Diet quality is associated with primary melanoma thickness.

BACKGROUND: Patients' diets can influence the outcome of several common cancers, but the effect on melanoma prognosis is unknown. OBJECTIVE: To assess the association between quality of melanoma patients' prediagnosis diets and primary tumour thickness, the main prognostic indicator for melanoma. METHODS: We used baseline data from patients newly diagnosed with tumour stage Ib to IV cutaneous melanoma, with completed questionnaires about food intake in the past year and other factors. Diet quality was measured by the Healthy Eating Index (HEI) and melanoma thickness was extracted from histopathology reports. We estimated prevalence ratios (PRadj ) and 95% confidence intervals (CIs) adjusted for confounding factors using Poisson regression models to assess associations between HEI scores and melanoma thickness. RESULTS: Of 634 study patients, 238 (38%) had melanomas >2 mm thick at diagnosis. Patients with the highest HEI scores were significantly less likely to be diagnosed with thick melanoma than patients with lowest HEI scores (PRadj 0.93, 95% CI 0.86-0.99) (Ptrend = 0.03). There was no evidence of effect modification by age, sex, previous melanoma or comorbidities. CONCLUSIONS: Melanoma thickness at diagnosis is significantly associated with quality of patients' diets before diagnosis.

Statins may reduce disease recurrence in patients with ulcerated primary melanoma.

BACKGROUND: Statins may restrict the cellular functions required for melanoma growth and metastasis. OBJECTIVES: To determine whether long-term statin use commenced before diagnosis of a primary melanoma is associated with reduced risk of melanoma recurrence. METHODS: We prospectively followed a cohort of patients newly diagnosed between 2010 and 2014 with localized tumour-stage T1b to T4b melanoma in Queensland, Australia. We used Cox regression analyses to examine associations between long-term statin use and melanoma recurrence for the entire cohort, and then separately by sex and by presence of ulceration, due to evidence of effect modification. RESULTS: Among 700 patients diagnosed with stage T1b to T4b primary melanoma (mean age 62 years, 59% male, 28% with ulcerated tumours), 94 patients (13%) developed melanoma recurrence within 2 years. Long-term statin users (n = 204, 29%) had a significantly lower risk of disease recurrence than nonusers [adjusted hazard ratio (HRadj ) 0·55, 95% confidence Interval (CI) 0·32-0·97] regardless of statin subtype or potency. Compared with nonusers of statins, risk of recurrence was significantly decreased in male statin users (HRadj 0·39, 95% CI 0·19-0·79) but not in female statin users (HRadj 0·82, 95% CI 0·29-2·27) and in statin users with ulcerated (HRadj 0·17, 95% CI 0·05-0·52) but not nonulcerated (HRadj 0·91, 95% CI 0·46-1·81) primary melanoma. CONCLUSIONS: Statins commenced before melanoma diagnosis may reduce the risk of melanoma recurrence, especially in men and in those with ulcerated tumours. Clinical trial evaluation of the potential role of statins in improving the prognosis of high-risk melanoma is warranted.

Influence of neo-adjuvant chemotherapy with 5-fluorouracil on colonic anastomotic healing: experimental study in rats.

PURPOSE: We studied the effect of neo-adjuvant chemotherapy on the operative outcome and colonic anastomotic healing in a rat model. METHODS: Firstly, we determined the maximum tolerated dose (MTD) of intraperitoneal 5-flurorouracil (5-FU) in Wistar rats. Secondly, animals were randomly divided into 3 groups: group CT-H received the MTD of 5-FU, group CT-L received 50% of the MTD and a control group received an equivalent volume of 0.9% saline, intraperitoneally. Colonic anastomosis was performed 4 days after chemotherapy. Animals were sacrificed 10 days after surgery. Evaluations were made of: weight evolution, surgical complications, anastomotic bursting pressure (BP) and histological analysis of the anastomotic site. RESULTS: A dose of 20 mg/kg 5-FU, intraperitoneally, for 5 consecutive days was found to be the MTD. A significant weight loss occurred in group CT-H in comparison to the control group either during chemotherapy (p < 0.01) or after surgery (p = 0.01). Postoperative complications were seen only in group CT-H (30% versus 0% in CT-L and control groups). More intense adhesion formation was observed in group CT-H in comparison to the control group (p < 0.01). Intraperitoneal 5-FU induced more inflammation and fibrosis in the submucosa, either with the low or the high-dose, compared to the control animals (p < 0.05) and more pronounced vascular sclerosis was noticed with a dose of 20 mg/kg (p = 0.03). No significant differences in BP were found between the chemotherapy groups and the control group. CONCLUSION: Neoadjuvant chemotherapy with 5-FU does not alter the strength of colon anastomosis in this rat model. A dose of 20 mg/kg induces significantly more intra-abdominal adhesions and histological alterations at the anastomotic site.

Healing of experimental colonic anastomoses: effects of combined preoperative high-dose radiotherapy and intraperitoneal 5-fluorouracil.

To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of the irradiation schedule, 5-fluorouracil (5-FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH]) or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high-dose 5-FU alone. 5-FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces more histological alterations at the anastomotic site.

Influence of preoperative combined radiochemotherapy on surgical outcome and colonic anastomotic healing: experimental study in the rat.

PURPOSE: To study the influence of combined preoperative hyperfractionated irradiation with intraperitoneal 5-fluorouracil (5-FU) on surgical outcome and colonic anastomotic healing in a rat model. METHODS: Male Wistar rats were given 41.6 Gy of preoperative radiotherapy (RT) or sham irradiation, with intraperitoneal 5-FU at low dose (10 mg/kg) or high dose (20 mg/kg). Animals were arranged in 6 groups: RT + low-dose 5-FU (RCT-L), RT + high-dose 5-FU (RCT-H), sham RT + low-dose 5-FU (CT-L), sham RT + high-dose 5-FU (CT-H), RT alone (R), and a control group (sham RT + intraperitoneal saline). Side-to-side colonic anastomoses were constructed from one irradiated and one nonirradiated limb 4 days after radiochemotherapy. Animals were sacrificed 10 days after surgery. RESULTS: Compared to controls, more complications occurred in group RCT-H (50% versus 0%, p = 0.01). Adhesion formation was more intense in groups RCT-H and CT-H (p < 0.001 and p = 0.001, respectively). After therapy, white blood cell counts dropped significantly in all irradiated animals (p < 0.01), and platelet counts decreased significantly in group RCT-H (p = 0.01). No significant differences were noticed in anastomotic bursting pressure when the treated groups were compared to each other or to the control group. CONCLUSIONS: Neoadjuvant radiochemotherapy has no adverse effect on the strength of colonic anastomosis in this rat model. However, the combined RT with high-dose 5-FU does increase operative morbidity and adhesion formation.

Influence of preoperative high-dose radiotherapy on postoperative outcome and colonic anastomotic healing: experimental study in the rat.

PURPOSE: Surgical treatment of rectal cancer is followed by local recurrence in up to 30 percent of cases. Recently, preoperative low-dose radiotherapy has been shown to improve both local recurrence rate and overall survival. Down-staging of locally advanced tumors, however, requires preoperative doses of at least 50 to 60 Gy. Most experimental studies investigating the effect of preoperative radiotherapy have made use of a single dose or a limited number of fractionated doses. Moreover, in most studies, both limbs of the anastomosis were irradiated, in contrast to clinical practice, in which one limb of the anastomosis consists of nonirradiated bowel. We studied the effect of a fractionated, clinically relevant scheme of high-dose preoperative radiotherapy on colonic anastomotic healing in the rat. METHODS: Male Wistar rats randomly received 0, 40, 60, or 80 Gy of preoperative radiotherapy on one limb of the anastomosis only. Radiotherapy doses were validated with implanted dosimeters; before the start of radiotherapy, the cecum was fixed outside the radiation field. A clinically used fractionation scheme of 2 Gy per day, 5 days per week for 4 to 8 weeks was used. The day after radiotherapy completion, a side-to-side colorectal anastomosis was performed. Rats were killed 10 days after surgery. The following parameters were determined: presence of abscess or peritonitis, anastomotic complications (stenosis, leak, or dehiscence), intestinal obstruction, anastomotic bursting pressure, and anastomotic hydroxyproline content. RESULTS: No significant differences were found in peritonitis rate, anastomotic complications, anastomotic bursting pressure, or hydroxyproline content. Irradiated animals gained weight more slowly than the control group. CONCLUSION: In this rat model, preoperative high-dose radiotherapy using a clinically relevant fractionation scheme does not affect outcome or anastomotic healing when only one limb of the anastomosis is irradiated.