Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors.

We have evaluated the effects of chemotherapeutic agents on the toxicity and antitumor benefit of therapy of established murine tumors by high-dose interleukin 2 (IL-2). Cyclophosphamide (Cy), doxorubicin, and bischloroethylnitrosourea were given to normal mice prior to IL-2 administration to test the effects of these agents on IL-2-induced toxicity. Cy at doses of 100 mg/kg and 150 mg/kg completely protected mice from a 100% lethal dose of IL-2, and doses of 50 mg/kg and 150 mg/kg allowed the administration of a median of 4.5 and 10.0 more doses of IL-2, respectively, before death from IL-2 toxicity occurred. Doxorubicin at 8 mg/kg and bischloroethylnitrosourea at 20 mg/kg did not impact on toxicity in IL-2-treated mice. In mice bearing pulmonary metastases of the weakly immunogenic MCA-105 sarcoma, IL-2 increased median survival time from 33 (no IL-2) to greater than 60 days for all doses of IL-2 tested when combined with a single injection of Cy at 75 mg/kg (P less than 0.002). Increasing doses of either Cy or IL-2 produced increasing benefits on survival which were always greater than either treatment alone. These effects of Cy and IL-2 were also seen in mice bearing the nonimmunogenic MCA-101 sarcoma and a murine adenocarcinoma (MCA-38). Doxorubicin and bischloroethylnitrosourea did not consistently enhance the effects of IL-2 treatment. Cy appears to reduce the yield of in vivo generated lymphokine-activated killer cells, but these lymphokine-activated killer cells are still lytic for fresh tumor targets in vitro. Thus, the mechanism of this synergy does not appear to involve stimulation of lymphokine-activated killer cell activity, but may in part involve reduction of tumor burden by the chemotherapeutic agent, an increase in susceptibility of tumor to cellular immune lysis, and/or a decrease in suppressor cell activity mediated by the chemotherapy.

Effect of immunotherapy with allogeneic lymphokine-activated killer cells and recombinant interleukin 2 on established pulmonary and hepatic metastases in mice.

The adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with the systemic administration of recombinant interleukin 2 (RIL-2) results in the regression of established pulmonary and hepatic micrometastases from a variety of immunogenic and nonimmunogenic murine tumors in syngeneic C57BL/6 mice. Recent studies have shown that this therapeutic approach can mediate the regression of cancer in humans as well. Because of the practical difficulties in obtaining syngeneic or autologous LAK cells for the therapy of cancer in humans we have now evaluated the antitumor efficacy of allogeneic LAK cells generated from different strains of mice. The in vitro lysis of fresh tumor targets by LAK cells is not a major histocompatibility complex-restricted phenomenon since LAK cells of BALB/c-H-2d, DBA/2-H-2d, and C3H-H-2k origin all exhibited lytic activity when tested against allogeneic MCA-102-H-2b tumor cells in short term 51Cr release assays. In vivo, the i.v. transfer of allogeneic LAK cells combined with i.p. injections of RIL-2 reduced the number of established pulmonary metastases induced by either MCA-105 or MCA-101 tumors which are syngeneic to C57BL/6 hosts. The extent of reduction of these pulmonary metastases by the allogeneic LAK cells was directly dependent upon the dose of RIL-2 given; increasing doses of systemically administered RIL-2 resulted in increasingly greater reduction in the numbers of established 3-day pulmonary sarcoma metastases. In dose titration experiments, adoptive transfer of at least 2 doses of 10(8) allogeneic LAK cells was necessary to achieve significant antitumor effect in vivo. Allogeneic LAK cells were also successful in mediating significant regression of hepatic micrometastases. Again, the i.v. transfer of allogeneic LAK cells had a smaller therapeutic benefit compared to i.v. transfer of syngeneic LAK cells. When allogeneic LAK cells were injected intraportally, however, they were as effective as syngeneic LAK cells. Allogeneic LAK cells had little, if any, therapeutic effect on established pulmonary and hepatic metastases when administered to recipients previously immunized to the histocompatibility antigens on the donor cells. Taken together, our results indicate that allogeneic LAK cells from several strains of mice are effective in lysing fresh MCA-102 tumor in vitro and that when given i.v. in sufficient numbers, in conjunction with RIL-2, they can mediate significant reduction in the number of established pulmonary and hepatic micrometastases in nonalloimmunized C57BL/6 mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of TNF on triacylglycerol in cultured vascular smooth muscle cells.

Smooth muscle cells (SMC) isolated from bovine aorta or human saphenous vein were cultured and used to study the putative effect of recombinant human tumor necrosis factor (TNF) on lipid metabolism in vascular cells. Addition of TNF to the culture medium for 24-48 h resulted in an increase of [3H]oleic acid uptake and esterification into lipids. The effect could be seen already with 0.3 ng/ml and was maximal with 30 ng/ml. The effect of TNF was mainly on the incorporation of [3H]oleic acid into triacylglycerol which increased by 140% in the bovine cells. There was also a significant increase in [3H]cholesteryl ester. In the human SMC there was a 40% increase in [3H]oleic acid into total lipids, while the rise in [3H]triacylglycerol ranged between 60-90%. TNF did not modulate cellular triacyglycerol synthesis in cultured mouse peritoneal macrophages. Since TNF was shown to be synthesized and secreted not only by macrophages but also by smooth muscle cells, it could play an autocrine role in lipid metabolism during development of atherosclerotic lesions. The cellular population of the lesions, i.e., predominance of macrophages or smooth muscle cells, could determine the relative proportion of triacylglycerol accumulation.

Modulation of lipoprotein lipase activity in mouse peritoneal macrophages by recombinant human tumor necrosis factor.

Thioglycollate-elicited mouse peritoneal macrophages spontaneously secrete lipoprotein lipase during culture. Exposure of the cultures to 50 ng/ml of recombinant human tumor necrosis factor (rTNF) for 48 h resulted in a 69% reduction in lipoprotein lipase activity in the culture medium with a concomitant decrease in cellular enzyme activity. The decrease in enzyme activity was not the result of rTNF-dependent reduction in the total protein synthesis, since the presence of rTNF did not affect [3H]leucine incorporation into cellular proteins. The effect of rTNF on lipoprotein lipase was reversible; upon TNF withdrawal, enzyme activity returned to basal levels after 60 h. The reduction of lipoprotein lipase in rTNF-treated cultures could be completely prevented by preincubation with a specific antiserum against recombinant human TNF. The late onset of decrease of lipoprotein lipase (LPL) activity suggests that rTNF might induce a mediator, which in turn suppresses LPL production. While rTNF was very effective in reducing lipoprotein lipase activity in mouse peritoneal macrophages, it did not affect lipoprotein lipase activity when added to the murine J774 cell line and to CT2 macrophage-like cells, a variant of the J774 cell line.

Lipoprotein lipase in heart cell cultures is suppressed by bacterial lipopolysaccharide: an effect mediated by production of tumor necrosis factor.

Exposure of rat heart cell cultures, consisting mainly of nonbeating mesenchymal cells, to 50 ng/ml of bacterial lipopolysaccharide (LPS) for 24 h resulted in a more than 80% reduction in lipoprotein lipase activity. The loss of enzymic activity was accompanied by a concomitant reduction in enzyme protein, as shown by immunoblotting. Addition of LPS to the culture medium resulted also in the production of tumor necrosis factor (TNF), and the fall in lipoprotein lipase in LPS-treated cultures could be prevented by an antibody to TNF. Addition of recombinant human TNF to the heart cell cultures also depressed lipoprotein lipase activity. LPS treatment of preadipocytes in culture resulted in a fall in lipoprotein lipase activity and TNF production. Since TNF is known as a macrophage product, the cultures were tested for phagocytic capacity, and only 0.2-1.3% of the cells were shown to engulf Staphylococcus albus. Immunofluorescent staining with monoclonal antibodies OX-1, which identify leukocyte common antigen, was negative, and only 0.1 +/- 0.07% of the cells were positive after staining with OX-42 antibody to iC3b receptor. Both antibodies stained more than 98% of rat peritoneal macrophages used as controls. Since LPS treatment of macrophages at numbers comparable to or exceeding the number of phagocytic cells present in the heart cell cultures did not induce measurable amounts of TNF, it is suggested that in the heart cell cultures, TNF may be produced by cells other than macrophages.

Mechanism of the hypertriglyceridemia induced by tumor necrosis factor administration to rats.

4 h after intravenous injection of recombinant HuTNF-alpha to fed rats, an increase in heart, diaphragm, and plasma lipoprotein lipase activity was observed. At the same time, a 40-60% decrease in enzymic activity in epididymal fat pad and kidney and 40% decrease in hepatic lipase activity in liver had occurred. Similar results were obtained 20 h after injection of recombinant HuTNF-alpha into fasted rats. Pretreatment with Indomethacin did not affect the changes in tissue lipoprotein lipase activity observed following recombinant HuTNF-alpha administration. Serum triacylglycerol concentration increased by 2- and 6-fold; 4 and 20 h after recombinant HuTNF-alpha administration. Disappearance of 14C-labeled triacylglycerol from the circulation after injection of small chylomicrons, biosynthetically labeled in their triacylglycerol and cholesterol moieties, was lower in TNF-treated than in control rats. However, the clearance rate of triacylglycerol was the same or even higher in recombinant HuTNF-alpha treated rats (assuming that 14C-labeled chylomicron triacylglycerol represents the serum triacylglycerol pool). The livers of recombinant HuTNF-alpha-treated rats and controls contained similar amounts of 14C-labeled lipids, but less [3H]cholesterol, suggesting that in recombinant HuTNF-alpha-treated rats, the liver took up chylomicron remnant particles enriched with triacylglycerol. Separation of the d less than 1.04 g/ml fraction of serum obtained from control and recombinant HuTNF-alpha treated rats by zonal ultracentrifugation revealed that in recombinant HuTNF-alpha-treated rats the lipoprotein particles were less lipolyzed than in controls. The secretion rate of [3H]triacylglycerol into the serum was determined 90 min after injection of [3H]palmitate albumin complex and Triton WR 1339. In recombinant HuTNF-alpha-treated rats, the secretion of [3H]triacylglycerol into plasma was 48% higher than in controls. It is suggested that the increase in lipoprotein lipase activity of heart and diaphragm resulted from an indirect effect of TNF. It is concluded that the increase in serum triacylglycerol in the recombinant HuTNF-alpha-treated rats is due mainly to an increased secretion of triacylglycerol by the liver. Impaired lipolysis, probably due to a fall in hepatic lipase could also contribute to the rise in plasma triacylglycerol.

Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study.

Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone.

Sulfate transport is not impaired in pendred syndrome thyrocytes.

Pendred syndrome is the most common form of syndromic deafness, characterized by dyshormonogenic goiter associated with sensory-neural deafness. The gene responsible for the disease (PDS) has been cloned, but its function is as yet unknown and the connection between thyroid goiter and sensory-neural deafness remains an enigma. PDS codes for a novel protein, pendrin, which is closely related to a number of sufate transporters. Mechanisms by which abnormal sulfate transport could deleteriously affect iodide organification have been proposed. We tested sulfate transport in thyrocytes obtained from Pendred syndrome patients and found that it was not defective. This suggests that pendrin in fact may not be a sulfate transporter, and emphasizes the importance of functional studies on this novel protein.

Salivary gland transplantation: a canine model.

Impaired salivary function with resultant severe dryness of the mouth, or xerostomia, may occur in association with a variety of systemic disorders or therapies. No adequate treatment exists for this debilitating condition, which impedes normal oral function, in particular alimentation and phonation. This study explores the feasibility of salivary gland autotransplantation, using a canine model. A salivary gland with its duct and surrounding blood vessels still attached was excised and reimplanted in the dog's thigh by anastomosing the graft's blood vessels to the femoral artery and vein. The duct was sutured to an artificial orifice cut in the thigh's skin, from which the saliva was collected. Salivary secretion was induced by a single intravenous bolus of pilocarpine (5 mg). Preoperative (normal) salivation was measured by collecting saliva from the gland in situ. Periodic functional studies showed normal saliva production during the first month after grafting, after which the salivary flow was reduced by 35% over the next 2 months. This reduction was interpreted as a sign of disuse atrophy resulting from the lack of autonomic innervation. To overcome this impediment, oral pilocarpine (5 mg/day) was administered to the recipient dog, after which normal levels of saliva were excreted through the graft during the 3-month follow-up period. The quality of the graft saliva was assessed by its protein and electrolyte levels, which showed close to normal values.

Hepatic arterial bolus chemotherapy for colorectal metastases using an implantable port.

Twenty-one patients with isolated colorectal liver metastases underwent hepatic artery infusion (HAI) port implantation for regional chemotherapy with bolus injections of 5-FU, LV and fast drip of cisplatin. Ten of the 21 patients had previously failed systemic chemotherapy before HAI. Toxicity was moderate and no need for modulation of the chemotherapeutic dose was required. The objective response rate of the whole group was 52.4%. The patients, who had not previously received systemic chemotherapy, had a significantly higher response rate of 81.8% compared to patients treated previously by systemic chemotherapy, who had a response rate of 20% (p=0.0089). In addition, there was a difference in cumulative survival between these two groups. The HAI combined chemotherapy with 5-FU, LV and cisplatin given by bolus injection through an implantable port is effective therapy with similar response rate but considerable reduced toxicity compared to continuous HAI with FUdR. We assume that this therapy might prolong survival significantly especially in patients not treated before by systemic chemotherapy.

Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro.

Recombinant human tumor necrosis factor-alpha (TNF) injection in mice was associated with a reduced blood glucose level, already manifest 6 hours following cytokine administration. Insulin levels were not affected. Glycogen content was decreased in a dose-dependent and time-response manner. The activity of glucose-6-phosphatase (G6Pase) was already reduced 6 hours after TNF injection and was sustained 12 hours afterward. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not affected initially (6 hours after injection), but a 50% reduction was observed 12 hours following cytokine administration compared with levels in fasting controls. Both liver G6Pase and PEPCK mRNAs were markedly reduced due to an inhibition of the transcriptional rate. A direct inhibitory effect of TNF on G6Pase promoter activity was demonstrated using HuH-7 cells transiently transfected with G6Pase promoter, fused to a reporter gene.

Lethal hypoglycemia and hypothermia induced by administration of low doses of tumor necrosis factor to adrenalectomized rats.

An increased sensitivity of adrenalectomized (Adex) rats to intravenous (IV) injection of recombinant human tumor necrosis factor (rHuTNF) was manifested by a marked increase in the rate of mortality. The rats that died exhibited severe hypoglycemia and hypothermia. Administration of 2.5 or 10 micrograms/100 g body weight (3% or 12%) of the lethal dose in sham-operated rats (90 micrograms/100 g body weight) rHuTNF caused a mortality rate of 50% or 100%, respectively, within 4 hours of its injection. Pre-administration of dexamethasone or intermittent glucose infusion protected the animals from the lethal effect of rHuTNF. Indomethacin did not change the mortality rate in rHuTNF-treated Adex rats, but prevented it in sham-operated rats. The rats that died exhibited a marked decrease in body temperature, but only Adex rats developed hypoglycemia after low doses of TNF. Pretreatment with dexamethasone prevented the hypothermia in both Adex and sham-operated rats, while indomethacin was effective only in sham-operated rats and did not prevent the hypothermia or the hypoglycemia in Adex rats. In the surviving rHuTNF-treated Adex rats, a rapid increase in body temperature occurred, blood glucose decreased to 30 mg/dL, serum insulin concentration decreased to 6 microU/mL, liver glycogen content was reduced by 98%, and a significant reduction in liver phosphoeonolpyruvate carboxykinase (PEPCK) and liver microsomal glucose-6-phosphatase activities was observed. Repeated administration of glucose IV to rHuTNF-treated Adex rats caused an increase in blood glucose and insulin concentrations, and some repletion in liver glycogen content. Injection of rHuTNF, 2.5 to 10 micrograms/100 g body weight, to sham-operated rats caused a significant but slower increase in body temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of splenectomy in Gaucher's disease.

Thirteen patients underwent splenectomy for Gaucher's disease. All patients were Jewish; 12, of Ashkenazi descent, had the chronic (type 1) form, and one child, of Sephardic (Persian) origin, probably had the intermediate (type 3) form. Hypersplenism was the indication for surgery in 11 patients, mechanical problems in the remaining two. The weight of the resected spleens ranged from 1.06 to 13 kg. Following surgery, hypersplenism (thrombocytopenia in particular) was improved, and the mechanical disturbances were relieved in all patients. There were no deaths and no morbidity related to the operative procedure. Long-term follow-up demonstrated progressive hepatomegaly without evidence of hepatic dysfunction in any of the patients. Bone marrow involvement manifested by osteoarticular complications appeared in five patients. Splenectomy is, we believe, a safe mode of treatment for type 1 Gaucher's disease.

Pancreaticogastrostomy after pancreatoduodenectomy. A retrospective study of 28 patients.

OBJECTIVE: To attempt to reduce the frequency and severity of postoperative anastomotic leakage from pancreaticojejunostomy in patients undergoing pancreatoduodenectomy. DESIGN: Retrospective case series. SETTING: Tertiary referral center, department of general surgery, in the 31-month period between April 1, 1993, and November 30, 1995. PATIENTS AND INTERVENTION: Twenty-eight patients underwent pancreatoduodenectomy with pancreaticogastrostomy. Indications for surgery included carcinoma of the pancreas (n = 14), carcinoma of the ampulla of Vater (n = 8), distal cholangiocarcinoma (n = 3), duodenal carcinoma (n = 1), an islet cell tumor (n = 1), and cystadenoma of the pancreas (n = 1). The median patient age was 62 years (range, 34-76 years). The median duration of surgery was 6.75 hours (range, 4-12 hours). MAIN OUTCOME MEASURES: An anastomotic leak was defined as a recovery of more than 50 mL/d of amylase-rich fluid from the drains (> 3 times the normal plasma levels) on or after the seventh postoperative day. RESULTS: An anastomotic leak that lasted between 7 and 14 days developed in 4 patients (14.3%). A pancreatic leak led to no major morbidity. In all cases, leakage was treated by temporary restriction of oral intake and nasogastric drainage. An intra-abdominal collection did not develop in any of these 4 patients. No patient required another surgical procedure for a pancreatic fistula or abdominal collection. One patient (3.6%) died postoperatively. The median duration of the postoperative hospital stay was 20 days (range, 12-43 days), and all patients were discharged from the hospital after restoration of normal oral feeding. CONCLUSIONS: Pancreaticogastrostomy is a safe method for reconstruction of the pancreatic remnant after pancreatoduodenectomy for periampullary tumors. It results in an acceptable incidence of anastomotic leakage that is easily controlled by conservative measures.

Role of total parenteral nutrition in the treatment of Crohn's disease.

We studied 49 patients with severe nonresponsive Crohn's disease receiving 73 courses of total parenteral nutrition (TPN) for a total of 2,153 days (30 +/- 18 days/admission). Forty-five percent of all courses of TPN resulted in patients not being operated on, whereas 55 percent resulted in surgical intervention. Fifty percent of patients who did not undergo operation initially as a result of a successful course of bowel rest and TPN had surgery within 15.4 +/- 13.9 months, whereas 75 percent of patients operated on immediately after a course of TPN did not need additional surgery during a follow-up of 36.1 +/- 31.2 months. Thus, a total of 80 percent of patients underwent gastrointestinal surgery sometime during the study and follow-up periods. TPN has an important role in replenishment of nutritional deficits and perioperative nutritional support; however, from the results of the present study, it is difficult to advocate it as the sole primary therapy for Crohn's disease.

Surgical morbidity in patients with systemic lupus erythematosus.

Thirty-six surgical procedures were performed on 29 patients with systemic lupus erythematosus (SLE). Nineteen cases involved active lupus at the time of surgery and 11 were performed on an emergent basis. Most patients had multiple organ involvement and were on some form of systemic therapy at the time of surgery. Thirty-seven postoperative complications were confined to 20 of these cases. Comparing this complicated group with the remaining 16 uncomplicated cases, the patients in the former group had a higher mean dose of steroid preoperatively, more organ involvement by SLE, and more frequent renal involvement; a higher percentage of the cases in this group were emergent rather than elective. The majority of factors examined failed to show predictive value in the outcome of surgery in lupus patients. We conclude that surgical complications are frequent in SLE patients and have identified four factors predictive of increased morbidity.

Pancreaticojejunostomy versus controlled pancreaticocutaneous fistula in pancreaticoduodenectomy for periampullary carcinoma.

BACKGROUND: Anastomotic leak of the pancreaticojejunostomy is a major cause of morbidity and mortality following pancreaticoduodenectomy. Reports have described a large variety of techniques for performing this anastomosis and managing the pancreatic stump. In an attempt to obviate the pancreaticojejunostomy, we prospectively studied the technique of ligating the pancreatic duct and using external drains to create a temporary controlled pancreaticocutaneous fistula. PATIENTS AND METHODS: Thirty-five consecutive patients who were to undergo pancreaticoduodenectomy for periampullary carcinoma were prospectively randomized to one of two groups: pancreaticojejunostomy (PJ) (n = 18) or controlled pancreaticocutaneous fistula (CPF) (n = 17). The groups were well matched for age, sex, coexisting medical illnesses, type of tumor, and preoperative condition. Except for the management of the pancreatic remnant, all patients in both groups underwent an identical procedure. Major morbidity, length of hospitalization, duration of the controlled pancreatic fistula, and mortality were analyzed over a mean follow-up interval of 26 months (range 5 months to 7.5 years). RESULTS: The CPF group experienced lower overall operative morbidity rates than the PJ group (24% versus 56%, P < 0.01). Two patients (11%) in the PJ group and none in the CPF group died (P = NS). Half the morbidity in the PJ group and both mortalities were related to anastomotic leak. The CPF and PJ groups left the hospital after mean stays of 26.4 and 42.2 days respectively (< 0.01). CONCLUSIONS: Compared to pancreaticojejunal anastomosis, creation of a temporary controlled pancreaticocutaneous fistula in patients who undergo pancreaticoduodenectomy for periampullary malignancy has no appreciable risk. It is associated with reduced morbidity and shorter length of hospitalization.

Metastatic adenocarcinoma in a thyroid colloid nodule: a rare presentation of colon cancer.

Colorectal cancer can remain asymptomatic for years. Frequently symptoms develop insidiously and may often remain unnoticed for long periods, even in the presence of disseminated disease. We herein report an unusual case of a patient with carcinoma of the sigmoid colon and multiple liver metastases. The diagnosis was established only after the patient was operated on for a large colloid nodule, a single microscopic metastatic focus being noticed in the histologic sections. The differential diagnosis compared with the columnar type of papillary carcinoma is discussed.

Laparoscopic cholecystectomy in octogenarians.

BACKGROUND: This study aimed to assess the outcome of laparoscopic cholecystectomy (LC) in patients 80 years old or older. METHODS: All consecutive patients 80 years old or older who underwent LC for symptomatic gallstone disease were evaluated. Data analysis included patients' age, gender, indication for surgery, comorbid condition, American Society of Anesthesiology (ASA) score, preoperative endoscopic retrograde cholangio pancreatography (ERCP), intraoperative cholangiogram, operative time, conversion to open surgery, morbidity, mortality, and length of stay. RESULTS: In this study, 67 patients (31 men and 36 women) with a mean age of 84 years (range, 80-90 years) were evaluated. Of these 67 patients, 38 (57%) underwent surgery for complicated diseases including acute cholecystitis in 15 patients (22%), gallstone pancreatitis in 17 patients (25%), cholangitis in 3 patients (4.5%), and obstructive jaundice in 3 patients (4.5%). A total of 38 patients (57%) had a preoperative ASA of 3 or 4; 23 (34%) had a preoperative ERCP; and 6 (9%) had intraoperative cholangiogram. The mean operative time was 94 +/- 20 min. Five patients (7.4%) underwent conversion to open surgery because of unclear anatomy. Complications occurred in 12 patients (18%) including pulmonary edema in 3 patients, myocardial infarction in 1 patient, atelectasis in 2 patients, common bile duct injury in 1 patient, urinary tract infection in 2 patients, wound infection in 2 patients, and intraabdominal infected hematoma in 1 patient. The mean length of stay was 5.3 days. There was no mortality. CONCLUSIONS: In octogenarians LC is safe and associated with acceptable morbidity and mortality. Therefore, it should be considered for this age group. The relatively high incidence of complicated gallstone disease in this age group may be decreased if surgery is offered to them at earlier stage of the disease, leading to further decrease in perioperative morbidity.

Laparoscopic vs open adrenalectomy for benign adrenal neoplasm.

BACKGROUND: The aim of this study was to compare the outcome of laparoscopic adrenalectomy (LA) performed for benign adrenal neoplasm to the open procedure in a similar group of patients. METHODS: All consecutive patients who underwent LA between June 1996 and February 1999 were evaluated. Data analysis included patient's age and gender, indication for surgery, histological diagnosis, size of specimen, comorbid conditions, length of stay and ileus, postoperative narcotic consumption, and time to return to normal activity. The results were compared retrospectively to a well-matched group of patients who underwent an open adrenalectomy (OA). RESULTS: Twenty-eight LA were performed in 24 patients for the following disorders: adrenocortical adenoma, 16 (four Cushing's syndrome, 12 Conn's syndrome); pheochromocytoma, 10; and nonfunctioning tumor, two. These cases were compared with a well-matched group of 28 patients who underwent OA in the same department. There were two conversions to open surgery (7%) in the laparoscopic group and no deaths in either group. Of all the evaluated parameters, the following statistically significant differences between the two groups were noted: The mean operative time was longer in the LA group (188 vs 139 min, p < 0.001.); however, this became insignificant in the last 10 cases of LA, when the mean length of surgery was reduced to 130 min. The overall morbidity was lower in the LA group (16% vs 39%, p = 0.05), as was the mean time to tolerate a regular diet (2 vs 3.9 days), mean meperidine consumption (mg) (109 vs 209), mean length of stay (4 vs 7.5 days), and mean time to return to normal activity (2.2 vs 5.2 weeks), (p < 0.001 for all). CONCLUSION: LA for benign adrenal disorders is a safe procedure that is associated with significantly lower morbidity, shorter ileus and hospitalization, reduced postoperative pain, and a faster return to normal activity than the open procedure.