Preoperative Chemoradiation for Extraperitoneal T3 Rectal Cancer: Acute Toxicity, Tumor Response, and Sphincter Preservation

Purpose: To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control.

Methods and Materials: Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m², Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m², Days 1–4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4–6 weeks after the end of chemoradiation.

Results: Total Grade 3–4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% [7] of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after the sphincter-saving procedure.

Conclusion: Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able to tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphincter preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate recorded, a more aggressive schedule should be applied in these resectable tumors.     

Discontinuation of tube feeding in young children by hunger provocation - a randomized controlled trial

Tijdschrift voor Kindergeneeskunde -     

Prostaglandins and angioplasty. An experimental study in canine arteries

To prevent platelet aggregation following percutaneous transluminal angioplasty (PTA), cyclooxygenase inhibitors such as acetylsalicylic acid (ASA) and indomethacin are recommended. However, ASA blocks both the proaggregating effects of thromboxane (TXA2) and the antiaggregating and vasodilating effects of prostacyclin (PGI2). The authors measured the contractile response of dilated canine carotid arteries in situ and in vitro using an isometric force transducer. Following PTA, contraction of the arterial wall was significantly reduced (p less than 0.01). By blocking cyclooxygenase with indomethacin (3 micrograms/ml), contraction was greatly improved (p less than 0.001). These results suggest that PTA may result in marked release of prostacyclin by the damaged arterial wall, which could account for the decreased responsiveness of the artery to exogenous norepinephrine.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Chemoradiation of Unresectable Pancreatic Carcinoma: Impact of Pretreatment Hemoglobin Level on Patterns of Failure

Aim: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. Patients and Methods: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m²/day, continuous i. v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs nC1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis (S 5 kg vs < 5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (< 40 mm vs S 40 mm). Results: Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hb h 11.5 g/dl and those with an Hb > 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb h 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0,010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb h 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb h 11.5 and > 11.5 g/dl; respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). Conclusion: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed between pretreatment Hb levels and metastasis-free survival, disease-free survival, and overall survival. Ziel: Ermittlung des Einflusses der Hämoglobinkonzentration vor Beginn einer Radiochemotherapie bei Patienten mit lokal fortgeschrittenem Pankreaskarzinom auf den Therapieerfolg anhand von klinischem Ansprechen, lokaler Kontrolle, metastasenfreiem Überleben, krankheitsfreiem Überleben und Gesamtüberleben. Patienten und Methoden: 30 Patienten, die Radiochemotherapie (5-FU, 1000 mg/m²/d, i. v. Dauerinfusion an den Tagen 1-4 der Strahlentherapie) und externe Strahlentherapie (50,4-59,4 Gy) erhielten, wurden, abhängig vom medianen Hämoglobinwert (11,5) in zwei Gruppen eingeteilt. Als weitere potentielle prognostische Faktoren wurden, neben der Hämoglobinkonzentration (Hb), Tumorlokalisation (Kopf/Korpus), Geschlecht (weiblich/männlich), Lymphknotenstatus (cN0/cN1), Dosierung der externen Strahlentherapie (50,4 Gy/59,4 Gy), Ikterus bei Diagnosestellung (ja/nein), Gewichtsverlust bei Diagnosestellung (S 5 kg/< 5 kg), epigastrisch-lumbaler Schmerz bei Diagnosestellung (ja/nein), maximaler Tumordurchmesser (< 40 mm/S 40 mm) geprüft. Ergebnisse: Die Hämoglobinkonzentration vor Therapiebeginn lag zwischen 9,6 and 15,0 g/dl. Es zeigten sich keine statistisch signifikanten Unterschiede hinsichtlich klinischem Ansprechen und lokaler Kontrolle zwischen Patienten mit Hb h 11,5 mit Hb > 11,5. Das metastasenfreie Überleben betrug 5,1 Monate bei Patienten mit Hb h 11,5 und 10,7 Monate bei Patienten mit Hb > 11,5 (p = 0,010). Das mediane krankheitsfreie Überleben betrug 5,1 und 10,2 Monate bei Patienten mit Hb h 11,5 bzw. Hb > 11,5 (p = 0,029: Das mediane Gesamtüberleben war 7,5 Monate und 10,3 Monate bei Patienten mit Hb h 11,5 bzw. > 11,5 (p = 0,039). Bei der multivariaten Analyse erwies sich die Hämoglobinkonzentration zum Diagnosezeitpunkt als der einzige prognostische Faktor, der mit dem metastasenfreien Überleben (p = 0,026), dem krankheitsfreien Überleben (p = 0,032) und dem Gesamtüberleben (p = 0,048) korrelierte. Schlussfolgerungen: In einer Patientengruppe, die wegen lokal fortgeschrittener Pankreaskarzinome Radiochemotherapie erhielt, wurde eine signifikante Korrelation zwischen dem Hämoglobinspiegel vor Therapiebeginn und metastasenfreiem Überleben, krankheitsfreiem Überleben und Gesamtüberleben beobachtet.     

Biophysical characteristics of skin in diabetes: a controlled study

Background  Cutaneous complications are common in diabetes. Previous assays suggest that hyperglycemia and decreased insulin signal are involved in the impairment of skin function. The aim of this study was to evaluate the biophysical characteristics of skin in patients with diabetes mellitus and compares them with healthy non-diabetic controls.
Objective  To measure biophysical characteristic of skin including transepidermal water loss (TEWL), water content, sebum and skin elasticity in patients with diabetes mellitus and compare them with healthy non-diabetic controls.
Methods  This case-control study was conducted on 38 patients with diabetes and 40 age- and sex-matched healthy people. The biophysical properties of skin including stratum corneum (SC) hydration, sebum content, TEWL and skin elasticity were measured and compared between the two groups at three different locations of the body.
Results  The measurement of SC hydration and TEWL showed no significant difference between diabetics and controls. The skin surface lipids on the forehead but not other sites were significantly lower in the diabetics than in the controls. Acoustic wave propagation speed, a measurement related to skin elasticity, was significantly lower in forearm and forehead of diabetics.
Conclusion  Diabetes affects some functional properties of epidermis and dermis that may responsible for many cutaneous manifestations of diabetes. These results suggest that patients with diabetes mellitus tend to show a normal hydration state of the SC together with decreased sebaceous gland activity and impaired skin elasticity, without any impairment of the SC barrier function.

Conflicts of interest

None declared     

Study of gamma-GTP activity in urine and renal tissue of experimental warm ischemic kidney

The acute changes of proximal tubule function and its pathological condition were investigated by measuring (gamma-GTP) activities in the urine and renal tissue using warm ischemic kidneys of adult dogs (n = 34). Eight kidneys were kept in a warm ischemic condition throughout the experimental period and the tissue was extirpated from the kidney at every hour, and 31 kidneys were released from the 30 min ischemic condition. The urine and the blood (peripheral and renal artery and vein) were collected from these kidneys at every hour up to 5 hr. The kidneys observed for urine outflow (n = 24) were divided into three groups with time; 7 kidneys (1 hr), 5 kidneys (3 hr), and 12 kidneys (5 hr), and they were extracted. The gamma-GTP activity of the urine showed the maximum value of 851 +/- 102 mIU/ml at 30 min and decreased to 217 +/- 56 mIU/ml, which declined to be close to the starting value of 133 +/- 26 mIU/ml, at 5 hr after the warm ischemic condition was released. The gamma-GTP activities of the cortex were 325 +/- 62 mIU/mg.p (1 hr), 527 +/- 37 mIU/mg.p (3 hr), and 266 +/- 44 mIU/mg.p (5 hr). However, no increase in gamma-GTP activity was observed either in the renal vein blood, or in the cortex obtained from the 8 kidneys kept in the warm ischemic condition. A histopathological examination showed the progressive changes in some parts of the proximal tubules after release from the ischemic condition.(ABSTRACT TRUNCATED AT 250 WORDS)