Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

Perioperative Systemic Chemotherapy,Cytoreductive Surgery,and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab.

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Evaluation of: Yang XJ, Huang CQ, Suo T et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a Phase III randomized clinical trial. Ann. Surg. Oncol. 18(6), 1575–15781 (2011).

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.     

细胞减灭术加腹腔热灌注化疗治疗结直肠癌腹膜转移癌病例对照研究

  目的  分析细胞减灭术（CRS）加术中腹腔热灌注化疗术（HIPEC）对结直肠癌腹膜转移癌的疗效及安全性。  方法  课题设计为回顾性病例对照研究, 收集结直肠癌腹膜转移癌（CRC PC）患者资料, 按临床病理参数匹配原则, 分为CRS组（CRS+术后全身化疗）29例, HIPEC组（CRS+HIPEC+术后全身化疗）33例。分析两组的总体生存期（OS）及严重不良事件（SAE）。  结果  两组患者临床病理学特征均衡可比, 术中PCI评分及器官/腹膜切除情况相似。两组中位随访时间分别为41.9个月（6.5~110.0个月）和32.0个月（10.5~95.9个月）, OS分别为8.5个月（95% CI: 4.9~12.1个月）和14.5个月（95% CI: 11.9~17.1月）（P=0.007）。术后30天内CRS组3例发生SAE, HIPEC组9例（P=0.126）。多因素分析显示, HIPEC、CC 0~1分、术后化疗周期≥6个周期为改善生存的独立预后因素。  结论  CRS+HIPEC可改善CRCPC患者生存期, SAE无显著增加, 安全性可接受。      

Outcomes in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for maximal volume (PCI 39) appendiceal tumours

BackgroundHigher Peritoneal Cancer Index (PCI) requires more extensive surgery and maybe associated with more limited outcomes. The aim of this study in a high-volume centre in Australia was to analyse the outcomes in PCI 39 patients regarding short and long term outcomes in appendiceal tumours.MethodsA retrospective analysis of prospectively maintained database of patients that underwent primary cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) with PCI 39 at St George Hospital, Sydney from 1996 to 2018. Patients with appendiceal tumours (inclusive of high and low grade) were analysed. Factors contributing to high grade (III/IV Clavien-Dindo) morbidity and mortality were assessed.ResultsOf the 1201 patients in the database, 58 patients had a PCI 39 from appendix tumours at their first operation. The overall survival rate at 1, 3 and 5 year was 91.2%, 79.5% and 62.9% respectively. The median survival was 87.2 months (96% CI 51.8-NR). The rate of major morbidity was 71%. The postoperative mortality incidence was 1.7%. The median hospital length of stay was 34 days (IQR:27–54 days).ConclusionsIn an experienced centre CRS + HIPEC is safe in selected patients with PCI 39. Despite the high morbidity, the overall survival for appendiceal tumours appear considerably better than debulking surgery.     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜癌的临床观察

目的 分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery, CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）治疗腹膜癌（peritoneal carcinoma, PC）的围手术期安全性及疗效。 方法 PC患者行CRS+HIPEC治疗,药物为洛铂50 mg/m2、多西他赛60 mg/m²,加入12 000 ml 0.9%氯化钠溶液加热至（43±0.5）℃持续灌注60 min。记录术后6天体温和心率变化、围手术期不良事件、血常规及血生化指标、术后患者恢复情况及生存结果。结果 90例PC患者行95次CRS+HIPEC,手术时间180~450 min (中位数485 min）;术后6天最高体温、心率分别为36.4℃~38.6℃（中位数37.5℃）、76~124 bpm（中位数100 bpm）,严重不良事件16例,包括围手术期死亡2例。中位生存期20.8月（95%CI: 13.1~25.8月）,1、3、5年生存率分别为75.6%、45.6%、43.3%。 结论 洛铂联合多西他赛进行CRS+HIPEC治疗PC安全性可接受,有助于延长患者生存期。     

CRS对比CRS+IP与CRS+HIPEC治疗上皮性卵巢癌辅助化疗时间及预后的前瞻性观察研究

  目的  完全肿瘤细胞减灭术（cytoreductive surgery,CRS）及术后辅助化疗,是晚期原发性上皮性卵巢癌（epithelial ovarian cancer,EOC）的重要预后因素。然而,EOC患者接受辅助化疗开始时机及其与预后的关系尚不明确,值得深入探讨。  方法  本研究选取2010年1月至2017年12月在印度班加罗尔马尼帕尔综合癌症中心接受完全细胞减灭术的185例晚期原发性EOC患者,其中部分患者接受腹腔化疗或辅助化疗,部分患者未接受腹腔化疗和辅助化疗。分别记录并分析术后开始进行辅助化疗的时间及其对预后的影响。  结果  接受单纯CRS、CRS联合经腹腔港的腹腔内化疗（intraperitoneal chemotherapy,IP）或腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）的患者分别为50例、60例和75例。CRS组术后开始接受辅助化疗的平均时间为32天,CRS+IP组为34天,CRS+HIPEC组为41天。CRS组中,术后化疗间隔时间>42天对无复发生存（relapse-free survival,RFS）期有显著影响（36个月 vs. 17个月:P=0.02）;在CRS+IP组中,患者RFS差异无统计学意义（35个月vs. 28个月;P=0.78）;CRS+HIPEC组,RFS差异无统计学意义（35个月 vs. 32个月;P=0.17）。如期行辅助化疗患者生存期较延迟化疗更好（88个月 vs. 71个月,P=0.49）。  结论  化疗时间延迟是单纯接受完全CRS患者RFS的不良预后因素。与非HIPEC组相比,化疗时间延迟对HIPEC组患者并未产生显著影响,其原因可能在于术中单次HIPEC弥补了化疗时间延迟带来的不利影响。      

Does early post-operative intraperitoneal chemotherapy (EPIC) for patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) make a difference?

Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early post-operative intraperitoneal chemotherapy (EPIC). We compared the morbidities, overall survival (OS) and disease free survival (DFS) between two groups of patients who underwent CRS and HIPEC alone and with EPIC at our institution. Methods: A retrospective review of 111 patients with PC who were treated with CRS?+?HIPEC or CRS?+?HIPEC?+?EPIC in a single institution between January 2008 and April 2014 was performed. EPIC with 5-fluorouracil or paclitaxel was utilised, depending on the primary tumour. Results: Patients who received EPIC had a higher proportion of grade III and above post- operative complications (58% versus 25%; p?=?0.048) and a longer duration of hospitalisation (16 days versus 13 days; p?=?0.019) than patients without EPIC. There were no significant OS and DFS differences between the EPIC and no EPIC groups (log-rank p?=?0.231 and p?=?0.144, respectively). Conclusion: The use of EPIC after CRS?+?HIPEC for PC potentially results in increased morbidity and longer hospitalisation, and is unlikely to affect survival outcomes. Based on our experience, EPIC is not recommended after CRS and HIPEC.     

Does having a gastrectomy delay time to feeding and prolong hospital stay in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

Aim: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used to treat selected patients with peritoneal carcinomatosis, but can be associated with prolonged hospital stay, significant morbidity and mortality. Our objective was to assess whether patients undergoing gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time and prolonged hospital stay.

Methods: Two hundred and fourteen consecutive patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and 2016 were stratified by whether CRS included gastrectomy (n?=?19, 9%) and compared. Primary outcomes were time to full feeds and rate of serious morbidity (Clavien–Dindo grades III–V). Secondary outcomes were durations of ICU and hospital stays.

Results: Of 214 patients undergoing CRS/HIPEC, those undergoing gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p?p?p?=?0.013). There was no significant increase in serious complications, although increased risk of pneumonia was noted (21% vs. 4.1%, p?=?0.011). Undergoing gastrectomy was not independently prognostic in multivariable analysis including high peritoneal tumour load (PCI >12), multiple CRS procedures (number >2) and operation duration (>480?min) in which operative duration remained independently prognostic (p?Conclusions: After surgery, early oral refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC. However, patients found to have high peritoneal tumour load with extended surgery and those who underwent gastrectomy should be considered for early post-operative TPN due to the significant risk of delayed time to full feeds.     

Misdiagnosis of appendiceal neoplasms as ovarian tumors: Impact of prior gynecologic surgery on definitive cytoreduction and HIPEC

BackgroundFemale patients with pelvic/adnexal masses often undergo gynecologic operations due to presumed ovarian origin. The diagnosis of an appendiceal tumor is often only made postoperatively after suboptimal cytoreduction has been performed. We hypothesized that an index gynecological procedure increases the morbidity of definitive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with appendiceal mucinous tumors.MethodsA single-center retrospective review was performed to identify female patients undergoing CRS/HIPEC for appendiceal tumors from 2012 to 2020.ResultsDuring the 8-year period, CRS/HIPEC was performed in 36 female patients with appendiceal mucinous tumors. Eighteen patients (50.0%) had received a prior pelvic operation by gynecologists (PPO Group) for presumed ovarian origin before referral for definitive CRS/HIPEC. The median peritoneal cancer index (PCI) was higher in the PPO group (21 vs. 9, p = 0.04). The median number of days from gynecologic procedure to definitive CRS/HIPEC was 169 days. Compared to patients who did not undergo a prior gynecologic operation, those in the PPO group had higher intraoperative blood loss (650 vs 100 mL, p < 0.01) during CRS/HIPEC as well as longer length of stay (12 vs 8 days, p = 0.02) and higher overall morbidity (72.3% vs 33.3%, p = 0.02). After controlling for PCI, prior gynecologic operation increased risk of 30-day morbidity after definitive CRS/HIPEC (OR 11.6, p < 0.01).ConclusionA multi-disciplinary approach is needed for the primary evaluation of patients with pelvic masses of undetermined origin. A gynecological resection is associated with increased morbidity during definitive cytoreduction and HIPEC for appendiceal mucinous tumors.     

腹腔热灌注联合全身静脉化疗在卵巢癌治疗中的不良反应评价

目的 评价肿瘤细胞减灭术后行腹腔热灌注联合全身静脉化疗在卵巢癌治疗中的不良反应及其对患者生存期的影响。方法 选取163例卵巢癌患者作为研究对象,所有患者均行肿瘤细胞减灭术并按照治疗方法分为观察组（47例）与对照组（116例）,观察组为术后行腹腔热灌注联合全身静脉化疗,对照组为术后单纯全身静脉化疗。观察两组患者的不良反应发生情况,并对所有患者进行术后随访。 结果 观察组低蛋白血症发生率高于对照组,而白细胞减少、血小板下降、腹胀及腹痛发生率低于对照组（P<0.05）,其余不良反应差异无统计学意义。当患者热灌注次数＞2次时D2聚体升高、低钙血症、血糖升高和恶心呕吐的发生率升高（P<0.05）。两组患者总生存率无显著差异,观察组无贫血或轻度贫血患者生存情况优于重度贫血患者（P<0.05）,其余不良反应的发生对患者整体生存率没有显著影响。结论 卵巢肿瘤细胞减灭术后行腹腔热灌注化疗联合静脉化疗并不会增加不良反应、尤其是严重不良反应的发生,但存在低蛋白血症发生率高的特点。     

细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移癌的临床研究

  目的   分析细胞减灭术（Cytoreductive surgery,CRS）加腹腔热灌注化疗（Hyperthermic intraperitoneal chemotherapy,HIPEC）治疗胃癌腹膜癌（Peritoneal carcinomatosis,PC）的疗效和安全性。   方法  对106例胃癌PC患者随机分为CRS组或CRS+ HIPEC组,前者行常规手术治疗,后者行CRS+HIPEC,药物为羟基喜素碱（HTPC）20 mg加丝裂霉素（MMC）30 mg,或多西他赛120 mg加顺铂120 mg,溶于生理盐水12 L,温度（43±0.5）℃,时间60~90 min。主要终点指标为总体生存期,次要终点指标为安全性。   结果  入组患者106例,CRS组45例,CRS+HIPEC组61例,两组的主要临床病理指标平衡。至患者的中位随访期30个月时,胃癌PC相关死亡率在CRS组为93.3%（42/45）,CRS+HIPEC组为77.0%（47/61,P < 0.05）。两组患者的中位生存期在CRS组是7.0个月（95%CI:5.8~8.2个月）,CRS+HIPEC组是11.1个月（95% CI:8.3~13.9个月,P=0.003）。治疗相关的严重不良事件在CRS组为6例,CRS+HIPEC组为8例（P>0.05）。多因素分析显示CRS+HIPEC治疗、胃癌同时性PC患者、肉眼可见完全肿瘤细胞减灭、不发生严重不良事件、系统性化疗6个周期以上为影响预后的独立参数。   结论  对于胃癌同时性PC患者,CRS+HIPEC可延长生存期,并不明显增加严重不良事件。      

阑尾源性腹膜假黏液瘤单中心诊疗经验

  目的   总结细胞减灭术加腹腔热灌注化疗（cytoreductive surgery & hyperthermic intraperitoneal chemotherapy，CRS+HIPEC）治疗阑尾源性腹膜假黏液瘤（pseudomyxoma peritonei，PMP）的单中心诊疗经验。   方法   回顾性分析2012年1月至2018年12月于航天中心医院收治，病理证实为阑尾源性PMP并经CRS+HIPEC治疗604例患者的临床数据，进行统计学分析。   结果   604例患者经历621次CRS+HIPEC治疗，平均年龄56.7岁，其中女性364例（60.3%），男性240例（39.7%），平均腹膜癌指数（peritoneal cancer index，PCI）为25.7。28.5%（172/604）的患者完全减瘤（CCR 0/1）。3~4级不良事件发生率为21.7%（131/604），围手术期死亡率为0.7%（4/604），术后5年生存率为53.6%。高级别病理类型、不完全减瘤（CCR 2/3）、PCI>20、3~4级不良事件是PMP患者预后不良的独立危险因素。   结论   阑尾源性PMP临床罕见，治疗方法特殊，对于怀疑或确诊PMP的患者，尽早行规范CRS+HIPEC治疗，有望取得良好的预后。      

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗同时性胃癌腹膜癌*

目的:分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery,CRS ）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy ,HIPEC）治疗同时性胃癌腹膜癌（peritoneal carcinoma,PC）的疗效及安全性。方法:50例胃癌PC患者接受52次CRS+HIPEC治疗,药物为洛铂100 mg、多西他赛120 mg,加入12000 mL生理盐水加热至（43± 0.5）℃ 持续灌注60min。主要终点指标为总生存期,次要终点评价指标为围手术期安全性。结果:患者中位随访期22.5 个月,中位生存期14.3 个月（95%CI:7.6～21.0）,1、2、3 年生存率分别为58% 、40% 、32% 。无围手术期死亡,12例（23.1%）出现严重不良事件。多因素分析显示,完全细胞减灭、术前肿瘤标记物水平正常、术后化疗≥ 6 个周期为影响预后的独立因素。结论:对于同时性胃癌PC患者,洛铂联合多西他赛行CRS+HIPEC可延长患者的总生存期,安全可行。      

Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence

Purpose: The aim of this study was to analyse feasibility, morbidity and outcome of repeat complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). CRS combined with HIPEC is becoming the gold standard treatment for resectable peritoneal carcinomatosis in highly selected patients. As yet treatment of isolated peritoneal recurrence with iterative CRS and HIPEC has not been thoroughly explored.

Materials and methods: We selected 16 patients presenting isolated peritoneal recurrence who had undergone iterative CRS and HIPEC from a dataset of 322 CRS associated with HIPEC performed between 1996 and 2012.

Results: Peritoneal carcinomatosis (PC) was due to colorectal and ovarian cancer, peritoneal mesothelioma and pseudomyxoma peritonei (PMP). Disease-free survival (DFS) was 13 months after the first procedure and 13.7 months after the second one. Overall morbidity rate was 43.7% (7/16) for all patients, with grade III–IV complications in three patients (18.7%).

Conclusions: Iterative procedures combining cytoreductive surgery and HIPEC are feasible with acceptable morbidity and mortality rates in strictly selected patients. DFS following repeated CRS and HIPEC is comparable to that registered after the first procedure.     

Do certain surgical steps increase postoperative morbidity after cytoreductive surgery and HIPEC- a retrospective analysis

IntroductionIt has been shown that cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for patients suffering from peritoneal malignancies. Despite good results, there is an ongoing debate about this treatment due to perioperative morbidity.The aim of this study is to identify relevant risk factors for an unfavorable postoperative outcome after CRS and HIPEC.Materials and methodsA retrospective analysis of a prospectively recorded database of all patients undergoing CRS and HIPEC between 2013 and 2020 in the Department of Surgery of the University Hospital Dresden was performed with a special focus on certain surgical steps of multivisceral resection, one- or 2- stage CRS/HIPEC and underlying diagnosis as possible risk factors for worse postoperative course.ResultsN = 173 CRS and HIPEC procedures were performed for various diagnoses. Relevant postoperative morbidity was 24% and 30d-mortality 1.2%. Simultaneous liver resections, preoperative hypalbuminemia and 2-staged CRS/HIPEC were significant risk factors for a worse postoperative course in multivariable analysis. Assessment of the association of simultaneous anastomoses and morbidity and mortality was inconclusive.ConclusionCRS and HIPEC is a safe treatment without relevant intraoperative morbidity and mortality and acceptable postoperative outcome. One-stage CRS/HIPEC should be preferred.     

Learning Curve of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy – an Analysis of Critical Perioperative and Surgical Outcomes among 155 Peritoneal Surface Malignancy Patients Treated at a Tertiary Care Cancer Centre

AimsVarious factors can influence the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Initiating CRS and HIPEC programmes in low- and middle-income countries is challenging due to resource constraints and limited availability of expertise. We present our experience of CRS and HIPEC from a learning curve perspective among a cohort 155 peritoneal surface malignancy patients.Materials and methodsPatients undergoing CRS and HIPEC between May 2015 and February 2019 were included in the study. Patients were divided into two consecutive cohorts: the first 73 cases comprised the learning phase, group 1; the subsequent cohort of 82 patients were considered as the implementation phase, group 2. A comparative analysis of clinical and surgical outcome parameters was carried out between the two groups.ResultsThe clinical spectrum was comparable among group 1/group 2. Most were ovarian (56.8%), colorectal (13.5%) and appendiceal (11.0%) malignancies. Group 2 had a higher number of moderate to high peritoneal cancer index patients (34.1% versus 19.1%), total peritonectomies (48.8% versus 45.2%), multi-visceral resections (colonic 41.5% versus 27.4%, small bowel 25.6% versus 19.1%, diaphragmatic 8.5% versus 6.5% and hepatic resections 8.5% versus 2.7%) and completeness of cytoreduction 0/1 rates (97.6% versus 93.1%). A lower incidence of intraoperative urological injuries (2.6% versus 12.3%) was noticed in group 2 (P = 0.007). Non-significant improvements seen in group 2 included surgery duration (6.0 ± 1.3 h versus 6.4 ± 1.7 h), intensive care unit stay (1.3 ± 1.1 days versus 1.8 ± 1.5 days), overall hospital stay (8.1 ± 0.9 days versus 8.8 ± 1.4 days) and reduction in Clavien-Dindo grade 3–4 complications (25.4% versus 36.9%).ConclusionsThe results of the current study indicate that by implementing standard protocols and mentoring by an experienced team, a learning curve of CRS and HIPEC can be achieved in fewer than 75 cases. The baseline expertise of the treating team can also influence the learning curve.     

Hyperthermic intraperitoneal chemotherapy with oxaliplatin and without adjuvant chemotherapy in stage IIIC ovarian cancer

ObjectiveTo assess the feasibility and efficacy of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) without adjuvant chemotherapy for relapsed or persistent advanced ovarian cancer.MethodsThis observational study included stage IIIC ovarian cancer patients due to undergo CRS (interval debulking or recurrent surgery) followed by HIPEC with oxaliplatin (460 mg/m²) for 30 min.ResultsTwenty-two patients (12 interval debulking procedures and 10 recurrence procedures) were enrolled between September 2003 and September 2007. HIPEC was not performed in four patients because of operative findings. No patient received adjuvant chemotherapy after HIPEC. Patients were followed up routinely until recurrence or death. Median peritoneal cancer index at surgery was 6 (range: 1-18). Before HIPEC, all patients had completeness of cytoreduction scores of 0 or 1. Median length of hospital stay was 21 days (range 13-65). Ten patients (55.6%) had CTCAE grade 3-4 toxicity, including three patients (16.7%) requiring reoperation. No postoperative mortality was observed. With a median follow-up of 38 months (CI 95% 23.8-39.2), median overall survival was not reached. The 3-year overall survival rate was 83% (CI 95% 54-95). Median disease-free survival was, respectively, 16.9 months (CI 95% 10.2-23.2) and 10 months (CI 95% 4.5-11.3) for patients undergoing interval debulking or recurrence surgery.ConclusionHIPEC without adjuvant chemotherapy is both feasible and safe, but with a high rate of grade 3-5 toxicity. Survival results are encouraging but should be confirmed in a randomized trial.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: Prognosis and treatment of recurrences in a cohort study

Background

Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyse the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

Methods

Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

Results

In the 151-patient cohort, the median OS was 34 months (range: 2–77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25 months (range: 2–188) with five-year survival at 18%. Open-and-close patients survived 6 months (range: 0–14) with no five-year survival (HIPEC vs. SPIC p = 0.047, SPIC vs. open-and-close p < 0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25 months vs. 10 months with best supportive care or palliative chemotherapy (p = 0.01).

Conclusion

Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.