Tat-Kin Tsang

Cisplatin and 5-fluorouracil in the primary management of squamous esophageal cancer

A combined treatment program consisting of chemotherapy with cisplatin and infusion 5‐fluorouracil (5‐FU) for three cycles followed by esophagectomy or radiation, or both, has been conducted in 26 patients with squamous cancer of the esophagus localized to the primary site. Eleven patients had objective evidence of partial or complete response to the chemotherapy. Fourteen patients were operated on and ten underwent total esophagectomy. Drug toxicity was considerable with severe mucositis and myelosuppression occurring in 11 and seven patients, respectively. There were no drug‐related deaths. Median survival is 17.8 months. Ten patients have lived more than 2 years. Six of these patients have undergone total thoracic esophagectomy after the induction chemotherapy. Determination of the ultimate benefits of combined modality therapy may require prospective randomized trials isolating the major treatment components but our data suggest that chemotherapy contributes to improved results in this disease and that drug therapy is emerging as an integral component of combined therapy.

Aminoglycoside nephrotoxicity in obstructive jaundice

PURPOSE Although it is known that liver disease predisposes to aminoglycoside nephrotoxicity, specific features of such disease that may predispose to aminoglycoside-induced renal injury have not been identified. We sought to identify such features. PATIENTS AND METHODS We undertook a retrospective review of the charts of 42 consecutive patients with biliary obstruction and/or cholangitis who had received more than three doses of an aminoglycoside. RESULTS Comparison of patients in whom aminoglycoside nephrotoxicity did and did not develop revealed no differences in age, race, sex, dose, and duration of aminoglycoside therapy; mean peak and trough aminoglycoside levels; initial pre-treatment levels of serum creatinine, aspartate transaminase, alkaline phosphatase, or albumin; or prothrombin time. The initial pre-treatment serum bilirubin level was higher in the patients in whom aminoglycoside nephrotoxicity developed (12.2 +/- 8.8 mg/dl versus 3.4 +/- 3.2 mg/dl, p less than 0.01). Aminoglycoside nephrotoxicity occurred in eight patients (19 percent): in seven of 15 patients (47 percent) with an initial bilirubin value greater than 5.0 mg/dl, but in only one of 27 patients (4 percent) with an initial bilirubin value below 5.0 mg/dl (p less than 0.01). The pre-treatment bilirubin level correlated with the change in creatinine during aminoglycoside therapy (n = 42, r = 0.66, p less than 0.01). CONCLUSION Aminoglycosides should probably be avoided in patients with biliary obstruction and a high serum bilirubin level.

Silicone-Covered Metal Stents (An In Vitro Evaluation for Biofilm Formation and Patency)

Self-expanding metal stents are being used morecommonly to prevent biliary tract obstruction.Silicone-covered self-expanding metal stents (Wallstent,Schneider, Inc.) have been developed to prevent tumor ingrowth. Biofilm formation and occlusionmaterial in siliconecovered self-expanding metal stentscompared to standard polyethylene stents were examinedin an in vitro model. Matched pairs of polyethylene and silicone-covered metal stents were perfusedwith infected bile for 8, 12, and 16 weeks at a rate of0.5 cc/min at 37°C. Two reservoirs fitted withsilicone-covered metal stents had ampicillin/sulbactam added and were perfused for 16 weeks. Thestents were then analyzed by scanning electronmicroscopy and light microscopy for biofilm formationand presence of occlusion material. The twoampicillin/sulbactam-treated stents showed no biofilm formation. Biofilm wasseen on all of the remaining stents. There was adifference in occlusion thickness between the 8- and16-week polyethylene stents, and no difference between the biofilm thickness at 8, 12, or 16 weeks inthe silicone-covered metal stents. Silicone-coveredself-expanding metal stents will likely extend patencyrates in malignant obstructive jaundice by providing a larger lumen for bile flow and allowingcyclical antibiotics to prevent bacterial biofilmformation.

Inhibition of biliary endoprostheses occlusion by ampicillin-sulbactam in an in vitro model

An important first step in stent occlusion is the formation of a bacterial biofilm. This is followed by deposition of granules similar to that found in brown pigment stones. Previous in vitro models for studying occlusion have used synthetic biles without bilirubin or pooled human bile, which is limited in supply. Our aim was to develop a new in vitro model of stent occlusion with porcine gallbladder bile and then, with the model, assess whether ampicillin-sulbactam can prevent biofilm formation and thus occlusion. Sterile porcine gallbladder bile was contaminated with Escherichia coli then divided into eight reservoirs, four of which then received ampicillin-sulbactam. The bile was then circulated through 10F polyethylene stents. Bile was changed weekly for 8 weeks. In the stents that were untreated, biofilm and sludge were seen in all four, whereas the four ampicillin-sulbactam-treated stents had no biofilm when viewed by electron microscopy. Furthermore, the levels of calcium, cholesterol, and bilirubin in the reservoirs decreased significantly in the untreated bile as compared with the treated bile (p < 0.05). In this in vitro model, the losses of calcium, cholesterol, and bilirubin are likely caused by deposition of granules into the biofilm matrix. Ampicillin-sulbactam can prevent biofilm formation if used continuously.

Reliability of balloon-mesh cytology in detecting esophageal carcinoma in a population of US veterans

A catheter, equipped with a terminal ballon covered with nylon mesh, was developed to study the reliability of abrasive cytology for the diagnosis of esophageal carcinoma. Eighty‐seven balloon cytology analyses were attempted in 82 subjects. Four patients were unable to swallow the balloon. In the 78 successful attempts, the initial diagnoses were: esophagitis (34) and esophageal carcinoma (13), established by endoscopic examination and histologic sampling; and normal esophagus (31) confirmed histologically in 25. The remaining 6 controls were younger than 40 years old, without any significant history of smoking, drinking and esophageal symptoms. For esophageal carcinoma, the sensitivity of balloon cytology was 91% and the specificity was 94% with four false‐positives. Balloon cytology was generally well‐tolerated and easily performed. This method is now being tested for screening high‐risk patients for esophageal carcinoma.

Detection of Helicobacter pylori gastritis by PCR: correlation with inflammation scores and immunohistochemical and CLOtest findings.

We developed a polymerase chain reaction (PCR) assay to detect Helicobacter pylori in gastric and/or gastroesophageal biopsy specimens of adults with dyspepsia, compared the method with immunohistochemical analysis and CLOtest (Ballard Medical Products, Draper, UT), and correlated the results of each test with the histologic features of infection. H pylori was identified in 36 (60%) of 60 patients irrespective of biopsy site and testing method. In the gastric biopsy specimens, PCR detected H pylori in 29 (52%) of 56 cases, including 11 (100%) of 11 immunohistochemically and/or CLOtest-positive cases. PCR-positive gastric biopsy specimens correlated with a higher average cumulative inflammatory score compared with PCR-negative specimens (P = .001). In gastroesophageal biopsy specimens, PCR detected H pylori in 15 (34%) of 44 cases, including 1 (20%) of 5 immunohistochemically positive specimens. PCR-positive gastroesophageal junction biopsy specimens did not correlate with a higher average cumulative inflammatory score. Overall, PCR detected an additional 23 cases negative by immunohistochemical analysis and/or CLOtest. This PCR assay identified a significant number of H pylori infections that would not be detected by immunohistochemical analysis and/or CLOtest.

Inhibition of Bacterial Adherence on the Surface of Stents and Bacterial Growth in Bile by Bismuth Dimercaprol

Bacterial infection and biofilm formation on the surface of biliary stents is believed to be one of the main factors in stent occlusion. This study explored the role of the new reagent, bismuth dimercaprol, in preventing bacterial adherence and bacterial biofilm formation on the surface of biliary stents. Sterile porcine bile preparations, infected separately with Escherichia coli, Klebsiella pneumoniae, Enterobacter, and Enterococcus, were used as the perfusion media in an in vitro perfusion system. The bacterial growth in the media and the bacterial adherence on the surface of stents were tested when different concentrations of bismuth dimercaprol were used in the perfusion media. BisBAL (5 μ M) did not inhibit the growth of any of the tested bacterial species. It did, however, significantly decrease the amount of bacteria adhering to the surface of stents for all bacterial strains except Escherichia coli. Bismuth dimercaprol (20 μ M) significantly inhibited the growth of Escherichia coli, Klebsiella pneumoniae, and Enterobacter and, thereby, significantly decreased the amount of these bacteria adhering to the surface of stents. The unique bactericidal and anitbiofilm activities of bismuth thiols might contribute to delaying the process of biliary stent occlusion if the effective concentrations of bismuth thiols could be delivered to the target sites. The feasibility of this application of bismuth thiols deserves further investigation.

Comparing Multiplex PCR and Rapid Urease Test in the Detection of H. pylori in Patients on Proton Pump Inhibitors

Background. This study was conducted to assess the diagnostic value of a multiplex PCR assay to detect H. pylori infection and to further evaluate the negative results from the CLOtest on patients with and without PPI treatment. Methods. This study is a retrospective cohort that included 457 patients with symptoms of dyspepsia, who underwent upper endoscopy at Evanston and Glenbrook Northshore Hospital from June 2003 to October 2007. A total of 556 samples were reported with some patients having more than one test over the time period. The CLOtest was performed first on the gastric specimen and from that specimen, the DNA was isolated and the one-step multiplex PCR was performed. Results. By M-PCR testing, H. pylori was detected in 143 (52.2%) of 274 cases in the control group and 130 (46.1%) of 282 cases in patients on PPI treatment (P = 0.1746). The CLOtest detected the presence of H. pylori in 4 (1.4%) of 282 cases from the same group receiving PPI treatment and 29 (10.6%) of 274 cases from the group not taking a PPI (P ≤ 0.0001). Conclusion. Our PCR is sensitive enough to detect the presence of H. pylori despite being on PPI treatment.

Severe hypokalemia in thyrotoxic periodic paralysis.

Thyrotoxic hypokalemic periodic paralysis is an uncommon but sometimes fatal disease in which early recognition and therapy may prevent untoward complications. The case of a 26-year-old Chinese man who presented to the emergency department with rapidly progressive profound weakness and severe hypokalemia (serum potassium, 1.2 mEq/L) is presented. The patient required endotracheal intubation, ventilatory assistance, and intravenous potassium administration. Emergency medical evaluation and management of this entity are discussed.

Use of oral GoLytely solution in relief of refractory fecal impaction.

Constipation and fecal impaction are commondisorders with multiple treatment options. We describethe use of GoLytely oral solution in 10 patientsadmitted to a community hospital and referred to asingle gastroenterologist for fecal impactionrefractory to conventional medical treatment. Sevenwomen and three men received enemas, bisacodylsuppositories, and digital fragmentation either solelyor in combination prior to the administration of GoLytely oralsolution. The patients had no clinical and radiologicalevidence of bowel obstruction. All had underlyingcardiovascular problems. Their mean age was 78.1 years (range 49-100 years). GoLytely oral solution(Braintree Laboratories, Inc.) was administered at arate of 100 ml/hr per orem to three patients, vianasogastric tube in six patients, and via gastrostomy tube in one patient. All 10 patients were ableto regularly pass feces and show radiographicalcolorectal clearing within 6.0 to 57.25 hr (mean 23.60hr). No significant complications were observed. Eight patients were discharged from the hospitalwithin 24 hr of termination of treatment while twopatients remained for unrelated medical conditions.GoLytely oral solution effectively relieved fecalimpaction in 10 patients refractory to conventionalmedical treatment.