Peritoneal cancer index (PCI) based patient selecting strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis: A single-center retrospective analysis of 125 patients

ObjectiveThe role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC.MethodsFrom a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs).ResultsThe median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8–43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8–8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7–10.2, months), CC-2 (5.6, 95%CI: 3.0–8.2, months) and CC-3 (6.5, 95%CI: 5.2–7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%.ConclusionsOnly complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.     

Adding diagnostic laparoscopy to computed tomography for the evaluation of peritoneal metastases in patients with colorectal cancer: A retrospective cohort study

BackgroundDespite its widespread use, computed tomography (CT) is not perfect for evaluating peritoneal metastases of colorectal origin before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). We therefore evaluated the value of adding diagnostic laparoscopy to CT when assessing patient eligibility for CRS + HIPEC.MethodsThis was a retrospective study of a consecutive series of 112 patients evaluated systematically by diagnostic laparoscopy and CT between January 2012 and January 2018. Patient eligibility for CRS + HIPEC was assessed by the peritoneal cancer index (PCI) both at the time of initial diagnostic laparoscopy and during the retrospective review of CT images. Two experienced radiologists who were blinded to the PCI result at laparoscopy then independently estimated the PCI based on CT imaging. The primary outcome was the number of patients eligible for CRS + HIPEC by each method.ResultsWe identified 112 patients, of whom 95 (85%) were eligible for CRS + HIPEC based on diagnostic laparoscopy and 84 underwent CRS + HIPEC. Overall, 14 patients (17%) experienced an “open-and-close” procedure. In contrast to diagnostic laparoscopy, 100 patients (89%) were identified as being eligible for CRS + HIPEC by CT (p = 0.13), which would have resulted in an additional five open-and-close procedures.ConclusionsAdding diagnostic laparoscopy to CT produced a clinically relevant, but statistically non-significant, reduction in the number of patients eligible for CRS + HIPEC. We conclude that diagnostic laparoscopy may be of use in preoperative assessments when systematic analysis by CT scores the PCI as greater than ten. Future research should focus on the cost-effectiveness of this approach.     

The impact of postoperative complications following cytoreductive surgery combined with oxaliplatin based heated intraperitoneal chemotherapy

IntroductionCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has become the mainstream treatment for peritoneal metastases of colorectal origin. This extensive treatment is known for its increased morbidity rate.In this study, the impact of postoperative complications on survival was evaluated in a high-volume centre.Patients and methodBetween November 2016 through October 2018, all 106 patients with peritoneal metastases of colorectal origin treated with CRS + HIPEC with oxaliplatin were evaluated. Data on patient characteristics, Peritoneal Carcinomatosis Index (PCI), operative procedure, post-operative complications (Clavien-Dindo classification grade III or higher) and survival were collected. In-hospital postoperative complications were analysed for their association with patient characteristics, tumour load (PCI), and operative procedure with logistic regression analyses. Survival was analysed with the Cox regression analysis.ResultsOf 106 patients, 78% had an un-eventful in-hospital recovery. Of those patients who experienced complications, 52% patients had one complication and 48% had more than one.The median follow-up time was 33.8 months. Median survival was 22.4 months (95% CI 12.2–NR) for patients who experienced complications and not reached for those who did not. Survival was significantly associated with complications (HR 2.2, 95% CI 1.2–4.0) as well as with PCI (HR 1.1, 95% CI 1.1–1.2) in univariate analyses. A stepwise Cox regression analysis showed both PCI and complications had an independent negative impact on survival.ConclusionPostoperative complications, independently of tumour load, led to reduced survival in patients with peritoneal metastases of colorectal origin when treated with CRS + HIPEC with oxaliplatin.     

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy vs. cytoreductive surgery alone for intrahepatic cholangiocarcinoma with peritoneal metastases: A retrospective cohort study

BackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefits in patients with intraperitoneal malignant lesions, but there is no study specific to intrahepatic cholangiocarcinoma (ICC).PurposeTo compare the prognosis of patients with advanced ICC undergoing CRS + HIPEC compared with CRS alone.MethodsThis study was a retrospective cohort study of patients with advanced ICC treated at the Shanghai Eastern Hepatobiliary Surgery Hospital between 01/2014 and 12/2018. The patients were divided into either CRS + HIPEC or CRS group based on the treatment they received. Overall survival (OS), complications, hospital stay, biochemical indicators, tumor markers, and number of HIPEC were examined.ResultsThere were 51 and 61 patients in the CRS + HIPEC and CRS groups, respectively. There were no differences between the groups regarding preoperative CA19-9 levels (421 ± 381 vs. 523 ± 543 U/mL, P = 0.208). The hospital stay was longer in the CRS + HIPEC group (22.2 ± 10.0 vs. 18.6 ± 7.6 days, P = 0.033). The occurrence of overall complications was similar in the two groups (37.2% vs. 34.4%, P = 0.756). The postoperative CA19-9 levels were lower in the CRS + HIPEC group compared with the CRS group (196 ± 320 vs. 337 ± 396 U/mL, P = 0.044). The median OS was longer in the CRS + HIPEC group than in the CRS group (25.53 vs. 11.17 months, P < 0.001). Compared with the CRS group, the CRS + HIPEC group showed a higher occurrence of leukopenia (7.8% vs. 0, P = 0.040) but a lower occurrence of total bilirubin elevation (15.7% vs. 37.7%, P = 0.032).ConclusionCRS + HIPEC could be a treatment option for patients with advanced ICC, with improved OS and similar complications and adverse events compared with CRS alone.     

Long-term outcomes of elderly patients with peritoneal metastases of colorectal origin after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

IntroductionCytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) were reportedly safe for the elderly. However, long-term survival data in this subgroup of patients are scarce. Our aim was to evaluate the peri-operative and long-term outcomes of CRS + HIPEC in colorectal peritoneal metastases (CRC-PM) in patients ≥70 years of age.Material and methodsWe retrospectively analyzed our combined institutional databases for patients who underwent CRS + HIPEC for CRC-PM. Clinical and pathological characteristics, as well as overall survival (OS) and progression-free survival (PFS) were compared between the groups. Tumor extent was measured by the peritoneal carcinomatosis index (PCI) and completeness of cytoreduction by the CCR score. Major morbidity was defined according to Clavien-Dindo classification.ResultsThe dataset of 159 patients included 33 elderly and 126 non-elderly patients. Clinical characteristics between the groups differed only in medical comorbidities (Charlson comorbidity index 10 vs. 7, P < 0.001) and delivery of post-HIPEC adjuvant treatment (12.5% vs. 43.8%, P = 0.004). Overall PCI and CCR0 rates were similar between the groups, as were length of stay and major morbidity and mortality rates. Long-term outcomes in the elderly group were lower than those of the non-elderly (median OS: 21.8 vs. 40.5 months, P < 0.001; median PFS: 6 vs. 8 months, P = 0.02, respectively).ConclusionsCRS + HIPEC in selected elderly patients can be safe in terms of postoperative morbidity and mortality. However, despite the same surgical extents and radicality, their long-term outcomes are inferior, possibly due to under-usage of systemic chemotherapy.     

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Long term oncologic outcomes from the international PSOGI registry

The laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) in highly selected patients was previously reported from the PSOGI registry with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to update this international PSOGI registry with a larger cohort of patients and a longer follow-up period.MethodsAn international registry was designed through a networking database (REDCAP®). All centers performing L-CRS + HIPEC were invited through PSOGI to submit data on their cases. Variables such as demographics, clinical outcomes, and survival were analyzed.ResultsA total of 315 L-CRS + HIPEC cases were provided by 14 worldwide centers. A total of 215 patients were included in the L-CRS + HIPEC group. The median peritoneal cancer index (PCI) was 3 (3–5). The median length of stay was 7 days (5-10) and the major morbidity (Clavien-Dindo ≥3) was 6.1% after 30 days. The 5-year disease-free survival (DFS) per tumor origin was: 94% for PMP-LG, 85% for PMP-HG, 100% for benign multicyst peritoneal mesothelioma (MPM), 37.4% for colonic origin, and 54%(at 3 years) for ovarian origin. The 5 years overall survival (OS) per tumor origin was: 100% for PMP-LG, PMP-HG and MPM; 61% for colonic origin, and 74% (at 3 years) for ovarian origin.In addition, a total of 85 patients were analyzed in the laparoscopic risk-reducing HIPEC (L-RR + HIPEC). The median length of stay was 5 days (4–6) and the major morbidity was 6% after 30 days. The 5-year DFS per tumor origin was: 96% for perforated low grade appendiceal mucinous neoplasm (LAMN II) and 68.1% for colon origin. The 5 years OS per tumor origin was: 98% for LAMN II and 83.5% for colonic origin.ConclusionsMinimally invasive CRS + HIPEC is a safe procedure for selected patients with peritoneal carcinomatosis in specialized centers. It improves perioperative results while providing satisfactory oncologic outcomes. L-RR + HIPEC represents a promising strategy that could be evaluated in patients with high risk of developing peritoneal carcinomatosis into prospective randomized trials.     

Peritoneal metastases found in routinely resected specimens after cytoreductive surgery and heated intraperitoneal chemotherapy

IntroductionPeritoneal metastases (PM) originating from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP) can be treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Certain sites in the peritoneal cavity are prone to contain PM and are, therefore, routinely resected. The aim of this study is to investigate the frequency of disease in CRS specimens routinely resected. Secondly, to investigate if the risk of finding PM in routinely resected specimen is associated with involvement of anatomic related peritoneal areas.Materials and methodsThis study investigated 433 patients diagnosed with PMP (n = 119) or PM from CRC (n = 314) and operated with CRS + HIPEC between June 2006 and November 2020 at a national center. Baseline data were prospectively registered. Pathology reports were reviewed for the presence of metastases in the routinely resected umbilicus, ligamentum teres hepatis, ovaries and greater omentum. Tumor extent was estimated using the Dutch region count.ResultsPM was found in 14.7% of umbilical resections, in 17.4% of the resected ligamentum teres hepatis, in 48.2% of the resected ovaries and in 49.5% of the greater omentum specimens. We found an association between macroscopic disease involvement of the nearest region and risk of PM found in the related resections. Seven of 31 women with no macroscopically visible disease in the pelvis had PM diagnosed in the resected ovaries.ConclusionsA substantial proportion of routine resections held histologic verified PM. Our results may advocate for a routinely performed resection of the umbilicus, ligamentum teres hepatis, ovaries and greater omentum.     

Urinary and fecal incontinence in patients with advanced ovarian cancer treated with CRS + HIPEC

PurposeThe objective of this work was to analyze the long-term prevalence of urinary and fecal incontinence and their impact on quality of life in patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (CRS + HIPEC).MethodsThis cross-sectional study included a series of patients with advanced and recurrent ovarian cancer treated by CRS + HIPEC, with a disease-free period of at least 12 months after the procedure. Urinary incontinence was evaluated using the International Consultation on Incontinence Questionnaire – Short Form (ICIQ-SF), fecal incontinence using the Wexner test and the Fecal Incontinence Quality of Life (FIQL) questionnaire and global quality of life using the Short Form 36 (SF-36) survey.ResultsA total of 64 patients were included in the study, with a median age of 55 years (range 28–78). The urinary incontinence rate was 45% and the fecal incontinence rate was 20%. Up to 14% of the patients presented both types of incontinence. The presence of urinary or fecal incontinence generated a significant negative impact on quality of life in relation to patients without incontinence.DiscussionUrinary and fecal incontinence is frequent in the follow-up of ovarian cancer patients treated with CRS + HIPEC. Reconsidering the approach to the pelvis without peritoneal metastases in the peritoneum could modify the incidence of these pelvic floor dysfunctions.     

Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases

The peritoneal cavity must be oncologically considered as an organ in its own right and peritoneal metastases (PM) must be treated with the same curative intent (and the same results) as liver metastases. The package combining complete cytoreductive surgery (CCRS) (treating the visible disease) plus hyperthermic intraoperative peritoneal chemotherapy (HIPEC) (treating the remaining non-visible disease) achieves cure in many patients. Twenty years of publication allow us to assemble sufficient background information and data to point out the good and poor indications for CCRS + HIPEC.HIPEC is the standard of care for the treatment of peritoneal pseudomyxomas and peritoneal mesotheliomas and also, recently for the treatment of colorectal PM with limited peritoneal extension.HIPEC is in the evaluation phase for gastric PM and ovarian PM after initially disappointing results, but it is highly probable that it will be useful in particular settings. PM from neuroendocrine tumours are in the same situation.HIPEC is not currently indicated for the treatment of PM from sarcomas, from GIST, and for small round-cell desmoplastic tumours, given the poor results obtained.HIPEC can be useful, on a case-by-case basis, to treat rare tumours complicated by isolated peritoneal diffusion (e.g. Frantz’s tumours).HIPEC can be used in the prophylactic setting to prevent PM in patients with a high risk of developing PM, and the first results of the ‘second-look’ approach are promising.Finally, CCRS + HIPEC appear to be indispensable tools in the oncologist’s armentarium.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: Upfront therapy,at first recurrence,or later?

Aim

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has been proposed as treatment for advanced epithelial ovarian carcinoma (EOC). No consensus exists on when to administer CRS + HIPEC during the natural history of the disease, namely, as upfront therapy, at first recurrence, or at second or subsequent recurrence.

Patients and methods

We analyzed a series of patients with advanced EOC collected prospectively in an institution with a peritoneal malignant disease treatment program. Patients were treated with CRS + HIPEC upfront, at first recurrence, and at second or subsequent recurrence.

Results

We treated 42 patients: 15 upfront, 19 at first recurrence, and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75% of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE v.3.0, grade 3–4) was 26%, and hospital mortality was 7%. After a median follow-up of 24 months, median overall survival was 77.8 months for patients treated upfront, 62.8 months for patients treated at first recurrence, and 35.7 months for patients treated at second or subsequent recurrence. Disease-free survival was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the upfront and first recurrence groups was similar, and statistically significant differences with the second recurrence group were identified (p < 0.03).

Conclusions

Treatment of advanced EOC using CRS + HIPEC is promising in terms of overall survival and disease-free survival when administered as upfront and at first recurrence therapy. These results warrant further evaluation in a randomized trial.     

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.     

Quality of life after cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: A systematic review

BackgroundCytoreductive Surgery (CRS) accompanied by Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a promising technique in the treatment of peritoneal metastatic disease. The complexity and the potential adverse effects of the procedure can significantly affect patients' Quality of Life (QoL). Few studies have assessed the impact of CRS + HIPEC in patients' QoL using structured and validated tools. This is a systematic review of the currently available published data, investigating the QoL after performing CRS + HIPEC for tumours of varying primary origin.MethodsWe performed a systematic review of the studies indexed in PubMed database until July 2014, using as key phrase “quality of life” and “intraperitoneal chemotherapy”, including studies using only validated questionnaires for assessing quality of life parameters.Results20 studies were identified that matched the criteria set. The results of these studies, although of significant heterogeneity, clearly demonstrate that although overall QoL scores drop in the immediate postoperative period, at an average of 3 months post procedure they recover to 80%–100% or even exceed baseline values. Furthermore, between 6 and 12 months postoperatively, overall QoL is improved in survivors compared to pre-operative status.ConclusionsCRS and HIPEC is feasible as a treatment modality in selected patients with peritoneal metastatic disease and can preserve or even improve patients' overall quality of life.     

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer

BackgroundPIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC.MethodsA retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0.ResultsOne hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32–74). Median PCI was 17 (1–39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1–12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC.ConclusionsPIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.     

Prophylactic hyperthermic intraperitoneal chemotherapy for patients with clinical T4 gastric cancer

IntroductionPatients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer.Materials and methodsWe retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups.ResultsA total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group.ConclusionsProphylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.     

Intraperitoneal chemotherapy in the management of pancreatic adenocarcinoma: A systematic review and meta-analysis

BackgroundPancreatic cancer represents one of the leading causes of cancer-related death worldwide. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proven with curative intent mainly for other tumors and there is a lack of consensus regarding possible benefits also in pancreatic cancer. The present systematic review and meta-analysis aim to provide an up-to-date overview of the effectiveness and safety of intraperitoneal treatments in the management of pancreatic cancer.MethodsA systematic review of articles was conducted according to PRISMA and AMSTAR-2 guidelines. 11 studies were included in the analysis.ResultsWe included in our analysis 212 patients subdivided in three groups: 64 in the HIPEC group (57 with prophylactic intent and 7 with curative intent), 55 in the PIPAC group and 93 in the NIPEC group. Primary outcomes were represented by survival rates; we evidenced at an observation time of three years a survival of 24% in the HIPEC group (25.5% in the prophylactic arm and 6.2% in the curative arm), 5.3% in the PIPAC group and 7.9% in the NIPEC group.ConclusionsHIPEC could be considered as a promising technique for prophylaxis and treatment of peritoneal metastasis (PM) in case of borderline resectable and locally advanced disease. Increased survival rates emerged without additional morbidity when surgical resection and CRS are possible. In addition, our data about PIPAC and NIPEC as palliative treatment in unresectable disease seems to identify more favorable survival rates compared to literature.     

Patients with colorectal peritoneal metastases and high peritoneal cancer index may benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundPeritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI ≤20 treated with CRS and HIPEC to those having open-close/debulking procedure only.MethodsAll patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004–2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI ≤20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking.ResultsOf 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI ≤20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14–27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI ≤20 the median survival was 33 months (95%CI 30–39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4–10 months), no one survived >5years.ConclusionPatients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken.     

Short and long-term outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal and appendiceal cancer peritoneal metastasis: Propensity score-matched comparison between laparoscopy vs. open approaches

BackgroundIn light of today's role of minimally access surgery in colorectal oncologic treatment, we analyzed the impact of laparoscopic cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in selected patients with peritoneal metastases (PM) originating from colorectal and appendiceal cancer (CRAC).MethodsPostoperative and oncologic outcomes were compared between patients with CRAC-PM treated by CRS/HIPEC undergoing laparoscopic (L-CRS/HIPEC) or open (O-CRS/HIPEC) procedures according to data collected from our tertiary referral hospital prospective database from April 2016 to April 2021. We excluded patients who did not undergo operation with curative intent. L-CRS was performed in patients who had no multifocal mesenteric lesions, no large abdominal mass, nor massive adhesions. Patients were matched by propensity scores 1:1 for peritoneal cancer index, completeness of cytoreduction score, concomitant resectable distal metastasis, primary tumor location, RAS mutation status and American Society of Anesthesiologists (ASA) classification.ResultsOf 106 eligible patients, 68 were matched (34 L-CRS/HIPEC; 34 O-CRS/HIPEC) by propensity scores. Compared with the open approach, L-CRS/HIPEC was associated with less overall surgical morbidities (14.7% vs. 38.2%; p = 0.028), shorter median hospital stay (10 [5-15] vs. 12 [8–33] days; p < 0.001) and reduced median waiting time before adjuvant chemotherapy (4.7 [3.0–13.2] vs. 5.7 [4.1–24.1] weeks; p = 0.047). No statistically significant difference was found in operative time or major morbidity rates between the two groups. After a median follow-up of 33.2 months, the rate of early peritoneal loco-regional recurrence, location of initial recurrence or 3-year survival outcomes were not statistically significantly related to the type of access (L-CRS/HIPEC vs. O-CRS/HIPEC).ConclusionsLaparoscopy for CRS/HIPEC is technically feasible and oncologically safe to treat selected patients with CRAC-PM. Further randomized control trials are required to confirm the benefits of minimal access surgery for the management of PM.     

Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI)

Abstract

Aim: The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from peritoneal metastases (PM) from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma.

Patients and methods: A questionnaire concerning patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for PM arising from unusual cancer sites of origin was sent to all centres, which routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network.

Results: Between September 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centres worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (n?=?224), sarcoma (n?=?189) and neuroendocrine tumours (n?=?127). The median PCI was 12 [0–39]. Grade III–IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively. After a median follow-up of 46?months, median overall survival (OS) was 39?months [33.18–44.05]. Five-year OS rate was 38.7%. For the three main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumours (39.9%), and from sarcoma (29.3%) (p?<?0.0001).

Conclusions: CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin, especially from rare ovarian carcinomas, PM from neuroendocrine tumours. The respective roles of CRS and HIPEC remain unclear and should be evaluated.     

The absence of benefit of perioperative chemotherapy in initially resectable peritoneal metastases of colorectal cancer origin treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective analysis

IntroductionThe aim of this study was to compare the outcome of patients with peritoneal metastasis (PM) of colorectal origin treated with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without perioperative systemic chemotherapy (PCT+/PCT-).Patients and methodsRetrospective analysis of 125 patients treated with complete CRS (R0/R1) and HIPEC for PM from colorectal origin in two Belgian academic centers between 2008 and 2017. Disease-free survival (DFS) and overall survival (OS) were assessed with regard to PCT. Statistical analyses were adjusted for non-balanced survival risk factors.ResultsThe PCT+ group (n = 67) received at least 5 cycles of PCT and the PCT-group (n = 56) did not receive PCT. The groups were well balanced for all prognostic factors except presentation of synchronous disease (more in PCT+). Survival analysis was adjusted to peritoneal cancer index and presentation of synchronous disease. After a median follow-up of 54±5-months, the 1, 3, 5-years OS in the PCT+ group were 98%, 59% and 35% compared to 97%, 77% and 56% in the PCT-group (HR = 1.46; 95% CI:0.87–2.47; p = 0.155). The 1,3 and 5 years DFS in the PCT+ group were 47%, 13% and 6% compared to 58%, 29% and 26% respectively in the PCT- (HR = 1.22; 95% CI:0.78–1.92; p = 0.376).ConclusionThis study does not show any clear benefit of PCT in carefully selected patients undergoing R0/R1 CRS and HIPEC for colorectal PM. The ongoing CAIRO6 trial randomizing CRS/HIPEC versus CRS/HIPEC and PCT will probably clarify the role of PCT in patients with resectable PM.     

Prognostic significance of visible cardiophrenic angle lymph nodes in the presence of peritoneal metastases from colorectal cancers

Background

Visible cardiophrenic angle lymph nodes (CPALN) (enlarged or not), detected on CT scan are correlated with the presence of peritoneal metastases (PM), and contribute to the diagnosis of PM in colorectal cancer patients.

Objective

To study whether visible CPALN exert a prognostic impact on survival after complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CCRS + HIPEC) treating PM.

Patients and methods

From 1999 to 2010, 114 patients with colorectal cancer and PM were treated with CCRS + HIPEC. CPALN were depicted in 64% of cases. The impact of visible CPALN on survival was investigated retrospectively.

Results

The mean peritoneal cancer index (PCI) score was 9.2, 21% of the patients had presented with associated liver metastases, and 71% of the women with ovarian metastases. Median follow-up was 3.9 years. Visible CPALN had no impact on OS nor on DFS, unlike the PCI score which was unequivocably the most potent prognostic factor in the multivariate analysis.

Conclusion

Although some arguments might suggest that CPALN are malignant, paradoxically, we found that visible CPALN did not exert a positive nor a negative impact on survival after CCRS + HIPEC.

Synopsis

Visible cardiophrenic angle lymph nodes (CPALN) on CT-scan are strongly associated with the presence of peritoneal metastases. But this study demonstrates that the presence of CPALN has no prognostic impact after optimal cytoreductive surgery plus HIPEC.