Biomedical subjects

Guy Lindberg

Publications and source records attributed to Guy Lindberg.

15 recordsLinked to original sources

PubMed2006

Large-volume laparoscopic partial nephrectomy using the potassium-titanyl-phosphate (KTP) laser in a survival porcine model.

OBJECTIVES: Laparoscopic partial nephrectomy (LPN) remains a technically challenging procedure primarily because of difficulties with hemostasis. In an attempt to develop a hemostatic cutting instrument for laparoscopic partial nephrectomy, we evaluated the potassium-titanyl-phosphate (KTP) laser for use during large-volume laparoscopic partial nephrectomy in a porcine model. METHODS: Transperitoneal lower pole laparoscopic partial nephrectomy was performed in six pigs. Two nonsurvival animals were used initially to develop the laser technique. Four animals underwent a right-sided laparoscopic laser partial nephrectomy followed by an identical left-sided procedure 2 weeks later. Renal hilar occlusion was used in all cases. A novel 365-mum end-firing laser fibre and 80-W KTP laser were used for resection and hemostasis. All renal remnants underwent retrograde pyelography and histologic examination. RESULTS: Laser resection and hemostasis was successfully completed in all cases, and no perioperative complications occurred. Mean estimated blood loss was 80 ml (25-250 ml). Mean laser and warm ischemia times were 35 and 34 minutes, respectively. Resection speed was limited by smoke formation but not by cutting or hemostatic efficiency of the laser. Mean resected kidney mass was 30 g or 25% of total kidney mass. There were no urinomas, but, on retrograde pyelogram, extravasation was noted in seven of eight kidneys (87.5%). CONCLUSIONS: The KTP laser provides hemostasis during large-volume resection in the porcine kidney. This technique appears promising for laparoscopic partial nephrectomy in humans.

Animals↗

PubMed2005

Expression and function of somatostatin receptors in peripheral nerve sheath tumors.

Although somatostatin receptors have been detected in many normal and neoplastic tissues, little is known of their expression and function in peripheral nerve tumors. In the present study, we examined the expression of all 5 somatostatin receptor subtypes (sst1-5) in 3 normal peripheral nerves, 3 traumatic neuromas, 27 schwannomas, 18 neurofibromas, and 177 malignant peripheral nerve sheath tumors (MPNSTs) by immunohistochemistry as well as by Western blot and reverse transcriptase-polymerase chain reaction investigations in 2 normal peripheral nerves, one neurofibroma, 5 schwannomas, and 5 MPNSTs. Immunoreactive somatostatin receptors were not detectable in normal peripheral nerve and in nonneoplastic Schwann cell proliferations. In contrast, sst2A mRNA and protein was present in 89% of schwannomas. This receptor subtype was less frequently detected in neurofibromas (22%) and MPNSTs (15%). Interestingly, sst4 was seen in 32% of MPNSTs and was almost exclusively expressed in this malignant tumor type. In support of a role in Schwann cell tumor growth control by somatostatin was the observation of induced internalization of sst2A and inhibition of cell proliferation in an NF1-associated MPNST cell line. Moreover, administration of an sst2A-selective agonist resulted in induction of MPNST cell apoptosis. We conclude that peripheral nerve sheath tumors often express at least one functional somatostatin receptor. Furthermore, our findings suggest a potential clinical role for somatostatin receptor agonists in tumor imaging and/or treatment of schwannomas and MPNSTs.

Animals↗

PubMed2004

Prevalence of malignancy within cytologically indeterminate thyroid nodules.

BACKGROUND: The optimal management of cytologically indeterminate thyroid nodules is controversial given the variable malignancy rates reported in this patient population. We examined the prevalence of malignancy within cytologically indeterminate follicular thyroid lesions in an attempt to predict malignancy based on cytologic features. METHODS: Cytopathology reports obtained after fine-needle aspiration biopsy (FNAB) examination of indeterminate follicular thyroid lesions were examined over a 4-year period. The prevalence of malignancy on final histology was determined in 4 indeterminate cytologic categories. RESULTS: A total of 107 records were available (91 women, 16 men). The mean patient age was 45.4 +/- 16 years. Forty-eight patients (45%) underwent surgery and had histopathologic diagnosis, while 57 patients did not have surgery. The prevalence of malignancy in patients who underwent thyroidectomy was 42% (20 of 48). CONCLUSIONS: The high prevalence of malignancy within indeterminate follicular lesions may necessitate thyroidectomy for patients with indeterminate follicular lesions on FNAB examination.

Adenocarcinoma, Follicular↗

PubMed2004

Acute histologic effects of temperature-based radiofrequency ablation on renal tumor pathologic interpretation.

OBJECTIVES: To describe the histopathologic changes and evaluate the interpretability of human renal tumor specimens obtained after temperature-based radiofrequency ablation (RFA). METHODS: RFA of 119 solid kidney tumors was performed percutaneously under computed tomography guidance, laparoscopically or during open surgery, using a temperature-based system. Of the 119 tumors, 70 were biopsied (two or more samples) after RFA, 39 immediately before ablation, and 10 were not biopsied. All specimens were pathologically classified, and for those specimens obtained after RFA, analysis of the acute histologic changes secondary to RFA was performed by a single pathologist using standard hematoxylin-eosin staining. RESULTS: Ablated tumor specimens maintained their tissue architecture and had predictable changes (cytoplasmic eosinophilia, nuclear elongation, cytoplasmic dissolution) easily recognizable by our pathologists. The diagnostic rate of renal cell carcinoma after RFA (72%) was comparable to the diagnostic rate reported for tumors less than 4 cm in other non-RFA biopsy series. Only 2.6% of specimens obtained before and 5.7% obtained after RFA were nondiagnostic secondary to the paucity of tissue obtained. In 8.3% of all tumors (regardless of RFA treatment), the distinction between oncocytoma and low-grade oncocytic renal cell carcinoma could not be made because of insufficient tissue. CONCLUSIONS: Acutely, RFA of renal tumors causes predictable histologic changes and preserves the tissue architecture. Obtaining two or more incisional biopsies after RFA provided sufficient tissue for reliable pathologic diagnosis.

Adenoma, Oxyphilic↗

PubMed2004

Ureteral replacement using small-intestinal submucosa and a collagen inhibitor in a porcine model.

PURPOSE: Small-intestinal submucosa (SIS) has been successful as an onlay graft in ureteral repair, but tubularized segment interposition of SIS has been unsuccessful. Our objective was to evaluate whether a type I collagen inhibitor, halofuginone, would prevent stricture formation in tubularized SIS interposition. MATERIALS AND METHODS: We performed either laparoscopic partial ureteral excision followed by an SIS onlay graft (N = 5) or complete laparoscopic ureteral excision followed by an SIS interposition graft (N = 7) in domestic pigs. Animals received either no (N = 3), low-dose (N = 5), or high-dose (N = 4) halofuginone. Animals had ureteral stenting for 2 weeks after surgery and were permitted to survive for 6 or 9 weeks. An intravenous urogram (IVU) was performed prior to sacrifice. Kidneys were examined grossly and histologically. RESULTS: One animal that received an onlay graft died of an unrelated illness. The remaining four ureteral onlay animals, including one control and two low-dose and one high-dose pig, had grossly normal kidneys at harvest. The IVU was normal in the control and high-dose animal but showed delayed excretion with mild hydroureteronephrosis in the low-dose animals. Pathologic examination of the SIS site revealed circumferential reepithelialization with inflammation and mild fibrosis. All seven tubularized interposition graft kidneys demonstrated either severe hydroureteronephrosis (N = 5) or renal atrophy (N = 2), and all had complete obstruction on IVU. Pathologic examination revealed a stenotic ureteral lumen with extensive surrounding inflammation and fibrosis. CONCLUSIONS: An SIS onlay graft was successful in the porcine model of ureteral injury. Halofuginone, a type I collagen inhibitor, did not demonstrate a significant beneficial effect in this technique. Ureteral tubularized interpositions with SIS are unsuccessful and not improved by halofuginone.

Animals↗

PubMed2004

T-cell prolymphocytic leukemia presenting as an ear canal mass.

OBJECTIVE: We discuss the first reported case of a chronic leukemia involving the external auditory canal. STUDY DESIGN: Case report and review of the literature (Medline, 1962-2003). METHODS AND RESULTS: An adult man in good health came to receive medical attention because of a sensation of aural fullness. Radiologic and physical examination demonstrated an ovoid soft tissue mass of the lateral external auditory canal that, after biopsy and flow cytometry studies, was found to be T-cell prolymphocytic leukemia. The patient presented with minimal disease in a highly symptomatic location, allowing early initiation of therapy and extending his life by nearly four times the average life expectancy for this aggressive chronic leukemia. CONCLUSION: Lymphomas of the external auditory canal are extremely rare neoplasms. Only a few cases have previously been reported, and all of the previous reports involve acute leukemias. This report indicates that chronic leukemias can present with otologic manifestations such as an external auditory canal mass.

Biopsy, Needle↗

PubMed2003

Interpretive disparity among pathologists in breast sentinel lymph node evaluation.

BACKGROUND: Immunohistochemical staining on breast sentinel lymph nodes (SLN) is controversial. METHODS: Twenty-five SLN cases were reviewed by 10 pathologists (three academic, seven private) including 5 negative by both hematoxylin and eosin (H&E) and immunohistochemistry, 11 micrometastases (<2 mm) negative by H&E but positive by immunohistochemistry, and 8 micrometastases and 1 macrometastasis (>2 mm) positive for both H&E and immunohistochemistry. Answers included "positive," "negative," and "indeterminate" for each slide. RESULTS: The mean number of incorrect responses was 6.6 for immunohistochemistry and 5 for H&E. Twelve percent of cases were correct by all 10 pathologists; 80% of positive IHC cases had at least one pathologist score it incorrectly. As tumor cells decrease in number, incorrect responses increase. When tumor cells numbered less than 10, more than 30% of pathologists answered incorrectly. CONCLUSIONS: As tumor cells decrease in number pathologists' ability to recognize them decreases. We propose adding "indeterminate" to "positive" and "negative" when tumor cells number less than 10.

Breast Neoplasms↗

PubMed2003

Infrared thermography and thermocouple mapping of radiofrequency renal ablation to assess treatment adequacy and ablation margins.

OBJECTIVES: The primary disadvantage of renal tumor RF ablation is the inability to monitor the intraoperative propagation of the RF lesion with real-time imaging. We sought to assess whether adequately lethal temperatures are obtained at the margins of the intended ablation zone using laparoscopic thermography to monitor radiofrequency (RF) lesions in real time, thermocouple measurements, and histopathologic evaluation. METHODS: Renal RF lesions were created under direct laparoscopic vision in the upper (1 cm diameter) and lower (2 cm) poles of the right kidney in 5 female pigs. The RF lesions were produced with the RITA generator and probe, set at 105 degrees C for 5-minute ablations. During RF treatment, a laparoscopic infrared (IR) camera measured the surface parenchymal temperatures, as did multiple thermocouples. The pigs were then either immediately killed (n = 3) or allowed to live for 2 weeks (n = 2). The kidneys were removed to correlate the temperature measurements with histologic analysis of the ablated lesion. RESULTS: Using a threshold temperature of greater than 70 degrees C for visual "temperature" color change, the IR camera identified the region of pathologic necrosis of the renal parenchyma during RF ablation. Thermocouple measurements demonstrated that the temperatures at the intended ablation radius reached 77.5 degrees C at the renal surface and 83.7 degrees C centrally, and temperatures 5 mm beyond the set radius reached 52.6 degrees C at the surface and 47.7 degrees C centrally. The average diameter of the gross lesion on the surface of the kidney measured 17.1 mm and 22.4 mm for 1-cm and 2-cm ablations, respectively. These surface measurements correlated with an average diameter of 16.1 mm and 15.9 mm (1-cm and 2-cm ablations, respectively) as measured with the IR camera. All cells within these ablation zones were nonviable by nicotinamide adenine dinucleotide diaphorase analysis. The average depth of the lesions measured 19 mm (1-cm ablation) and 25 mm (2-cm ablation) on gross histologic examination. CONCLUSIONS: The laparoscopic IR camera is able to monitor the surface renal temperatures during RF treatment. Thermocouple measurements during RF ablation confirmed the thermographic findings and demonstrated that lethal temperatures at the margin of the intended treatment zone are routinely obtained and that a rapid decline in temperature occurs beyond the predicted ablation margin.

Animals↗

PubMed2003

Regional and systemic cytokine responses to acute inflammation of the vermiform appendix.

OBJECTIVE: To measure local (peritoneal fluid) and systemic (plasma) cytokine profiles in patients with infection-inflammation of the vermiform appendix, a relatively mild, localized inflammatory process. SUMMARY BACKGROUND DATA: The systemic host response to invading microorganisms, often termed the systemic inflammatory response syndrome (SIRS), includes changes in heart rate, respiratory rate, body temperature, and circulating white blood cell numbers. Although these changes can be induced experimentally by administering proinflammatory cytokines, the mediators that appear in the bloodstream during early, localized infection in humans have not been defined. METHODS: The authors studied 56 patients with pathologically proven appendicitis. Blood was obtained before the induction of anesthesia, when 82% of the patients met the criteria for SIRS. Peritoneal fluid (PF) was obtained by intraoperative lavage. Cytokines were measured by immunoassay. To assess the net impact of the mediators within plasma, the authors studied the ability of patient plasma to augment or suppress bacterial lipopolysaccharide (LPS) stimulation of monocytes in vitro. RESULTS: Of the proinflammatory cytokines, tumor necrosis factor-alpha was present in PF but not in plasma, interleukin (IL)-1beta and interferon-gamma were found in low concentrations in both PF and plasma, and IL-12 (p70) was detectable in plasma but not PF. In contrast, IL-6 and IL-1 receptor antagonist (IL-1ra) were the most abundant cytokines in the PF and plasma, and the concentrations of IL-4 and IL-10 were also elevated in both compartments. Patients with more severe appendicitis had higher plasma levels of IL-6 and IL-10 and lower plasma levels of IL-12 and interferon-gamma than did those with uncomplicated disease. Patient plasma inhibited LPS-induced stimulation of a monocyte cell line, and this inhibition was accentuated by complicated disease. CONCLUSIONS: As judged from the pattern of soluble cytokines in plasma and the effect of the plasma on monocyte activation by LPS, mild, localized infection can induce a systemic response that is predominantly anti-inflammatory.

Acute Disease↗

PubMed2003

Infection by gram-negative organisms via the biliary route results in greater mortality than portal venous infection.

Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD(50)) for E. coli injected into the bile duct was 50 CFU/animal; the LD(50) for E. coli injected into the portal vein was 5 x 10(7) CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.

Animals↗

PubMed2002

Ureteral replacement using porcine small intestine submucosa in a porcine model.

OBJECTIVES: To investigate an alternative technique using an onlay patch of porcine small intestine submucosa (SIS) allograft to bridge a ureteral defect. For ureteral strictures that fail endourologic management, few options are available for minimally invasive repair or reconstruction. Although laparoscopic interposition of a tubularized allograft of porcine SIS has great promise, animal studies have yielded mixed results. METHODS: In 9 anesthetized female pigs, cystoscopy and retrograde pyelography were performed, and a ureteral stent was placed. Transperitoneal laparoscopic access was obtained, and a segment of ureter 2 cm long and encompassing one half the ureteral circumference was excised. An oval-shaped patch of SIS was sutured to the native ureter to cover the defect. In one control survival animal, the ureter was excised and a stent placed, but no SIS onlay was performed. Two pigs were killed immediately. In the survival group (6 pigs), the stents were removed at 1 week (n = 2), 2 weeks (n = 2), or 4 weeks (n = 2) and the corresponding animals were killed at 3 weeks (n = 2), 6 weeks (n = 2), and 9 weeks (n = 2). Intravenous urography was performed to evaluate renal function, and retrograde pyelography was performed after harvest to identify ureteral stricture or obstruction. The ureteral grafts were measured and examined histologically. RESULTS: All 6 kidneys from the survival group were grossly normal, appeared promptly on intravenous urography, and were patent on retrograde pyelography. The control animal demonstrated complete ureteral obstruction. By 9 weeks, the SIS graft was replaced with ureteral tissue, including the muscle layers. The epithelium was primarily transitional epithelium, with focal intestinal metaplasia. The submucosa and ureteral musculature appeared histologically normal. CONCLUSIONS: In the porcine model, a patch graft technique using SIS appears to induce ureteral regrowth. Renal function remained intact, and no evidence of stricture was demonstrated on radiographic imaging. Before clinical application of this technique, evaluation in a stricture model is required.

Animals↗

PubMed2002

Laparoscopic interstitial laser coagulation of renal tissue with and without hilar occlusion in the porcine model.

PURPOSE: To evaluate the safety and efficacy of interstitial laser coagulation (ILC), applied via a laparoscopic approach, with and without hilar occlusion in the porcine model. MATERIALS AND METHODS: In nine female farm pigs, bilateral renal mobilization was performed via a transperitoneal laparoscopic approach. Using a 600- micro m bare-tip silicon diode laser fiber inserted 0.5 cm into the lower pole of each kidney, diode laser energy (wavelength 805 nm) was applied for 15 minutes at 6 W. In each pig, the left renal hilum was clamped during ILC. Animals were sacrificed immediately (N = 3) or at 2 weeks (N = 3) or 4 weeks (N = 3). The kidneys were inspected grossly, and the lesions were evaluated microscopically. Nicotinamide adenine dinucleotide (NADH) histochemical staining was performed to assess viability. RESULTS: Grossly, parenchymal lesions appeared firm and white with a central zone of carbonization, cavitation, or both. Histopathology examination revealed cellular inflammation in acute lesions; chronic lesions demonstrated coagulative necrosis with progressive fibrosis. The NADH staining showed residual viable cells within the treatment zone of survival animals but not in acute animals. The mean size of the treatment zone in kidneys with unoccluded blood flow was 2.4 x 2.1 x 2.0 cm, 4.0 x 3.3 x 2.8 cm, and 3.3 x 3.5 x 2.0 cm in the acute, 2-week, and 4-week group, respectively. Hilar occlusion resulted in a slightly, but statistically insignificantly, larger lesion. In the 2-week survival group, one animal had a left subcapsular hematoma on the hilar-occluded side. In another 2-week animal, extension of the ILC zone was noted beyond the kidney into the psoas muscle. In the 4-week survival group, two animals developed gross hematuria; one had a left perinephric urinoma and urine leak noted at necropsy. CONCLUSIONS: Renal ILC may represent an alternative minimally invasive technique for ablation of renal tumors. However, histologic evidence of viable cells within the treatment zone mandates refinement of the technique in the animal model before further application in humans. Hilar occlusion does not appear to enhance tissue ablation.

Animals↗

PubMed2002

Laparoscopic partial nephrectomy with a diode laser: porcine results.

PURPOSE: To develop a safe and effective technique for laparoscopic partial nephrectomy without need for hilar occlusion. MATERIALS AND METHODS: Laparoscopic transperitoneal lower-pole partial nephrectomy was performed in five 45- to 50-kg female farm pigs using a 980-nm diode laser. Standard transperitoneal access was obtained, and a four-port approach was used to perform a laparoscopic right partial nephrectomy using a diode laser (23 W) without hilar occlusion. The pigs were allowed to recover and 2 weeks later underwent a left laparoscopic partial nephrectomy. Postoperatively, renal function was monitored by serial serum creatinine measurements. Both kidneys and ureters were removed for ex-vivo retrograde pyelograms and histologic analysis. RESULTS: The 980-nm diode laser resulted in successful lower-pole partial nephrectomy without hilar occlusion in all 10 of the kidneys. In three cases, laser hemostasis was insufficient, and adjunctive hemostatic clips were necessary to stop bleeding. The mean operative time was 126 minutes, and the mean laser time was 84 minutes. An average of 23% (range 13%-33%) of the kidney parenchyma was resected. The mean blood loss was 150 mL (range 50-300 mL). There was no evidence of urinary extravasation on ex-vivo retrograde pyelograms at 2 weeks in any of the kidneys. CONCLUSION: Laparoscopic partial nephrectomy without hilar occlusion using the 980-nm diode laser is feasible in the porcine model. Because adjunctive hemostatic measures may be necessary in some cases, clinical trials in humans should be limited to small exophytic tumors.

Animals↗

PubMed2002

Radiofrequency coagulation of renal parenchyma: comparison of effects of energy generators on treatment efficacy.

PURPOSE: We compared experimental renal lesions created with temperature-based or impedance-based radiofrequency (RF) generators using normal renal parenchyma in an animal model with protocols recommended by the manufacturer. MATERIALS AND METHODS: Bilateral renal mobilization was completed in seven farm pigs in preparation for RF ablation, and the tines of each RF probe were expanded to a 2-cm diameter. Pigs were sacrificed immediately (N = 3) or at 24 hours (N = 4) after treatment. Lesions were examined grossly and microscopically after hematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) staining. RESULTS: Gross lesions were firm and white with a hemorrhagic border, regardless of RF generator. Staining with H&E revealed preservation of renal architecture but loss of distinct cytoplasmic features with both RF systems. Staining for NADH showed no viable cells within the lesions produced by either RF system. Immediately and after a 24-hour survival, the mean sizes of the treatment lesions were 1.6 x 1.8 x 1.3 cm and 2.0 x 1.6 x 1.9 cm, respectively, for the temperature-based RF generator and 2.7 x 2.4 x 2.5 cm and 2.2 x 2.1 x 1.8 cm, respectively, for the impedance-based RF generator. CONCLUSION: Use of a specific RF energy generator with recommended treatment protocols does not appear to affect coagulation of normal renal parenchyma in the porcine model.

Animals↗

PubMedDate not supplied

Laparoscopic partial nephrectomy using holmium laser in a porcine model.

OBJECTIVE: To evaluate the utility of the holmium laser for partial nephrectomy in a porcine model. METHODS: Transperitoneal lower pole laparoscopic partial nephrectomy was performed in 5 farm pigs. All animals underwent a left-sided laparoscopic partial nephrectomy and were kept alive for 2 weeks (survival group). Subsequently, a right laparoscopic partial nephrectomy was performed (acute group), and the animals were sacrificed. A 1000-microm (n=6) or 550-microm (n=4) end-fire holmium laser fiber set at 0.2 joules and 60 pulses per second was used to transect the lower pole of the kidney 1 cm below the level of the hilum. The cut parenchymal surface was then sealed with fibrin glue in the survival animals. The operated on kidneys were inspected grossly and evaluated microscopically. RESULTS: Laser transection was successfully completed in all cases, and hemostasis proved adequate without any adjunctive measures. No perioperative complications occurred. Estimated blood loss was less than 50 cc for each laparoscopic partial nephrectomy. The acute and survival pigs showed no statistically significant differences in specimen size or weight. Serum creatinine levels were normal in all survival animals. Extravasation was noted on retrograde pyelograms of 2 animals in the survival group. CONCLUSIONS: The Holmium:YAG laser provides an efficacious modality for transecting the kidney in a porcine model. Clinical trials are necessary to determine its role in laparoscopic partial nephrectomy in humans.

Animals↗