Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives

BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.

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.

Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy on hepatocarcinoma-bearing rats,and examine the action between calcium channel blockers and cytotoxic drugs. Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of liver carcinoma-bearing rats.All experimental animals were divided into four groups.On the sixth day post implantation,in group A (control group) 6ml of saline was injected intraperitoneally once a day for 3 days.In group B(single chemotherapy group) 6ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days.In group C(combination of treatment group)both 5-Fu(75mg/kg) and verapamil (25mg/kg) were administered simultaneously as in A and B.In group D(simple verapamil group)only 6ml of verapamil(25mg/kg)was administered as above. Results Compared with groups A, B and D,The volume of cancer and the contents of liver cancer DNA and protein were significantly reduced.The rates of inhibiting cancer(89.9% in group C and 35.4% in group B)were significantly increased in groupC. Group C had significantly long survival time compared to groups A, B and D(P<0.05).By light microscopy, a number of focal necroses were found in cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitonea chemotherapy to liver cancer;The use of verapamil can not increase the toxicity of 5-Fu.

Chemotherapy with laparoscope-assisted continuous circulatory hyperthermic intraperitoneal perfusion for malignant ascites

AIM:To investigate the procedure, feasibility and effects of laparoscopeassisted continuous circulatory hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) in treatment of malignant ascites induced by peritoneal carcinomatosis from gastric cancers. METHODS: From August 2006 to March 2008, the laparoscopic approach was used to perform CHIPC on 16 patients with malignant ascites induced by gastric cancer or postoperative intraperitoneal seeding. Each patient underwent CHIPC three times after laparoscopeassisted perfusion catheters placing. The first session was completed in operative room under general anesthesia, 5% glucose solution was selected as perfusion liquid, and 1500 mg 5 fluorouracil (5FU) and 200 mg oxaliplatin were added in the perfusion solution. The second andthird sessions were performed in intensive care unit, 0.9% sodium chloride solution was selected as perfusion liquid, and 1500 mg 5FU was added in the perfusion solution alone. CHIPC was performed for 90 min at a velocity of 450600 mL/min and an in flow temperature of 43 ± 0.2℃.RESULTS: The intraoperative course was uneventful in all cases, and the mean operative period for laparoscopeassisted perfusion catheters placing was 80 min for each case. No postoperative deaths or complications related to laparoscopeassisted CHIPC occurred in this study. Clinically complete remission of ascites and related symptoms were achieved in 14 patients, and partial remission was achieved in 2 patients. During the followup, 13 patients died 29 mo after CHIPC, with a median survival time of 5 mo. Two patients with partial remission suffered from port site seeding and tumor metastasis,and died 2 and 3 mo after treatment. Three patients who are still alive today survived 4, 6 and 7 mo, respectively. The Karnofsky marks of patients (5090) increased significantly (P < 0.01) and the general status improved after CHIPC. Thus satisfactory clinical efficacy has been achieved in these patients treated by laparoscopic CHIPC. CONCLUSION: Laparoscopeassisted CHIPC is a safe, feasible and effective procedure in the treatment of debilitating malignant ascites induced by unresectable gastric cancers.

A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy

Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy.It has become a new standard of care in the management of diffuse malignant peritoneal mesothelioma and peritoneal dissemination of appendiceal malignancy.Numerous recent publications on carcinomatosis from colorectal cancer and gastric cancer identify groups of patients that would benef it from this local-regional approach for prevention and treatment of carcinomatosis.This review focuses on pharmacological information regarding intraperitoneal chemotherapeutic agents commonly used in gastrointestinal oncology.

Intraperitoneal chemotherapy and its evolving role in management of gastric cancer with peritoneal metastases

Advanced gastric cancer （GC） has been recognized as lethal disease when peritoneal metastases （PM） occurred.There is no standard treatment for advanced GC with PM.Until 1980s,the therapeutic arena for these patients had remained stagnant,with no therapeutic approach having shown a survival gain in GC with PM.However,cytoreductive surgery （CRS） with peritonectomy procedures and intraperitoneal chemotherapy （IPC） promising new combined therapeutic approach to achieve disease control for GC with PM.The recent publications changed the GC with PM treatment landscape by providing an evidence that CRS and IPC led to prolongation in overall survival （OS）.This review will provide an overview of the evolving role of CRS and IPC in the management of advanced GC with PM in the current era.

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.

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.

Intraoperative intraperitoneal chemotherapy increases the incidence of anastomotic leakage after anterior resection of rectal tumors

BACKGROUND Intraoperative intraperitoneal chemotherapy is an emerging treatment modality for locally advanced rectal neoplasms. However, its impacts on postoperative complications remain unknown. Anastomotic leakage (AL) is one of the most common and serious complications associated with the anterior resection of rectal tumors. Therefore, we designed this study to determine the effects of intraoperative intraperitoneal chemotherapy on AL. AIM To investigate whether intraoperative intraperitoneal chemotherapy increases the incidence of AL after the anterior resection of rectal neoplasms. METHODS This retrospective cohort study collected information from 477 consecutive patients who underwent an anterior resection of rectal carcinoma using the double stapling technique at our institution from September 2016 to September 2017. Based on the administration of intraoperative intraperitoneal chemotherapy or not, the patients were divided into a chemotherapy group (171 cases with intraperitoneal implantation of chemotherapy agents during the operation) or a control group (306 cases without intraoperative intraperitoneal chemotherapy). Clinicopathologic features, intraoperative treatment, and postoperative complications were recorded and analyzed to determine the effects of intraoperative intraperitoneal chemotherapy on the incidence of AL. The clinical outcomes of the two groups were also compared through survival analysis. RESULTS The univariate analysis showed a significantly higher incidence of AL in the patients who received intraoperative intraperitoneal chemotherapy, with 13 (7.6%) cases in the chemotherapy group and 5 (1.6%) cases in the control group (P = 0.001). As for the severity of AL, the AL patients who underwent intraoperative intraperitoneal chemotherapy tended to be more severe cases, and 12 (92.3%) out of 13 AL patients in the chemotherapy group and 2 (40.0%) out of 5 AL patients in the control group required a secondary operation (P = 0.044). A multivariate analysis was subsequently performed to adjust for the confounding factors and also showed that intraoperative intraperitoneal chemotherapy increased the incidence of AL (odds ratio = 5.386;95%CI: 1.808-16.042;P = 0.002). However, the survival analysis demonstrated that intraoperative intraperitoneal chemotherapy could also improve the disease-free survival rates for patients with locally advanced rectal cancer. CONCLUSION Intraoperative intraperitoneal chemotherapy can improve the prognosis of patients with locally advanced rectal carcinoma, but it also increases the risk of AL following the anterior resection of rectal neoplasms.

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.

Intraperitoneal Chemotherapy as a Multimodal Treatment for Gastric Cancer Patients with Peritoneal Metastasis

Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively;however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors.

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.

Complications and risk factors for complications of implanted subcutaneous ports for intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis

Objective:Intraperitoneal(IP)chemotherapy through subcutaneous port is an effective treatment for gastric cancer(GC)patients with peritoneal metastasis(PM).The objective of this study is to assess the port complications and risk factors for complications in GC patients with PM.Methods:In retrospective screening of 301 patients with subcutaneous ports implantation,249 GC patients with PM who received IP chemotherapy were screened out for analysis.Port complications and risk factors for complications were analyzed.Results:Of the 249 analyzed patients,57(22.9%)experienced port complications.Subcutaneous liquid accumulation(42.1%)and infection(28.1%)were the main complications,and other complications included port rotation(14.1%),wound dehiscence(12.3%),inflow obstruction(1.7%)and subcutaneous metastasis(1.7%).The median interval between port implantation and occurrence of complications was 3.0 months.Eastern Cooperative Oncology Group(ECOG)performance status[odds ratio(OR),1.74;95%confidence interval(95%CI),1.12-2.69],albumin(OR,3.67;95%CI,1.96-6.86),implantation procedure optimization(OR,0.33;95%CI,0.18-0.61)and implantation groups(OR,0.37;95%CI,0.20-0.69)were independent risk factors for port complications(P<0.05).ECOG performance status was the only factor that related to the grades of port complications(P=0.016).Conclusions:Port complications in GC patients who received IP chemotherapy are manageable.ECOG performance status,albumin,implantation procedure and implantation group are independent risk factors for port complications in GC patients with PM.

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.

Cytoreductive surgery and hyperthermic intraperitonealchemotherapy 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.

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.

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 between1999 and 2013 with a combined population of 2838patients 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.

Respiratory distress due to malignant ascites palliated by hyperthermic intraperitoneal chemotherapy

Malignant ascites is a common symptom in patients with peritoneal cancer. Current assumption is that anincreased vascular permeability and obstruction of lymphatic channels lead to the accumulation of fluid in the abdominal cavity. This case report describes a severely symptomatic patient with malignant ascites. The previously healthy 73-year-old male was presented with abdominal distention causing respiratory distress. Computed tomography revealed large amounts of ascites, a recto-sigmoidal mass with locoregional lymphadenopathy and an omental cake. Biopsy taken during colonoscopy revealed an adenocarcinoma of the colon with signet cell differentiation. A widespread peritoneal carcinomatosis was found during a diagnostic laparoscopy. The extent of peritoneal disease rendered the patient not suitable for cytoreductive surgery with curative intent. The ascites proved to be refractory to ultrasound-guided paracentesis; thus, a decision was made to perform palliative hyperthermic intraperitoneal chemotherapy without cytoreductive surgery. Consequently, ascites production stopped, and the respiratory distress was relieved thereafter. The postoperative recovery was uneventful. Ascites recurred eight months later, and a second hyperthermic intraperitoneal chemotherapy procedure was performed. The patient was still alive at the time of writing, 16 mo after the initial diagnosis.

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.

Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer

BACKGROUND Adjuvant chemotherapy using intraperitoneal(IP)treatment has demonstrated survival benefit over intravenous(IV)therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer.Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy.IP chemotherapy has not been widely adopted in clinical practice for a number of reasons.Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied.AIM To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting,and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment.METHODS We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery(group 1)or after neoadjuvant chemotherapy followed by interim surgery(group 2).RESULTS Thirty eight patients were treated with IP chemotherapy,median age was 54 years old(range 38.6 to 71 years).In group 1(n=25),12(48%)of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery;while in group 2(n=13),8(61.5%)of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery,and 2(15.4%)more patients tolerated more than 3 cycles.In those patients who did not get planned IP chemotherapy,most of them were treated with substitutional IV chemotherapy,and the completion rate for 6 cycles of IV+IP was 92%.Abdominal pain,(64%in group 1 and 38%in group 2),vomiting,(36%in group 1 and 30.8%in group 2),dehydration(16%in group 1 and 15.4%in group 2),and hypomagnesemia(12%in group 1 and 15.4%in group 2)were the most common adverse effects in all patients,while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia,fatigue and renal insufficiency.Progression free survival(PFS)was 26.5 mo(95%CI 14.9,38.0)in group 1 and 27.6 mo(95%CI 13.1,42.1)in group 2.The overall survival was 100.2 mo(95%CI 67.9,132.5)for group 1 and 68.2 mo(95%CI 32.2,104.0)for group 2.For the entire cohort,PFS was 26.5 mo(95%CI 15.9,37.0)and OS was 78.8 mo(95%CI 52.3,105.4).CONCLUSION The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting.The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable.Despite various modification of the IP regimen,incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.