Search PubMed⌕ Search

Biomedical subjects

L Nathanson

Publications and source records attributed to L Nathanson.

At least 37 records · Page 2Linked to original sources

Laparoscopic choledochoduodenostomy.

Choledochoduodenostomy is less often performed since the advent of ERCP and endoscopic sphincterotomy (ES). It may, however, still prove necessary in patients where ERCP and ES fail to provide long-term biliary drainage or when CBD stones recur after ES. We have performed laparoscopic choledochoduodenostomy in two patients (aged 66 and 71 years). Surgery was performed in one patient for recurrent CBD stones 25 years after cholecystectomy where three attempts at ERCP failed to cannulate the CBD. In the second patient it was performed for recurrent CBD stones 16 years after cholecystectomy and after two previous endoscopic sphincterotomies. Surgery was completed in just over 3 h in both cases and postoperative stay was 4 days. Laparoscopic choledochoduodenostomy is a viable technique which may prove valuable in the management of patients in whom ERCP and ES has failed to provide long-term biliary drainage.

Aged↗

Laparoscopic Nissen fundoplication and postoperative dysphagia-can it be predicted?

Temporary swallowing difficulty has been reported in up to 100% of patients after laparoscopic Nissen fundoplication for gastro-oesophageal reflux, but the long-term prevalence of dysphagia is not known. If reliable predictors of persistent postoperative dysphagia exist, their identification may permit tailoring of the fundoplication for specific cases at risk. Of 475 consecutive cases of laparoscopic fundoplication, 202 have undergone detailed symptom scoring at 1 year postoperatively. In each case, a short, 360 degrees loose wrap was constructed over an intra-oesophageal bougie, and short gastric vessels were divided when insufficient fundal mobility was encountered. At one year postoperatively, 24% complained of grade 1 dysphagia (intermittent sensation of food sticking), 9% of grade 2 (food sticking requiring liquids to clear) and 1 patient had regular dysphagia for solids (grade 3). Gender, preoperative complaint of dysphagia, endoscopic grade of oesophagitis, oesophageal motility, lower oesophageal sphincter pressure, and division of short gastric vessels were reviewed in relation to dysphagia. Dysphagia is common after laparoscopic Nissen fundoplication, but is less prevalent than before operation. It is usually mild, intermittent and improves with time. Those with division of short gastric vessels had a reduced risk of postoperative dysphagia.

Adolescent↗

Prognosis and staging in melanoma.

For patients who have primary cutaneous melanoma, tumor thickness is the most significant prognostic factor. In addition, other factors, including Clark's level (In thin melanoma), anatomic site of tumor, tumor histology (especially ulceration), patient age, and gender all have prognostic significance. With regional lymph node metastases, the number of lymph nodes involved, and secondarily the presence of nodal capsular invasion, are the most important prognostic features. In distant metastatic disease, the number (I versus > I) and site of metastatic lesions, were the most important prognostic variables. Staging of primary melanoma with extensive radiological imaging is not cost effective, but patients who have positive lymph nodes or other sites of metastases should have such studies to include magnetic resonance imaging of the brain. The follow-up of patients with high risk or advanced melanoma should reflect the fact that metastatic disease is largely incurable, and most recurrences are discovered on history, physical examination, and chest x-ray. Elaborate laboratory and imaging studies should only be used in patients for whom more extensive disease is suggested by simple and limited evaluation.

Age Factors↗

Laparoscopic exploration of the common bile duct: lessons learned from 129 consecutive cases.

Since the introduction of laparoscopic cholecystectomy there has been widespread debate about the best way to manage common bile duct (CBD) calculi. Between August 1991 and July 1994, 129 patients underwent laparoscopic exploration of the CBD. Fifteen patients of median age 52 years were managed by glucagon-induced relaxation of the sphincter of Oddi and saline flushing of the bile duct through a cholangiogram catheter. This had a success rate of 73 per cent and took a median of 90 min including cholecystectomy. The technique has now been replaced by Dormia basket exploration of the CBD. Transcystic common duct exploration using a Dormia basket was used in 79 patients of median age 47 years. Duct clearance was achieved in 96 per cent of cases with a median operating time of 55 min. Thirty-five patients of median age 52 years were managed by choledochotomy and T tube placement, with a 91 per cent duct clearance rate and a median operating time of 120 min. Overall duct clearance was achieved in 92 per cent of patients with an operative morbidity rate of 5.4 per cent. Duct clearance using either a Dormia basket or choledochotomy and T tube placement was obtained in 95 per cent of patients. Laparoscopic exploration of the CBD is an important alternative in the management of common duct calculi.

Adult↗

Inhibition of the melanoma cell cycle and regulation at the G1/S transition by 12-O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity.

The growth of malignant melanoma cells is inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA) while the growth of normal melanocytes is stimulated. We previously demonstrated that TPA inhibits the growth of Demel melanoma cells and leads to arrest at both at the G1/S and G2/M cell cycle transitions. To investigate the mechanism by which TPA arrests melanoma cell growth at the G1/S transition we have examined its effects on the levels of cyclins and cyclin dependent kinases (CDKs) and activation of CDK2 kinase activity. Addition of TPA in G1 blocked the increase in the level of p34cdc2 mRNA, but not of CDK2 mRNA. When TPA was added in G1, it inhibited the mobility shift of CDK2 reflecting a change in phosphorylation state. This corresponded to inhibition of the increase in CDK2 histone H1 kinase activity. There was little effect on the level of CDK4. Treatment with TPA during G1 caused a three to four fold increase in cyclin D1 mRNA expression, but blocked the increase in the expression of cyclin A and cyclin B mRNAs later in the cell cycle. TPA caused a small increase in levels of cyclin D1 and had little effect on cyclin E, suggesting these G1 cyclins were not limiting. Addition of TPA in G1 prevented an increase in cyclin A levels, suggesting cyclin A might play an important role in mediating the growth inhibition. Examination of the levels of the CDK inhibitors p21Cip1 and p27Kip1 showed that the level of these inhibitors was higher in G1 and dropped as cells entered S phase. In the presence of TPA this decrease did not occur. These results demonstrate that TPA blocks the G1/S transition in Demel melanoma cells in late G1 by mechanisms which regulate phosphorylation and activation of the CDK2 kinase. These mechanisms include preventing the decrease in p21Cip1 and p27Kip1 kinase inhibitors and limiting the amount of cyclin A.

CDC2 Protein Kinase↗

Laparoscopic antegrade biliary stenting.

BACKGROUND AND STUDY AIMS: Laparoscopic common bile duct exploration is successful in 90% of patients, but 10% of patients may have retained stones or impaired biliary drainage at the end of surgery. This study presents the results of laparoscopic biliary stenting in three such patients. PATIENTS AND METHODS: Three patients with choledocholithiasis, aged 51, 82, and 100 were treated by laparoscopic antegrade placement of biliary stent. RESULTS: Biliary drainage was established in all three cases. Follow-up at six months revealed all patients to be asymptomatic, with two aged 82 and 101 with the stents still in place. CONCLUSIONS: Laparoscopic antegrade biliary stenting deserves consideration when the surgeon encounters impaired biliary drainage after laparoscopic exploration of the common bile duct.

Aged↗

Laparoscopic splenectomy and lymph node biopsy for hematologic disorders.

OBJECTIVE: The authors audit the introduction of laparoscopic splenectomy and laparoscopic intra-abdominal lymph node biopsy and compare outcomes with a parallel cohort of patients undergoing open splenectomy. SUMMARY BACKGROUND DATA: Laparoscopic splenectomy was first reported in 1992. It was introduced into clinical practice at the Royal Brisbane Hospital in 1991. Between June 1991 and March 1994, 24 patients have undergone laparoscopic splenectomies and 23 patients have had laparoscopic intra-abdominal lymph node biopsies. METHODS: Laparoscopic splenectomy was performed using a four- or five-port technique. The splenic hilum was secured using a linear stapler cutter, and the spleen was removed after placing it in a laparoscopic bag. Lymph node biopsy was performed using a three- or four-port technique, depending on the site and size of the lymphadenopathy. RESULTS: Laparoscopic splenectomy was completed in 22 patients (92%). Median hospital stay was 3 days (range 2-7 days) and morbidity occurred in two patients (8%). Lymph node biopsy was completed laparoscopically in 21 of 23 patients (91%), with morbidity in two cases (9%). Median hospital stay was 2 days (range 1-6 days), with a diagnostic accuracy of 90%. Comparison with open splenectomy revealed that the laparoscopic approach took significantly longer to perform (p = 0.0002), but resulted in a significantly shorter hospital stay (p = 0.0005). CONCLUSIONS: Both laparoscopic splenectomy and laparoscopic lymph node biopsy currently are used as the treatments of choice for hematologic disease in our institution.

Adolescent↗

Laparoscopic biliary and gastric bypass: a useful adjunct in the treatment of carcinoma of the pancreas.

Over 90% of patients with inoperable carcinoma of the pancreas are successfully palliated by endoscopic retrograde cholangiopancreatography and stent insertion. Treatment of the residual 10% of patients often entails a laparotomy, which is difficult to justify when median survival of these patients is only 150 days. Laparoscopic biliary and gastric bypass offers a less invasive alternative than open surgery with shorter hospital stay and more rapid return to normal activity. Between August 1991 and March 1994, 16 patients (median age 69 years, range 31-85) had laparoscopic bypass surgery. The indications for surgery were gastric outlet obstruction at initial presentation (n = 4), blocked biliary stent (n = 8), and metastatic tumour at laparoscopy (n = 4). Surgery took the form of cholecystjejunostomy (n = 7), gastroenterostomy (n = 5), both procedures (n = 3), and failed operation (n = 1). Operative duration was 75 minutes (range 45-190) and hospital stay four days (range 3-33) and all apart from two patients were discharged from hospital in seven days or less. Morbidity occurred in two patients (13%) in the form of a cerebrovascular accident and delayed gastric emptying. Median survival in 10 patients who have died is 201 days (range 20-525). Laparoscopic biliary and gastric bypass is possible in most patients in whom endoscopic stenting has failed and in those who subsequently develop gastric outlet obstruction. Hospital stay is shorter than after open surgery and recovery more rapid.

Adult↗

Chemohormone therapy of metastatic melanoma with megestrol acetate plus dacarbazine, carmustine, and cisplatin.

BACKGROUND: Chemotherapy with dacarbazine, carmustine, and cisplatin produces a modest objective response rate in melanoma. Megestrol acetate may ameliorate cachexia, abrogate drug resistance, and increase survival time in melanoma. METHODS: Nineteen patients with metastatic melanoma (16 evaluable) treated with dacarbazine (220 mg/m2/day for 3 days, intravenously [IV]), cisplatin (25 mg/m2/day for 3 days IV) every 3 weeks, and carmustine (150 mg/m2 IV single dose every 6 weeks) together with megestrol acetate (160 mg/day by mouth continuously) starting 2 days before chemotherapy. RESULTS: This regimen was well tolerated and resulted in a mean net weight gain of 1.45 kg. A 47% objective response rate was observed in all patients, including visceral sites of response, with a 39+ week median duration of response and median survival time of 16.7+ months in all evaluable patients. CONCLUSIONS: In this small Phase II study, the authors showed that megestrol acetate may contribute to a high objective response rate and prolonged median survival when used with a chemotherapy regimen of dacarbazine, carmustine, and cisplatin.

Adult↗

12-O-tetradecanoylphorbol-13-acetate induces transient cell cycle arrest in G1 and G2 in metastatic melanoma cells: inhibition of phosphorylation of p34cdc2.

The growth of Demel human metastatic melanoma cells was inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA) and other nonphorbol tumor promoters including palytoxin and okadaic acid. Using flow cytometry, we have demonstrated that the cells arrested growth in G1 and G2 phases of the cell cycle. Detailed analysis of the kinetics of the growth arrest in unsynchronized cells showed that (a) the growth arrest was transient and peaked 16-20 h following addition of TPA; (b) effects of TPA on cell growth began within 1-2 h after the addition; and (c) cells completed S phase and arrested in G2. In addition, TPA induced a pronounced morphological change, which peaked by 1 h and gradually subsided over 24 h. In populations of cells synchronized in G1 using lovastatin, (a) addition of TPA blocked the onset of DNA synthesis up to the end of G1; (b) the lag between addition of the drug and onset of DNA synthesis was less than 30 min; and (c) addition of TPA at the end of G1 prevented the increased phosphorylation of p34cdc2, as determined by immunoprecipitation. The experiments reported here show that TPA transiently blocked the proliferation of Demel melanoma cells at the G1-S border and in G2, thus preventing cells from progressing through the cell cycle. These experiments suggest that pathways involving protein kinase C interact with and rapidly alter the molecular pathways involving p34cdc2 which regulate the onset of DNA synthesis and the G2-M transition.

Breast Neoplasms↗

Carcinoma of the anal canal.

During the period 1973 to 1982, 35 patients with carcinoma of the anal canal were seen at this hospital. The main form of treatment was abdominoperineal excision, unless specific contraindications to this procedure were present. Between 1982 and 1984, a further 18 such patients were seen; the primary method of treatment then was combination chemotherapy and radiotherapy. Abdominoperineal excision was reserved for those patients who failed to respond to therapy or whose carcinoma recurred during the period of follow-up. The over-all five-year survival rate for the first 35 patients was 50%; the actuarial disease-free survival at two years for those who went into complete remission was 78% in the 18 patients who were seen in the second part of the study. We conclude that conservative treatment by chemoradiation is of value in the management of anal carcinomas.

Adult↗