Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial.

BACKGROUND: Female breast cancer patients with a BRCA1/2 mutation have an increased risk of contralateral breast cancer. We investigated the effect of rapid genetic counselling and testing (RGCT) on choice of surgery. METHODS: Newly diagnosed breast cancer patients with at least a 10% risk of a BRCA1/2 mutation were randomised to an intervention group (offer of RGCT) or a control group (usual care; ratio 2 : 1). Primary study outcomes were uptake of direct bilateral mastectomy (BLM) and delayed contralateral prophylactic mastectomy (CPM). RESULTS: Between 2008 and 2010, we recruited 265 women. On the basis of intention-to-treat analyses, no significant group differences were observed in percentage of patients opting for a direct BLM (14.6% for the RGCT group vs 9.2% for the control group; odds ratio (OR) 2.31; confidence interval (CI) 0.92-5.81; P=0.08) or for a delayed CPM (4.5% for the RGCT group vs 5.7% for the control group; OR 0.89; CI 0.27-2.90; P=0.84). Per-protocol analysis indicated that patients who received DNA test results before surgery (59 out of 178 women in the RGCT group) opted for direct BLM significantly more often than patients who received usual care (22% vs 9.2%; OR 3.09, CI 1.15-8.31, P=0.03). INTERPRETATION: Although the large majority of patients in the intervention group underwent rapid genetic counselling, only a minority received DNA test results before surgery. This may explain why offering RGCT yielded only marginally significant differences in uptake of BLM. As patients who received DNA test results before surgery were more likely to undergo BLM, we hypothesise that when DNA test results are made routinely available pre-surgery, they will have a more significant role in surgical treatment decisions.

Comparison of conventional anterior surgery and laparoscopic surgery for inguinal-hernia repair.

BACKGROUND: Inguinal hernias can be repaired by laparoscopic techniques, which have had better results than open surgery in several small studies. METHODS: We performed a randomized, multicenter trial in which 487 patients with inguinal hernias were treated by extraperitoneal laparoscopic repair and 507 patients were treated by conventional anterior repair. We recorded information about postoperative recovery and complications and examined the patients for recurrences one and six weeks, six months, and one and two years after surgery. RESULTS: Six patients in the open-surgery group but none in the laparoscopic-surgery group had wound abscesses (P=0.03), and the patients in the laparoscopic-surgery group had a more rapid recovery (median time to the resumption of normal daily activity, 6 vs. 10 days; time to the return to work, 14 vs. 21 days; and time to the resumption of athletic activities, 24 vs. 36 days; P<0.001 for all comparisons). With a median follow-up of 607 days, 31 patients (6 percent) in the open-surgery group had recurrences, as compared with 17 patients (3 percent) in the laparoscopic-surgery group (P=0.05). All but three of the recurrences in the latter group were within one year after surgery and were caused by surgeon-related errors. In the open-surgery group, 15 patients had recurrences during the first year, and 16 during the second year. Follow-up was complete for 97 percent of the patients. CONCLUSIONS: Patients with inguinal hernias who undergo laparoscopic repair recover more rapidly and have fewer recurrences than those who undergo open surgical repair.

The learning curve for totally extraperitoneal laparoscopic inguinal hernia repair.

BACKGROUND: Several laparoscopic techniques have been introduced to re pair inguinal hernia, the newest and most promising being a totally extraperitoneal approach. Nevertheless, the surgeon may encounter several complications and technical difficulties associated with the transition from the conventional anterior operation. METHODS: In late 1993 and 1994, 120 patients were operated on for inguinal hernia using the totally extraperitoneal approach by four laparoscopic surgeons inexperienced in this new technique in a secondary referral setting. Their learning curve was assessed through operation time, perioperative and postoperative complications, and technical difficulties. RESULTS: Median operative time decreased significantly (P = 0.0003) when going through the learning curve. During the initial part of the learning curve, conversion to another technique was necessary in 10 (8%) cases, and in 6 of these cases, conversion was needed for a peritoneal tear (relative risk for conversion if peritoneal tear was present: 4.0; 95% confidence interval 1.2 to 13.1, P = 0.025). The median operative time for Nyhus type IIIb and IVb hernias was significantly longer than for other types (70 versus 55 minutes, P = 0.003). Median postoperative stay was 2 days (range 0 to 7). There were 10 recurrences within 6 months due to technical or judgement errors. CONCLUSIONS: For surgeons, the learning curve for totally extraperitoneal laparoscopic hernia repair can be overcome; however, the presence of an experienced surgeon during the procedure is vital, as this may prevent unnecessary recurrences.

Prospective randomized double-blind trial of branched chain amino acid enriched versus standard parenteral nutrition solutions in traumatized and septic patients.

The addition of branched chain amino acids (BCAA) to total parenteral nutrition (TPN) solutions of balanced aminoacid composition has been reported to result in improved nitrogen balance, preservation of plasma protein levels, and improved immune function; however, only a few large clinical studies have been performed, yielding conflicting results. We, therefore, studied in a prospective, randomized double blind trial, the effects of BCAA enrichment of an otherwise isonitrogenous and isocaloric TPN solution on plasma protein levels in 101 traumatized and septic patients. TPN-derived nitrogen intake was similar in both study groups. Nitrogen balances in the BCAA group (n = 49) were not different from those in the standard group (n = 52). Plasma total protein levels increased significantly in the standard group resulting in a significant difference between study groups on day 7. Pre-albumin levels increased significantly in the BCAA group and in the standard group. The number of neutrophils (rods) was significantly lower in the standard group compared to the BCAA group on day 7. Lymphocytes increased significantly in the standard group as did the number of platelets, resulting in a significant difference between study groups on day 7. We conclude that BCAA enrichment of standard TPN solutions does not result in more efficient nitrogen metabolism in septic or traumatized patients.

Effects of infusion of branched chain amino-acids enriched TPN solutions on plasma amino-acid profiles in sepsis and trauma patients.

Total parenteral nutrition with branched chain amino-acids enriched solutions has been advocated in patients with sepsis and stress because of favourable effects on nitrogen balance, protein synthesis and immune competence. The rationale for the use of BCAA-enriched solutions is based on their potential to correct the plasma amino-acid imbalances seen in these patients. In a 7-day prospective randomised study we investigated the effects on plasma amino-acid concentrations of a standard amino-acid solution (15.6% BCAA) and a branched chain amino-acid enriched solution (50.2% BCAA) in 101 parenterally fed patients with carefully assessed sepsis and/or stress scores. The infusion of the BCAA-enriched solution led to an imbalance of the essential plasma amino-acids. The branched chain amino-acids valine, leucine and isoleucine increased significantly while the non-BCAA essential amino-acids decreased significantly. In the standard solution the non-BCAA-essential amino-acids increased significantly with a slow and insignificant rise in the levels of the branched chain amino-acids. We conclude that infusion of a BCAA enriched TPN formulation induced amino-acid profile derangements that can be considered ill-suited to the achievement of anti-catabolic effects.

Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial.

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.

Peri-operative blood transfusions in colorectal cancer.

Clinical studies report reduced recurrence-free survival and increased cancer-related death after surgical treatment for cancer, when peri-operative blood transfusions were given. In this study we collected transfusion data of 212 patients who participated in a prospective study of two different resection techniques for colorectal cancer. One hundred and fifty-eight patients were transfused and 54 were not. The follow-up period for almost all patients was 5 years. The 5-year survival rate was 52% both for the transfused patients and the nontransfused patients. For subgroups of patients with Dukes' B and Dukes' C tumours no statistically significant differences were found. In the group of patients that were transfused the number of transfusions did not affect survival. In this study we could not confirm the deleterious effect of peri-operative blood transfusions on survival.

Plasma-amino acid profiles in sepsis and stress.

Sepsis has been associated with specific plasma amino acid patterns. Sixty-five patients were prospectively investigated as to whether these patterns are indeed sepsis specific, or specific for metabolic stress without concomitant sepsis, or associated with the presence of organ failure. Virtually all aminoacid levels were decreased by 10-30% (p less than 0.05), whereas cystine and phenylalanine were significantly elevated. These changes were more pronounced in severe sepsis. Organ failure was not associated with significantly altered amino acid profiles. No differences were found between sepsis and stress without signs of sepsis. In addition, imminent death was not associated with aberrant amino acid profiles. We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles, but that such changes are aspecific and therefore poor indicators of disease severity.

Hemangioma of the mediastinum.

Benign hemangiomas of the mediastinum are rare. Histologically they can be differentiated into a capillary or a cavernous form. In general these are well-encapsulated and slow-growing tumors, but infiltrative growth is not unusual. Metastases never occur. Often these tumors are accidentally found on routine chest roentgenograms. Phleboliths are characteristic. Symptoms are mostly caused by compression or invasion of mediastinal structures. The benign hemangioma should be treated surgically and must be removed as completely as possible. The prognosis is favorable.

Airless paint-gun injuries of the hand: a report of three cases.

Three patients were treated for airless paint-gun injuries. High-pressure paint-guns have been used by commercial painters for 20 years. The causes of the inflammation are discussed. The importance of early surgical treatment is stressed. This treatment should consist of exploration and complete excision of contaminated tissue. A satisfactory result can be obtained in most cases.

[Monensin poisoning in dairy cattle. Report of a case (author's transl)]. / Een geval van monensin-vergiftiging bij melkvee.

A herd of dairy cattle were fed concentrates in which monensin had been incorporated in error in a concentration of 366 mg/kg. Particularly those animals which were highly productive, showed a marked drop in production within two days after the herd had been fed this lot. The animals were sluggish, did not ruminate, had watery, alkaline rumen contents and failed to ingest anything. When hay was supplied ad lib., the symptoms disappeared within approximately three days.

[Some results obtained in artificial insemination on a large rabbit farm (author's transl)]. / Enige ervaringen met K.I. op een groot konijnenbedrijf.

In commercial rabbit-farming, activities associated with mating take up a great deal of the working hours required. Efforts were made to help to obtain optimum results in rabbit-farming by carrying out artificial insemination. The conception rates following insemination of does which are not prepared to mate naturally, are too low. After preliminary treatment of these animals with 20 I.U. of pregnant mare serum forty-eight hours prior to insemination, the results obtained were more satisfactory. It is concluded that artificial insemination in rabbit farming does not present any technical problems and that satisfactory results should be obtainable on healthy farms.