Vascular endothelial growth factor and dexamethasone release from nonfouling sensor coatings affect the foreign body response.

Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in the surrounding tissue after 2 weeks of implantation compared to hydrogel-coated fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers and had reduced capsule vascularity compared to VEGF-releasing hydrogel-coated fibers. Hydrogels that released both VEGF and DX simultaneously also showed reduced inflammation at 2 weeks implantation; however, no enhanced vessel formation was observed indicating that the DX diminished the VEGF effect. At 6 weeks, there were no detectable differences between drug-releasing hydrogel-coated fibers and control fibers. From this study, hydrogel drug release affected initial events of the foreign body response with DX inhibiting VEGF, but once the drug depot was exhausted these effects disappeared.

In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings.

Anti-fouling hydrogel coatings, copolymers of 2-hydroxyethyl methacrylate, 1-vinyl-2-pyrrolidinone, and polyethylene glycol, were investigated for the purpose of improving biosensor biocompatibility. These coatings were modified to incorporate poly(lactide-co-glycolide) (PLGA) microspheres in order to release dexamethasone (DX) and/or vascular endothelial growth factor (VEGF). DX and VEGF release kinetics from microspheres, hydrogels, and microspheres embedded in hydrogels were determined in 2-week and 1-month studies. Overall, monolithic, non-degradable hydrogel drug release had an initial burst followed by release at a significantly lower amount. Microsphere drug release kinetics exhibited an initial burst followed by sustained release for 1 month. Embedding microspheres in hydrogels resulted in attenuated drug delivery. VEGF release from embedded microspheres, 1.1+/-0.3 ng, was negligible compared to release from hydrogels, 197+/-33 ng. After the initial burst from DX-loaded hydrogels, DX release from embedded microspheres was similar to that of hydrogels. The total DX release from hydrogels, 155+/-35 microg, was greater than that of embedded microspheres, 60+/-6 microg. From this study, hydrogel sensor coatings should be prepared incorporating VEGF in the hydrogel and DX either in the hydrogel or in DX microspheres embedded in the hydrogel.

Accuracy of aspiration cytology in detecting breast cancer.

To evaluate the role of needle placement in determining accuracy and to establish criteria for clinical decision making, we used aspiration cytology to diagnose 49 palpable breast masses in patients undergoing excisional biopsy. Closed cytology, obtained by percutaneous aspiration, and open cytology, obtained by aspiration of the excised mass, were compared with histology. Nineteen (39%) of the breast masses were carcinoma. Unsatisfactory cytologic findings were frequent after both closed (37%) and open (24%) aspiration. Most of these aspirates were from mammary dysplasia, suggesting that acellularity rather than needle placement was responsible. Closed aspiration was falsely negative in one patient and falsely suggestive of cancer in five. If atypical, suspicious or malignant cytologic findings were considered to be carcinoma; closed cytology had high sensitivity (94%), low specificity (64%), and a false positive fraction of 36%. The positive predictive value was 76% and the negative predictive value 90%. Accuracy was 81%. If only suspicious or malignant results were considered positive, specificity and positive predictive value increased at the expense of sensitivity and negative predictive value but accuracy did not change. Even with optimal needle placement (open aspiration), accuracy of aspiration cytology was less than 90%.

Utility of thyroid aspiration biopsy.

The utility of fine-needle aspiration biopsy to detect carcinoma in thyroid nodules was evaluated by a decision-analysis approach in 102 patients. The procedure caused no morbidity. Cytologic diagnoses were categorized as unsatisfactory (4), no abnormality detected (61), atypical (13), suspicious for malignancy (14), malignancy (2), and inflammation (8). The duration of follow-up averaged 13 months. Of 21 thyroidectomy patients, 10 (48%) had carcinoma. Half of the ten patients operated upon for suspicious cytologic findings were found to have malignancy. Assuming criterion I, that atypical, suspicious, or malignancy results indicated cancer, sensitivity was 90%, specificity 77%, false positive fraction 23%, positive predictive value 31%, negative predictive value 99%, and accuracy 79%. Assuming criterion II, that only suspicious or malignancy cytologic findings represented carcinoma, sensitivity was 70%, specificity 90%, false positive fraction 10%, positive predictive value 44%, negative predictive value 96%, and accuracy 88%. We conclude that sensitivity and specificity of fine-needle aspiration biopsy vary depending upon the use of criterion I or II. Accuracy is highest if atypical results are not considered to represent carcinoma. Positive predictive values remain low and negative predictive values are high in either case. The utility of fine-needle aspiration biopsy when interpreted in relation to clinical criteria is supported by these results.

Insulin protects against muscle proteolysis induced by septic plasma.

Sepsis, like trauma, causes proteolysis of skeletal muscle. Insulin normally protects against muscle protein degradation. In earlier work using a rat muscle preparation, insulin inhibition of proteolysis decreased in the presence of plasma from injured patients. The current experiments tested the effect of plasma from septic patients on insulin inhibition in the same model. The mean value of protein degradation among eight septic plasma samples was 49% greater than the mean value among five normal plasma samples in soleus muscle and 45% greater in extensor digitorum longus muscle. In the presence of insulin, 10(3) mU/L, the increases in degradation with septic plasma were 42% in soleus muscle and 48% in extensor digitorum longus muscle. Insulin reduced degradation an average of 6% (soleus) and 10% (extensor digitorum longus) in normal plasma and 10% (soleus) and 8% (extensor digitorum longus) in septic plasma. In contrast to results of other studies, these experiments show that the protective effect of a moderate concentration of insulin in resisting muscle protein degradation is not significantly different in the muscle protein degradation is not significantly different in the presence of septic human plasma compared with normal plasma. This finding supports clinical efforts to decrease proteolysis in septic patients by the administration of insulin.

Operative choice and technique following pancreatic injury.

During a five-year period, 50 patients were operated on for pancreatic injury. Forty had open trauma and ten closed. Half of each group were treated by drainage alone. Overall mortality was 14%, with all deaths following open injuries due to gunshots. Deaths were more frequent after drainage than after resection. Substantial complications occurred in 70%, with more frequent amd more serious morbidity in drained patients. Sump drainage was associated with less morbidity than Penrose drainage. Guidelines for management of pancreatic trauma are (1) resection of sinistral gland for perforating injuries of the body or tail; (2) drainage of perforations of the pancreatic head when the major duct is intact; (3) resection of duodenum and pancreatic head for devitalizing injury of both structures.

Accuracy and cost of needle localization breast biopsy.

The success and cost of needle localization biopsy (NLB) performed with local anesthesia in an outpatient procedure room (81 biopsies, group 1) or under general anesthesia in an operating room (36 biopsies, group 2) were compared in a longitudinal study. Only 78% of operations in group 1 successfully removed the target breast lesion; definite failure occurred in 17%, and results were indeterminate in 5%. Among lesions sought by group 2 procedures, 92% of lesions were removed successfully, 5% were missed, and 3% were indeterminate. The incidence of carcinoma in breast specimens was 17% in group 1 and 22% in group 2. Wound infection occurred after 6% of group 1 biopsies. The total cost of NLB was $775 in group 1 and $1960 in group 2. The difference in cost represented by the use of general anesthesia was $1260. The added expense of NLB done in an operating room under general anesthesia can be justified by a high rate of success in removing the breast lesion, by patient comfort, and by technical ease.

Condyloma. A new epidemic.

Condyloma acuminatum of the anus is an increasingly frequent disease that may require a combination of therapies. Large bulky lesions can be reduced with topical freezing, cautery, or the scapel. Topical chemotherapy with podophyllum resin can be supplemented with cancer chemotherapeutic agents. Many of these drugs probably act, at least in part, by stimulating a strong local cellular immune reaction. Dinitrochlorobenzene was used to eradicate lesions that had been resistant to treatment with podophyllum resin. 5-Flourouracil was used as a control. All 23 patients studied were initially skin tested with both agents and randomized to either treatment group. All but one of the dinitrochlorobenzene-treated patients had excellent regressions. Immunotherapeutic agents, such as dinitrochlorobenzene, warrant further study as adjuvant therapeutic agents for this disease.

Accuracy of ultrasound in diagnosing abdominal masses.

B-mode ultrasonography was performed in 246 patients with suspected abdominal masses over a seven-year period. In 105 (40 percent), the accuracy of ultrasonic diagnosis was evaluated surgically. Sonography was proven correct in 60 (57 percent) patients who had undergone operation. Among 141 patients who had not undergone operation and whose diagnoses were established by other means, ultrasonography agreed with the clinical diagnosis in 69 (31 percent). Ultrasound accuracy, as confirmed by operation, was highest for splenic masses (100 percent) and for aortic aneurysm (88 percent). Liver masses were correctly identified in 56 percent of patients and gallbladder lesions in 38 percent. While only a 48 percent accuracy was obtained in diagnosing pancreatic disease, 64 percent of all pseudocysts were localized. Ultrasonography correlated positively with operative findings in 56 percent of renal masses. Intraperitoneal abscess was accurately diagnosed in 61 percent of patients but retroperitoneal adenopathy in only 33 percent. Abdominal ultrasonography, while accurately diagnosing splenic and aortic masses, failed to identify approximately half of other mass lesions. Improved techniques hold promise of improving this diagnostic accuracy.

Endoscopic cholangiography and stone removal prior to cholecystectomy. A more cost-effective approach than operative duct exploration?

Would economic benefit result from performing endoscopic cholangiography and removal of common bile duct stones prior to cholecystectomy in patients who are suspected preoperatively of having choledocholithiasis? In this study, 173 patients had cholecystectomy and 30 (17%) had common bile duct exploration. Records of these patients were reviewed as were those of 31 patients who had only endoscopic cholangiography and endoscopic stone removal. Cost estimates were based on local charges. Cholecystectomy with common bile duct exploration was $6730 more per patient than cholecystectomy alone. Endoscopic cholangiography and endoscopic stone removal was 87% successful in removing duct stones. Had endoscopic cholangiography and endoscopic stone removal been performed preoperatively in patients undergoing cholecystectomy who had suspected choledocholithiasis, 21 of 30 common bile duct explorations could theoretically have been eliminated. This would have saved $85,526 or $2851 per patient undergoing common bile duct exploration. Our analysis suggests that patients who require cholecystectomy and have suspected choledocholithiasis may be treated more cost-effectively by performing endoscopic cholangiography and endoscopic stone removal immediately prior to cholecystectomy than by cholecystectomy and operative common bile duct exploration.

Selective intra-arterial vasopression in fusion for upper gastrointestinal tract hemorrhage: a controlled trial.

In a prospective randomized study, 38 patients with massive upper gastrointestinal tract hemorrhage, mostly due to esophageal varices or erosive gastritis, were treated with either standard medical therapy or standard therapy plus selective intra-arterial vasopressin infusion. Cessation of hemorrhage occurred more frequently in the vasopressin-treated group. The study design did not permit meaningful comparisons of mortality of transfusion requirements. We conclude that in patients bleeding from esophageal varices or gastritis, selective intra-arterial vasopressin is more effective in controlling hemorrhage than standard therapy.

Outcome of operations for upper gastrointestinal tract bleeding.

The outcome of operations for upper gastrointestinal tract bleeding during a six-year period was compared with that of the previous four years, in which indications for operation and guidelines for surgical procedures were similar. Between 1973 and 1978, 392 patients were hospitalized for hemorrhage. Endoscopy diagnosed a bleeding lesion in 92% of 234 patients studied. Of 75 patients (19%) who required operation for uncontrollable hemorrhage, 20 (27%) died and two (3%) rebled postoperatively. Most deaths (80%) were caused by esophageal variceal bleeding. Among 47 patients with nonvariceal hemorrhage, mortality was only 9%. No patient with stress ulcer bleeding was encountered. Compared with our 1969 to 1972 experience, the present study shows no improvement in overall mortality. Rebleeding was less frequent than earlier. The most significant differences in outcome were decreased mortality in alcoholic gastritis patients, no deaths from stress ulcer, and increased mortality after portosystemic shunting. Endoscopy, used frequently from 1973 to 1978, helped to improve preoperative diagnostic rates (85% vs 65%). Combined with innovations in nonoperative treatment, such as infusion of vasopressin, it did not appear to decrease the proportion of patients requiring operation.

A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery.

Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision.

Does drainage of intraabdominal pus reverse multiple organ failure?

Intraabdominal abscess induced multiple organ failure in 21 patients. Sepsis was most often due to perforation of the colon and was located with almost equal frequency in the upper and lower abdomen. Four patients died after single laparotomy for drainage. Seventeen were drained operatively more than once (average 3.4 operations) at mean intervals of 10 days. Sixteen of the 21 patients (76 percent) died with multiple organ failure despite drainage. Organ function improved temporarily in only one patient. Autopsy showed that pus had persisted or recurred in three patients. No significant predictors of survival were identified, although the advantage appears to lie with the younger patient in whom multiple organ failure develops relatively late after sepsis (mean 13 days) and who needs ventilatory assistance for less than 1 week. The location, size, and bacteriologic characteristics of abscesses do not appear to influence outcome. This study shows that early and repeated drainage of intraabdominal pus will not reverse multiple organ failure in the majority of patients.

Massive cecal dilation: pseudoobstruction versus cecal volvulus?

Seven patients with acute and progressive abdominal distension secondary to massive cecal and right colon ileus are analyzed. Five had pseudoobstruction of the colon and two had cecal volvulus. Two of the patients with pseudoobstruction and one with cecal volvulus died from preexisting diseases. Pseudoobstruction of the colon is not a rare complication of elderly, sick, bedridden patients. Differential diagnoses include cecal and sigmoid volvulus and acute gastric dilation. Initial conservative therapy is warranted if no peritoneal signs are present. If the cecal diameter is more than 12 cm, colonoscopic decompression with a fiberscope should be attempted. If unsuccessful, tube cecostomy will provide curative, life-saving therapy even if taenia splitting is present. Perforation or widely scattered areas of necrosis make resection mandatory.

Morbidity of colostomy closure.

An unexpectedly high morbidity (28 per cent) followed colostomy closure in 100 patients. One patient died postoperatively because of sepsis resulting from disruption of the colon anastomosis. Wound infection (10 per cent), intraperitoneal abscess (1 per cent), bowel obstruction (7 per cent), and fecal fistula (4 per cent) were other significant complications. Wound sepsis was greater after primary than after delayed wound closure. Obstruction did not correlate with the use of either an open or closed technic of anastomosis. Three patients required reoperation for complications. Temporary colostomy was constructed for colon injury in 85 per cent of patients. In view of the considerable morbidity of colostomy closure, alternate technics of managing colon trauma should be considered. Such technics include primary closure and exteriorization of repaired colon. When temporary colostomy is unavoidable, closure is best done by open, two layer anastomosis with delayed wound closure. Colostomy should be recognized as an important procedure associated with significant morbidity.

Clinical indications and accuracy of gray scale ultrasonography in the patient with suspected biliary tract disease.

One hundred patients with suspected biliary tract disease underwent gray scale cholecystosonography (GSCS) and had diagnostic confirmation by oral cholecystogram (OCG) and/or operation. Ultrasonography demonstrated the gallbladder in 94 of the 100 patients; 2 patients had had previous cholecystectomy and 3 of the 4 remaining patients had documented stones with no confirmation of a nonvisualizing OCG in the other patient. Among the 88 patients with OCG, GSCS findings correlated in 91 per cent (2 per cent false-positive; 7 per cent false-negative). Among the 43 operative patients, GSCS was proven correct in 91 per cent (no false positive; 9 per cent false-negative). Of 12 patients with jaundice GSCS correlated with operative findings in 75 per cent (no false-positive; 25 per cent false-negative). Diagnostic errors occurred in patients with very small biliary calculi, particularly when a single stone was impacted in the cystic duct. Failure to identify the gallbladder with ultrasound signifies probable cholelithiasis in the patient without previous cholecystectomy. On the basis of this experience, we conclude that (1) GSCS is most useful when jaundice or acute illness precludes conventional studies; (2) GSCS provides an inexpensive, quick, accurate means of diagnosing cholelithiasis with a very high specificity (97 per cent) and moderate sensitivity (88 per cent); and (3) GSCS is the optimal diagnostic procedure for evaluating the biliary tract in the acutely ill, jaundiced, vomiting, allergic, and/or pregnant patient.

Caroli's: a surgical challenge.

A patient operated upon for acalculous cholecystitis was later found to have Caroli's disease, congenital ectasis of intrahepatic bile ducts. Cholangitis, calculi and abscesses occurred in both lobes of the liver. Sepsis was not controlled despite open drainage, hepatic segmentectomy and ductal lavage with antibiotics and saline. At autopsy the liver contained a dozen unsuspected cavities filled with calculi, bile and pus. Diagnosis of Caroli's disease is best made by operative cholangiography in patients with atypical biliary disease. Management with antibiotics alone is seldom successful. Hepatic resection is better than drainage procedures for unilateral lesions. In patients with bilateral abscesses and no extrahepatic ductal obstruction or dilation, surgical treatment is often ineffective.