Prediction of malignancy in cystic neoplasms of the pancreas: a population-based cohort study.

OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. The aims of this study were to determine the incidence of malignancy and develop an imaging-based system for prediction of malignancy in PCN. METHODS: We conducted a retrospective cohort study of patients ≥18 years of age with confirmed PCN from January 2005 to December 2010 in a community-based integrated care setting in Southern California. Patients with history of acute or chronic pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst diagnosis was considered as pre-existing. Subsequent incidence of malignancy during surveillance was calculated based on person-time at risk. Age- and gender-adjusted standardized incidence ratio (SIR) was calculated with the non-cyst reference population. Recursive partitioning was used to develop a risk prediction model based on cyst imaging features. RESULTS: We identified 1,815 patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with cyst-related malignancy during the study period. The surveillance cohort consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of malignancy was 0.4% per year during surveillance. The overall age- and gender-adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6, 46.0). Using recursive partitioning, we stratified patients into low (<1%), intermediate (1-5%), and high (9-14%) risk of harboring malignant PCN based on four cross-sectional imaging features: size, pancreatic duct dilatation, septations with calcification as well as growth. Area under the receiver operator characteristic curve for the prediction model was 0.822 (training) and 0.808 (testing). CONCLUSIONS: Risk of pancreatic malignancy was lower than previous reports from surgical series but was still significantly higher than the reference population. A risk stratification system based on established imaging criteria may help guide future management decisions for patients with PCN.

Short- and long-term outcomes of intracorporeal versus extracorporeal ileocolic anastomosis in laparoscopic right hemicolectomy for colon cancer.

BACKGROUND: We assessed the short- and long-term outcomes of intracorporeal ileocolic anastomosis (IA) in laparoscopic right hemicolectomy for colon cancer compared with extracorporeal anastomosis (EA). METHODS: A retrospective chart review of 86 consecutive patients who underwent laparoscopic right hemicolectomy for colon cancer from March 2005 to June 2010 was performed. RESULTS: There were 51 and 35 patients who underwent intracorporeal and extracorporeal anastomosis, respectively. The two groups were demographically comparable. The conversion rate to open surgery was 8.6 % in the EA group, but none in the IA group (p = 0.064). There was no significant difference in operative time, estimated blood loss, complications (intra-abdominal abscess, anastomotic leak, ileus, and wound infection), and length of hospital stay between the groups. There was no perioperative mortality in both groups. There was no significant difference in median number of retrieved lymph node. The overall survival and the disease-free survival at 3 years were not different between the groups. CONCLUSIONS: Compared with the extracorporeal anastomosis technique, intracorporeal ileocolic anastomosis produces comparable short- and long-term outcomes in laparoscopic right hemicolectomy for colon cancer.

Pancreatic endometrioma : a rare differential diagnosis for a pseudocyst.

Pancreatic endometriosis is extremely rare with only 14 cases reported in the medical literature and its diagnosis on radiological imaging poses a great challenge. We report a case of a 31-year-old female patient with recurrent admissions for pancreatitis of unknown aetiology and no relevant previous medical history. Sectional imaging showed a cystic lesion in the tail of the pancreas and the diagnosis of a post-pancreatitis pseudocyst or a less likely pre-malignant mucinous cystadenoma was considered. On post-robotic resection of the pancreatic cyst, the histopathology analysis was positive for endometrial stroma. Pancreatic endometriosis although rare should be considered as a differential diagnosis for cystic lesions especially in patients who are known to have pelvic endometriosis. Nevertheless, the gold standard for the definite diagnosis of pancreatic endometriosis remains histopathological.

Racial and ethnic disparities in outcomes with radiation therapy for rectal adenocarcinoma.

BACKGROUND: Race/ethnicity may modify cancer outcomes and manifest as survival disparities for patients with rectal cancer. Our objective was to determine whether disparate rectal cancer outcomes result from variable efficacy of radiation therapy for major racial/ethnic groups. METHODS: The Los Angeles County Cancer Surveillance Program (CSP) identified patients with rectal adenocarcinoma between the years 1988 and 2006. Patients who underwent curative-intent surgery were grouped by race/ethnicity and by receipt (yes vs. no) and timing (neoadjuvant vs. adjuvant) of radiation therapy. The impact of receipt and timing of radiation therapy on overall survival was then assessed. RESULTS: Of 4,961 patients in CSP, 2,229 (45%) received radiation therapy. Overall, there was no difference in survival among patients according to receipt of radiation therapy. We then examined the radiation cohort, wherein 919 (41%) and 1,310 (59%) patients received neoadjuvant or adjuvant radiation, respectively. Overall, patients who received neoadjuvant compared to adjuvant radiation had improved survival (median survival (MS), 9.4 vs. 6.8 years, respectively; p < 0.001). Among those patients who received neoadjuvant radiation, whites, Hispanics, and Asians had significantly longer survival than blacks (MS, 10.4, 10.4, and 10.4 vs. 4.4 years, respectively; p = 0.003). On multivariate analysis, race/ethnicity was an independent predictor of survival (p = 0.001). CONCLUSIONS: To our knowledge, this is the first study examining the efficacy of radiation therapy for racial/ethnic groups with rectal cancer. Disparate outcomes were observed for the administration of radiation therapy for select racial/ethnic groups. The reasons for these disparities in outcomes should be investigated to better optimize radiation therapy for patients with rectal cancer.

Robot-assisted total mesorectal excision: is there a learning curve?

BACKGROUND: Laparoscopic total mesorectal excision (TME) is associated with a steep learning curve, but the learning curve for robotic TME is unknown. This study aimed to evaluate the learning curve for robotic TME. METHODS: Between November 2004 and April 2009, 80 patients underwent robotic TME performed by a single surgeon. The operative experience was divided into two groups: group 1 (the first 40 cases) and group 2 (the subsequent 40 cases). Patient demographics, operative characteristics, and morbidities were compared. RESULTS: The two patient populations selected did not differ statistically in age, body mass index (BMI), preoperative risk assessment, stage, preoperative chemoradiotherapy, or tumor location. The mean operative times in group 1 (310 min) and group 2 (297 min) were similar (p = 0.55), and the mean robotic TME time did not differ between the two groups (60 vs. 64 min; p = 0.65). In addition, the operative times did not improve during the course of the study. There were no differences in EBL, margin status, or number of lymph nodes harvested. Furthermore, there were no differences in conversion rate, time to resumption of diet, length of hospital stay, or postoperative complications. CONCLUSION: Robot-assisted TME may attenuate the learning curve for laparoscopic rectal cancer resection. Further studies are necessary to establish the role of robotic surgery in minimally invasive rectal operations.

Oncological outcomes of laparoscopic colon resection for cancer after implementation of a full-time preceptorship.

BACKGROUND: The learning curve for laparoscopic colectomy (LC) is considered long and difficult. The presence of a preceptor may shorten the learning curve of LC and ensure adequate oncologic and short-term results. City of Hope implemented a full-time LC preceptorship between September 2004 and March 2006 with one experienced surgeon assisting other surgeons. We review our outcomes with laparoscopic colon resection for colon adenocarcinoma after implementation of this preceptorship. METHODS: All cases of laparoscopic colon resection for adenocarcinoma performed from September 2004 to April 2009 were retrospectively reviewed. We compared the patients in two groups: group 1 had surgery performed during the preceptorship period from September 2004 to March 2006 (n = 39) and group 2 had procedures done between April 2006 and April 2009 (n = 74). Clinical characteristics evaluated included sex, age, body mass index (BMI), ASA level, and history of previous abdominal surgery. Postoperative variables evaluated included type of operation, conversion to open surgery, estimated blood loss (EBL), operation time, stage, number of harvested lymph nodes, time to liquid diet, postoperative stay, complications, and 30-day mortality rate. Kaplan-Meier survival curves were constructed based on disease-free survival (DFS) and overall survival (OS). RESULTS: One hundred thirteen patients underwent LC for adenocarcinoma during the study period. Mean age and BMI were similar between the groups. There was also no significant difference in conversion rates (10.3% vs. 13.5%, p = 0.77) or total complications (25.6% vs. 41.9%, p = 0.088) between groups 1 and 2, respectively. There was a significantly greater number of lymph nodes removed in the post-preceptor period (20.3 vs. 15.8, p = 0.007). The 3-year DFS rate was 96.5%, with a mean follow-up of 22.8 months, and the 3-year OS rate was 88.9%, with mean follow-up of 22.1 months, for the entire cohort. CONCLUSION: Implementation of a program with a full-time preceptorship can help institutions overcome the challenges of laparoscopic colectomy and achieve acceptable postoperative and oncologic outcomes.

Residency training in the time of COVID-19: A framework for academic medical centers dealing with the pandemic.

BACKGROUND: As cases of COVID-19 climb worldwide, academic medical centers (AMCs) are scrambling to balance the increasing demand for medical services while maintaining safe learning environments. The scale and nature of the current pandemic, limitations on key resources, risks of transmission, and the impact on trainee wellbeing pose additional challenges to AMCs. We propose a framework for AMCs to utilize in facilitating health system, organization and program-level adjustments to meet the needs of medical trainees during the pandemic. APPROACH: In February 2020, we developed a three-level approach to the pandemic response of training programs at our AMC. The first level involved AMC alignment and engagement with regulatory stakeholders. The second level utilized the graduate medical education committee and leveraged organizational functions such as human resources, finance, and clinical departments. The third level of intervention focused on common approaches used by programs to ensure continuity of learning in the context of dynamic changes in workflows and service operations. EVALUATION: Outcomes at each level are reported. These include the co-development of a national framework on medical trainee responses to COVID-19, the composition of an operational guidance document, organizational protocols to accommodate novel challenges posed by the pandemic, and multiple program-level interventions. REFLECTION: This methodical approach, employed during a global crisis, was critical in facilitating interventions required to fulfill the mission of AMCs. Future steps include assessing the impact of these changes on trainee performance and the applicability of the approach in diverse settings.

Porcelain Gallbladder: No Longer an Indication for Prophylactic Cholecystectomy.

Porcelain gallbladder (PG) was historically associated with gallbladder cancer (GBC), (range 12-62%, largest series n = 26). Presently, cholecystectomy is still performed in many patients with PG. The objective of this study was to determine the incidence of GBC in patients with radiographic diagnosis of PG. We conducted a retrospective chart review of the Kaiser Permanente southern California electronic medical record database and identified patients with radiographic diagnosis of PG between 2008 and 2013. Extracted were patient demographics, imaging modality, symptoms, surgical and observational outcomes, and pathology results. Out of 192 PG patients, 102 underwent cholecystectomy, and 90 were observed. None of the patients in the surgery group had GBC on pathology review, and none of the observed patients developed GBC during follow-up (mean 3.5 years). In the surgery group, 82 per cent of the patients were asymptomatic with a perioperative complication rate of 10.7 per cent. Among symptomatic patients, the complication rate was 16.7 per cent. Rate of conversion to open surgery was 5 per cent. Complications led to eight endoscopic or percutaneous interventions and five additional operations. PG is not associated with increased risk of GBC but is associated with high risk of postoperative complications. Cholecystectomy should not be recommended in asymptomatic patients with PG.

Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia.

PURPOSE: To evaluate the molecular responses of vascular endothelial growth factor (VEGF) and its receptors to dexamethasone (Dex) and celecoxib (Cel) during hyperoxia and during hyperoxia followed by recovery in room air, in newborn rabbit retinas. METHODS: Newborn rabbits at 3 days postnatal age (n = 96) received room air or oxygen (80%-100%) for 4 days, during which they were administered saline (Sal), Dex, vehicle (Veh), or Cel (n = 12/treatment group). Six animals from each group were killed immediately after hyperoxia (or room air) and the remainder exposed to room air for 5 days. Retinal mRNA expression of VEGF(121), VEGF(165), VEGF receptor-1 (VEGFR-1, or Flt-1), and VEGFR-2 (or KDR/Flk-1) was determined. RESULTS: Hyperoxia resulted in increased retinal expression of mRNA of the VEGF splice variants in the groups treated with Sal, Dex, and Veh, whereas a decrease in VEGF(121) was noted in the Cel-treated group. In contrast, retinal Flt-1 receptor mRNA was markedly increased in the Cel-treated group only, whereas retinal VEGFR-2 (KDR/Flk-1) receptor mRNA was suppressed in all the treatment groups. Hyperoxia followed by recovery in room air resulted in a minimal decrease in expression of retinal Flt-1 mRNA in the Sal and Dex groups. Cel treatment abolished its expression. CONCLUSIONS: The findings of increased retinal expression of VEGF mRNA in the newborn rabbit in response to hyperoxia are most likely due to species differences. Selective targeting of VEGF(121) and Flt-1 mRNA by Cel may represent one regulatory pathway for their anti-inflammatory effects. Further studies are needed to evaluate the therapeutic benefits of cyclooxygenase (COX)-2 inhibitors for the treatment and/or prevention of diseases associated with neovascularization.

Antenatal administration of celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, appears to improve placental perfusion in the pregnant rabbit.

To investigate the effects of celecoxib on fetal growth, and placental prostanoid and nitric oxide (NO) production in fetal rabbits, pregnant rabbits received celecoxib (30 mg/kg per day) from 13 to 20 days (Cel-A), from 13 to 28 days (Cel-B), or vehicle from 13 to 28 days gestation. Fetal body and organ weights, and measurements of linear growth were recorded. The placentas were weighed and analyzed for prostaglandins (PGs), NO oxidation products (NOx), and total cellular protein levels. Placental prostaglandin E2 (PGE2) and NOx levels increased (P < or = 0.05), while thromboxane B2 levels were suppressed (P < or = 0.01) in Cel-B group. Tail length and brain weight were greater, while lung weights were lower in the Cel-B group (P < or = 0.05). Maternal administration of celecoxib appears to preferentially increase placental vasodilators and decrease placental TxA2, suggesting that the drug may increase uteroplacental perfusion without adverse fetal outcome.

In vitro response of prostaglandin E2 receptor (EP3) in the term pregnant rat uterus and cervix to misoprostol.

We examined and compared the in vitro effects of misoprostol (synthetic prostaglandin E1 (PGE1) analogue) on prostaglandin E2 (PGE2) secretion and EP3 receptor mRNA expression in the pregnant rat myometrium and cervix at 19 days gestation. Myometrial and cervical tissue samples were exposed to media with or without misoprostol (50 or 100 pg/ml) and incubated for 15 and 30 min, and 1, 3, 6, 12, and 24 h. Media and tissue samples were collected for quantification of PGE2 and mRNA expression of rEP3alpha and rEP3beta receptor, respectively. PGE2 secretion increased (P < or = 0.05) in the myometrium exposed to 50 and 100 pg/ml misoprostol. Cervical PGE2 secretion increased following exposure to the 100 pg/ml dose only. In the myometrium, 50 and 100 pg/ml misoprostol induced elevations in rEP3alpha and rEP3beta receptor mRNA expression. rEP3alpha and rEP3beta receptor mRNA expression in the cervix was not different from controls. These data demonstrate that the EP3 receptor is differentially expressed in the myometrium and cervix in response to misoprostol. This may account for the ability of misoprostol to stimulate the myometrium when administered for cervical ripening.

Differential regulation of prostacyclin and thromboxane by dexamethasone and celecoxib during oxidative stress in newborn rabbits.

To compare the effects of dexamethasone (Dex) and celecoxib (Cel) on F-isoprostane, prostacyclin (PGI2), and thromboxane A2 (TxA2) following hyperoxia, and hyperoxia followed by recovery in room air (RA), newborn rabbits were exposed to hyperoxia (80-100% oxygen) for 4 days, during which they were treated with saline (Sal, i.m.), Dex (i.m.), vehicle (Veh, PO), or Cel (PO, n = 12 per group). Six animals in each group were sacrificed immediately following hyperoxia, and the remainder allowed to recover in RA for 5 days. The control litters were treated simultaneously in RA with all conditions other than atmospheric oxygen being identical. Blood samples were assayed for 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), 6-keto prostaglandin F1alpha (6-ketoPGF1alpha), and TxB2. Dex and Cel decreased 8-epi-PGF2alpha during hyperoxia and the recovery period. Dex increased 6-ketoPGF2alpha following hyperoxia, while similar increments were noted during recovery with Cel. Although TxB2 was decreased only during the recovery period, TxB2/6-ketoPGF1alpha ratio was lower during hyperoxia and recovery in both treated groups. The effect of Cel on 8-epi-PGF2. and TxA2/PGI2 ratio confirm the formation of a COX-derived F2-isoprostane that is possibly linked to TxA2 receptors. Further studies are required to examine whether Cel can be used as a therapeutic alternative to Dex for oxygen-induced injury in the newborn.

Ingestion of magnetic toys: report of serious complications requiring surgical intervention and a proposed management algorithm.

CONTEXT: Increasing popularity of strong magnets as toys has led to their ingestion by children, putting them at risk of potentially harmful gastrointestinal tract injuries. OBJECTIVES: To heighten physician awareness of the potential complications of magnetic foreign body ingestion, and to provide an updated algorithm for management of a patient who is suspected to have ingested magnets. DESIGN: A retrospective review of magnet ingestions treated over a two-year period at our institutions in the Southern California Permanente Medical Group. Data including patient demographics, clinical information, radiologic images, and surgical records were used to propose a management strategy. RESULTS: Five patients, aged 15 months to 18 years, presented with abdominal symptoms after magnet ingestion. Four of the 5 patients suffered serious complications, including bowel necrosis, perforation, fistula formation, and obstruction. All patients were successfully treated with laparoscopic-assisted exploration with or without endoscopy. Total days in the hospital averaged 5.2 days (range = 3 to 9 days). Average time to discharge following surgery was 4 days (range = 2 to 7 days). Ex vivo experimentation with toy magnetic beads were performed to reveal characteristics of the magnetic toys. CONCLUSIONS: Physicians should have a heightened sense of caution when treating a patient in whom magnetic foreign body ingestion is suspected, because of the potential gastrointestinal complications. An updated management strategy is proposed that both prevents delays in surgical care and avoids unnecessary surgical exploration.

Spontaneous massive hemoperitoneum: A potentially life threatening presentation of the wandering spleen.

CONTEXT: Wandering spleen is an unusual condition characterized by the absence or maldevelopment of one or all of the ligaments securing the spleen in its normal position in the left upper abdomen. Pedicular tortion with a complete vascular disruption is a rare but known potential complication of this mostly congenital disorder. Spontaneous hemoperitoneum with acute abdomen however, is a life threatening situation that has not been adequately reported in the adult literature. CASE REPORT: A forty four year old man presented to the emergency department with an acutely distended and rigid abdomen. His past medical history was only significant for mild mental retardation. The patient denies prior abdominal operation or recent trauma. On initial examination, he appeared to be anxious, pale, and tachycardic. Fullness in the midpelvic region was easily appreciated on palpation. An enlarged pelvic spleen and free intraperitoneal fluid consistent with blood were seen on a CT scan. The patient was promptly taken for an exploratory laparotomy where a large rush of blood was encountered upon entering the abdomen. A volvulus of the splenic pedicle with an infarcted spleen was found mandating a splenectomy. CONCLUSIONS: Abnormally located spleen, splenomegaly, and finding of hemoperitoneum are highly suggestive of wandering spleen with tortioned pedicle. Despite its life threatening presentation, immediate laparotomy and splenectomy invariably result in good outcome.

Ganglioneuroma of the adrenal gland and retroperitoneum: A case report.

CONTEXT: Ganglioneuromas are benign tumors of the sympathetic nervous system that rarely arise in the adrenal gland. Majority of cases are detected incidentally since they are usually asymptomatic. Up to the current era of laparoscopic adrenal mass excision, this unusual entity has not been adequately reported in the surgical literature. CASE REPORT: A 51 year old male with history of hypertension was found to have abdominal bruit during a regular physical examination. A 4 cm right adrenal mass with upper pole calcification and a 6 cm retro-pancreatic mass were subsequently found on a computed tomography scan. Endoscopic ultrasound-guided needle biopsy was indeterminate. Preoperative endocrine evaluation showed mildly elevated vanillyl mandelic acid with normal 24-hour cathecolamine, metanephrine and cortisol levels. Histopathologic examination after an uneventful laparoscopic excision was consistent with ganglioneuroma. CONCLUSIONS: Ganglioneuroma occurs rarely in adrenal gland and preoperative diagnosis is difficult since symptoms are usually nonspecific. Due to widespread utilization of abdominal imaging, however, it should be included in differential diagnosis of adrenal or retroperitoneal mass. Histopathologic examination is currently the mainstay of diagnosis.

Identification of a natural compound by cell-based screening that enhances interferon regulatory factor-1 activity and causes tumor suppression.

The transcription factor interferon regulatory factor-1 (IRF-1) is induced by many tumor-suppressive stimuli and can mediate antiproliferative and proapoptotic effects in cancer cells. Thus, identifying agents that enhance IRF-1 activity may be an effective approach to cancer therapy. A cell-based screening assay was developed to identify extracts and compounds that could enhance IRF-1 activity, using an IRF-1-dependent luciferase reporter cell line. Through this approach, we identified a natural product extract and a known active component of this extract, baicalein, which causes a marked increase in IRF-1-dependent reporter gene expression and IRF-1 protein, with modulation of known IRF-1 targets PUMA and cyclin D1. Baicalein causes suppression of growth in vitro in multiple cancer cell lines in the low micromolar range. IRF-1 plays a role in this growth suppression as shown by significant resistance to growth suppression in a breast cancer cell line stably transfected with short hairpin RNA against IRF-1. Finally, intraperitoneal administration of baicalein by repeated injection causes inhibition of growth in both xenogeneic and syngeneic mouse models of cancer without toxicity to the animals. These findings indicate that identifying enhancers of IRF-1 activity may have utility in anticancer therapies and that cell-based screening for activation of transcription factors can be a useful approach for drug discovery.

Preoperative weight loss before bariatric surgery.

HYPOTHESIS: Preoperative weight loss reduces the frequency of surgical complications in patients undergoing bariatric surgery. DESIGN: Review of records of patients undergoing open or laparoscopic gastric bypass. SETTING: A comprehensive, multidisciplinary obesity treatment center at a tertiary referral center that serves central Pennsylvania. PATIENTS: A total of 881 patients undergoing open or laparoscopic gastric bypass from May 31, 2002, through February 24, 2006. INTERVENTION: All preoperative patients completed a 6-month multidisciplinary program that encouraged a 10% preoperative weight loss. MAIN OUTCOME MEASURES: Loss of excess body weight (EBW) and total and major complication rates. RESULTS: Of the 881 patients, 592 (67.2%) lost 5% or more EBW and 423 (48.0%) lost more than 10% EBW. Patients referred for open gastric bypass (n = 466) were generally older (P < .001), had a higher body mass index (P < .001), and were more often men (P < .001) than those undergoing laparoscopic gastric bypass (n = 415). Total and major complication rates were higher in patients undergoing open gastric bypass (P < .001 and P = .03, respectively). Univariate analysis revealed that increasing preoperative weight loss is associated with reduced complication frequencies for the entire group for total complications (P =.004) and most likely for major complications (P = .06). Controlling for age, sex, baseline body mass index, and type of surgery in a multiple logistic regression model, increased preoperative weight loss was a predictor of reduced complications for any (P =.004) and major (P = .03) complications. CONCLUSION: Preoperative weight loss is associated with fewer complications after gastric bypass surgery.

Effect of the antenatal administration of celecoxib during the second and third trimesters of pregnancy on prostaglandin, cytokine, and nitric oxide levels in rabbits.

OBJECTIVE: The purpose of this study was to examine the effects of celecoxib on prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13 to 28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Blood and tissue were assayed for prostaglandin, cytokine, and nitric oxide oxidation products. RESULTS: Preterm delivery occurred in 4 of 11 controls, 0 of 9 in celecoxib-A, and 0 of 8 in celecoxib-B. Plasma prostaglandin F(2alpha) was reduced in both treated groups at 20 days and at delivery in celecoxib-B. Plasma thromboxane B(2) was suppressed in celecoxib-B at 20 days and delivery. Cervical prostaglandin E(2) was increased; uterine and cervical plasma thromboxane B(2) declined in celecoxib-B. Celecoxib administration suppressed plasma nitric oxide oxidation products at delivery and cervical nitric oxide oxidation products in celecoxib-B. Uterine and cervical interleukin-1beta and interleukin-6 were decreased, and uterine tumor necrosis factor-alpha increased in celecoxib-B. CONCLUSION: Further studies are required to evaluate the therapeutic benefits of cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.

Response of fetal prostanoids, nitric oxide, and ductus arteriosus to the short- and long-term antenatal administration of celecoxib, a selective cyclo-oxygenase-2 inhibitor, in the pregnant rabbit.

OBJECTIVE: The purpose of this study was to test the hypothesis that the maternal administration of therapeutic doses of celecoxib would not affect ductus arteriosus patency or alter renal and hepatic prostanoids in the fetal rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13-28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Fetal serum and lung tissue were analyzed for nitric oxide oxidation products. Fetal plasma, liver, and kidney were analyzed for prostaglandin levels. RESULTS: The ductus arteriosus was patent in both treatment groups. Celecoxib induced elevations of plasma prostaglandin E(2) production. In celecoxib-B liver and kidney, the 6-keto-prostaglandin F(1alpha) and prostaglandin F(2alpha) levels were increased, and the prostaglandin E(2) and thromboxane B(2) levels were decreased substantially. CONCLUSION: This preliminary evaluation demonstrates that the maternal administration of celecoxib does not influence fetal ductus arteriosus patency adversely in rabbits.