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The results of this treatment are evident from the beginning even though the average number of procedures performed was 3 , with improved quality of life due to a decrease in pain, ascites, abdominal distension and gastrointestinal symptoms. In addition, in all procedures, peritoneal biopsies were taken to analyze the histological response of the tumor to successive treatments, which demonstrated significant tumor regression. Despite the relative innocuity of the procedure, Alyami et al. Following the established protocol, 10 doxorubicin and cisplatin were administered at doses of 1. The treatment was applied to a year-old patient with ovarian carcinomatosis previously considered by our group as unresectable due to massive involvement of the small intestine and a peritoneal cancer index PCI of At the time of the intervention, the patient had a PCI of During the procedure, cc of ascitic liquid were extracted and peritoneal biopsies were taken to compare with biopsies from the following procedures.

The patient was discharged on the second postoperative day without incident.. In conclusion, PIPAC is a new, relatively innocuous and beneficial technique for patients with unresectable carcinomatosis. More studies are needed to accurately determine its efficacy and range of application.. We would like to thank Drs. Reymond and Struller for their kind collaboration to implement this procedure at our hospital.. Cir Esp. ISSN: Previous article Next article. Issue 3. Pages March Download PDF. Corresponding author. This item has received. Article information.

The origin is usually gastrointestinal or gynecological tumors, and less frequently sarcomas, stromal and peritoneal tumors.

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During the remainder of their lives, these patients experience progressive clinical deterioration pain, distension, dyspnea, ascites and intestinal obstruction , resulting in declining quality of life. Therefore, it is a coadjuvant procedure to systemic chemotherapy, which does not lose its fundamental role.

The patient was discharged on the second postoperative day without incident. More studies are needed to accurately determine its efficacy and range of application. Reymond and Struller for their kind collaboration to implement this procedure at our hospital. Cytoreductive surgery and perioperative chemotherapy for peritoneal surface malignancy: textbook and video atlas. Cine Med, Inc. Van Driel, S.

Koole, K. Sikorska, J. Schagen van Leeuwen, H. Schreuder, R. Hermans, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med, , pp.

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Tempfer, U. Giger-Pabst, Z. Hilal, A. Dogan, G. Pressurized intraperitoneal aerosol chemotherapy PIPAC for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Arch Gynecol Obstet, , pp.

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Reymond, W. PIPAC: pressurized intraperitoneal aerosol chemotherapy: cancer under pressure. Walter de Gruyter GmbH, ,. Girshally, C. Albayrak, J. Zieren, C. Tempfer, M. Pressurized intraperitoneal aerosol chemotherapy PIPAC as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol, 14 , pp.

Jacquet, O. Stuart, D. Chang, P. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs, 7 , pp. Esquis, D. Consolo, G. Magnin, P. No significant difference was found when inflammatory response was compared before and after different PIPAC applications. The extent of inflammatory response after consecutive PIPAC procedures was similar with no significant difference for any of the candidate markers Figure 4. Synopsis of systemic toxicity and inflammation after different treatments for peritoneal carcinomatosis.

In this cohort, PIPAC was followed by a modest and transitory inflammatory response that was commensurate to the disease extent. The findings of the present study need to be discussed in the setting of four available treatment options for advanced peritoneal carcinomatosis: systemic chemotherapy, hyperthermic intraperitoneal chemotherapy HIPEC after cytoreductive surgery CRS , intraperitoneal catheter chemotherapy and PIPAC Table 2.

Of note, it is not the intention to formally compare those treatment approaches due to their very different nature but to provide a comprehensive overview on what is known on toxicity and inflammatory response under the respective treatment. Systemic chemotherapy represents a first line therapy in patients with peritoneal carcinomatosis, especially with extraperitoneal spread of tumor [ 20 ]. New drugs such as antibodies or irinotecan allowed for better survival in recent years, but pharmacokinetic limitations such as peritoneum-plasma barrier impede proper penetration of cytostatics in peritoneal tumor nodes [ 21 , 22 ].

Parenteral drug concentrations need thus to be high to achieve a therapeutic effect. Up to tenfold higher concentrations were described for systemic chemotherapy as compared to intraperitoneal use, and side effects for most therapies are common [ 4 ]. Chemotherapy induced peripheral neuropathy represents a well-known side effect of platin-based chemotherapy regimens [ 23 ]. Cisplatin is eliminated by the kidney, and dose-dependent renal toxicity of cisplatin and its metabolites has been described [ 26 ].

Taken together and in the light of pharmacokinetic limitations of systemic therapy for the treatment of peritoneal carcinomatosis, alternative locoregional treatments were considered. Cytoreductive surgery combined with HIPEC represents the only potentially curative treatment option in few selected patients who are fit enough to tolerate this complex treatment option with important morbi-mortality [ 5 , 27 ].

Intraperitoneal administration permits higher drug concentration with better tumor penetration as compared to systemic chemotherapy [ 28 , 29 ]. Even if no formal consensus exists, common drugs for HIPEC are cisplatin, mitomycin C and oxaliplatin in different combinations and doses, depending on the primary tumor [ 27 ]. In high volume centers, mortality rates of up to 5. PIPAC as a minimally invasive treatment option might thus represent an alternative for frail patients who are not eligible for this curative approach given the multitude of surgery- and drug-related side effects.

Repetitive administration through intraperitoneal catheters in an adjuvant setting after optimally debulked stage III ovarian cancer represents an alternative to HIPEC [ 32 ]. Intraperitoneal administration of paclitaxel and cisplatin combined with intravenous paclitaxel significantly improved survival compared to patients receiving the same drugs exclusively intravenously [ 32 ]. However, patients in the intraperitoneal group experienced more pain and presented more hematologic, gastrointestinal and neurologic toxic effects Table 2.

A former study compared intraperitoneal cisplatin to intravenous cisplatin to demonstrate improved survival and fewer toxic effects in the intraperitoneal group [ 33 ]. PIPAC combines the advantages of intraperitoneal administration, allowing for higher tumor concentrations [ 28 ] and administration under pressure, which permits higher intra-tumoral concentrations despite lower drug doses [ 3 ]. In a pilot study of the pioneer group from Herne, Germany, peripheral drug concentrations of doxorubicin were very low with 4.

PIPAC Pressurized IntraPeritoneal Aerosol Chemotherapy Capnomed

As a consequence, only modest and transitory inflammatory response was observed in former studies and in the present cohort [ 34 - 36 ]. This response might be a consequence of drug-induced chemical peritonitis after intraperitoneal vaporisation, which provides an explanation for abdominal pain as main postoperative complaint after PIPAC [ 34 ].

Similar to the present findings, Blanco described liver and renal parameters within the normal range with no cumulative toxicity [ 35 ]. Similarly, an Italian group described no clinically relevant liver cytolysis without metabolic nor synthetic hepatic and renal dysfunction [ 36 ]. Both groups concluded that PIPAC caused less hepatic and renal toxicity than other chemotherapy delivery routes due to lower therapeutic doses and favorable kinetics [ 35 , 36 ].

The present findings confirm the previously reported results. As a consequence of low toxicity, encouraging results regarding quality of life and tolerance of the procedure have been described by our group and by others [ 8 , 9 , 37 ]. Several limitations of the present study need to be discussed beyond retrospective study design and small patient cohort. Given the very short median hospital stay, only few patients were available for blood drawings after POD 3 and inflammatory parameters beyond POD 3 should therefore not be considered representative for the entire PIPAC cohort.

Systemic toxicity was low in the present study, which might be due to low administered drug concentrations. The proposed regimens did not derive from a dose escalation protocol and hence, drug choices and doses rely on empirical protocols. Despite favorable short-term results regarding clinical and histological response rates [ 34 , 38 , 39 ], sustained long-term impact of PIPAC under presently applied conditions needs yet to be proven.

In conclusion, there was no relevant systemic toxicity after PIPAC with the current treatment standard even when repeatedly applied. Inflammatory response was modest and transitory. It is important to repeat this type of studies for new treatment standards, especially when using higher drug concentrations. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy.

Annals of surgical oncology. Description of a novel approach for intraperitoneal drug delivery and the related device. Surgical endoscopy. High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy with oxaliplatin: an experimental study.

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Annals of surgery. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1, patients. Verwaal VJ. Cancer journal. Pharmacodynamic aspects of intraperitoneal cytotoxic therapy. Cancer Treat Res. Gastroenterol Res Pract. Developing a consensus classification system for acute renal failure. Curr Opin Crit Care.

Critical care. Meisner M. Update on procalcitonin measurements. Ann Lab Med. Elevated serum C-reactive protein as a predictive factor for anastomotic leakage in colorectal surgery. Int J Surg. Increased levels of C-reactive protein and leukocyte count are poor predictors of anastomotic leakage following laparoscopic colorectal resection.

Dan Med J. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N and N Journal of clinical oncology: official journal of the American Society of Clinical Oncology. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Flessner MF. The transport barrier in intraperitoneal therapy.

Am J Physiol Renal Physiol. Minimizing chemotherapy-induced peripheral neuropathy: preclinical and clinical development of new perspectives. Expert Opin Drug Saf.