Primary repair with no flaps for lower lip defects (30-80 %) after cancer excision.

Reconstruction of the lip is a necessary procedure when lip tumors are excised. Although many good techniques have been described, they often have disadvantages such as necrosis and extensive suture lines. In our approach, we aim to minimize the suture line and avoid tissue necrosis for medium-sized lip defects (30-80 %). This is a surgical technique report from a single center. After tumor resection, we made a bilateral 15 mm horizontal skin and mucosa incision from the angles of the lip to the lateral sides. The mucosa and skin were dissected from the underlying muscle, and the muscle was cut approximately 15 mm on each side. The lip defect was then closed and sutured in four layers. Finally, the released mucosa was sutured to the corner of the incised skin. We followed the patients for 36 months and found that their speech intelligibility, sensation, mobility, and aesthetic satisfaction were preserved. The scars were also less pronounced compared to flaps, and there were no signs of edema or drooling. In conclusion, our technique offers many advantages for moderate defects of lower lip tumors. By avoiding the use of flaps, we eliminate the complications associated with flap surgery while achieving aesthetically satisfactory results. However, further evaluation by other surgeons is necessary to fully examine the technique's benefits.

RhoGDI2 is an invasion and metastasis suppressor gene in human cancer.

To discover novel metastasis suppressor genes that are clinically relevant in common human cancers, we used isogenic human bladder cancer cell lines and used DNA microarray technology to identify genes whose expression diminishes as a function of invasive and metastatic competence. We then evaluated the expression profile of such genes in 105 pathologically characterized tumors from seven common organ sites, and we identified one gene, RhoGDI2, whose expression was diminished as a function of primary tumor stage and grade. When RhoGDI2 was transferred back into cells with metastatic ability that lacked its expression, it suppressed experimental lung metastasis but did not affect in vitro growth, colony formation, or in vivo tumorigenicity. In addition, RhoGDI2 reconstitution in these cells blocked invasion in an organotypic assay and led to a reduction of in vitro motility. These results indicate that RhoGDI2 is a metastasis suppressor gene, a marker of aggressive human cancer, and a promising target for therapy.

The role of Ral A in epidermal growth factor receptor-regulated cell motility.

Tumor cell motility is one of the rate-limiting steps of invasion, which defines progression toward a more malignant phenotype. Elevated expression of epidermal growth factor (EGF) receptor in many cancers is associated with progression of superficial to invasive forms of the disease and is sometimes found in tumors that also have activating Ras mutations, suggesting that both events contribute to tumor invasion. Here we show that EGF stimulates motility in human tumor cell lines, which harbor activating Ha-RasV12 via a novel signal transduction pathway mediated by the small GTP-binding proteins RalA and RhoA but independent of Rac1 and Cdc42. On EGF stimulation, RalA localizes to the cell membrane. In addition, activation of RalA and expression of Rho were increased by EGF stimulation in both the nonmetastatic and metastatic variants of the same cell line. However, elevated levels of constitutively activated RalA were only found in the metastatic variant. This is the first demonstration of an essential role for Ral in EGF-mediated cell motility and its potential contribution to tumor metastasis in human cancer.

Gynecology and obstetrical conditions requiring intensive care admission.

OBJECTIVE: Gynecological admissions to the surgical intensive care unit vary from the obstetrical cases. Pregnant women are of prime age and can tolerate the pregnancy and delivery well. There are certain rare conditions or complications, which make the pregnant women's life pass through a critical time. These are dealt with in a high dependency area, which is short of the intensive care unit. In King Khalid University Hospital there is no such arrangement, so the mildly affected and critically ill patients together are cared for in the surgical intensive care unit. The objective of this study is to study the gynecological and obstetrical conditions requiring intensive care admission in King Khalid University Hospital, surgical intensive care unit. METHODS: All obstetrical and gynecological patients who were admitted to the surgical intensive care unit were included. The demographic particulars, reason for admission, the course of the surgical intensive care unit stay and outcome were studied. RESULTS: During the study period of 3 years, there were 83, (100%) obstetrical and gynecological admissions to the surgical intensive care unit. Two (2%) cases were due to anesthesia complications. The majority of causes of admissions were due to obstetrical (n=63, 76%) complications or combination of medical and surgical conditions. Gynecological admissions comprised only 18 (22%) cases. There was no mortality in the group studied. CONCLUSION: Management of major obstetrical emergencies and gynaecological patients require an understanding of medical conditions' influence on the patients, and the physiological changes of normal and abnormal pregnancies. Intensive care unit management is an essential part in raising the level of patient care; health personnel training and continuing health care education may be improved.

Effect of bile acids on formation of azoxymethane-induced aberrant crypt foci in colostomized F344 rat colon.

The effect of bile acids on the formation of azoxymethane induced aberrant crypt foci (ACF) was investigated using the fecal stream-excluded colons of colostomized F344 rats. The excluded colon was irrigated with saline or bile acids (1 mg/0.5 ml per day, 5 days/week) for 4 weeks. The mean numbers of ACF per colon in rats given cholic acid, deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), lithocholic acid, and ursodeoxycholic acid (UDCA) were 160.8, 118.2, 227.8, 150.7 and 87.3, respectively, while that of the control was 174.0. The number of ACF was significantly larger in CDCA, but smaller in UDCA and DCA-treated rats than the control (P<0.01). DCA did not induce apoptosis in the colon under the present conditions.

Molecular determination of perivesical and lymph node metastasis after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Current methods used to determine the pathological stage of the primary tumor and associated lymphatics after radical cystectomy are tedious, costly, and may lack the sensitivity afforded by molecular approaches such as reverse transcription-PCR (RT-PCR) for markers specific for urothelial tissue such as the uroplakin II (UPII) gene. Thus, we sought to evaluate an objective and sensitive molecular approach for the assessment of perivesical extension and lymph node status after radical cystectomy, based on the detection of UPII expression using RT-PCR and compare this assay to standard clinical and pathological examination. EXPERIMENTAL DESIGN: From November 1999 to September 2000, 27 patients with clinical T(a)-T(3)N(0)M(0) urothelial bladder cancer underwent radical cystectomy, 19 (70%) of which also had pelvic lymphadenectomy. At the completion of cystectomy, systematic biopsies of the external surface of the bladder specimen as well as from the largest palpable lymph node found at lymphadenectomy were obtained for molecular analysis. RT-PCR analysis for UPII mRNA was carried out on these biopsy specimens, and results were compared with data obtained from conventional pathological examination. RESULTS: Pathologically organ-confined tumors had a 42% (5 of 12) incidence of positive signals in the perivesical tissues and 17% (1 of 7) in the lymph nodes. Corresponding percentages for pT(3a)N(0) and pT(3b)-T(4)N(0) lesions were 67% (4 of 6)/25% (1 of 4) and 67% (4 of 6)/33% (2 of 6), respectively. Overall, pathologically node-negative cancers had a perivesical positivity rate of 54% (13 of 24) and a lymph node positivity rate of 25% (4 of 16). All patients with pathologically positive nodes had positive UPII signals in the lymph node sample. CONCLUSIONS: This molecular assay aimed at assessing perivesical extension and lymph node status after radical cystectomy appears to identify patients that may harbor residual disease not appreciated by conventional histology. Larger studies with 5-7-year follow-up will be required to determine the prognostic significance of such molecular information.

Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication.

Breast cancer progresses toward increasingly malignant behavior in tumorigenic and metastatic stages. In the series of events in the metastatic stage, tumor cells leave the primary tumor in breast and travel to distant sites where they establish secondary tumors, or metastases. In this report, we demonstrate that cell-cell communication via gap junctions is restored in the metastatic human breast carcinoma cell line MDA-MB-435 when it is transfected with breast metastasis suppressor 1 (BRMS1) cDNA. Furthermore, the expression profile of connexins (Cxs), the protein subunits of gap junctions, changes. Specifically, the expression of BRMS1 in MDA-MB-435 cells increases Cx43 expression and reduces Cx32 expression, resulting in a gap junction phenotype more similar to normal breast tissue. Taken together, these results suggest that gap junctional communication and the Cx expression profile may contribute to the metastatic potential of these breast cancer cells.

Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13.

We previously showed that introduction of a normal, neomycin-tagged human chromosome 11 reduces the metastatic capacity of MDA-MB-435 (435) human breast carcinoma cells by 70-90% without affecting tumorigenicity, suggesting the presence of one or more metastasis suppressor genes encoded on human chromosome 11. To identify the gene(s) responsible, differential display comparing chromosome 11-containing (neo11/ 435) and parental, metastatic cells was done. We describe the isolation and functional characterization of a full-length cDNA for one of the novel genes, designated breast-cancer metastasis suppressor 1 (BRMS1), which maps to human chromosome 11q13.1-q13.2. Stably transfected MDA-MB-435 and MDA-MB-231 breast carcinoma cells still form progressively growing, locally invasive tumors when injected into mammary fat pads but are significantly less metastatic to lungs and regional lymph nodes. These data provide compelling functional evidence that breast-cancer metastasis suppressor 1 is a novel mediator of metastasis suppression in human breast carcinoma.

The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in lineage related human bladder cancer cell lines.

We have recently characterized a human bladder cancer cell line T24 and a more aggressive lineage related variant of it, T24T. To gain further insights, we have studied their metastatic ability in an in vivo model system. Results show that T24 forms significantly fewer [4/12 (1/11) mice had metastases with 1-2 lesions/mouse] metastasis in SCID/bg mice than T24T [14/14 (6/6) mice had metastases with a mean of 24-28 lesions/mouse]. To begin exploring the mechanisms underlying this difference, we evaluated the mRNA and protein expression levels of metastasis-suppressor genes, known to be important in the progression of other cancers, in our model of bladder cancer progression. A higher mRNA expression of BRMS1, a metastasis suppressor in breast cancer, was observed in T24 cells. In addition, RhoGDI2 mRNA expression was only observed in T24 when compared to T24T, suggesting that Rho activation might play a significant role in the metastatic cascade. However, a basal level mRNA expression of KISS1, described as metastasis suppressor in melanoma and breast, was observed in both the lines and had slightly higher expression in T24T. No difference of Nm23-H1, KAI1, MKK4/SEK1 and E-Cadherin protein levels were noted between these two lines. In summary, it appears that the T24/T24T paired cell lines constitute a useful model for the study of human bladder cancer metastasis that will allow both the discovery and mechanistic evaluation of genes potentially involved in this process.

Analysis of mechanisms underlying BRMS1 suppression of metastasis.

Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70-90% without affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435 led to the discovery of a human breast carcinoma metastasis suppressor gene, BRMS1, which maps to chromosome 11q13.1-q13.2. Stable transfectants of MDA-MB-435 and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively growing, locally invasive tumors when injected in mammary fat pads of athymic mice but exhibit significantly lower metastatic potential (50-90% inhibition) to lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action, we measured the ability of BRMS1 to perturb individual steps of the metastatic cascade modeled in vitro. Consistent differences were not observed for adhesion to extracellular matrix components (laminin, fibronectin, type IV collagen, type I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix metalloproteinases, heparanase, or invasion. Likewise. BRMS1 expression did not up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1 or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30-60%) compared to parental and vector-only transfectants. Ability to grow in soft agar was also decreased in MDA-MB-435 cells by 80-89%, but the decrease for MDA-MB-231 was less (13-15% reduction). Also, transfection and re-expression of BRMS1 restored the ability of human breast carcinoma cells to form functional homotypic gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis of human breast carcinoma by complex, atypical mechanisms.

15 years of experience with cardiopulmonary resuscitation in the Kingdom of Saudi Arabia: a critical analysis.

The objective of this review is to establish a framework about the educational activities of the Cardiopulmonary Resuscitation (CPR) National Committee of the Saudi Heart Association (SHA) and determine if it has had any effect on the survival rate in daily hospital work. Further, the review puts forward recommendations regarding the key to success for future implementations and improvement in the outcome of heart attacks in the Kingdom of Saudi Arabia (KSA). Cardiopulmonary resuscitation (CPR) was introduced into the Kingdom of Saudi Arabia in the 1980s. The birth of CPR in the Kingdom was conducted by the American Heart Association (AHA) provision of the first instructor course in Basic Cardiac Life Support (BCLS) and Advanced Cardiac Life Support (ACLS) in the spring of 1984. This educational activity was initiated by the Postgraduate Center of the College of Medicine and currently is a function of the Saudi Heart Association (SHA). The National Heart Center (NHC) continually expands its activities. The number of courses organized, conducted, and reported herein totaled 459 for providers and instructors in BCLS and ACLS. This resulted in certification of 916 and 204 instructors in basic and advanced CPR respectively. There were 80 centers established in the Kingdom over the span of 15 years. They all provide BCLS courses; only 13 provide ACLS courses. The SHA issued a total of 84,659 certificates.

Critical incident reports.

We describe a retrospective analysis of critical incident reports in two teaching hospitals. We included significant observations, involving unsafe practices during cardio-pulmonary resuscitation intensive care management and during anesthesia. Of the 143 critical incidents reported, 87% did not lead to negative out-come, out of these 13% were reports on deaths of patient resuscitated by CPR team or emergency department, underwent surgery, and or managed in the intensive care unit. Human errors and lack of communications were common factors for the majority of the incidents. Wrong drug labeling and irresponsible behavior were the most frequent among the human errors. The analysis aimed to regularize the method of reporting and also to determine the causes of complications, offer solutions and prevent occurrence of such incidents in the future.

Laparoscopic cholecystectomy for cholelithiasis during infancy and childhood: cost analysis and review of current indications.

Eleven consecutive laparoscopic cholecystectomies (LCs) were performed between January 1994 and June 1996 compared with seven open cholecystectomies (OCs) performed previously at King Khalid University Hospital. The comparison included surgical, clinical, and economic factors, together with a review of the literature. In the laparoscopic group the main indication for cholecystectomy was symptomatic gallstones. Other indications include mucocele of the gallbladder and chronic cholecystitis. A total of eight children in both group had sickle cell disease. The first two LCs were performed in the presence of an experienced laparoscopic surgeon. There is a learning curve to pass through with LC. The operating time for LC ranged between 65 and 135 minutes (mean +/- SD 89.81 +/- 21.89 minutes). There was no major morbidity or mortality. The average postoperative parenteral analgesia required for LC (50.45 +/- 24.57 mg) was significantly less than for OC (135.14 +/- 62.02 mg), and the mean length of hospitalization for LC was significantly shorter than that for OC (1.68 +/- 0.46 vs. 6.07 +/- 0.30) days. Although the average operative cost per LC (2522 SR) was significantly more expensive than for OC (350 SR), the ultimate cost of LC was significantly less than for OC (5790.00 +/- 787 vs. 12,343 +/- 139 SR) because the total period of hospitalization was much shorter. In conclusion, LC is safe, effective, and less expensive than OC and therefore is the approach of choice for cholecystectomy in children.

Perioperative antinociceptive effects of tramadol. A prospective, randomized, double-blind comparison with morphine.

PURPOSE: To compare the efficacy of tramadol and morphine for intra- and postoperative analgesia in patients undergoing laparoscopic cholecystectomy. METHODS: In a prospective, randomized, double-blind study 100 patients were allocated randomly into two groups. Ten minutes before induction of anaesthesia, patients in group 1 received 100 mg tramadol and those in group 2 received 10 mg morphine i.v. Anaesthesia was induced with 5 mg.kg-1 thiopental and was maintained with O2, N2O plus isoflurane with additional doses of tramadol or morphine as decided by the attending anaesthetist. Postoperatively, patients in group 1 and group 2 received tramadol and morphine, respectively, from a patient-controlled analgesia (PCA) device. Pain, analgesic consumption, vital signs and side effects were recorded postoperatively for 24 hr. RESULTS: Intraoperative consumption of tramadol and morphine were 137 +/- 37 and 12.2 +/- 3 mg, respectively. Compared with morphine, patients receiving tramadol had higher blood pressures and required greater mean ETisQ to control haemodynamic variables (P < 0.05). Postoperatively, there were no differences in observer pain score or visual analogue pain score during the first 24 hr between groups except at 30, 45, and 90 min where patients in the tramadol group reported higher pain scores (P < 0.05). The cumulative, 24 hr PCA consumption was 111 +/- 93 and 7.5 +/- 6.6 mg of tramadol and morphine, respectively. CONCLUSIONS: There was no difference between the use of tramadol and morphine to treat pain after laparoscopic cholecystectomy from 90 min after the end of surgery. Morphine was more effective than tramadol as an intraoperative analgesic.

Effects of dietary bile acids on formation of azoxymethane-induced aberrant crypt foci in F344 rats.

The present study has demonstrated the influence of bile acids (BAs) on the development and growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF). Male F344 rats were treated with two doses of AOM (15 mg/kg) at 7 days apart and fed either basal MF or MF plus 0.4% of cholic (CA), deoxycholic (DCA), chenodeoxycholic (CDCA), lithocholic (LCA) and ursodeoxycholic (UDCA) acid mixed diets for 8 weeks after the first AOM dose. The mean number of ACF/colon of the rats fed CA, DCA, CDCA and LCA were higher than that of MF-fed group and the differences were statistically significant (P < 0.005). But the mean number of ACFs/colon was significantly (P < 0.005) lower in UDCA diet-fed rats compared to MF. UDCA-fed rats also showed a significant decrease in average crypt multiplicity (number of crypts/focus) of ACF compared to MF alone. The mean number of ACF with > or =5 crypts was about 2.5-3.7 times higher in case of CA, DCA, CDCA and LCA and about 8.2 times lower in UDCA compared to the control MF diet group. In a parallel study, feeding for 18 weeks of the same BAs mixed diets without AOM administration did not significantly induce ACF. Therefore, these data suggest that dietary BAs by themselves do not induce ACF in F344 rats but enhance or, in the case of UDCA, suppress the development and growth of AOM-induced ACF.