Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease.

HER-2 overexpression, a predictive marker of tumour aggressiveness and responsiveness to therapy, occurs in 20-30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 measurement is carried out in primary tumour. This study aims to evaluate HER-2 overexpression in primary and metastases and its effect on treatment decisions. Biopsies from primary breast cancer and corresponding metastases from 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically in all primary and metastatic sites. Positive overexpression in primary and/or metastases was confirmed by fluorescence in situ hybridisation (FISH). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (eight of 58 patients). Concordance was found in 50 (86%) of patients (95% CI: 77-95). In one patient (2%), HER-2 was negative in metastasis but positive in primary. In seven (12%) patients, HER-2 was positive in metastases and negative in primary (95% CI: 3.7-20), and three of them responded to trastuzumab. Gene amplification by FISH was found in all cases with HER-2 positive (+2 and +3) by immunohistochemistry. Our data suggest that a possible discordance of HER-2 overexpression between primary and metastases should be considered when making treatment decisions in patients with primary HER-2-negative tumours.

Spillage of stones from the gallbladder during laparoscopic cholecystectomy and complication of a retroperitoneal abscess mimicking gluteal abscess in elderly patients.

Gallbladder perforation during laparoscopic cholecystectomy with spillage of bile and gallstones occurs in a substantial percentage of patients (up to 40%). We report the case of a 77-year-old woman who presented with fever of unknown etiology and a complication of retroperitoneal abscess mimicking a gluteal abscess with gallstones and clips the abscess. Spillage of gallstones from perforation of the gallbladder is a well-recognized complication of laparascopic cholecystectomy, especially several months after the initial surgery, as in the reported case.

Alfentanil dose-response relationships for relief of postoperative pain.

The aim of this study was to characterize within-patient alfentanil dose-response curves for the relief of spontaneous postoperative pain and to test the closeness of relationships 1) between pain intensity and alfentanil analgesic requirements, and 2) between alfentanil requirements for analgesic and nonanalgesic (sedative and miotic) effects. The effects of alfentanil were studied in 23 patients after elective abdominal surgery. During a 40- to 60-min testing session, the patient received two intravenous (i.v.) injections of saline (placebo) and up to six 3-micrograms/kg increments of alfentanil at 5-min intervals. The patient rated the pain intensity with a visual analog scale, and in a subgroup of 15 patients the blinded observer rated patients' sedation and measured pupil diameter. Spontaneous postoperative pain was completely relieved in all patients with cumulative doses of alfentanil ranging from 6 to 8 micrograms/kg. The within-patient alfentanil dose-analgesic response curves were primarily quantal in nature: a precipitous decrease in pain intensity (representing > or = 2/3 of the total effect) after the injection of only one of the increments of alfentanil was observed in 15 of 23 patients. When the analgesic effect of alfentanil was presented as the collective response of a group of individuals, the quantal nature of the response was concealed by the wide interindividual variability of the response. No statistically significant relationship was noted between predrug pain intensity and the cumulative dose of alfentanil necessary to produce pain relief. A strong correlation was found between interpatient variabilities in the analgesic and sedative effects of alfentanil (r = 0.75, P < 0.002). At the same time, the relationship between alfentanil requirements for pain relief and that for pupil constriction did not demonstrate any significant correlation. The results suggest that, in a population of patients with postoperative pain, the intensity of spontaneous pain cannot be the primary factor determining the dose of alfentanil necessary for its relief.

Ketamine enhances local anesthetic and analgesic effects of bupivacaine by peripheral mechanism: a study in postoperative patients.

Patients with unilateral (n = 14) and bilateral (n = 4) herniorrhaphy participated in this study. With bilateral herniorrhaphy, at the end of the surgery, the wound was infiltrated with a solution of bupivacaine 0.5% and ketamine 0.3% on one side and a solution of bupivacaine 0.5% only, on the other. With unilateral herniorrhaphy, the patients were randomly assigned to one of two groups (n = 7). One group at the end of the surgery received the infiltration with a solution of bupivacaine 0.5% and ketamine 0.3%, the other group received the infiltration with a solution of bupivacaine 0.5% only. The duration of the local anesthetic (response to a von Frey filament) and postoperative analgesic (time to mild spontaneous pain) effects of the infiltrations, as well as wound pain threshold 24 h after surgery (pressure algometry), were determined. In patient with unilateral herniorrhaphy, the addition of ketamine for wound infiltration enhanced the duration of infiltration anesthesia (206 +/- 76 versus 343 +/- 108 min, P < 0.02) and analgesia (240 +/- 45 versus 420 +/- 151 min, P < 0.03). Similar enhancement of the local anesthetic effect was observed in patients with bilateral herniorrhaphy. The increase in pain threshold to pressure on the wound with the addition of ketamine was evident in bilateral herniorrhaphy patients and also with a combination of bilateral and unilateral results (1.39 +/- 0.40 versus 2.35 +/- 0.92 kg, P < 0.02). In the group of five volunteers, the subcutaneous infiltration with 0.3% ketamine produced a local anesthetic effect lasting only 10-20 min. The results indicate that ketamine acting via a peripheral mechanism can profoundly enhance anesthetic and analgesic actions of a local anesthetic administered for infiltration anesthesia.