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AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.
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@#Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC). CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified. However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines. Remarkable increase of cytokine level is a major characteristics of CRS. However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction. CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients. Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients. This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.
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Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.
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Corona virus disease 2019 (COVID-19) is an infec¬tious disease endangering the respirator)' traet and multiple or¬gans of the whole body caused by severe aeute respirator)' syn¬drome coronavirus 2 ( SARS-CoV-2).More than 200 million people in the world have been infected with the disease, which is an unprecedented global plague.Most patients with C0VID-19 only show mild symptoms with a good prognosis, but about 20% of them may develop into severe cases and eause serious compli-cations, including acute respirator)' distress syndrome ( ARDS) , systemic inflammatory response syndrome (SIRS) , cytokine re¬lease syndrome (CRS) , etc.Pyroptosis is a kind of programmed cell death characterized by significant inflammatory response.It is often mediated by inflammatory caspase and the gasdermin family of membrane perforating proteins is the final effector mol¬ecules, resulting in cell membrane swelling and rupture to death, accompanied by the release of a large number of pro-in¬flammatory cytokines (such as IL-lp and IL-18, etc).Pyropto- sis affects the occurrence, progression and treatment of many diseases due to its inflammatory and morphological characteris¬tics, and also plays an important role in severe COVID-19.Therefore, drugs that target key molecules in the pyroapoptotic pathway could he a promising breakthrough for treating severe COVID-19.This article reviews the role of pyroptosis in severe COVID-19 complications ARDS and CHS.
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Abstract The objective of this systematic review is to provide efficacy and safety data in the application of Intra-Abdominal Hyperthermia Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS) in patients with Peritoneal Pseudomyxoma (PMP) of origin in the cecal appendix. The databases Medline and Central Cochrane were consulted. Patients with PMP of origin in the cecal appendix, classified as low grade, high or indeterminate, submitted to HIPEC and CRS. The results were meta-analyzed using the Comprehensive Metanalysis software. Twenty-six studies were selected to support this review. For low-grade PMP outcome, 60-month risk of mortality, Disease-Free Survival (DFS), and adverse events was 28.8% (95% CI 25.9 to 32), 43% (95% CI 36.4 and 49.8), and 46.7% (95% CI 40.7 to 52.8); for high-grade PMP, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 55.9% (95% CI 51.9 to 59.6), 20.1% (95% CI 15.5 to 25.7) and 30% (95% CI 25.2 to 35.3); PMP indeterminate degree, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 32.6% (95% CI 30.5 to 34.7), 61.8% (95% CI 58.8 to 64.7) and 32.9% (95% CI 30.5 to 35.4). The authors conclude that the HIPEC technique and cytoreductive surgery can be applied to selected cases of patients with PMP of peritoneal origin with satisfactory results.
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@#[摘 要] 嵌合抗原受体基因修饰T淋巴细胞(CAR-T)免疫治疗尤其在复发/难治性恶性血液病的临床应用中显示出卓越的疗效,被认为是最有前景的肿瘤治疗方法之一,但是CAR-T免疫治疗中可引发独特的毒性作用,其中细胞因子释放综合征(cytokine release syndrome,CRS)和免疫效应细胞相关神经毒性综合征(immune effector cell-associated neurotoxicity syndrome,ICANS)在临床应用中最为常见,并具有潜在的致死性,使得CRA-T疗法的广泛应用受到一定的限制,因此如何最大程度地利用CAR-T免疫治疗的同时努力减少或预防CRS和ICANS的发生是目前临床研究的重点,深入了解CRS和ICANS的发生机制能为新的预防措施提供思路。早期识别相关危险因素及鉴定生物预测标志物,熟悉其分级与治疗措施,有利于规范CAR-T免疫疗法的临床应用和患者安全管理。本文就CRS和ICANS的危险因素、发生机制、临床表现、分级与治疗和预防措施等方面进行综述,旨在为CAR-T疗法常见毒性作用的规范管理提供帮助。
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@#[Abstract] Objective: To investigate whether AP1903, a small-molecule chemical inducer, can terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vivo and in vitro. Methods: CD19CAR-T cells over-expressing iCasp9 (iCasp9-CD19CAR-T) were constructed and co-incubated with AP1903. Then, the cell phenotype and apoptosis were detected by Flow cytometry, and the iCasp9/CID suicide gene system was verified on K562 and T cells, respectively. The cytotoxicity of iCasp9-CD19CAR-T cells was detected in vivo (survival rate of NCG mice bearing Raji cell transplanted xenograft) and in vitro (cell killing function was detected by Flow cytometry) under the administration of AP1903. Results: Compared with CD19CAR-T cells, iCasp9-CD19CAR-T cells showed in significant difference in proliferation, phenotype and cytotoxicity both in vitro and in vivo (all P>0.05). At 2 h after AP1903 administration, the apoptosis rates of K562 and T cells co-expressing iCasp9 and CD19CAR were (33.8±0.9)% and (27.95±0.35)%, respectively; and at 24 h after AP1903 administration, the apoptosis rates reached 100% in both cell lines. The in vitro cytotoxicity of iCasp9-CD19CAR-T cells induced by AP1903 was significantly lower than that without AP1903 treatment (P<0.01); the 60-day survival rate of mice bearing Raji cell transplanted tumor treated with AP1903-induced iCasp9-CD19CAR-T cells was also significantly lower than those treated with iCasp9-CD19CAR-T cells alone (P<0.01). Conclusion: AP1903 can effectively terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vitro and in vivo.
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【Objective】 To investigate the clinical application value of low dose dexamethasone in CRS prevention after CD19 CAR-T therapy. 【Methods】 67 cases of acute lymphoblastic leukemia(ALL) patients from January 2018 to March 2021 were selected as the research subjects. According to the admission time, patients were divided into dexamethasone prevention(DDD≤5 mg)group(n=36)and the control(n=31). The incidence of severe CRS and treatment outcome were compared. 【Results】 In the dexamethasone prevention group and the control, the incidence of severe CRS were 8.3%(3/36)vs 38.7%(12/31)(P0.05), the complete remission rate was 91.7%(33/36)vs 87.1%(27/31)(P>0.05), and the infection rate was 33.3%(12/36)vs 35.4%(11/31)(P>0.05). 【Conclusion】 The low dose dexamethasone as a prophylactic could significantly reduce the incidence of severe CRS, but had no influence on CAR-T cell proliferation and treatment outcome.
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Objective:To explore the effects of Shenwei Ningyu pills (SNP), a new Chinese medicine for depression, on the immunoinflammatory response mediated by Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway in the hippocampus of rats exposed to chronic restraint stress (CRS). Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group, a model group, an escitalopram group, and an SNP group. Except for the rats in the normal group, all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram (30 mg·kg<sup>-1</sup>) and SNP (18 mg·kg<sup>-1</sup>) one hour prior to CRS, respectively. The changes in body weight, sucrose preference index, horizontal movement scores, and vertical movement scores were observed by body weight assessment, sucrose preference test, and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1<italic>β</italic> (IL-1<italic>β</italic>), IL-10, and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) was detected by enzyme-linked immunosorbent assay (ELISA). Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However, significant differences were found among the groups following different interventions. The body weight, sugar preference index, horizontal movement score, and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group (<italic>P</italic><0.01). The above indicators in the SNP<italic> </italic>group and the escitalopram group were higher than those in the model group (<italic>P</italic><0.01), which indicated that SNP<italic> </italic>exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group, the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1<italic>β</italic> and TNF-<italic>α </italic>(<italic>P</italic>˂0.01) and dwindled serum IL-10 (<italic>P</italic>˂0.01), while SNP<italic> </italic>and escitalopram reversed the conditions in the model group (<italic>P</italic>˂0.01) except for TNF-<italic>α</italic>. Conclusion:The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.
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Peritoneal carcinomatosis is obtaining extensive attention because of its late detection and poor prognosis. Lately, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are widely used for the treatment of this condition and could be effective in some carefully selected patients. Different chemotherapies are combined with CRS or HIPEC, and different drug administration routes are used, such as intraperitoneal or pressurized intraperitoneal aerosol chemotherapy. Furthermore, the results of many clinical trials differed among patients with different types of cancer. Herein, we reviewed recent studies in patients with gastric, colon, and ovarian cancer to evaluate the progress of chemotherapy for peritoneal carcinomatosis.
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Objective: To construct a predictive model to assess the completeness of cytoreduction (CC) and help guiding selection for cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) in patients with gastric cancer with peritoneal metastasis (GCPM). Methods: GCPM patients treated with CRS+HIPEC at Beijing Shijitan Hospital were enrolled in this study. The major clinicopathologic and therapeutic characteristics were compared between those with complete CRS (CCRS) and incomplete CRS (ICRS). A nomogram based on a Logistic regression model was constructed for predicting the risk of ICRS. The nomogram was evaluated using area under receiver operating characteristic curve (AUC) and validated using the bootstrap resampling method. The probability of CCRS was predicted using the nomogram. Results: Among the included 125 patients with GCPM, 52 had CC0 cytoreduction and 73 had CC1-3 cytoreduction. The median overall survival (mOS) was 30.0 (95% CI: 16.8-43.3) months in the CC0 group, which was significantly longer than the mOS of 7.3 (95% CI: 5.8-8.8) months in the CC1-3 group (P<0.001). As there were no significant differences in OS among the CC1, CC2, and CC3 groups, CC0 patients were included in the CCRS group and CC1-3 patients were included in the ICRS group. Multivariate Logistic regression demonstrated that the time of peritoneal metastasis development (OR=14, 95% CI: 2.0-97.9, P= 0.008), preoperative tumor markers (TM) (OR=6.5, 95% CI: 2.1-37.8, P=0.037), and peritoneal cancer index (PCI) (OR=1.5, 95% CI: 1.3-1.8, P<0.001) were independent predictive factors for ICRS. The AUC of the nomogram was 0.985. Internal validation displayed good accuracy and consistency between the predictions and the actual observations. The cutoffs of PCI, with the probability of CCRS set at ≥ 50%, were ≤16, ≤12, ≤10, and ≤5 for synchronous GCPM with normal TM, synchronous GCPM with abnormal TM, metachronous GCPM with normal TM, and metachronous GCPM with abnormal TM, respectively. Conclusions: Complete CRS+HIPEC improves the survival of some patients with GCPM. A selection strategy based on PCI combined with the time of peritoneal metastasis development and TM may be a practical way for selecting patients with GCPM eligible for CCRS.
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Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is gradually being accepted as the standard treatment for PMP. At Aerospace Hospital, we have been treating patients with PMP since 2008 and performing total peritoneal resection since 2016. This study summarizes the experience at our center and collates past data. Methods: We performed a retrospective analysis of a prospectively maintained database of all patients who had undergone CRS and HIPEC for PMP at our center. Clinical data, such as the surgical approach, completeness of cytoreduction, and surgical complications, were collected. The results from follow-up were analyzed to simultaneously evaluate the clinical value of CRS+HIPEC and peritonectomy procedures. Results: A total of 854 consecutive patients with PMP were included in the study. Their mean age was 50 years. The median modified peritoneal cancer index (PCI) was 29. Of the patients, 25.5% under-
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Peritoneal cancer originates from a wide range of tumor sources and is associated with poor prognosis. Standardized therapy is of great significance in the treatment for patients with peritoneal cancer. The Peritoneal Surface Oncology Group International (PSOGI) instituted guidelines for peritoneal metastases. This article uses the Chinese version, which is divided into four parts: preoperative evaluation, surgery, chemotherapy, and clinical pathway. The preoperative evaluation consists of preoperative computed tomography, prognostic evaluation model, diagnostic laparoscopic exploration, the peritoneal cancer index, and the cytoreduction score. Peritoneal cancer treatment primarily consists of comprehensive treatment with cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy. However, complete CRS is the key to the long-term survival of patients. Peritoneal cancer chemotherapy generally includes perioperative chemotherapy and regional chemotherapy. Finally, this guide outlines the clinical pathways. The Chinese version of the guidelines was published under the permission of the Secretary-General of the PSOGI Executive Committee.
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The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.
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Humanos , Terapia Baseada em Transplante de Células e Tecidos , Imunoterapia Adotiva , Linfoma/terapia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos QuiméricosRESUMO
OBJECTIVE: To investigate the hygroscopicity of vitamin B12 and the related problems of its chemical reference substance (CRS) that should be paid attention to. METHODS: UV absorption coefficient was determined at 361 nm, using water as solvent. Dynamic vapor absorption analysis (DVS) was applied to evaluate the moisture sorption trend and capacities of vitamin B12 under different humilities. RESULTS: Owing to the strong hygroscopicity of vitamin B12, deviation in the process of weighing might result in smaller UV absorption coefficient compared with the actual value, especially for dried and low moisture content raw materials in high-humidity environment. CONCLUSION: In the study of drug quality control for vitamin B12, the strong hygroscopicity of the raw material should be paid attention to, particularly in the research and application of vitamin B12 CRS.
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Humanos , Prontuários Médicos , Métodos , Prurido , Recidiva , Rinite , Rinite Alérgica , Pele , EspirroRESUMO
Objective: To investigate the clinicopathological features and treatment strategy of pseudomyxoma peritonei (PMP) of ex-tra-appendiceal origin. Methods: Clinical data of 34 patients diagnosed with PMP of extra-appendiceal origin who were treated by cy-toreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the Aerospace Center Hospital from September 2011 to February 2019 were retrospectively analyzed. Clinical and imaging features were summarized and the Log-rank test was used for survival analysis. Results: The clinical manifestations of the 34 patients with PMP of extra-appendiceal origin were mainly abdomi-nal distension (58.8%) and abdominal pelvic mass (52.9%), which are very similar to those of appendiceal PMP. The incidence of main complications after CRS and HIPEC was 14.7%. During the follow-up period of a median of 12 months (range 1-46 months), 9 patients died, and the 1-and 3-year overall survival rates were 69.6% and 53.5%, respectively. In the univariate analysis, peritoneal cancer in-dex (PCI)>20, no HIPEC, and non-radical surgery were significant risk factors for poor prognosis, while gender, age, origin, and patho-logical type did not show significant correlations. Conclusions: The clinical features of PMP of extra-appendiceal origin are not differ-ent to those of PMP originating from the appendix. It is difficult to ascertain the primary lesion before the operation; however, regard-less of the origin, CRS combined with HIPEC is always a safe and effective treatment choice.
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Objective To study the load transfer mechanics between residual limb and prosthetic socket, as well as stress distributions below the residual limb, so as to provide a theoretical basis for designing and optimizing of prosthetic socket and improving the wearing comfort. Methods Aiming at compression-release stabilization (CRS), the finite element software ABAQUS was used to analyze the stress distribution at the interface between the residual limb and CRS socket. The soft tissues were defined using the Mooney-Rivlin function. The interface pressures and shear stresses between the residual limb and CRS socket during mid-stance were obtained. A three-dimensional finite element model of the patellar tendon bearing (PTB) socket was established, and the results were compared. Results The interface pressures between the residual limb and CRS socket were mainly distributed at lateral tibia, media tibia and popliteal depression regions, which were similar to the main force regions of PTB socket. The mean interface pressures on the end of stump for CRS socket was increased by 19 kPa over PTB socket. Conclusions CRS socket had better breathability and reasonable stress distributions. The stress distribution of biomechanical interface was different due to the different shapes of socket. Therefore, the optimization of prosthetic socket can help to improve the wearing comfort of prosthetic limbs.
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Background: Chronic rhinosinusitis (CRS) is a pathogenic disease of infection commonly affected the ear, nose and throat. Chronic Rhinosinusitis (CRS) has a serious negatively impact over quality of life of patients. Quality of life, nature of job and environmental conditions are the primary reasons of spread of rhinosinusitis. Most of the symptoms of CRS are not life threatening but generally these leads to poor quality of life by affecting the efficiency of individuals. Methods: This prospective study was conducted in the department of ENT in tertiary care hospital among the 50 patients with clinical presentation, endoscopy examination and CT-scan changes of chronic rhinosinusitis (CRS) without a polyp. The history of the patients were taken and then the different ENT examinations were done like endoscopic examination of the nose and CT-scan imaging. All the surgeries like uncinectomy, middle meatal antrostomy, anterior and posterior ethmoidectomy, or opening of the sphenoid sinus were performed under general anesthesia with orotracheal intubation and hypotensive technique. All the patients were regularly given the postoperative antibiotic and nasal steroid treatments and reviewed regularly. Sinonasal Assessment Questionnaire - 11 (SNAQ-11) were used for the collection of data because this questionnaire contains 11 questions covering most of the symptoms of sinonasal diseases. Results: ‘Total 50 patients were included in this study among them 32 (64%) were male and 18 (36%) were females. All the patients was between 18-60 years among them 16 (32%) were the age group 25-35 years, followed by age group 35-45 years 14 (28%). The most common preoperative complaint of the patients was nasal obstruction (100%) patients, followed by nasal congestion (96%), facial pain (94%), running nose (90%), anterior nasal discharge (76%), and least complaint was sneezing (28%) and earache (28%). Conclusion: The study concludes, this study shows the significant outcome of improvement in the quality of life of patients in all the three subgroups of chronic rhinosinusitis which can be assessed by using SNOT-11 questionnaire. The Functional endoscopic sinus surgery performed in patients with chronic rhinosinusitis has statistically significant with the association of improvement in the QoL after twenty 24 month follow up. There is paucity of data so more studies are required to the scientific evidence gathered on the effectiveness of surgery offered to our population, as seen in studies performed in other countries.
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Peritoneal metastases (PM) are the common endpoint for patients with advanced gastrointestinal cancers. PM from these cancers are often managed in a similar fashion to other sites of systemic metastases, but the following must be taken into consideration. (a) PM do not respond to systemic chemotherapy in the same fashion as liver and lung metastases. (b) PM cause local problems, resulting in disruption of chemotherapy. (c) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) actually work for PM. (d) PM are not easily detected on imaging modalities. There has been mounting evidence of the effectiveness of CRS-HIPEC at prolonging survival in selected patients with colorectal and gastric PM, but there remains a reluctance to explore this treatment modality. This is likely because of the perceived morbidity and mortality. An effective management strategy employing CRS-HIPEC for selected patients with gastrointestinal PM can only be achieved if a concerted effort is made to understand this disease and address the concerns regarding this treatment.