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.

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.

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.

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 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.

“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.

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.

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.

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.

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.

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.

Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.

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.

Laparoscopy-assisted resection of colorectal cancer with situs inversus totalis: A case report and literature review

BACKGROUND Situs inversus totalis(SIT)is a rare anomaly in which structures are located opposite to their usual positions.It is not a premalignant condition and the association with colorectal cancer(CRC)is rare.We here report a patient with SIT who underwent laparoscopic radical resection of sigmoid colon cancer,and review the pertinent literature.CASE SUMMARY A 53-year-old woman presented with CRC and SIT and underwent a complete examination after admission.The patient then underwent laparoscopic radical resection of sigmoid colon cancer and hyperthermic intraperitoneal chemotherapy.The operation duration was 120 min,and no intraoperative complications occurred.The final pathological report showed stage T4aN0M0.Postoperative chemotherapy was administered and no evidence of recurrence was observed during 18 mo of follow-up.CONCLUSION Surgery in a patient with CRC and SIT can be safely performed on the basis of routine preoperative clinical examination.

Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade

AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTS There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms.