Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Harmonic analysis of mandibular form and symmetry with computerized tomographic views.

OBJECTIVE: To quantitatively describe the isotropic (ie, orientation independent) morphologic characteristics of a standardized computed tomographic image of the mandible with the use of the elliptic Fourier series. STUDY DESIGN: Spiral CT scans parallel to the mandibular plane and enclosing both mental foramina were obtained in 17 adults (9 edentulous women, mean age, 75 years; 4 edentulous men, mean age, 68 years; and 4 dentate men, mean age, 30 years). The mandibular outline was traced, digitized, and mathematically reconstructed with the elliptic Fourier series. Mandibular area, shape, and individual symmetry were quantified. RESULTS: Mandibular area and symmetry were larger in men than in women (P <.05). In men, no effect of edentulousness was observed in either area or symmetry. Mandibular shape seemed to be influenced neither by sex nor by the presence of teeth. CONCLUSION: Mandibular size and symmetry in the analyzed computed tomographic scan (which included only the mandibular basal bone) seemed to be sex related but independent of the dental status. Mandibular shape did not seem to be modified by sex or edentulousness. Different findings may be obtained in the analysis of a section of the alveolar bone.