Distal Margin Requirements After Preoperative Chemoradiotherapy for Distal Rectal Carcinomas: Are ≤ 1 cm Distal Margins Sufficient?

Background:Sphincter-sparing alternatives to abdominoperineal resection (APR) in the treatment of rectal cancer often are underused out of concern for inadequate distal margins and local failure. The present study addresses whether sphincter-sparing techniques with distal margins 1 cm adversely influence oncological outcome in patients given preoperative chemoradiotherapy.Methods:Thirty-seven patients with rectal cancer 8 cm from the anal verge were enrolled in the study. Preoperative external beam radiotherapy (5400 Gy) was administered together with continuous infusion of 5-fluorouracil (300 mg/m²/day). Surgical resection was performed in 36 patients with pathological assessment of tumor response and margins. Patients with sphincter-sparing resection and distal margins > 1 cm or 1 cm and those who underwent APR were compared.Results:Thirty-six patients completed preoperative chemoradiotherapy, with successful sphincter-preservation in 28 patients. At a median follow-up of 33 months, there were 12 recurrences overall, which included 11 distant failures and four pelvic failures. Disease-free survival (DFS) was not different between those who had an APR compared with sphincter-sparing resection with distal margins 1 cm. DFS was worse (P < .02) when radial margins were 3 mm compared with > 3 mm.Conclusions:Sphincter preservation is feasible in more than 75% of patients with tumors 8 cm from the anal verge after preoperative chemoradiotherapy. Sphincter-sparing surgery with distal margins 1 cm can be used without adversely influencing local recurrence or DFS. Limited radial margins ( 3 mm), however, are associated with increased disease recurrence.Presented at the 1998 Annual Meeting of the Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 18, 1998     

Preventive treatment of nephrolithiasis with alkali citrate—a critical review

Using the keywords urolithiasis and citrate treatment, nephrolithaisis and citrate treatment, kidney stones and citrate treatment, a Medline search revealed 635 articles published between 1 January 1966 and 1 December 2004. For the present analysis, only studies meeting all of the following criteria were included: (1) publications in English or German, (2) studies on preventive alkali citrate treatment in patients with calcium oxalate, uric acid and infection stone disease, (3) clinical studies including at least ten subjects, and (4) treatment phases of at least 1 week duration. A total of 43 studies met the inclusion criteria and were further subclassified according to intermediate or ultimate endpoints as well as to study design. With stone recurrence as the ultimate endpoint, 21 uncontrolled studies in almost 1,000 patients demonstrated a reduction in stone forming rate by 47–100%. In four randomized controlled trials including 227 patients, 53.5% on alkali citrate vs 35% on placebo remained stone-free after at least 1 year of treatment (P<0.0005). Similar values (66% vs 27.5% for alkali citrate vs placebo, P<0.0005) were obtained in 104 patients from two randomized trials with dissolution/clearance of residual stones as endpoint. Unfortunately, up to 48% of alkali citrate treated patients left the studies prematurely, primarily due to adverse effects such as eructation, bloating, gaseousness or frank diarrhea.     

Small intestinal lymphoma

This paper reviews small intestinal lymphoma. Although a major emphasis is placed on primary small intestinal lymphoma of the Western type, the important topic of lymphoma in celiac disease is discussed. Our own recent experience of 7 patients with lymphoma in celiac disease is presented. The lymphoma of immunoproliferative small intestinal disease (Mediterranean lymphoma) and the associated -chain disease are also reviewed, with emphasis on the differences from the Western type of primary small intestinal lymphoma.

---

Resumen Este artículo revisa el tema del linfoma intestinal. Aunque se hace énfasis principal en el linfoma intestinal primario del tipo Occidental, también se discute el tópico relativo al linfoma en la enfermedad celiaca. Se presenta un estudio sobre nuestra experiencia reciente con 7 pacientes con linfoma en enfermedad celiaca. También se revisan la enfermedad inmunoproliferativa del intestino delgado (linfoma Mediterráneo) y la enfermedad de cadena asociada, con énfasis en sus diferencias con el tipo Occidental de linfoma primario del intestino delgado.

---

Résumé Cet article est consacré au lymphome de l'intestin grÊle. Bien que centré sur le lymphome primitif (dit lymphome de type occidental) il concerne également le lymphome qui traduit une manifestation d'une maladie immunoproliférative de l'intestin (qualifié de lymphome de type méditerranéen) et ce à partir d'une expérience de 7 malades présentant une maladie coeliaque. Ce second type et la maladie associée de la chainealpha sont également étudiés en s'attachant à souligner les éléments distinctifs qui les séparent du lymphome primitif.

     

Standardization of Ischemic Hepatic Failure in Pigs as a Model for Bioartificial Liver Assessment

Purpose. A standard protocol of ischemic liver failure in pigs was examined to establish a system for assessing the efficacy of a bioartificial liver, based on clinical practice. Methods. The portal blood flow was extracorporeally bypassed into the cervical jugular vein, using a centrifugal blood pump. The portal vein and hepatic artery were then ligated. Results. The maintenance protocol was established as follows: (1) the concentration of the inhaled anesthetic was decreased by 0.2% when the systolic blood pressure was 100mmHg; (2) the volume of an infusion containing 5% glucose was increased to 10ml/kg per hour when central venous pressure was 5mmHg; (3) 20ml of 50% glucose was injected intravenously when the blood glucose was 50mg/dl; (4) 2000 units of heparin was injected intravenously when the activated clotting time was 150s; (5) sodium bicarbonate was given when the blood pH was 7.3; (6) tidal volume was increased by 1ml/kg when the pCO₂ was 80mmHg; (7) oxygen was increased by 25% when the pO₂ was 100mmHg. No vasopressors were used in the experiment. Conclusion. Our protocol reduced the operating time and minimized the risk of data deviation that can arise from variations in operating techniques and individual animal conditions. This experimental model is also easy to use as a bridge to transplantation.     

KB-R9032, newly developed Na<Superscript>+</Superscript>/H<Superscript>+</Superscript> exchange inhibitor,attenuates reperfusion-induced arrhythmias in isolated perfused rat heart

Purpose This study was conducted to elucidate the effects of KB-R9032, a newly developed Na⁺-H⁺ exchange inhibitor, on reperfusion-induced ventricular arrhythmia in the isolated perfused rat heart.Methods Male Wistar rat hearts (n = 48; 12 for each group) were perfused with modified Krebs-Ringers solution equilibrated with 5% carbon dioxide in oxygen by means of the Langendorff technique. An occluder was placed around the left anterior descending coronary artery (LAD). Heart rate, coronary flow, and ECG were monitored. Drug-free perfusate was used for 10min before switching to a perfusate containing various concentrations of KB-R9032. The added concentrations of KB-R9032 varied in the range of 0 (control) to 1 × 10^–5mol·l^–1. Each heart was subjected to regional ischemia (occlusion of LAD for 11min) and to 3min of reperfusion (release of the ligation).Results In the control group, reperfusion-induced ventricular fibrillation (VF) occurred in 91.7%, and the duration was 158.2 ± 14.4s (mean ± SEM); however, 1 × 10^–7, 1 × 10^–6, and 1 × 10^–5mol·l^–1 KB-R9032 reduced the incidence of VF to 75.0%, 42.9%, and 6.7%, respectively (P < 0.05 at 1 × 10^–5mol·l^–1 of KB-R9032) and reduced the duration of VF to 64.8 ± 22.1, 16.8 ± 10.1, and 1.2 ± 1.2s, respectively (P < 0.05 at 1 × 10^–6 and 1 × 10^–5mol·l^–1 of KB-R9032).Conclusion It was shown in this study that the Na⁺/H⁺ exchange inhibitor KB-R9032 suppresses reperfusion arrhythmias in the ischemia-reperfusion model of isolated rat heart.     

The effects of calcitonin on bone resorption in hyperthyroidism: a placebo-controlled clinical study

The effects of intranasal calcitonin on bone metabolism were investigated in patients with hyperthyroidism. Urinary deoxypyridinoline (uDPD) levels were measured as a bone turnover marker and lumbar spine (L2) bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 7 patients who were given only antithyroid drug (group 1), in 10 patients who were given antithyroid drug plus intranasal calcitonin (group 2), and in 10 healthy subjects who were given placebo (group 3) at the beginning and at the end of the study. The study continued until the patients with hyperthyroidism became euthyroidic according to the laboratory values. This period was approximately 3 months in groups 1 and 2. At the beginning of the study, uDPD was 21.5 ± 2.6nM DPD/mM creatinine in group 1, 23.3 ± 3.6nM DPD/mM creatinine in group 2, and 4.3 ± 1.2nM DPD/mM creatinine in group 3. uDPD levels measured in groups 1 and 2 were significantly higher than those in group 3 (P 0.001). Area BMD Z scores of the patients in groups 1 and 2 were significantly lower than the healthy controls (P 0.01, for both). At the end of the study, uDPD was 11.5 ± 1.6nM DPD/mM creatinine in group 1, 5.3 ± 0.6nM DPD/mM creatinine in group 2, and 4.4 ± 1.3nM DPD/mM creatinine in group 3. The levels of uDPD obtained in group 1 were significantly higher than those obtained in groups 2 and 3 (P 0.05, for both). The difference between groups 2 and 3 was not significant. Area BMD Z scores measured at the end of the study were found to be increased in groups 1 and 2 compared to early values, but the values were slightly lower than the normal values. In comparison of early and late uDPD values, the decrease in late period was statistically significant in groups 1 (P 0.05) and 2 (P 0.001). We concluded that bone turnover is high in hyperthyroidism. The treatment of hyperthyroidism decreases the rate of bone turnover, but it is not sufficient to prevent the degradation of bone in hyperthyroidism. The addition of intranasal calcitonin to the treatment of hyperthyroidism prevents the degradation of bone.     

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A

The levels of alpha-1 microglobulin ( ₁m) and beta-2 microglobulin ( ₂m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pretransplant levels, the highest levels of ₁m and ₂m were found during impairment of renal function, i.e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs (P<0.001). The ₁m levels were less elevated during infections and acute graft-versus-host disease (P<0.01), while ₂m levels were markedly elevated during the same conditions (P<0.001). The linear correlations between serum creatinine and ₁m and creatinine and ₂m were r=0.7 and 0.8, respectively (P<0.001). The overall correlation between ₁m and ₂m was 0.4 (P<0.001). It is concluded that ₁m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.     

A comparative study of coagulation effects on the cortex of the rat using Nd-YAG (1.32 μm), Nd-YAG (1.06 μm) and CO2 lasers

This paper represents a comparative study on brain tissue of three lasers: Nd-YAG (1.32m); Nd-YAG (1.06 m); and CO₂ laser. The experimental studies were performed on rats. They consisted of a comparison between the thermal effects and the consequent histological lesions produced. The surface temperature of the cortex induced by each laser shot was measured with an infrared camera. The results show that there exists an excellent correlation between surface temperature and the histology of the lesions produced. It appears that for equivalent surface temperatures the cortical lesions 8 days after irradiation were similar for Nd-YAG (1.32m) and for CO₂ lasers but significantly different for the Nd-YAG (1.06m) laser. For example the depth of coagulation necrosis varied between 20 to 250m with the CO₂ laser using the power of 3 to 10 W at an exposure of 0.05 s with a fluence of 5J/cm² and varied from 210 to 260m using the Nd-YAG (1.32m) with the power of 5 to 14 W with an exposure of 0.4 s with a fluence of 50–170 J/cm². With the Nd-YAG (1.06m) the depth of coagulation necrosis varied from 490m to 550m using a power of 12 to 19 W with an exposure of 0.4 s with a fluence of 150–250 J/cm². It would appear that the Nd-YAG laser at a wavelength of 1.32m should be valuable in neurosurgery as this wavelength is highly absorbed by brain parenchyma and is transmissible with a fibre optic delivery system.

---

Résumé Les auteurs presentent une étude comparative de la coagulation du parenchyme cérébral au moyen de différents lasers. Les études expérimentales ont été effectuées sur le cortex du rat. Elles ont consisté à comparer les effets thermiques et histologiques de 3 longueurs d'onde: Nd-YAG (1.32m), Nd-YAG (1.06m) et CO₂ (10.6m). La température corticale de surface induite par le tir laser a été mesurée au moyen d'une caméra infrarouge. Les courbes du profil thermique de chaque tir et de son évolution au cours du temps ont ainsi été obtenues. Les résultats montrent qu'il existe une excellente corrélation entre les données thermiques et les données histologiques recueillies pour chaque tir. Il apparaît ainsi que pour des augmentations de température équivalentes, les lésions corticales 8 jours après le tir sont similaires pour les lasers Nd-YAG (1.32m) et CO₂, mais significativement différentes pour le laser Nd-YAG (1.06m).Par exemple, le profondeur de nécrose varie entre 200 et 250m pour le laser CO₂ utilisé avec une puissance de 3 à 10 W, un temps d'exposition de 0.05 s et une fluence de 5 J/cm². La profondeur de nécrose varie entre 210m et 260m lorsqu'on utilise le laser Nd-YAG (1.32m) avec une puissance de 5 à 14 W, un temps d'exposition de 0.4 s et une fluence de 50 à 170 J/cm². Avec le laser Nd-YAG (1.06m), la profondeur de nécrose est beaucoup plus importante. Elle varie entre 490m et 550m pour une puissance comprise entre 12 et 19 W, un temps d'exposition de 0.4 s et une fluence de 150 à 250 J/cm².Ces résultats expérimentaux montrent que la longueur d'onde 1.32m est bien adaptée à la neurochirurgie puisqu'elle est bien asbsorbée par le parenchyme cérébral et qu'elle est transmissible par une fibre optique.

     

The distribution of extracellular matrix vesicles in healing of rat tibial bone three days after intramedullary injury

Summary The distribution of extracellular matrix vesicles on the third day of bone healing was studied by morphometric analysis of transmission electron micrographs. Detection and grouping of the vesicles was performed according to type, diameter, and distance from the calcified front. The different types were selected as follows: vesicles with electron-lucent contents (empty), vesicles with amorphous electron-opaque contents (amorphic), vesicles containing crystalline depositions (crystal), and vesicles containing crystalline structures with ruptured membranes (rupture). The majority of vesicles were between 0.07 µm and 0.12 m in diameter and were located at less than 3 m from the calcified front. The distribution of the empty, amorphic, crystal, and rupture vesicles was 23.2%, 74%, 2.5%, and 0.3% respectively. Their sequence of arrangement according to diameter was as follows: empty, amorphic, crystal, and rupture, the empty vesicles constituting the smallest and the rupture the largest type. Distances from the calcified front were similar for the empty, amorphic, and crystal vesicles, while the rupture type was located nearest to the front. The present observations support the widely acknowledged hypothesis on the role of extracellular matrix vesicles in mineralization. It is thought that the secretion of empty vesicles from the cell is followed by intravscular accumulation of amorphous Ca and Pi to form a hydroxyapatite crystal that, in turn, ruptures the vesicle's membrane. The maturation process is accompanied by an increase of the vesicular diameter and its approximation to the calcifying front.     

Integrin laminin receptors and breast carcinoma progression

This review explores the mechanistic basis of breast carcinoma progression by focusing on the contribution of integrins. Integrins are essential for progression not only for their ability to mediate physical interactions with extracellular matrices but also for their ability to regulate signaling pathways that control actin dynamics and cell movement, as well as for growth and survival. Our comments center on the 6 integrins (61 and 64), which are receptors for the laminin family of basement membrane components. Numerous studies have implicated these integrins in breast cancer progression and have provided a rationale for studying the mechanistic basis of their contribution to aggressive disease. Recent work by our group and others on mechanisms of breast carcinoma invasion and survival that are influenced by the 6 integrins are discussed.