exclusion criteria,we retrospectively analyzed 77 patients admitted between March 2014 and April 2018 with advanced and recurrent ovarian cancer treated with CRSHIPEC in Beijing Shijitan Hospital of Capital Medical University.Risk factors for delayed gastric emptying were analyzed using univariate analysis.All of the statistically significant variables in the univariate analysis were entered into the multivariable logistic regression model to determine factors independently associated with delayed gastric emptying.RESULTS Among the 77 included patients,36.4%(28/77)had delayed gastric emptying after CRS-HIPEC.The median age and body mass index of all patients were 59 years and 22.83 kg/m^(2),respectively.Preoperative chemotherapy was administered in 55 patients(71%).Sixty-two patients(81%)had a history of at least one previous pelvic surgery.The median operation time and intraoperative hemorrhage volume were 630 min and 600 mL,respectively.Omentectomy was performed in 32 cases of primary ovarian cancer and 24 cases of recurrence.The median peritoneal cancer index was 16.The risk factors for delayed gastric emptying from the univariate analysis were body mass index<23 kg/m2(X2=5.059,P=0.025),history of pelvic surgery(X^(2)=4.498,P=0.034),history of chemotherapy(X^(2)=4.334,P=0.037),operation time≥7 h(X2=4.827,P=0.047),and intraoperative hemorrhage≥800 mL(X^(2)=7.112,P=0.008).Multivariable analysis revealed that age≥70 years(HR=7.127;95%CI 1.122-45.264;P=0.037)and intraoperative hemorrhage≥800 mL(HR=3.416;95%CI 1.067-10.939;P=0.039)were independently associated with postoperative delayed gastric emptying after CRS-HIPEC.CONCLUSION Postoperative gastrointestinal management,including prolonged nasogastric intubation,should be promoted for patients over 70 years or those with intraoperative bleeding exceeding 800 mL.

Hyperthermic intraperitoneal chemotherapy and colorectal cancer:From physiology to surgery

The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy(HIPEC) and cytoreductive surgery(CRS) used in colorectal cancer(CRC).We focus on principal biological aspects of CRC,hyperthermia effects,and surgical procedures.We searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment(CRS + HIPEC) against local and advanced CRC.In the literature,from several studies,it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall survival.Despite these studies,there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with CRC.Even if the concept is still not very clear and shared,after a careful evaluation of the published data,and after some technical and pathophysiological descriptions,we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced(pT4) CRC with peritoneal metastases.

The impact of urological resection and reconstruction on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Objective:Cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)are increasingly being used to treat peritoneal malignancies.Urological resections and reconstruction(URR)are occasionally performed during the surgery.We aim to evaluate the impact of these procedures on peri-operative outcomes of CRS and HIPEC patients.Methods:A retrospective review of a prospectively maintained database of all patients who underwent CRS-HIPEC from April 2001 to February 2016 was performed.Outcomes between patients who had surgery involving,and not involving URR were compared.Primary outcomes were the rate of major complications and the duration of stay in the intensive care unit(ICU)and hospital.Secondary outcomes were that of overall survival(OS)and prognostic factors that would indicate a need for URR.Results:A total of 214 CRS-HIPEC were performed,21 of which involved a URR.Baseline clinical characteristics did not vary between the groups(URR vs.No URR).Urological resections comprised of 52%bladder resections,24%ureteric resections,and 24%involving both bladder and ureteric resections.All bladder defects were closed primarily while ureteric reconstructions consisted of two end-to-end anastomoses,one ureto-uretostomy,five direct implantations into the bladder and three boari flaps.URR were more frequently required in patients with colorectal peritoneal disease(p Z 0.029),but was not associated with previous pelvic surgery(76%vs.54%,p Z 0.065).Patients with URR did not suffer more serious complications(14%vs.24%,p Z 0.42).ICU(2.2 days vs.1.4 days,p Z 0.51)and hospital stays(18 days vs.25 days,p Z 0.094)were not significantly affected.Undergoing a URR did not affect OS(p Z 0.99),but was associated with increased operation time(570 min vs.490 min,p Z 0.046).Conclusion:While concomitant URR were associated with an increase in operation time,there were no significant differences in postoperative complications or OS.Patients with colorectal peritoneal metastases are more likely to require a URR compared to other primary tumours,and needs to be considered during pre-operative planning.

Immune response activation following hyperthermic intraperitoneal chemotherapy for peritoneal metastases:A pilot study

BACKGROUND Hyperthermic intraperitoneal chemotherapy(HIPEC)for peritoneal metastases(PM)is considered to be feasible,safe and to improve survival.AIM To investigate whether an immune response is activated following HIPEC for PM.METHODS Six patients were enrolled in this study.Peripheral blood samples were obtained from each patient prior to(day 0)and post-procedure(day 30),and used to evaluate the number of CD3+total,CD3+/CD4+T-Helper,CD3+/CD8+cytotoxic T,CD3+/CD56+natural killer and CD19+B lymphocyte numbers,and CD4+:CD8+T lymphocyte ratios.RESULTS The total numbers of CD3+,CD3+/CD4+T-Helper,CD3+/CD8+cytotoxic T,CD3+/CD56+natural killer and CD19+B lymphocytes,and CD4+:CD8+lymphocyte ratios were increased in all but one patient 30 d following the cytoreductive surgery-HIPEC procedure,and these increases were significant(P≤0.05)for CD3+/CD4+T Helper and CD3+/CD8+cytotoxic T lymphocyte numbers.CONCLUSION This report provides the first evidence that HIPEC exhibits immunomodulating activity in PM patients,resulting in generalized activation of the adaptive immune response.Moreover,the majority of lymphocyte populations increased following HIPEC and continued to be elevated several weeks following the procedure,consistent with a potential authentic immunomodulating effect rather than a normal inflammatory response,to be fully characterised in future studies.

Quality of life and symptom distress after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(CRS/HIPEC)for peritoneal surface malignancy can effectively control the disease,however it is also associated with adverse effects which may affect quality of life(QoL).AIM To investigate early perioperative QoL after CRS/HIPEC,which has not been discussed in Taiwan.METHODS This single institution,observational cohort study enrolled patients who received CRS/HIPEC.We assessed QoL using the Taiwan residents version of the MD Anderson Symptom Inventory(MDASI-T)and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire(EORTC QLQ-C30).Participants completed the questionnaires before CRS/HIPEC(S1),at the first outpatient follow-up(S2),and 3 mo after CRS/HIPEC(S3).RESULTS Fifty-eight patients were analyzed.There was no significant perioperative difference in global health status.Significant changes in physical and role functioning scores decreased at S2,and fatigue and pain scores increased at S2 but returned to baseline at S3.Multiple regression analysis showed that age and performance status were significantly correlated with QoL.In the MDASI-T questionnaire,distress/feeling upset and lack of appetite had the highest scores at S1,compared to fatigue and distress/feeling upset at S2,and fatigue and lack of appetite at S3.The leading interference items were working at S1 and S2 and activity at S3.MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results.CONCLUSION QoL and symptom severity improved or returned to baseline in most categories within 3 mo after CRS/HIPEC.Our findings can help with preoperative consultation and perioperative care.

Postoperative complications and critical care management after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy: A systematic review of the literature

BACKGROUND Cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)is a comprehensive treatment option performed for peritoneal surface malignancies.Postoperatively almost all patients are transferred to the intensive care unit electively.AIM To describe the common and rare postoperative complications,postoperative mortality and their critical care management after CRS-HIPEC.METHODS The authors assessed 54 articles for eligibility.Full text assessment identified 14 original articles regarding postoperative complications and critical care management for inclusion into the final review article.RESULTS There is an exaggerated metabolic and inflammatory response after surgery which may be termed as physiological in view of the nature of surgery combined with the use of heated intraperitoneal chemotherapy with/out early postoperative intravenous chemotherapy.The expected postoperative course is further discussed.CRS-HIPEC is a complex procedure with some life-threatening complications in the immediate postoperative period,reported morbidity rates between 12%-60%and a mortality rate of 0.9%-5.8%.Over the years,since its inception in the 1980s,postoperative morbidity and survival have significantly improved.The commonest postoperative surgical complications and systemic toxicity due to chemotherapy as reported in the last decade are discussed.CONCLUSION CRS-HIPEC is associated with a varying rate of postoperative complications including postoperative deaths and needs early suspicion and intensive care monitoring.

Early and long-term postoperative management following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Peritoneal surface malignancies have been traditionally regarded as end-stage conditions amenable to merely palliative options. The combination of aggressive cytoreductive surgery (CRS), involving peritonectomy procedures and multivisceral resections, with intra-operative hyperthermic intra-peritoneal chemotherapy (HIPEC) and/or early postoperative intra-peritoneal chemotherapy (EPIC) to treat the microscopic residual tumor is a new concept. In recent years, promising results have been reported for peritoneal mesothelioma and carcinomatosis of gastrointestinal and gynaecologic origin treated by this combined protocol. However, CRS with HIPEC and/or EPIC is a complex procedure associated with high rates of potentially life-threatening complications. Furthermore, disease progression following comprehensive treatment is not uncommon and represents a relevant cause of treatment failure. The present paper reviews the available information on early postoperative management and long-term follow-up in patients treated with CRS and intraperitoneal chemotherapy. The peculiar clinical and biological alterations that can be expected during an uncomplicated postoperative course, as compared to standard digestive surgery, are discussed. Early recognition and appropriate management of the most common adverse events are addressed, in order to minimize the impact of treatment-related morbidity on survival and quality of life results. Since re-operative surgery with additional HIPEC, has proven to be useful in selected patients with recurrent disease, long-term surveillance aiming at early detection of postoperative disease progression has become a relevant issue. Current results on follow-up investigations are presented.

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.

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 classifi ed 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/m2 plus mitomycin C 16 mg/m2,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 re-operated. 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 signifi cant 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 association of CCR and HIPEC can be considered as the standard treatment for PMP. The OS and DFS results confi rm the validity of this combined approach for the treatment of this rare neoplasm. The impact of preoperative chemotherapy on OS,in our opinion,is due to a major aggressiveness of tumors in treated patients.

Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis.Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier.Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients.Patient selection for this multimodal approach is one of the most critical issues,and calls for interdisciplinary evaluation by radiologists,medical and surgical oncologists,and anaesthetists.This article sets forth criteria for selection of gastric cancer patients suffering from peritoneal carcinomatosis.

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.

MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers(AGCs) before and after cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC). METHODS: A miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patientswith AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells. RESULTS: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo(0.5 vs 0.78, P < 0.05).CONCLUSION: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.

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.