Soft Tissue Clearance Research Articles

Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents.

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)5 and fac-[NEt4]2[ReBr3(CO)3] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)3] (5a) and fac-[Re(SNO)(CO)3] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[99mTc(CO)3]+ core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[99mTc][Tc(OH2)3(CO)3]+ precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC50 = 8.85 ± 2.62 μM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC50 value of 26.11 nM. Biodistribution studies of the 99mTc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system.

Assessment of Bone and Soft Tissue Margins in Resection of Mandibular Ameloblastoma: An Institutional Series

<h3>Introduction</h3> The treatment of gnathic ameloblastoma remains controversial. When resection is undertaken, a planned linear bone margin of at least 1.0 cm is often recommended for mandibular tumors. For cases in which tumor has extended beyond bone, inclusion of the adjacent anatomic barrier is recommended, however little attention has been devoted to the margin reporting of non-osseous margins. <h3>Materials and Methods</h3> Emory University records were searched for patients undergoing resection for ameloblastoma between 1/1/2020 and 3/01/2021. Twenty-one consecutive patients underwent surgical resection during the fourteen-month interval. In six cases, specimen fragmentation precluded margin evaluation. In three cases, only rare tumor islands remained microscopically in the resection specimen after initial biopsy inadvertently removed much of the lesion. The twelve remaining patients formed the study cohort. <h3>Results</h3> Patients ranged from 22 to 78 years of age, and 6 were male. Segmental mandibular resection was performed in 10 cases and marginal mandibular resection accomplished in 2. Average tumor size was 4.9 cm. In 10 of 12 cases, ameloblastoma extended beyond the mandibular bone. In all ten cases, the soft tissue margin was grossly identified as the margin nearest to tumor. Microscopically, soft tissue margin clearance measured 1.0 mm or less and in one, tumor involved the soft tissue margin. All bone margins measured 0.6 cm or greater from tumor, with 10 of 12 mandibular bone resection margins showing a linear distance of 1.0 cm or more from tumor. <h3>Conclusion</h3> In ameloblastoma perforating bone, soft tissue margins are most likely to represent the closest margin. Narrow clearance of soft tissue margins in ameloblastoma may be related to the lack of a specific guiding measurement in the literature. Close soft tissue margins can be identified grossly, and the clinical significance of ample bone margin clearance in the setting of narrow soft tissue clearance remains uncertain.

Surgical Considerations for an Osseointegrated Steady State Implant (OSIA2®) in Children.

Surgical Considerations for an Osseointegrated Steady State Implant (OSIA2®) in Children.

Postoperative chyle leak after pancreatic surgery - Is treatment effective?

With increasing soft tissue clearance in pancreatic cancer surgery, postoperative chyle leak (CL) has become a more commonly observed complication. Recently, a new consensus definition was established by the International study group of pancreatic surgery (ISGPS). The aim of the present analysis was to evaluate risk factors and treatment options of patients with CL after pancreatic surgery. Two hundred and twenty-eight patients with serous or chylous drainage after pancreatic surgery were included in this analysis of a prospectively collected database between 01/2014 and 12/2016. Risk factors for CL and treatment options were compared. A subgroup analysis on those patients, who had drain removal despite of persistent CL with respect to the need of subsequent percutaneous drainage or reoperation within three months postoperatively, was performed. Sixty patients with CL were identified. Of those, 41 patients were treated with medium-chain triglyceride-diet, with a median duration of therapy of 12 days. In patients with CL, the type of treatment had no effect on time to drain removal (P=0.29) and morbidity (P=0.15). Furthermore, morbidity was not increased in patients who had their drains removed despite persistent CL (P=0.84). None of the latter patients had percutaneous drainage or reoperation for CL after removal of the surgical drains. Dietary treatment may not be very effective in treating CL. Further research is warranted to explore the effect and necessity of CL treatment.

Effect of Ursodeoxycholic Acid on the Biodistribution and Excretion of Technetium-99m Radiopharmaceuticals in Rat: A Potential Image Quality Enhancer.

PurposeThis study aimed to investigate the effect of ursodeoxycholic acid (UDCA) on the biodistribution and excretion of technetium-99m (Tc-99m)-labeled radiopharmaceuticals.Materials and MethodsTc-99m hydroxy-methylene-diphosphonate (HDP), Tc-99m pertechnetate, and Tc-99m dimercaptosuccinic acid (DMSA) were injected via the tail vein of rats. After 30 min, the control group was administered saline, and the UDCA group was given UDCA orally. Scintigraphy images were acquired after 30 min and 1, 2, 3, and 4 h. Radioactivity and rate of change were compared. Tc-99m mercaptoacetyltriglycine (MAG3) imaging was also performed.ResultsIn image analysis of Tc-99m HDP, radioactivity of the buttock was lower in the UDCA group at 4 h. Rates of change in the buttock were significantly different at 3 h–30 min and 4 h–30 min, and buttock radioactivity in the UDCA group had decreased more. In analysis of Tc-99m pertechnetate, radioactivity of the buttock was higher in the control group. Rates of change in the thyroid gland and buttock were different at 1 h–30 min, 3 h–30 min, and 4 h–30 min, with radioactivity in the UDCA group decreasing more. In the analysis of Tc-99m DMSA, while the radioactivity of the kidneys in the control group showed little decrease at 1 h–30 min, that in the UDCA group increased. In the analysis of Tc-99m MAG3 images, radioactivity and radioactivity/total body radioactivity (TBA) values for the kidneys were higher in the UDCA group at 2 min. At 5 and 10 min, radioactivity/TBA values for soft tissue in the UDCA group were lower than those in the control group.ConclusionThis study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of radiopharmaceuticals. This investigation could contribute to the broadening of applications of UDCA.

Treatment of postoperative chyle leak after pancreatic surgery – A single center experience

Background: Postoperative chyle leak (CL) is a common complication in pancreatic surgery, where extensive soft tissue clearance is indispensable. Currently, the efficacy of different treatment options for CL is unclear. The aim of the present study was to evaluate treatment options of patients with CL after pancreatic surgery. Methods: CL was defined according to the recently published definition of the International Study Group of Pancreatic Surgery. 228 patients with CL or serous drainage after pancreatic surgery between 01/2014 and 03/2016 were included in this retrospective analysis. Early (≤5 days) and late drain removal were compared regarding the risk for CL and morbidity. A subgroup analysis on those patients who had drain removal despite of persistent CL with respect to the need of subsequent CT-guided drainage within three months postoperatively was performed. Results: At total of 60 patients with CL was identified. 41 patients with CL were treated with medium-chain triglyceride-diet, with a median duration of therapy of 12 days. Early drain removal is associated with a decreased risk or detection rate of CL (p = 0.008) and is not associated with an increased morbidity. After drain removal despite of persistent CL, none of the patients had CT-drainage with proof of CL within three months postoperatively. Conclusion: Early drain removal and removal of the surgical drains despite of persistent CL may be as safe as continuous drainage until complete resolution of CL.

Failure rates for stainless steel versus titanium alloy infrazygomatic crest bone screws: A single-center, randomized double-blind clinical trial.

To compare failure rates for stainless steel (SS) and titanium alloy (TiA) bone screws (BSs) placed in the infrazygomatic crest (IZC). A total of 386 consecutive patients (76 male, 310 female; mean age 24.3 years, range 10.3-59.4 years) received IZC BSs (SS or TiA) via a double-blind, split-mouth design. BSs penetrated attached gingiva (AG) or moveable mucosa (MM) with 5 mm of soft tissue clearance. All BSs were immediately loaded and reactivated monthly with ≤14 oz (397 g or 389 cN) applied directly to the upper archwire bilaterally for 6 months to retract the maxilla to correct Class II or bimaxillary protrusion. Of the 772 devices, there were 49 (6.3%) failures: 27 SS (7.0%) and 22 TiA (5.7%). The 1.3% difference was not statistically significant ( P = .07). There was no significant relationship between SS or TiA failures relative to (1) right vs left side, (2) unilateral vs bilateral, or (3) age at failure. Significantly ( P < .05) increased failure rates were noted for SS screws in only two subgroups: AG site (7.4%) and right side (7.8%). Unilateral failure occurred in 21 patients (5.4%), and bilateral failures occurred in 14 of the total 772 patients (1.8%). The overall success rate of 93.7% indicates that both SS and TiA are clinically acceptable for IZC BSs.

A New Method for Staining Ligaments and Tendons of Small Vertebrates

Clearing and staining techniques are widely used to study the structure of small vertebrates. These techniques consist mainly of soft tissue clearance by enzymatic or caustic digestion and staining of bone, cartilage, or nerves. However, although there is an increasing need to describe other soft-anatomy structures, such as ligaments and tendons, the methods available to visualize these tissues are a challenge that requires very fine dissections and three-dimensional reconstructions using tissue sections or microtomography. In this paper we present a simple and economical method for staining fibrous connective tissues, particularly ligaments and tendons. The method begins with an enzymatic proteolysis that prevents unselective soft tissue degradation. Then the bones are stained to facilitate understanding the structure associated with the bone tissue of interest. Subsequently, the connective tissues are stained in two steps, first with a deep stain and then with an alcoholic differentiation. The final pro...

Preparation and preliminary bioevaluation of a 99mTc(CO)3‐glucose derivative prepared by a click chemistry route

Development of a 99mTc‐labelled glucose derivative as a single‐photon emission computed tomography analogue to [18F]‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) is considered of great interest. Herein, we present the synthesis and preliminary bioevaluation of a 99mTc(CO)3‐glucose derivative. Derivatization of glucose at C2 was achieved using the so‐called ‘click chemistry’, forming a histidine‐like, 1,4‐disubstituted triazole adequate as donor atom system for Tc(I)‐tricarbonyl complexes. Synthesis of the intermediate azide derivative was achieved by conventional organic chemistry. Because of the efficiency and selectivity of this cycloaddition, labelling was performed in ‘one pot’, adding the tricarbonyl precursor fac‐[99mTc(CO)3(H2O)3]+ to the same vial where the click reaction has taken place without any further purification. A single product with radiochemical purity higher than 90% was obtained. It was stable for at least 4 h in reaction milieu and exhibited high hidrophilicity (log P of −1.2) and low binding to plasma proteins (5 ± 1%). Biodistribution in C57BL/6 mice bearing induced Lewis murine lung carcinoma is characterized by low blood and liver uptake and rapid urinary excretion. 99mTc complex showed moderate tumour uptake but significant retention until 2 h post‐injection. Soft tissue clearance was fast leading to significantly higher uptake in tumour in comparison to muscle (p = 0.05) at all time points. Overall, biodistribution of our compound was very similar to that of [18F]‐FDG. However, tumour uptake was significantly higher for [18F]‐FDG, probably because of high hidrophilicity of our derivative that may hinder cell penetration. Similarity to biodistribution of FDG is a promising outcome, and modifications of the chelator and linker might improve biological results. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Management of Giant Cell Tumor of Bone: Computerized Tomography Based Selection Strategy and Approaching the Lesion Through the Site of Cortical Break

A retrospective study was carried out in patients with giant cell tumor of bone to compare the functional and radiographic outcome of curettage and bone grafting using a novel CT based selection strategy to that of patients of a similar age treated with anatomic/standard curettage and bone grafting. Curettage and bone grafting after CT classification was performed in 31 patients and curettage and bone grafting without CT classification in 20. The surgical approach for curettage in the CT classified group of patients was through the site of the cortical break, irrespective of the standard approach to the particular region of bone involved. The aim of this approach was to achieve wide excision of the possibly involved soft tissue. At similar duration of follow up (72 months) in patients with a similar mean age (33 years), Musculoskeletal Tumor Society (MSTS) scores for CT classified patients were similar to those of patients who had undergone standard curettage. However, the postoperative recurrence rate in the CT classified group was significantly less (12.9%) than in the non-CT classified group. A CT based selection strategy is a valid preoperative tool for evaluation of giant cell tumor. Further, for curettage these lesions are better approached through the site of cortical break, irrespective of standard approaches, so that adequate soft tissue clearance can be achieved.

Biodistribution and Imaging of 1-(2-Deoxy-β-D-Ribofuranosyl)-2,4-Difluoro-5-[123/125I]Iodobenzene (dRF[123/125I]IB), A Nonpolar Thymidine-Mimetic Nucleoside, in Rats and Tumor-Bearing Mice

1-(2-Deoxy-β-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (dRFIB) is a putative bioisostere of iododeoxyuridine (IUdR). The advantages of dRFIB over IUdR for in vivo studies include resistance to both phosphorolytic cleavage of the nucleoside bond and de-iodination. dRFIB was radioiodinated (dRF123/125IB) by copper-catalyzed exchange using commercial sodium [123/125I]iodide. The in vivo biodistribution of dRF[125I]IB in BALBc mice and imaging of dRF[123I]IB in Sprague-Dawley rats are reported. In vivo data for rats show rapid clearance of radioactivity from blood (>95%ID in 15 minutes), extensive excretion in urine (56%ID/24 hours), concentration in the hepatobiliary-small intestine system and very little fecal excretion (∼3%ID/24 hours). Pharmacokinetic data for dRF[125I]IB (i.v. 48.7 ug/kg) in rats (t1/2[h] = 0.51 ± 0.14, AUCinf[μg.min/mL] = 3.7 ± 0.4, Cl[L/kg/h] = 0.75 ± 0.12, Vss[L/kg] = 0.96 ± 0.18) confirm previously reported dose-dependent pharmacokinetics. Scintigraphic images of rats dosed with dRF[123I]I were compatible with rapid soft-tissue clearance and extensive accumulation of radioactivity in bladder/urine and liver/small intestine. In tumor-bearing mice, thyroid and stomach radioactivity was indicative of moderate deiodination. An unidentified polar radioactive metabolite was detected in serum.

Synthesis and characterization of rhenium and technetium-99m tricarbonyl complexes bearing the 4-[3-bromophenyl]quinazoline moiety as a biomarker for EGFR-TK imaging

Aiming at the development of technetium-99m ( 99mTc) complexes for early detection and staging of EGFR positive tumors, the tyrosine kinase inhibitor 6-amino-4-[(3-bromophenyl)amino]quinazoline was derivatized with pyridine-2-carboxaldehyde to generate the imine 6-(pyridine-2-methylimine)-4-[(3-bromophenyl)amino]quinazoline suitable for reacting with the fac-[ 99mTc(CO) 3] + core as an N, N bidentate ligand. The labelling was performed in high yield (>90%) by ligand exchange reaction using fac-[ 99mTc(OH 2) 3(CO) 3] + as precursor. The 99mTc complex was characterized by comparative HPLC analysis using the analogous rhenium (Re) complex as reference. The Re complex was prepared by ligand exchange reaction using the fac-[ReBr 3(CO) 3] 2− as precursor and was fully characterized by NMR and IR spectroscopies and elemental analysis. In vitro studies indicate that both the ligand and its Re complex inhibit the EGFR autophosphorylation (IC 50: 17 ± 3.7 and 114 ± 23 nM respectively) in intact A431 cells, bind the receptor in a reversible mode, and inhibit A431 cell growth (IC 50: 5.2 ± 1.1 and 2.0 ± 0.98 μM respectively). Biodistribution of the 99mTc complex in healthy animals showed a rather fast blood and soft tissue clearance between 1 and 15 min p.i. with excretion occurring mainly via the hepatobiliary system.

Importance of extended radical resection for treatment of pancreatic head cancer

Objective To investigate the importance of extended lymphadenectomy and retro-peritoneal soft tissue clearance for the patients with ductal adenocarcinoma of the pancreas,and mor-bidity,mortality and survival of patients with ductal adenocarcinoma of the pancreas receiving pancrea-tectomy with en bloc portal vein resection. Methods The clinical data of 56 patients with ductal ade-nocarcinoma of the pancreas undergoing extended radical resection in our hospital between 2001 and 2004 were retrospectively analyzed. In addition, they were categorized into two groups according to whether there were positive lymph nodes: group A (n=40) of positive lymph nodes and group B (n=16) of negative lymph nodes. They were also categorized into two groups according to whether there was combined superior mesenteric-portal vein(SMPV) resection: group Ⅰ (n = 39) of no combined SMPV resection and group Ⅱ (n= 17) of combined SMPV resection. Results The morbidity and mor-tality of the 56 patients were 30% and 2%, respectively. The overall 1-, 3-and 5-year survival rates were 63%, 29% and 16%, respectively. Postoperative pathological examination found 40 cases (71%)of positive lymph node. Of those 11 cases of paraaortic lymph node involvement, 16 (29%) were of negative lymph node. There were no significant difference in 1-,3-and 5-year survival rates between group A and B,while the survival curve for those with paraaortic lymph node involvement was signifi-cantly worse than group A and B. The combined SMPV resection was performed in 17 cases, no signif-icant differences in 1-,3-and 5-year survival rates between group Ⅰ and Ⅱ were found. The mean surviv-al of patients with microscopically positive margin (n = 5) was only 9 months as compared with 23months in those with microscopically negative margin (n= 51). Conclusion If selected carefully, ex-tended lymphadenectomy and retroperitoneal soft tissue clearance combined with SMPV resection canbe performed safely. Extended radical resection will be benefit to some patients with positive lymphnode, but can not increase the survival rate of patients with positive paraaortic lymph node. SMPV re-section should be performed only when a margin-negative resection is expected to be achieved. SMPV invasion are not associated with histological parameters suggesting a poor prognosis. Key words: Pancreatic neoplasms; Pancreaticoduodenectomy; Extended lymphadenectomy; Superior mesenteric-portal vein resection

Survival benefit of extended resection in pancreatic cancer

Extended resection for pancreatic cancer has been performed successfully in many centers around the world. The approaches currently used include extended lymph node dissection with extended soft-tissue clearance and resection of adherent vessels in patients with cancer in the pancreatic head. Recently, these approaches have been extended to include simultaneous resection of minimal metastatic disease and resection for locally recurrent disease. The results of several controlled clinical trials did not support the use of extended lymph node dissection; however, it is likely that these studies are underpowered to show a survival benefit. With regard to portal/superior mesenteric vein (PV/SMV) resection, no controlled study is available, but it appears that the procedural risk is identical to standard resection. Therefore, the concept of PV/SMV resection seems justified to establish negative resection margins. The value of pancreatic resection in the setting of minimal metastatic disease and re-resection for locally recurrent disease should be proved in clinical studies because data are unavailable to generally support this approach. In summary, extended pancreatic resections are often tailored to highly selected patients and according to the center’s experience. The latter issue is especially critical because there is no scientific evidence for a survival benefit, and, therefore, the procedural risk has to be equally as low as in standard resection.

Synthesis, Characterization, and Biological Evaluation of M(I)(CO)3(NNO) Complexes (M = Re, 99mTc) Conjugated to 2-(4-Aminophenyl)benzothiazole as Potential Breast Cancer Radiopharmaceuticals

The synthesis and biological evaluation of new M(I)(CO)3(NNO) (M = Re, 99mTc) complexes attached to the antitumor agent 2-(4-aminophenyl)benzothiazole are reported. The fluorescent rhenium complex enters MCF-7 breast cancer cells but does not enter normal HFFF-2 and MRC-5 cells. The analogous radioactive 99mTc complex produces fast blood and soft tissue clearance when administered to healthy mice. These complexes are promising candidates for developing radiopharmaceuticals for imaging (99mTc) and targeted radiotherapy (186Re, 188Re) of breast cancer.

Evaluation of the use of technetium Tc 99m diethylenetriamine pentaacetic acid and technetium Tc 99m dimercaptosuccinic acid for scintigraphic imaging of the kidneys in green iguanas ( Iguana iguana )

To evaluate the use of scintigraphy involving technetium Tc 99m diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) or technetium Tc 99m dimercaptosuccinic acid ((99m)Tc-DMSA) for the determination of kidney morphology and function in green iguanas (Iguana iguana). 10 healthy iguanas weighing >1.6 kg. Renal scintigraphy was performed by use of (99m)Tc-DTPA in 6 of the iguanas and by use of (99m)Tc-DMSA in all 10 iguanas. After the injection of (99m)Tc-DMSA, scans were performed for each iguana at intervals during a 20-hour period. Renal biopsies were performed in all 10 iguanas after the final scintigraphic evaluation. In iguanas, the use of (99m)Tc-DTPA for renal scintigraphy was nondiagnostic because of serum protein binding and poor renal uptake of the isotope; mean +/- SD (99m)Tc-DTPA bound to serum proteins was 48.9 +/- 9.9%. Renal uptake of (99m)Tc-DMSA produced distinct visualization of both kidneys. Renal uptake and soft tissue clearance of (99m)Tc-DMSA increased over the 20-hour imaging period; mean +/- SD renal uptake of (99m)Tc-DMSA was 11.31 +/- 3.06% at 20 hours. In each of the 10 iguanas, ultrasonographic and histologic examinations of biopsy specimens from both kidneys revealed no abnormalities. Results indicate that the kidneys of iguanas can be evaluated scintigraphically by use of (99m)Tc-DMSA; this technique may be potentially useful for the diagnosis of renal failure in iguanas.

Outcome of paraaortic node-positive pancreatic head and bile duct adenocarcinoma

Background This retrospective study aimed to identify the clinicopathologic features and surgical results of paraaortic node-positive periampullary adenocarcinoma. Methods Between 1995 and 1999, 101 patients underwent pancreatectomy with regional and paraaortic lymphadenectomy. Fifteen (15%) patients had histologically proven paraaortic lymph node disease. Results The 15 patients included 9 (26%) of 34 patients with pancreatic head carcinoma and 6 (17%) of 36 patients with bile duct adenocarcinoma. All 15 patients had locally advanced tumor invading adjacent structures. The 1-, 2-, and 3-year survival rates were 33%, 27%, and 0%, with median survival of 12 months (range 3 to 33). In patients with pancreatic head carcinoma or bile duct adenocarcinoma, survival curve for those without paraaortic lymph node metastasis was significantly better than that for those with involved paraaortic lymph nodes ( P = 0.0033 or P = 0.0149). Conclusions When the paraaortic lymph nodes obtained from sampling biopsy are histologically positive, radical pancreatectomy with extended lymphatic and soft tissue clearance should be abandoned owing to poor outcome.

Patella resurfacing in total knee replacement: functional evaluation and complications

Three different knee replacements, with three trochlear designs, were prospectively evaluated clinically and radiographically for patellar function and presence of patellar complications. They included the Insall-Burstein (IB) I and the IB-II (posterior cruciate ligament substituting) and the Meniscal Bearing Knee (MBK; posterior cruciate ligament recession). The trochlea of the IB-I was short and shallow with an anterior sharp edge of the intercondylar box (later modified to a smoother edge) and the femoral component had a prominent "shoulder." In the IB-II the trochlea was deeper to allow for soft tissue clearance. In the MBK the trochlea was more prolonged, with R and L components and the "shoulder" was less prominent. In all the cases the patella was resurfaced with an all polyethylene dome prosthesis. Knees with tibiofemoral problems were excluded. From the data of the present study the following conclusions can be drawn: (a) The most frequent problem was impingement (clunks) with the early version of the IB-I. Smoothening of the anterior edge significantly reduced the incidence of clunks to 5% in the modified IB I. (b) With the IB-II deepening the trochlea for soft tissue clearance improved the degree, not the incidence of clunks (4.5%), compared to the modified IB I. (c) With the MBK clunks were very rare and patellar function improved. (d) Throughout the three series patellar stress fractures and instability were rare and loosening or wear not evident. (e) Normal function (including stairs ascending and descending) can be expected in over 80% of category A patients. (f) Of the various radiological parameters only patella baja was correlated with symptoms in the IB prostheses. (g) We still prefer the dome design because is more tolerant and with cold flow may better conform to the trochlea increasing contact area.

Small carcinoma of the pancreas. Factors of prognostic relevance.

Tumor size seems to be one of the primary prognostic factors that influence outcome in pancreatic cancer patients. This finding is reflected in both the Japanese and the International Union against Cancer (UICC) staging systems, in which T categories have a major influence on stage grouping. To investigate whether small tumor size is a prognostic indicator in patients with pancreatic carcinoma, we evaluated (in a prospective study) patients with a small pancreatic cancer, categorized as T1a (<2 cm) or T1b (<4 cm) tumors according to the UICC (1997). Of 670 treated patients with pan-creatic malignancies, 26 (3.8%) had a small pancreatic tumor (20 T1b; 6 T1a), Twenty-one patients were treated by pylorus-preserving duodenopancreatectomy, 4 patients re-ceived a left pancreatic resection, and 1 patient underwent a total pancreatectomy. All procedures included extensive soft tissue clearance. Local growth pattern was analyzed according to the Japan Pancreas Society (JPS) criteria for pancreatic cancer, i.e., lymph node involvement - N1 (limited to group 1 nodes) was found in 6/26 patients. Serosal infiltration - S1 (single area) was found in 6/26 and S2 (multiple areas) in 6/26; S3 (infiltration to adjacent organs) was found in 1/26. Retroperitoneal infiltration - Rp1 (adjacent to the pancreas) was found in 7/26 and Rp2 (not limited to adjacent tissues, but no other organs involved) was found in 3/26. Venous involvement (Pv2) was found in 1/26. The 5- and 10-year survival rate for the 26 patients was 46%. Interestingly, the T1a tumor patients had a significantly lower 5 year survival rate than the T1b patients (32% vs 58%; P < 0.05). Of prognostic relevance was lymph node metastasis, and retroperitoneal and serosal involvement and these patients had a significantly lower 5-year survival rate than those without such involvement regardless of tumor size (P < 0. 01). An overall 5-year survival rate of 46% is exceptionally good. Unfortunately, among pancreatic cancer patients those with a small carcinoma represent a highly selected group, representing less than 5% in our series. Interestingly tumor size is of less prognostic relevance than lymph node, retroperitoneal, and serosal involvement. Radical resection with extensive soft tissue clearance therefore seems essential to achieve such a high survival rate.

New bisphosphonates in osteoporosis.

Bisphosphonates are non-biodegradable compounds characterized by a phosphorus-carbon-phosphorus bond. By substituting the hydrogens on the carbon atom, a variety of bisphosphonates can be synthesized, each with distinct physical-chemical, biologic, therapeutic, and toxicologic characteristics. Bisphosphonates have in general a strong affinity to calcium phosphates, both in vitro and in vivo. They inhibit bone resorption through a cellular mechanism that is not yet completely understood. When given in large amounts, some bisphosphonates can inhibit normal and ectopic mineralization through a physical-chemical mechanism. The main difference among the various compounds appears to be their potency in inhibiting bone resorption, which can vary from 1 to 10,000. The potential efficacy of bisphosphonates in osteoporosis has been investigated extensively in animals. In the growing rat, they induce an increase in intestinal absorption and body retention of calcium. Various types of experimental osteoporosis, such as induced by immobilization, ovariectomy, administration of corticosteroids, or low calcium diet, can be prevented. Bisphosphonates are rapidly cleared from plasma, with 20%-60% deposited in bone and the remainder excreted in the urine. The half-life in bone is, however, very long. The toxicity of bisphosphonates is low, probably because of their rapid plasma and soft tissue clearance. It varies greatly from compound to compound. Bisphosphonates are used successfully in diseases with increased bone turnover, such as Paget's disease of bone, tumoral bone disease, and recently, osteoporosis. Most results in osteoporosis have been obtained with etidronate and pamidronate. Both of these compounds, as well as other bisphosphonates, such as tiludronate, alendronate, and clodronate, inhibit bone loss and sometimes even increase bone mass.(ABSTRACT TRUNCATED AT 250 WORDS)