Prediction of postoperative pain from assessment of pain induced by venous cannulation and propofol infusion.

BACKGROUND: Postoperative pain may lead to delayed mobilization, persisting pain, and psychosocial distress. There are no simple and reliable techniques for prediction of postoperative pain. This study was designed to evaluate if pain induced by venous cannulation or propofol injection can be used to predict postoperative pain. METHODS: This prospective study included 180 patients scheduled for laparoscopic cholecystectomy. Pain intensity associated with peripheral venous cannulation and administration of propofol preoperatively and pain intensity, and use of opioid postoperatively was recorded. RESULTS: Patients scoring cannulation-induced pain intensity > 2.0 VAS units were given postoperative opioid more often (65% vs. 36%; P < 0.001), earlier (12 min vs. 90 min; P < 0.001), and in higher doses (4.8 mg vs. 0 mg; P < 0.001), and also reported higher levels of postoperative pain intensity (5.8 vs. 2.9 VAS units; P < 0.001). There were also significant (P < 0.01) correlations with postoperative pain intensity (rs = 0.24), time to opioid administration (rs = -0.26), and total dose of opioid (rs = 0.25). Propofol-induced pain intensity correlated significantly (P < 0.05) with postoperative pain intensity (rs = 0.19). CONCLUSION: Pain intensity associated with venous cannulation and propofol infusion can easily be evaluated at bedside before surgery without specific equipment or training. Patients scoring > 2.0 VAS units on venous cannulation were found to have 3.4 times higher risk of postoperative pain after laparoscopic cholecystectomy. Low pain intensity associated with venous cannulation and propofol infusion indicate lower risk of postoperative pain.

Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort.

Background: Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer. Methods: Patients included in the cohort were identified from a registry of patients treated through expanded access to nivolumab before and after Health Canada approval. Demographics were collected from the application forms. Outcome data for the duration of treatment and survival were collected retrospectively. Results: In contrast to the randomized clinical trial populations, our study cohort included patients who were older (median age: 66 years; range: 36-92 years) and who had an Eastern Cooperative Oncology Group performance status of 2 (8.9%). Despite the poorer-prognosis cohort, median overall survival was 12.0 months, which is comparable to the survival demonstrated in the randomized phase iii trials of nivolumab in lung cancer. Median time to treatment discontinuation was 3.45 months and was similar for all patient subgroups, including poorer-prognosis groups such as those with a performance status of 2, those 75 years of age and older, and those with brain metastases. Conclusions: Nivolumab given in a real-world clinical setting was associated with results similar to those reported in the phase iii clinical trial setting.

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Invasive carcinoma of the uterine cervix following diagnosis and treatment of in situ carcinoma. Record linkage study within a National Cancer Registry.

56117 women registered in the Swedish National Cancer Registry with the diagnosis carcinoma in situ of the uterine cervix were followed up and the risk for developing an invasive carcinoma of the uterine cervix was studied. The studied cohort provided 453 362 women years at risk. The primary treatment for carcinoma in situ in Sweden is generally conization. Hysterectomy is carried out in relatively few cases and intracavitary radium treatment was given to a limited number during the period studied. Cryosurgery and laser conization were of less quantitative importance during this period. The incidence rates of invasive carcinoma of the uterine cervix were compared with expected rates calculated from the National Cancer Registry. The ratio between observed and expected number of cases of invasive carcinomas of the uterine cervix is roughly 2.5 from the first year of observation after treatment of the in situ carcinoma until 20 years. There seems to be a distinct difference in risk for development of an invasive carcinoma of the uterine cervix for different age groups. In age group 50 years and older at time for treatment of the in situ lesion, 66 cases of invasive cancer were observed against 10.7 expected - O/E = 6.2. In ages 49 years or less, 145 cases were observed compared with 77.4 expected - O/E = 1.9. The conclusion from this study is that women treated for an in situ lesion are at a higher risk for an invasive carcinoma than the common female population and should be carefully followed up for a long time after treatment of the in situ lesion.

Mixed müllerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases.

One hundred and forty-seven women with uterine mixed Müllerian tumours (UMMT) treated at Radiumhemmet from 1936 through 1981 were reviewed. The prognostic value of clinical and histopathologic data was analysed with bivariate and multivariate techniques. Stage, age and abdominal pain were found to be significant predictors of survival. Surgery and combined radiotherapy (intracavitary + external irradiation) gave in stage I, a lower local failure rate (p = 0.006) and better overall survival (p = 0.001) than surgery in combination with either intracavitary or external irradiation.

Evaluation of screening for cervical cancer in Sweden: trends in incidence and mortality 1958-1980.

Papanicolaou screening for cancer of the uterine cervix was introduced in Sweden in the late 1950's. Screening programmes covering the age groups 30-49 years were organized in various countries between 1965 and 1973. The approximate number of smears rose from 100 000 in 1960 to one million in 1970, in a female population of four million. Almost 60 000 cases of in situ carcinoma and 17 100 invasive carcinomas of the uterine cervix were registered in Sweden between 1958 and 1980. The age-standardized incidence of invasive carcinoma fell in this period by about 40%. Within the screened cohorts and age groups, the incidence was reduced by two-thirds and there was a parallel fall in mortality from the disease. At least part of these reductions seemed to be explained by the intensity of screening.

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Retinoic acid enhances the cytotoxic effects of gemcitabine and cisplatin in pancreatic adenocarcinoma cells.

INTRODUCTION: Retinoids, which are derivatives of vitamin A, are important factors involved in the control of biologic functions such as cell growth and differentiation, development, and carcinogenesis. We have shown previously that the naturally occurring retinoids all-trans-retinoic acid (ATRA) and 9-cisretinoic acid (9cRA) induce growth inhibition followed by apoptosis in pancreatic adenocarcinoma cells in vitro. AIM: To evaluate the efficacy of retinoids in combination with the chemotherapeutic drugs gemcitabine and cisplatin. METHODOLOGY: In vitro growth inhibition and induction of apoptosis by different combinations of retinoids and cytotoxic drugs were studied by using the T3M-4 and BxPc-3 cell lines. For in vivo studies, T3M-4 cells were injected subcutaneously in nude mice. RESULTS: Pre-treatment of pancreatic adenocarcinoma cells with ATRA or 9cRA before the addition of the drugs resulted in significant reduction in cell number compared with treatment with the drugs alone. Pre-treatment with 9cRA followed by gemcitabine or cisplatin alone also resulted in a strong increase in the percentage of cells undergoing programmed cell death, or apoptosis. Furthermore, there was an indication that the combination of ATRA and gemcitabine caused increased apoptosis in vivo. CONCLUSION: Our results clearly suggest the need for additional studies exploring the potential role of the combination of retinoids and gemcitabine in the management of pancreatic cancer.

Paget's disease of the vulva: the Radiumhemmet series 1975-1990.

Twenty-eight patients with a diagnosis of 'extramammary Paget's disease of the vulva' were referred to the Radiumhemmet, Karolinska Sjukhuset, Stockholm, during the period 1975-1990. A clinical and histopathologic retrospective review was undertaken. Six patients had associated malignancies (21.4%). The disease was considered primary invasive in three cases, whereas three patients later developed an invasive cancer. Surgery-local resection, hemivulvectomy or vulvectomy-was performed in 24 cases. Twelve patients, in which surgery was supposed to be radical with respect to free margins, had a significantly longer recurrence-free survival than 12 patients in which the surgical margins were dubious.

Carcinoma of the fallopian tube. A clinical and histopathologic review. The Radiumhemmet series.

A histopathologic and clinical review of the Radiumhemmet series of primary fallopian tube carcinoma (PFTC) treated from 1923 to 1991 revealed that 128 cases fulfilled the diagnostic criteria for PFTC. These cases were staged according to the new FIGO staging rules for PFTC. Survival was studied with respect to prognostic factors such as age, stage, histologic subgroups, degree of differentiation and mode of treatment. The mean age at diagnosis was 56 years. Seventy-four per cent were found to be in stage Ia-IIa and 26 % in stage III-IV. Forty-five per cent were nulliparous and 22 % had evidence of previous pelvic inflammatory disease. Treatment modalities changed during the studied period. Thirty-three per cent of patients underwent surgery with total abdominal hysterectomy and bilateral salpingo-oophorectomy while 67 % were incompletely operated. A trend towards improvement in results was noticed-however, it was not statistically significant. Among the 14 prognostic variables tested in the multivariate analysis the first in rank were stage (P = 0.001) and degree of differentiation of the tumors (P = 0.070). Patients receiving chemotherapy had superior survival rates compared with those without chemotherapy (P = 0.0006) and patients with cisplatinum-containing chemotherapy did better than those without cisplatin.