Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines.

AIM: This systematic review aimed to provide an overview of (inter)national guidelines on the treatment of peritoneal metastases of colorectal cancer origin (PMCRC) and to determine the degree of consensus and available evidence with identification of topics for future research. METHOD: A systematic search of MEDLINE, Embase, PubMed as well as Tripdatabase, National Guideline Clearinghouse, BMJ Best Practice and Guidelines International Network was performed to identify (inter)national guidelines and consensus statements from oncological or surgical societies on PMCRC. The quality of guidelines was assessed using the AGREE-II score. Topics followed by recommendations were extracted from the guidelines. The recommendations, highest level of supporting evidence and the degree of consensus were determined for each topic. RESULTS: Twenty-one guidelines were included, in most (15) of which cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) was recommended in selected patients based on level 1b evidence. Substantial consensus was also reached on the benefit of multidisciplinary team discussion and the achievability of a (near) complete cytoreduction (CC0-1) without supporting evidence. Both evidence and consensus were lacking regarding other aspects including preoperative positron emission tomography/CT, second look surgery in high risk patients, the optimal patient selection for CRS/HIPEC, procedural aspects of HIPEC and (perioperative) systemic therapy. CONCLUSION: In currently available guidelines, evidence and consensus on the treatment strategy for PMCRC are lacking. Updates of guidelines are ongoing and future (randomized) clinical trials should contribute to multidisciplinary and international consensus on treatment strategies for PMCRC.

Isolation, identification and determination of sulfadiazine and its hydroxy metabolites and conjugates from man and rhesus monkey by high-performance liquid chromatography.

The following metabolites of sulfadiazine (S) were isolated from monkey urine by preparative HPLC: 5-hydroxysulfadiazine (5OH), 4-hydroxysulfadiazine (4OH) and the glucuronide (5OHgluc) and sulfate conjugate of 5OH (5OHsulf). The compounds were identified by NMR, mass and infrared spectrometry and hydrolysis by beta-glucuronidase. The analysis of S, the hydroxymetabolites (4OH, 5OH) and conjugates N4-acetylsulfadiazine (N4), 5OHgluc and 5OHsulf in human and monkey plasma and urine samples was performed using reversed-phase gradient HPLC with UV detection. In plasma, S and N4 could be detected in high concentrations, whereas the other metabolites were present in only minute concentrations. In urine, S, the metabolites and conjugates were present. The limit of quantification of the compounds in plasma varies between 0.2 and 0.6 microgram/ml (S 0.31, N4 0.40, 4OH 0.20, 5OH 0.37, 5OHgluc 0.33 and 5OHsulf 0.57 microgram/ml). In urine it varies between 0.6 and 1.1 micrograms/ml (S 0.75, N4 0.80, 4OH 0.60, 5OH 0.80, 5OHgluc 0.80 and 5OHsulf 1.1 micrograms/ml). The method was applied to studies with healthy human subjects and Rhesus monkeys. The metabolites 5OH, 5OHgluc and 5OHsulf were present in Rhesus monkey and not in man. Preliminary results of studies of metabolism and pharmacokinetics in Rhesus monkey and man are presented.

Isolation, identification and determination of sulfamethoxazole and its known metabolites in human plasma and urine by high-performance liquid chromatography.

From human urine the following metabolites of sulfamethoxazole (S) were isolated by preparative HPLC: 5-methylhydroxysulfamethoxazole (SOH), N4-acetyl-5-methylhydroxysulfamethoxazole (N4SOH) and sulfamethoxazole-N1-glucuronide (Sgluc). The compounds were identified by NMR, mass spectrometry, infrared spectrometry, hydrolysis by beta-glucuronidase and ratio of capacity factors. The analysis of S and the metabolites N4-acetylsulfamethoxazole (N4), SOH, N4-hydroxysulfamethoxazole (N4OH), N4SOH, and Sgluc in human plasma and urine samples was performed with reversed-phase gradient HPLC with UV detection. In plasma, S and N4 could be detected in high concentrations, while the other metabolites were present in only minute concentrations. In urine, S and the metabolites and conjugates were present. The quantitation limit of the compounds in plasma are respectively: S and N4 0.10 micrograms/ml; N4SOH 0.13 micrograms/ml; N4OH 0.18 micrograms/ml; SOH 0.20 micrograms/ml; and Sgluc 0.39 microgram/ml. In urine the quantitation limits are: N4 and N4OH 1.4 micrograms/ml; S 1.5 micrograms/ml; N4SOH 1.9 micrograms/ml; SOH 3.5 micrograms/ml; and Sgluc 4.1 micrograms/ml. The method was applied to studies with healthy subjects and HIV positive patients.