Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) delivered via a modified perfusion system for peritoneal carcinomatosis of colorectal origin.

BACKGROUND AND PURPOSE: The long-term survival of patients with peritoneal carcinomatosis of colorectal origin has been achieved with cytoreductive surgery, which removes all macroscopic implants, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The current technology for administering intraperitoneal heated chemotherapy is expensive and, for some institutions, unaffordable. We conducted this study to assess the temperature stability provided by a modified, inexpensive system, to offer a simple and low cost alternative to the standard HIPEC delivery equipment. METHODS: Ten patients with histologically diagnosed peritoneal metastases of adenocarcinoma or pseudomyxoma peritonei underwent cytoreductive surgery and received HIPEC with 5-fluorouracil for 90 min, delivered via our modified system. The temperature was recorded from two probes: one in the inflow catheter and one in the outflow catheter. The intra-abdominal temperature was monitored meticulously to maintain it at between 41 and 42 °C. RESULTS: All patients underwent cytoreductive surgery and HIPEC using our modified delivery system. Temperature stability was achieved in all patients, with a mean of 41.4°. There were no thermal injuries associated with any of the ten perfusions. The mean hospital stay was 15 days and the median survival was 30 months. CONCLUSION: Analysis of this data demonstrates that the uniform delivery of HIPEC at 41° with this modified system is feasible and safe. The outcome of the patients treated with cytoreductive surgery and HIPEC with this modified system compares favorably to other published series. Its low cost and simple design will give more patients with peritoneal carcinomatosis access to this treatment.

Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia.

The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR, 1 APOB) were identified in 38 index cases. A total of 162 individuals with ADH were identified using familial segregation analysis performed in 269 relatives of the index cases. In addition, a novel PCSK9 mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the following characteristics: (1) four mutations are novel: c.695 -1G>T, c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3); (3) five mutations were identified in 3 or more apparently unrelated probands; (4) three mutations were observed in a true homozygous state; and (5) four index cases were compound heterozygous, and one was a carrier of two mutations in the same allele. These results suggest that, in Mexico, ADH exhibits allelic heterogeneity with 5 relatively common LDLR mutations and that mutations in the APOB gene are not a common cause of ADH. This knowledge is important for the genotype-phenotype correlation and for optimising both cholesterol lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of ADH in Mexico.