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Mehrdad Nikfarjam

Publications and source records attributed to Mehrdad Nikfarjam.

17 recordsLinked to original sources
PubMed2006

Altered growth patterns of colorectal liver metastases after thermal ablation.

BACKGROUND: Thermal ablation by radiofrequency or laser is used increasingly for the treatment of colorectal liver metastases. Recurrence after thermal ablation is common and occurs both locally and at distant sites. One possible cause of this recurrence may be a result of growth stimulation of micrometastases in the remaining liver. This study examined the impact of thermal ablation on growth patterns of hepatic micrometastases. METHODS: Colorectal liver metastases were induced in male CBA-strain mice via an intrasplenic injection of a murine-derived cancer cell line. Subtotal thermal ablation of the left posterior lobe of the liver (30% of total liver volume) was performed by neodymium yttrium-aluminum-garnet laser 7 days after induction of metastases. The distribution, number, cross-sectional diameter, volume, and proliferation rate of established neoplasms were compared with controls at 21 days after tumor induction. The effect of thermal ablation of 7% of the total liver volume by laser on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor 2 (FGF-2), transforming growth factor beta, and cellular proliferation (Ki-67 antigen) adjacent to the ablated site was assessed by immunohistochemistry in separate groups of animals at specific time points after therapy. RESULTS: Thermal ablation did not alter the overall volume, number, size, and proliferation rate of neoplasms 21 days after laser ablation. There were no extrahepatic metastases after therapy. The number of neoplasms in the regenerated posterior lobe was equivalent to control despite subtotal ablation (29 +/- 2 vs 27 +/- 2; P = NS). A greater amount of metastases occupied the regenerated thermal-ablated lobe compared with controls (55% +/- 4% vs 29% +/- 3%; P < .04). Thermal ablation stimulated liver proliferation adjacent to the treatment site at 12 hours compared with untreated controls. Stimulation peaked at 72 hours (20% +/- 1% vs 1% +/- 1%; P < .001) and persisted to 21 days after therapy. FGF-2 and VEGF expression increased in liver tissue adjacent to the ablation site compared with baseline, peaking at 12 hours (112% +/- 2% vs 102% +/- 1%; P < .001) and 72 hours (114% +/- 2% vs 101% +/- 1%; P < .001), respectively. CONCLUSIONS: Thermal ablation promotes the progression of micrometastases to form macroscopically detectable neoplasms in treated regenerating liver. This effect may relate to an increased expression of VEGF and FGF-2 adjacent to the treatment site.

Angiogenesis Inducing Agents↗
PubMed2006

Retroperitoneal lymphangioma.

Lymphangiomas are rare cystic tumours that may present as cystic masses in the retroperitoneum. Retroperitoneal lymphangiomas account for approximately 1% of all lymphangiomas. Confusion with other cystic tumours of the retroperitoneum including those arising from the liver, kidney and pancreas is common. A case of a retroperitoneal cystic lymphangioma occurring in a 41-year-old woman raising interesting diagnostic and management issues is reported. The patient presented with vague abdominal pain and persistent nausea. Radiological imaging demonstrated a large multiloculated thin-walled cyst involving the upper retroperitoneum. Surgical resection was complete, revealing a benign cavernous lymphangioma. The patient made a complete recovery and was disease-free 30 months postoperatively.

Adult↗
PubMed2005

Effect of thalidomide on colorectal cancer liver metastases in CBA mice.

BACKGROUND AND AIMS: Thalidomide has undergone resurgence in the treatment of specific malignancies. One of the possible actions of thalidomide may be an antiangiogenic effect. This study investigates the effects of thalidomide on tumor growth and long-term survival in a murine model of colorectal liver metastases. METHODS: Liver metastases were produced in male CBA mice by intrasplenic injection of a dimethyl hydrazine induced MoCR colon cancer murine cell line. Thalidomide was administered daily at doses ranging from 50 to 300 mg/kg by intraperitoneal injection. Tumor growth was assessed using quantitative stereological analysis. The effect on long-term survival was determined at the maximum tolerated dose using Kaplan-Meier analysis. The microvascular effects of thalidomide were assessed by laser Doppler flowmetry (LDF) and microvascular resin casting. Immunohistochemistry was used to determine vascular endothelial growth factor (VGEF) and basic fibroblast growth factor (bFGF) expression. RESULTS: Thalidomide, (50-300 mg/kg) caused no significant reduction in tumor growth by day 21 following induction of liver metastases and caused systemic toxicity at a dose of 300 mg/kg. At a dose of 200 mg/kg given beyond 35 days, thalidomide significantly reduced tumor growth compared to control, (P = 0.029). No significant impact on survival was however observed (P = 0.93). LDF and microvascular resin casting showed no differences in blood flow or tumor microvascular architecture. VGEF and FGF were expressed in tumors, but remained unaltered by thalidomide administration compared to matched controls. CONCLUSIONS: Thalidomide caused a significant reduction in the volume of colorectal liver metastases during the late phase of tumor growth. There was however no improvement in survival. Tumor growth reduction in this model did not appear to be due to microvascular changes or altered expression of VGEF or basic FGF. Further investigation into potential mechanisms of action of thalidomide and its synergistic use with other therapies is required.

Analysis of Variance↗
PubMed2005

Mechanisms of focal heat destruction of liver tumors.

BACKGROUND: Focal heat destruction has emerged as an effective treatment strategy in selected patients with malignant liver tumors. Radiofrequency ablation, interstitial laser thermotherapy, and microwave treatment are currently the most widely applied thermal ablative techniques. A major limitation of these therapies is incomplete tumor destruction and overall high recurrences. An understanding of the mechanisms of tissue injury induced by focal hyperthermia is essential to ensure more complete tumor destruction. Here, the currently available scientific literature concerning the underlying mechanisms involved in the destruction of liver tumors by focal hyperthermia is reviewed. METHODS: Medline was searched from 1960 to 2004 for literature regarding the use of focal hyperthermia for the treatment of liver tumors. All relevant literature was searched for further references. RESULTS: Experimental evidence suggests that focal hyperthermic injury occurs in two distinct phases. The first phase results in direct heat injury that is determined by the total thermal energy applied, tumor biology, and the tumor microenvironment. Tumors are more susceptible to heat injury than normal cells as the result of specific biological features, reduced heat dissipating ability, and lower interstitial pH. The second phase of hyperthermic injury is indirect tissue damage that produces a progression of tissue injury after the cessation of the initial heat stimulus. This progressive injury may involve a balance of several factors, including apoptosis, microvascular damage, ischemia-reperfusion injury, Kupffer cell activation, altered cytokine expression, and alterations in the immune response. Blood flow modulation and administration of thermosensitizing agents are two methods currently used to increase the extent of direct thermal injury. The processes involved in the progression of thermal injury and therapies that may potentially modulate them remain poorly understood. CONCLUSION: Focal hyperthermia for the treatment of liver tumors involves complex mechanisms. Evidence suggests that focal hyperthermia produces both direct and indirect tissue injury by differing underlying processes. Methods to enhance the effects of treatment to achieve complete tumor destruction should focus on manipulating these processes.

Animals↗
PubMed2005

Progressive microvascular injury in liver and colorectal liver metastases following laser induced focal hyperthermia therapy.

BACKGROUND AND OBJECTIVES: Focal hyperthermia by laser or radiofrequency is currently the preferred method for local ablation of liver tumors. The underlying mechanism of action of focal hyperthermia, in particular the relationship between the microvascular and tissue effect is uncertain and was investigated in a murine model. STUDY DESIGN/MATERIALS AND METHODS: Focal hyperthermia produced by a Neodymium-Yttrium-Aluminium-Garnet laser (wavelength 1,064 nm) was applied to the normal liver and colorectal cancer liver metastases in inbred male CBA strain mice at 2 W for 50 seconds (100 J). Tissue injury was assessed at 0, 24, 48, 72, 120, and 168 hours following therapy by measurements of necrosis in tissue sections stained for nicotinamide adenine dinucleotide (NADH) diaphorase activity. Characteristics of microvascular injury were assessed at the various time points by scanning electron microscopy (SEM) of vascular resin casts, Laser Doppler flowmetry, and confocal in vivo microscopy. RESULTS: Focal hyperthermia produced progressive tissue and vascular injury. There was an initial reduction in blood flow and increased vascular permeability in the microcirculation of both tumor and liver tissue immediately following heat application as assessed by laser Doppler flowmetry and confocal in vivo microscopy, respectively. SEM of vascular casts showed heterogeneous regions of microvascular injury immediately following heat application. The extent of initial vascular disruption or occlusion on SEM of vascular resin casts (mean+/-SE) was significantly less than the tissue necrosis in liver (1.9+/-0.1 mm vs. 3.0 mm+/-0.2 mm P<0.001), but was equivalent to the tissue injury in tumor tissue (3.5 mm+/-0.2 mm vs. 3.6 mm+/-0.1 mm P = 0.907). This was followed by a progressive increase in both microvascular and tissue injury in liver and tumor that peaked by 72 hours following treatment. The peak microvascular injury and tissue damage in liver (6.6 mm+/-0.2 and 6.3 mm+/-0.2 mm, respectively) was significantly greater than the extent of microvascular and tissue damage in tumors (4.8 mm+/-0.2 mm and 4.5 mm+/-0.2 mm, respectively) (P<0.001). The progression of microvascular injury in liver and tumor at times preceded the tissue injury. CONCLUSION: Focal hyperthermia produces both progressive microvascular and tissue damage in liver and colorectal liver metastases. An increase in tissue injury following focal hyperthermia may be a direct result of progressive microvascular damage. Tumor vessels appear more susceptible to direct focal hyperthermia destruction than liver sinusoids. The liver sinusoids are however more susceptible to progressive damage or occlusion following the initial laser thermal stimulus.

Animals↗
PubMed2005

Focal hyperthermia produces progressive tumor necrosis independent of the initial thermal effects.

Focal hyperthermia, produced using laser, radio frequency, and microwave, is used to treat liver tumors. The exact mechanisms of tissue destruction using focal hyperthermia are, however, unknown. Clinical and experimental studies suggest a progression of injury after cessation of the initial heat stimulus. This study investigates the mechanisms and time sequence of progressive tissue necrosis induced using focal hyperthermia in a murine model of colorectal liver metastases. Focal hyperthermia produced using a neodymium-yttrium aluminum garnet (Nd-YAG) laser source was applied to the normal liver and colorectal cancer liver metastases in inbred male CBA strain mice. The extent of direct lethal thermal injury was assessed histochemically using vital stain for nicotinamide adenine dinucleotide (NADH) diaphorase immediately after laser application. Tissue injury at subsequent time points was assessed using both NADH diaphorase staining and routine histology to determine the temporal relationship between tissue necrosis and time. Thermal injury occurring immediately after the application of 100 joules of energy was greater in the tumor tissue than in the normal liver (mean [standard error of the mean (SEM)]), measuring 23.5 (3.4) and 16.3 (2.6) mm(3), respectively (P=0.046), despite similar tissue temperature profiles. There was a significant increase in tissue necrosis after initial injury that was greater in the normal liver than in the tumor tissue. In the normal liver, the peak volume of necrosis was 137.4 (9.8) mm(3) and occurred at 3 days, whereas in the tumor tissue the peak was 49.0 (3.5) mm(3) at 4.5 days (P < 0.001). Focal hyperthermia produces tissue necrosis that occurs in two phases. The first phase is caused by the direct lethal thermal injury followed by a second phase involving a progression of necrosis beyond the initial thermal effects. The normal liver and the tumor tissue responded differently to focal hyperthermia. In the tumor tissue, the direct injury is more pronounced, whereas the progression of injury is more rapid and extensive in the normal liver.

Animals↗
PubMed2005

Comparison of 980- and 1064-nm wavelengths for interstitial laser thermotherapy of the liver.

OBJECTIVE: Interstitial laser thermotherapy (ILT) of liver tumors is generally performed using neodyium yttrium-aluminium-garnet (Nd-YAG) lasers. More versatile diode units, developed predominantly for other clinical applications, may be equally suitable for ILT. This study compares the efficacy of diode and Nd-YAG lasers in achieving maximum tissue necrosis, at low power, in a murine model. METHODS: Thermal ablation was induced in the liver of CBA strain mice by diode (980-nm wavelength) and Nd-YAG (1064-nm wavelength) lasers using 400-microm diameter bare fibers. Treatment time prior to tissue charring was determined for both lasers at a power output of 2 W. Tissue temperature was recorded upon completion of therapy 3 mm from the fiber insertion site. The maximum diameter of necrosis was accurately assessed by nicotinamide adenine dinucleotide (NADH) diaphorase tissue staining. RESULTS: Maximum diameter of tissue necrosis prior to charring occurred at 20 s (40 J) with the diode laser compared to 50 s (100 J) with the Nd-YAG laser. The maximum diameter of necrosis (mean [SEM]) produced by the diode laser, 5.9 mm (0.14), was equivalent to the necrosis induced by the Nd-YAG laser, 5.9 mm (0.14) (p = 0.963). Tissue temperature 3 mm from the fiber application site immediately following ILT in the diode laser group, 40.8 degrees C (0.93), was not statistically different than that of the Nd-YAG laser group, 39.0 degrees C (0.86) (p = 0.452). Tissue charring consistently prevented treatment beyond 20 s at 2W by the diode laser. CONCLUSION: Low power ILT with diode and Nd-YAG lasers achieves equivalent maximal necrosis when applied to the liver by a bare fiber. Treatment time to produce maximal necrosis is however significantly shorter with the diode laser.

Animals↗
PubMed2004

Long-term survival of patients with unresectable colorectal liver metastases treated by percutaneous interstitial laser thermotherapy.

In situ ablation of colorectal cancer (CRC) liver metastases is an accepted form of treatment for selected patients. It is associated with low morbidity and mortality and increases the number of patients who may benefit from therapy compared to resection alone. This study assesses the impact of interstitial laser thermotherapy (ILT) on local tumor control and long-term survival in patients with unresectable CRC liver metastases. Percutaneous ILT was performed in patients with unresectable CRC liver metastases between January 1992 and December 1999 using a bare-tip quartz fiber connected to an Nd:YAG laser source. This was prior to the routine use of a diffusing fiber for ablative therapy. Treatment was monitored with real-time ultrasonography. Tumors were considered unresectable based on their anatomic location or the extent of liver involvement. Patients with extrahepatic disease, more than five liver metastases, or tumors larger than 10 cm in diameter were excluded from this study. Local tumor control was assessed by dynamic computed tomography (CT) 6 months after therapy. Long-term follow-up was undertaken, and the impact of various factors on survival was analyzed. Eighty patients with a mean age of 63.8 years were suitable for ILT. In total, 168 liver tumors with a median diameter of 5 cm (range 1-10 cm) were so treated. There were no procedure-related deaths. The overall complication rate was 16%, with all cases managed conservatively. Bradycardia (n = 5), pneumothorax (n = 3), and persistent pyrexia (n = 3) were the most common complications. Complete tumor ablation was noted in 67% of patients assessed by CT 6 months following the initial therapy. Median follow-up was 35 months (range 4-96 months), with 10 patients alive at the end of this period. Altogether there were 67 deaths, which were related to hepatic disease in 55 cases and to extrahepatic disease in 9; they were unrelated to malignancy in 3 others. Three patients were excluded from follow-up after ILT down-staging of tumors that allowed complete surgical resection. The median disease-free survival of patients treated by ILT was 24.6 months, with a 5-year survival of 3.8%. Poor tumor differentiation and the presence of more than two hepatic metastases were associated with lower overall survival (p < 0.01). Fourteen patients treated by ILT for postoperative hepatic recurrences had the best outcome, with a median overall survival of 36.3 months and a 5-year survival of 17.2%. Percutaneous ILT is a minimally invasive, safe, effective technique that appears to improve overall survival in specific patients with unresectable CRC liver metastases, compared to the natural history of untreated disease reported in the literature.

Aged↗
PubMed2003

Effect of interstitial laser hyperthermia in a murine model of colorectal liver metastases: scanning electron microscopic study.

Interstitial laser hyperthermia (ILH) is an in situ ablative technique used to treat colorectal liver metastases. The relatively high recurrence of tumor after treatment by ILH may be related to incomplete destruction. Little is known about the effectiveness of ILH for destroying tumor microvasculature. The aim of this study was to define the changes to the microvascular architecture of tumors after treatment with ILH, specifically focusing on the completeness of tumor vasculature destruction. An intrasplenic induction model of liver metastases in 4- to 6-week-old male inbred CBA mice was used. Laser hyperthermia was applied to liver and tumor tissue using a bare optical quartz fiber from a Medilas Fibertom 4100 Nd:YAG surgical laser generator. The animals underwent microvascular corrosion casting of the livers immediately after application of ILH. Microvascular casts were then prepared and studied by scanning electron microscopy. ILH produced complete, uniform destruction of the tumor microvasculature with compete hemostasis. Blood flow in vessels larger than 100 microm diameter had a relatively protective effect, although ILH was able to overcome this barrier effectively by increasing the energy applied. ILH produces complete destruction of tumor microvasculature with hemostasis. The protective effect of blood flow in larger vessels can be overcome by the appropriate use of higher energy levels.

Animals↗
PubMed2002

Autoimmune pancreatitis.

The recommended treatment for a focal mass in the head of the pancreas is pancreaticoduodenectomy. Preoperative biopsy is not advised in patients who are candidates for resection because of the documented risk of tumour dissemination along the needle tract and significant false negative results.1 Autoimmune pancreatitis is a relatively uncommon condition that can present as a pancreatic mass and mimic malignancy. It may respond to glucocorticoid therapy, and further assessment of such treatment is indicated.2 Such experience will only accumulate if wider knowledge of this condition leads to clinical suspicion.

Adult↗
PubMedDate not supplied

A model of partial hepatectomy in mice.

A versatile, simple, and reproducible model of hepatectomy is essential for the study of liver regeneration and its effects on various pathological processes. A murine model of liver resection and regeneration suitable for research is described. Male inbred CBA mice 6-8 wk old were used in all experiments. The contribution of the hepatic lobes to the total liver mass was determined by wet weight measurements. Resection of 37% (n = 10) and 70% (n = 10) liver volume was performed using hemostatic clips to ligate the hepatic lobe pedicles. Animals were recovered and subsequently killed 21 days postoperatively Liver mass was determined and compared to control animals (n = 17) to assess the completeness of liver regeneration. There were no operative deaths in animals undergoing either 37% or 70% hepatectomy. The procedures could be performed expediently, and animal recovery was complete. Liver mass (grams) assessed 21 days postoperatively [mean (SE)] in both the 37% resection, 1.76 g (0.07), and 70% resection, 1.56 g (0.05), groups was not significantly different from control animals, 1.64 g (0.07) (p =.265). Thus, partial hepatectomy can be performed safely and rapidly in mice using haemostatic clip ligation of hepatic lobes, with no impairment to the subsequent process of liver regeneration.

Animals↗
PubMedDate not supplied

Impact of blood flow occlusion on liver necrosis following thermal ablation.

BACKGROUND: Laser, radiofrequency and microwave are common techniques for local destruction of liver tumours by thermal ablation. The main limitation of thermal ablation treatment is the volume of necrosis that can be achieved. Blood flow occlusion is commonly advocated as an adjunct to thermal ablation to increase the volume of tissue necrosis based on macroscopic and histological assessment of immediate or direct thermal injury. This study examines the impact of blood flow occlusion on direct and indirect laser induced thermal liver injury in a murine model using histochemical methods to assess tissue vitality. METHODS: Thermal ablation produced by neodymium yttrium-aluminium-garnet laser (wavelength 1064 nm) was applied to the liver of inbred male CBA strain mice at 2 W for 50 s (100 J). Treatment was performed with and without temporary portal vein and hepatic artery blood flow occlusion. Animals were killed upon completion of the procedure to assess direct thermal injury or at 24, 48 and 72 h to assess the progression of tissue damage. The maximum diameter of necrosis was assessed by vital staining for nicotinamide adenine dinucleotide (NADH) diaphorase. Microvascular changes were assessed by laser Doppler flowmetry, confocal in vivo microscopy and scanning electron microscopy. RESULTS: The direct thermal injury (mean SE) assessed by NADH diaphorase staining was significantly greater following thermal ablation treatment without blood flow occlusion than with blood flow occlusion (3.3 (0.4) mm vs 2.9 (0.3) mm; P = 0.005). Tissue disruption, cracking and vacuolization was more pronounced adjacent to the fibre insertion site in the group treated with thermal ablation combined with blood flow occlusion. There was an equivalent increase in the extent of injury following therapy in both groups that reached a peak at 48 h. The maximum diameter of necrosis in the thermal ablation alone group at 48 h was significantly greater than the thermal ablation combined with blood flow occlusion group (5.8 (0.4) mm vs 5.3 (0.3) mm; P = 0.011). The patterns of microvascular injury were similar in both groups, varying in extent. CONCLUSION: Temporary blood flow inflow occlusion appears to decrease the extent of initial injury measured by vital staining techniques and does not alter the time sequence of progressive tissue injury following thermal ablation therapy.

Animals↗
PubMedDate not supplied

The apoptotic response of liver and colorectal liver metastases to focal hyperthermic injury.

BACKGROUND: Ablation of liver tumours by focal hyperthermia causes tissue injury not only by direct effects, but also by progressive tissue damage following the initial heat application. The mechanism by which this progressive injury occurs remains undefined. Stimulation of apoptosis following the initial heat stimulus may be involved in this progression. The role of apoptosis in the subsequent progression of focal hyperthermia injury was investigated in liver and colorectal liver metastases in a murine model. MATERIALS AND METHODS: Focal hyperthermia produced by laser (Nd-YAG--wavelength 1064 nm) was applied to the liver and colorectal liver metastases in CBA mice (2 Watts for 50 seconds). The animals were killed at 0, 12, 24, 48, 72, 120 and 168 hours after the application of focal hyperthermia. Haematoxylin and eosin staining and immunohistochemistry were performed on paraffin sections to assess the extent of tissue necrosis. Apoptosis was examined by assessment of DNA fragmentation using terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labelling (TUNEL) and activated Caspase 3 immunostaining. The sequence of the apoptotic response was determined at the treated tissue margins and compared to untreated liver and tumour. RESULTS: Focal hyperthermia produced progressive tissue injury in both liver and colorectal liver metastases. TUNEL labelling was less specific than activated Caspase 3 in detecting apoptotic cells. Apoptosis was detected and peaked at 12 hours following therapy based on activated Caspase 3 staining, before returning to baseline at 72 hours. In tumour tissue, the apoptotic response was more sustained, peaking at 24 hours before returning to baseline levels by 96 hours following therapy. CONCLUSION: Increased apoptosis occurs following the application of focal hyperthermia to normal liver and colorectal metastases. The apoptotic response is more sustained in tumour tissue and contributes to the progressive injury that is evident after the initial heat stimulus.

Animals↗