Peter Grant

Prevalence of Delirium with Dexmedetomidine Compared with Morphine Based Therapy after Cardiac Surgery A Randomized Controlled Trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study)

Background:Commonly used sedatives/analgesics can increase the risk of postoperative complications, including delirium. This double-blinded study assessed the neurobehavioral, hemodynamic, and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia. Methods:A total of 306 patients at least 60 yr old were randomized to receive dexmedetomidine (0.1–0.7 &mgr;g · kg−1 · h−1) or morphine (10-70 &mgr;g · kg−1 · h−1) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2–4. Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care. Secondary outcomes included ventilation time, additional sedation/analgesia, and hemodynamic and adverse effects. Results:Of all sedation assessments, 75.2% of dexmedetomidine and 79.6% (P = 0.516) of morphine treatment were in the target range. Delirium incidence was comparable between dexmedetomidine 13 (8.6%) and morphine 22 (15.0%) (relative risk 0.571, 95% confidence interval [CI] 0.256–1.099, P = 0.088), however, dexmedetomidine-managed patients spent 3 fewer days (2 [1–7] versus 5 [2–12]) in delirium (95% CI 1.09–6.67, P = 0.0317). The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine (3 of 20 [15%] versus 9 of 25 [36%]) (relative risk 0.416, 95% CI 0.152–0.637, P = 0.001). Dexmedetomidine-treated patients were more likely to be extubated earlier (relative risk 1.27, 95% CI 1.01–1.60, P = 0.040, log-rank P = 0.036), experienced less systolic hypotension (23% versus 38.1%, P = 0.006), required less norepinephrine (P < 0.001), but had more bradycardia (16.45% versus 6.12%, P = 0.006) than morphine treatment. Conclusion:Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation, less hypotension, less vasopressor requirement, and more bradycardia versus morphine regimen.

Secondary cytoreductive surgery for recurrent epithelial ovarian cancer.

OBJECTIVE To review our experience with secondary cytoreductive surgery for recurrent epithelial ovarian cancer with regard to its feasibility, morbidity, mortality, patient selection, and survival. METHODS Forty‐six patients who underwent secondary cytoreductive surgery at the Royal Hospital for Women, Sydney, between July 1988 and October 1996 were retrospectively reviewed. The mean age at surgery was 50.3 years, and the median disease‐free interval was 26 months. Eighty‐nine percent of patients had a disease‐free interval of at least 12 months. Twenty‐five patients (54%) had localized disease at the time of surgery. Univariate survival outcomes were analyzed using the log rank test, and survival curves were calculated using the method of Kaplan‐Meier. RESULTS Two patients (4%) were inoperable and 19 patients (41%) were cytoreduced to no macroscopic disease. There was one postoperative death (2%), and four patients (8.7%) had significant postoperative morbidity. With a median follow‐up of 88 months, the overall median survival was 22.5 months. Patients with a disease‐free interval of less than 12 months after their initial treatment had a median survival of 6 months, compared with 11 months if the disease‐free interval was 12–24 months and 39 months for those with a disease‐free interval of 24 months or more (P = .001, log rank). Patients who had any residual disease had a median survival of 11 months, whereas those with no residual disease had a median survival of 38 months (P = .002, log rank). CONCLUSION For carefully selected patients with recurrent epithelial ovarian cancer: 1) complete surgical resection is feasible more commonly than with primary cytoreduction, 2) serious morbidity and mortality are acceptable, and 3) significant survival benefit accrues when a) all macroscopic disease can be resected, or b) the disease‐free interval is 24 months or more.

Abnormalities of the RB1 pathway in ovarian serous papillary carcinoma as determined by overexpression of the p16(INK4A) protein.

Summary:Dysfunction of proteins involved in the G1 to S transition of the cell cycle, such as p16(INK4A) and RB1, is common in many cancer types. A screen of p16 protein expression was performed in benign, borderline, and invasive ovarian tumors, together with endometrial cancers, aligned on a tissue microarray. We observed frequent p16 overexpression in serous papillary carcinomas of ovarian and endometrial origin. An extended cohort of ovarian serous papillary carcinomas was examined to further evaluate the frequency of p16 overexpression. Strong, uniform staining in the majority of cancer cells occurred commonly in invasive serous papillary ovarian cancers, particularly in grade 3 carcinomas. RB1 protein expression abnormalities were rare. Our data indicate that abnormalities in the retinoblastoma pathway, as determined by p16 overexpression, are common in serous papillary carcinomas and are probably an early event.

Adjuvant small field pelvic radiation for patients with high risk, Stage IB lymph node negative cervix carcinoma after radical hysterectomy and pelvic lymph node dissection : A pilot study

After radical hysterectomy and pelvic lymph node dissection, an identifiable subgroup of patients with International Federation of Gynecology and Obstetrics Stage IB lymph node negative cervix carcinoma remains at high risk of pelvic recurrence. This study attempted to determine whether postoperative small field of pelvic radiation can improve the disease free survival (DFS) of this high risk group of patients without producing significant morbidity.

Placental site trophoblastic tumor. Report of three cases and review of the literature.

Three cases of placental site trophoblast tumor (PSTT) are added to 74 cases in the English language literature. One case presented with an anorexic syndrome, the other two with amenorrhea and abnormal vaginal bleeding. The three patients, whose lesions were confined to the uterus, were treated by total hysterectomy and their follow-up has been uneventful. Review of the literature showed that 62 patients with PSTT were alive and 15 had died, two as a complication of treatment. The diagnosis of PSTT may be difficult on a dilatation and currettage specimen. Metastases are a powerful indicator of adverse outcome. Prognosis, as assessed on pathologic criteria, is unreliable; however, a mitotic count of more than five mitoses per 10 high power fields is significant. Surgery is the mainstay of treatment. Hysterectomy is generally indicated, but young patients who wish to remain fertile may be treated by conservative surgery. In a few cases of progressive disease, chemotherapy has achieved remission, but generally chemotherapy and radiotherapy are ineffective. Long-term follow-up is essential as PSTT may progress after years of remission. Serum human chorionic gonadotrophin (hCG) levels are the best available marker of disease, but the disease may still progress even if hCG levels are not raised.

Prognostic value of bilateral positive nodes in squamous cell cancer of the vulva.

Objectives: The aim of the current study was, first, to determine whether laterality of lymph node metastases has prognostic significance, independent of the number of lymph node metastases. Second was to determine the prognostic significance of extracapsular spread irrespective of the number of lymph node metastases. Methods: Data on 134 patients with stage III/IVA vulva cancer from 1982 till 2004 and treated with curative intent in either the Academic Medical Centre in Amsterdam or the Mercy Hospital for Women in Melbourne were reviewed. The impact of the number of lymph node metastases, extracapsular spread, and bilateral existence of lymph node metastases on survival was determined. Results: The bilateral presence of lymph node metastases is not a significant predictor for survival if a correction is made for the number of lymph node metastases (hazards ratio, 1.31; 95% confidence interval, 0.68-2.51; P = 0.420). If extracapsular spread is put into the model as well, this is the only parameter of prognostic significance in multivariate analysis (hazards ratio, 5.27; 95% confidence interval, 2.60-10.67; P < 0.001). The five-year survival of patients with extracapsular spread is only 31%, which is considerably lower than the 80% survival of patients with only intracapsular metastases. Conclusions: In conclusion, there is growing evidence that bilateral existence of lymph node metastases is not a sufficient variable to qualify stage. Extracapsular spread, however, seems to be the most valuable lymph node-associated prognostic factor for survival.

Grapelike leiomyoma of the uterus

A 24-year-old nulliparous woman underwent laparotomy for a large pelvic mass. Grapelike tumor extending from the uterus into the broad ligaments and peritoneal cavity was found. A diagnosis of sarcoma appeared likely, but radical surgery was avoided when frozen sections indicated a histologically benign smooth muscle tumor.

Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer

BACKGROUND Vitamin D status might be associated with cancer survival. Survival after ovarian cancer is poor, but the association with vitamin D has rarely been examined. OBJECTIVE We evaluated the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and ovarian cancer survival. DESIGN Participants were women with invasive ovarian cancer diagnosed between 2002 and 2005 who participated in the Australian Ovarian Cancer Study. Serum samples, collected at diagnosis (n = 670) or after completion of primary treatment and before recurrence (n = 336), were assayed for 25(OH)D. Sociodemographic, dietary, and lifestyle data came from questionnaires self-completed at recruitment, and clinical and survival data were from medical records, supplemented by linkage to the Australian National Death Index (October 2011). Cox proportional hazards regression was used to estimate HRs and 95% CIs for the association between circulating 25(OH)D and survival. RESULTS Overall, 59% of the women died during follow-up, with 95% of deaths resulting from ovarian cancer. Circulating 25(OH)D concentrations (mean: 44 nmol/L) were significantly associated with age, state of residence, season of blood collection, and body mass index but not with tumor histology, stage or grade, or comorbidities. Higher 25(OH)D concentrations at diagnosis were significantly associated with longer survival (adjusted HR: 0.93; 95% CI: 0.88, 0.99 per 10 nmol/L), but there was no significant association with progression-free survival or for 25(OH)D measured after primary treatment. CONCLUSIONS In our cohort, higher serum 25(OH)D concentrations at diagnosis were associated with longer survival among women with ovarian cancer. If confirmed in other studies, this suggests that vitamin D status at diagnosis may be an independent predictor of prognosis. Furthermore, if the association is found to be causal, improving vitamin D status may improve ovarian cancer survival rates.

Extrauterine malignant mixed müllerian tumor of primary peritoneal origin

&NA; The case of an extrauterine heterologous malignant mixed müllerian tumor (MMMT) of primary peritoneal origin occurring in a 63 yr old woman is presented. The tumor was a 19 cm, soft, friable mass arising from the serosa of the sigmoid colon and spreading to adjacent pelvic peritoneum. The uterus, tubes and ovaries were uninvolved. It was composed of sarcomatous areas showing cartilaginous and rhabdomyoblastic differentiation and sharply demarcated carcinomatous areas showing endometrioid and serous differentiation. This is the thirteenth reported case of an extragenital MMMT. It demonstrates the pluripotentiality of female pelvic peritoneum to differentiate into tumors resembling those of the genital tract.

Unusual variants of vaginal adenosis: A challenge for diagnosis and treatment

Two unusual cases of vaginal adenosis in non-diethylstilbestrol (DES)-exposed patients are presented. These cases created an initial difficulty in histological classification and exclusion of the diagnosis of adenocarcinoma. The first case presented a problem of atypical columnar epithelium with simple gland architecture, while the second showed a pseudoinfiltrative pattern of small glands, but without cytological atypia. A diagnosis of glandular dysplasia (atypical columnar epithelium) was finally made in the first case and vaginal adenosis with unusual architectural features in the second. The first patient was treated by excision and the second expectantly. Subsquently, neither patient has developed carcinoma. The spectrum of glandular changes in vaginal adenosis appears analogous to that of the cervix. Until the natural history of sufficient numbers of these variants of vaginal adenosis have been studied, the analogous cervical condition may serve as a guide to prognosis. The diagnosis of invasive adenocarcinoma should be made cautiously unless there are both architectural and cytological features of malignancy.