Surgery For Peritoneal Carcinomatosis Research Articles

Current need for guidelines in emergency surgery in peritoneal carcinomatosis

Malignant bowel obstruction caused by peritoneal carcinomatosis is a common complication that affects a large proportion of gastrointestinal and ovarian oncology patients and predicts poor longterm survival. The management strategy for these patients includes a variety of medical therapies and surgical options; however, how to choose the best treatment strategy remains a mystery. The purpose of this narrative review was to summarize the most recent evidence on multimodal malignant bowel obstruction treatment and determine whether or not progress had been made. We should work to establish consensus guidelines, where possible, to ensure that this unique patient group receives the appropriate treatment or compassionate care during this often terminal event.

The Road to Technical Proficiency in Cytoreductive Surgery for Peritoneal Carcinomatosis: Risk-Adjusted Cumulative Summation Analysis.

BackgroundCytoreductive surgery (CRS) is a technically demanding procedure, and there is considerable debate about its safe application. This study investigated the learning curve for CRS and the clinical outcomes of consecutive patients treated by a single surgeon at a single institution.MethodsWe collected 251 consecutive patients who underwent CRS for peritoneal metastases by a single surgeon at Fondazione Policlinico Universitario A. Gemelli IRCCS, between January 2016 and December 2020. The learning curve was estimated using the cumulative summation analysis (CUSUM) for operative time (OT). Risk-adjusted CUSUM (RA-CUSUM) charts were developed using a composite variable (surgical failure), defined as the occurrence of at least one of the following events: major postoperative complications (Clavien–Dindo grade ≥3), blood loss ≥500 mL, incomplete cytoreduction. Three learning phases were thus derived from the RA-CUSUM analysis, and were compared in terms of perioperative outcomes.ResultsCUSUM-OT showed that the operation time improved significantly after the 161th case. RA-CUSUM analysis allowed to break the CRS learning curve into three different phases: phase 1, “the learning phase” (cases 1–99), phase 2 “the experienced phase” (cases 100–188), and phase 3, “the mastership phase” (cases 189–251). The rate of major postoperative complications decreased significantly over the three phases (p = 0.019). Operative time decreased significantly as well (p = 0.031) and was significantly shorter in phase 3 with respect to the other two phases (phase 3 vs phase 2: 420 min vs 500 min, p = 0.017; phase 3 vs phase 1: 420 min vs 503 min, p = 0.021). Blood loss consistently decreased throughout the three phases (p = 0.001). The rate of incomplete cytoreduction was significantly lower in phase 3 than in phase 2 (4.8% vs 14.6%, p = 0.043).ConclusionThe CRS failure rate stabilized after the first 99 cases, and the complete surgical proficiency was achieved after 189 cases. A standardised and mentored learning model is a safer strategy to shorten the learning process, to reduce morbidity and mortality, to improve oncologic outcomes.

Tumor-Specific Imaging with Angiostamp800 or Bevacizumab-IRDye 800CW Improves Fluorescence-Guided Surgery over Indocyanine Green in Peritoneal Carcinomatosis

Complete surgical removal of lesions improves survival of peritoneal carcinomatosis and can be enhanced by intraoperative near-infrared fluorescence imaging. Indocyanine green (ICG) is the only near-infrared fluorescent dye approved for clinical use, but it lacks specificity for tumor cells, highlighting the need for tumor-selective targeting agents. We compared the tumor-specific near-infrared fluorescent probes Bevacizumab-IRDye 800CW and Angiostamp800, which target tumor angiogenesis and cancer cells, to ICG for fluorescence-guided surgery in peritoneal carcinomatosis of ovarian origin. The probes were administered to mice with orthotopic peritoneal carcinomatosis prior to conventional and fluorescence-guided surgery. The influence of neoadjuvant chemotherapy was also assessed. Conventional surgery removed 88.0 ± 1.2% of the total tumor load in mice. Fluorescence-guided surgery allowed the resection of additional nodules, enhancing the total tumor burden resection by 9.8 ± 0.7%, 8.5 ± 0.8%, and 3.9 ± 1.2% with Angiostamp800, Bevacizumab-IRDye 800CW and ICG, respectively. Interestingly, among the resected nodules, 15% were false-positive with ICG, compared to only 1.4% with Angiostamp800 and 3.5% with Bevacizumab-IRDye 800CW. Furthermore, conventional surgery removed only 69.0 ± 3.9% of the total tumor burden after neoadjuvant chemotherapy. Fluorescence-guided surgery with Angiostamp800 and Bevacizumab-IRDye 800CW increased the total tumor burden resection to 88.7 ± 4.3%, whereas ICG did not improve surgery at all. Bevacizumab-IRDye 800CW and Angiostamp800 better detect ovarian tumors and metastases than the clinically used fluorescent tracer ICG, and can help surgeons completely remove tumors, especially after surgery neoadjuvant chemotherapy.

Conversion Surgery in Gastric Cancer Carcinomatosis.

BackgroundAfter the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer.MethodsAll patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received.ResultsA total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a <6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8–64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2–26.8) and after upfront surgery 14.7 (10.9–21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2–29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2–60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8–64.0) in those partially regressed (p = 0.742).ConclusionsConversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.

Cytoreductive surgery in peritoneal carcinomatosis.

Cytoreductive surgery in peritoneal carcinomatosis.

Does hyperthermic intraperitoneal chemotherapy influence the rate of infective complications and change the pattern of infectious agents in patients undergoing cytoreductive surgery for peritoneal carcinomatosis? Pattern of Infectious Agents in HIPEC

Does hyperthermic intraperitoneal chemotherapy influence the rate of infective complications and change the pattern of infectious agents in patients undergoing cytoreductive surgery for peritoneal carcinomatosis? Pattern of Infectious Agents in HIPEC

Metastases resection after FOLFIRI-aflibercept (FA) in oxaliplatin-refractory colorectal cancer patients (ORF-CRC).

862 Background: Recent data suggest resection of colorectal metastases after second-line chemotherapy offers similar overall survival (OS) benefit compared to what described in first-line. The improvement in response rate with FA in second-line may increase the number of patients eventually undergo metastases resection. Methods: We performed a retrospective analysis of 32 patients from 26 Spanish hospitals who underwent surgical resection after FA in ORF-CRC in real-life setting. Our aim was to analyze the impact of metastases resection in different organs (liver, lung, etc.) in terms of OS and progression-free survival (PFS) and post-surgical mortality and morbidity. Results: Clinical characteristics: Median age: 65 years (43-83). Sex: 78.1% male, 21.9% female. ECOG 0/1 53.1/46.9%. Ras: wild-type/mutated 25/75%. Type of tumor: colon 75.0%, rectal 25.0%. Location: right 28.1%, transverse 9.4%, and left-side 62.5%. Previous treatment: oxaliplatin combinations (100%), bevacizumab 37.5%, cetuximab 21.97%. Ras wild-type patients received previous anti-EGFR therapy. FA in second-line 93.7% and beyond second-line 6.3%. Median FA cycles before surgery: 6.5 (range 3-44). Type of surgery: liver metastases 46.9%, lung metastases 25.0%, cytoreductive surgery for peritoneal carcinomatosis 15.6%, supraadrenalectomy 3.1%, simultaneous liver and peritoneal carcinomatosis 9.4%. Better tumor response with FA (RECIST1.1): partial response 56.3%, complete response 3.1%, stable disease 40.6%. Median follow-up: 20.9 months [m] (range 3.8-57.3 m). Median PFS from surgery: 8.0 m (confidence interval [CI] 95% 2.5-13.5 m). Median OS from surgery: 37.3 m (CI 95% 23.3-51.4 m). No significant difference between right and left-side tumors in OS or PFS were observed. 90-day postoperative mortality/morbidity: 18.8/0% Reoperation rate: 9.4%. Resection rates: R0 75.0%, R1 15.6%, R2 9.4%. Aflibercept after surgery: 22% patients. Conclusions: Metastases resection following FA in ORF-CRC offers encouraging OS with favorable surgical mortality and morbidity. Salvage surgery should be considered in highly selected patients in second-line setting with oligometastatic disease.

Near infrared fluorescence imaging after intraoperative injection of indocyanine green to improve the staging during cytoreductive surgery for peritoneal carcinomatosis of colorectal origin: results of a pilot prospective study (NCT02032485)

Near infrared fluorescence imaging after intraoperative injection of indocyanine green to improve the staging during cytoreductive surgery for peritoneal carcinomatosis of colorectal origin: results of a pilot prospective study (NCT02032485)

Efficacy of Surgical Treatment of Peritoneal Carcinomatosis in Patients with Colorectal Cancer

Colorectal cancer is one of the most common types of cancer in Ukraine. Prognosis for patients with peritoneal carcinomatosis is unfavorable, and life expectancy is typically less than 6 months. Cytoreductive surgery was introduced as a new method of treating these patients to prolong their survival time.The objective of the research was to evaluate and compare the efficacy of cytoreductive surgery, chemotherapy and symptomatic treatment of patients with colorectal cancer and peritoneal carcinomatosis.Materials and methods. The research included 93 patients with colorectal cancer and peritoneal carcinomatosis. All patients were divided into 3 groups depending on the method of treatment being used after the detection of peritoneal carcinomatosis: Group I - cytoreductive surgery, Group II - palliative chemotherapy, Group III - symptomatic treatment. Cumulative overall survival in three groups was analyzed using the Kaplan-Meier method.Results. Statistically significant difference in overall survival was observed between patients treated with different methods. The median overall survival of patients of Group I (n=44) was 15.5 months; the median overall survival of patients of Group II (n=27) was 5.9 months; in patients of Group III (n=22) it was 3.1 months (p &lt;0.0001). The analysis of patients’ survival in Group I depending on the application of palliative chemotherapy after cytoreductive surgery showed no significant difference in overall survival: 16.5 months with chemotherapy versus 14.2 months without chemotherapy (p = 0.12).Conclusions. Overall survival of patients with colorectal cancer and peritoneal carcinomatosis was higher when treated with cytoreductive surgery compared to palliative chemotherapy and symptomatic treatment. Palliative chemotherapy had no effect on survival after cytoreductive surgery for peritoneal carcinomatosis.

Su1739 Risk Factors for Pulmonary Embolism Following Cytoreductive Surgery and Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis

Introduction: Peritoneal carcinomatosis denotes extensive tumour involvement of the peritoneum, and is often regarded as terminal. There has been a paradigm shift in treatment, with the application of cytoreductive surgery combined with intra-peritoneal chemotherapy. The extensive nature of the surgery and malignancy-associated hypercoagulable state should increase the risk of PE, which can further increase morbidity and/or mortality. Incidence and risk factors for pulmonary embolism (PE) in this population have not been investigated in detail. Aims: To establish the incidence and specific operative risk factors for developing PE in patients with peritoneal carcinomatosis post peritonectomy and peri-operative intraperitoneal chemotherapy. Methods: A cohort of 596 patients that underwent cytoreductive surgery (peritonectomy) over a 12-year period was identified using the prospective database from St George Hospital Peritonectomy Unit. A case-control study was undertaken whereby cases were defined by the development of PE within 60 days of peritonectomy. A diagnosis of PE was based on computed tomography pulmonary angiography confirmation. The prospective database was reviewed to obtain the following clinical information for both cases (with PE) and controls (without PE): length of surgery, use of hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC), peritoneal carcinomatosis index (PCI) and number of intraoperative blood transfusions. Results: The mean age of the cohort was 52.7 ± 13.1 years, with no significant difference in the ages of cases or controls; 43.3% were male and 56.7% were female. Primary malignancies in these patients were pseudomyxoma peritonei, appendiceal, ovarian or colorectal cancer, and mesothelioma. Out of the 596 patient cohort, 34 were identified as having PE post cytoreductive surgery (5.7%). When compared to controls, the PE group had longer mean operative time of 10.4 ± 2.8 hours vs 8.9 ± 3.1 hours (p=0.01) and higher mean PCI values at 23 ± 12 vs 18 ± 11 (p=0.02). An operative time of more >9 hours increased the risk of developing PE (OR 3.3, 95% CI 1.41-7.72, p=0.006) as did having a PCI of >20 (OR 2.4, 95% CI 1.18-4.9, p=0.02). There was no difference in mean transfusion requirements (6.6 vs 6.0; p=0.67). No significant association was found between HIPEC and development of PE (x2=2.87, 1 df, P=0.9) or EPIC and subsequent PE (x2=0.001, 1 df, P=1). Conclusions: There is a relatively high incidence of pulmonary embolism in patients following cytoreductive surgery for peritoneal carcinomatosis. Patients at highest risk of developing PE postoperatively are those with PCI of more than 20 and those who have operations lasting more than 9 hours. Peri-operative chemotherapy and blood transfusions are not risk factors for PE.

Su1740 30-Day Mortality After Emergency Surgery for Colorectal Cancer: Who Is At Risk?

Introduction: Peritoneal carcinomatosis denotes extensive tumour involvement of the peritoneum, and is often regarded as terminal. There has been a paradigm shift in treatment, with the application of cytoreductive surgery combined with intra-peritoneal chemotherapy. The extensive nature of the surgery and malignancy-associated hypercoagulable state should increase the risk of PE, which can further increase morbidity and/or mortality. Incidence and risk factors for pulmonary embolism (PE) in this population have not been investigated in detail. Aims: To establish the incidence and specific operative risk factors for developing PE in patients with peritoneal carcinomatosis post peritonectomy and peri-operative intraperitoneal chemotherapy. Methods: A cohort of 596 patients that underwent cytoreductive surgery (peritonectomy) over a 12-year period was identified using the prospective database from St George Hospital Peritonectomy Unit. A case-control study was undertaken whereby cases were defined by the development of PE within 60 days of peritonectomy. A diagnosis of PE was based on computed tomography pulmonary angiography confirmation. The prospective database was reviewed to obtain the following clinical information for both cases (with PE) and controls (without PE): length of surgery, use of hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC), peritoneal carcinomatosis index (PCI) and number of intraoperative blood transfusions. Results: The mean age of the cohort was 52.7 ± 13.1 years, with no significant difference in the ages of cases or controls; 43.3% were male and 56.7% were female. Primary malignancies in these patients were pseudomyxoma peritonei, appendiceal, ovarian or colorectal cancer, and mesothelioma. Out of the 596 patient cohort, 34 were identified as having PE post cytoreductive surgery (5.7%). When compared to controls, the PE group had longer mean operative time of 10.4 ± 2.8 hours vs 8.9 ± 3.1 hours (p=0.01) and higher mean PCI values at 23 ± 12 vs 18 ± 11 (p=0.02). An operative time of more >9 hours increased the risk of developing PE (OR 3.3, 95% CI 1.41-7.72, p=0.006) as did having a PCI of >20 (OR 2.4, 95% CI 1.18-4.9, p=0.02). There was no difference in mean transfusion requirements (6.6 vs 6.0; p=0.67). No significant association was found between HIPEC and development of PE (x2=2.87, 1 df, P=0.9) or EPIC and subsequent PE (x2=0.001, 1 df, P=1). Conclusions: There is a relatively high incidence of pulmonary embolism in patients following cytoreductive surgery for peritoneal carcinomatosis. Patients at highest risk of developing PE postoperatively are those with PCI of more than 20 and those who have operations lasting more than 9 hours. Peri-operative chemotherapy and blood transfusions are not risk factors for PE.

The Effects of Adjuvant Experimental Radioimmunotherapy and Hyperthermic Intraperitoneal Chemotherapy on Intestinal and Abdominal Healing after Cytoreductive Surgery for Peritoneal Carcinomatosis in the Rat

Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.

Pharmacokinetic and phase II study of heated intraoperative intraperitoneal melphalan

Peritoneal surface malignancy resulting from local dissemination is a common manifestation of treatment failure of gastrointestinal cancers. Although the management of carcinomatosis has been improved with an aggressive surgical approach of extensive cytoreduction followed by heated intraoperative intraperitoneal chemotherapy, no patients are cured when there is residual disease after surgery. Melphalan (L-phenylalanine mustard) is a well-known antineoplastic alkylating agent which has markedly increased pharmacological activity with heat. The use of heated intraoperative intraperitoneal melphalan may provide a pharmacokinetic and clinical advantage in this group of gastrointestinal cancer patients who cannot be made cancer-free with cytoreductive surgery. Thirteen patients with residual disease following cytoreductive surgery for peritoneal carcinomatosis were included in this study. After surgical resection and prior to anastomotic reconstruction, patients received intraperitoneal melphalan (70 mg/m2) in 3 l of 1.5% dextrose peritoneal dialysis solution at 41-42 degrees C for 90 min. Concentrations of melphalan were assessed in the peritoneal fluid, blood, urine and tumor nodules using high-performance liquid chromatography. During the 90 min of treatment 87.2 +/- 4.3% of the drug was absorbed from the perfusate/peritoneal fluid and 11.9 +/- 2.1% was excreted in the urine. The area-under-the-curve ratio of peritoneal fluid to plasma was 33.3 +/- 11.8 with an average peak plasma concentration of 0.82 +/- 0.24 microg/ml occurring at 28.5 +/- 13.1 min. Concentrations of melphalan in tumor nodules on the peritoneal surface were approximately ten times higher than in plasma with an average peak concentration of 7.2 +/- 4.2 microg/gm. The grade III/IV morbidity was 38%; there was no mortality. Approximately 90% of the drug was absorbed during the 90-minute procedure with a 30 times greater exposure of drug at the peritoneal surfaces than in the blood. Concentrations of the drug in peritoneal surface tumor nodules were approximately ten times greater than concentrations in the blood. These data demonstrate that heated intraoperative intraperitoneal melphalan could have a significant impact on the treatment of peritoneal surface malignancies.

29 ORAL Radioimmunotherapy is an effective adjuvant therapy to cytoreductive surgery for peritoneal carcinomatosis of Colonic Origin

29 ORAL Radioimmunotherapy is an effective adjuvant therapy to cytoreductive surgery for peritoneal carcinomatosis of Colonic Origin

Surgery for Peritoneal Carcinomatosis from Colorectal Origin: Techniques and Limitations

Surgery for Peritoneal Carcinomatosis from Colorectal Origin: Techniques and Limitations

Prognostic Implications of Chemoresistance-Sensitivity Assays for Colorectal and Appendiceal Cancer

A major problem with pharmacologic treatments for cancer is the unpredictable nature of the clinical response. Therefore, many patients are treated but few benefit from chemotherapy. Selection of patients for drug treatment would greatly benefit both responders and nonresponders. Mitomycin C (MMC) and 5-fluorouracil (5-FU) are important drugs widely used in the treatment of patients with gastrointestinal malignancies. In a prospective study, an in vitro chemoresistance-sensitivity assay (CR-SA) was performed for 95 patients at the time of surgery for peritoneal carcinomatosis from colorectal and appendiceal cancer. Following cytoreductive surgery, all of these patients had minimal-to-moderate residual disease. All patients were treated with the same chemotherapy regimen regardless of the results of the in vitro assay in the postoperative period. Clinical status of patients was correlated to the assay predictions, and the results were statistically evaluated. When resistance was correlated with outcome, there was no statistical difference. In addition, the mean percentage of growth inhibition was not increased when responders and nonresponders were compared. Finally, more patients who had > or = 95% in vitro growth inhibition of cancer did not survive than did those with < or = 95% growth inhibition. The in vitro test did not predict sensitivity or resistance to cancer when regional chemotherapy was administered in a clinical setting of peritoneal carcinomatosis.