bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of cytotoxic granules in the apoptosis of aplastic anaemia
Authors: Xu J. L. , Nagasaka T. , Nakashima N.
Published: March 2003

Summary. To study the involvement of cytotoxic granules in apoptosis of aplastic anaemia (AA), we analysed bone marrow clot sections of AA for apoptosis and perforin, granzyme B and T‐cell intracellular antigen‐1 (TIA‐1) expression. Perforin, TIA‐1 expression and apoptosis were significantly increased in AA patients compared with control subjects, but granzyme B was not. TIA‐1 was significantly correlated with apoptotic cells of AA. No correlation was found between perforin and apoptotic cells of AA. These results suggest that perforin and TIA‐1 play a role in the pathogenesis of AA. TIA‐1 is implicated as an effector in the apoptosis of AA.
Neutropenia and anaemia associated with T‐cell large granular lymphocyte leukaemia responds to fludarabine with minimal toxicity
Authors: Sternberg Alexander , Eagleton Helen , Pillai Nithiya , Leyden Kevin , Turner Susan , Pearson Danita , Littlewood Timothy , Hatton Chris
Published: March 2003

Summary. T‐cell large granular lymphocyte leukaemia (T‐LGL) is a clonal disorder of T cells associated with neutropenia and anaemia. The clinical consequences are recurrent infections and transfusion dependence. The optimum treatment for severely affected patients remains to be defined. Current therapies require long‐term administration to maintain an effect. We report the reversal of severe neutropenia and/or anaemia in four patients treated with fludarabine which has been maintained since stopping treatment. The therapeutic side‐effects were restricted to one episode of fever not associated with neutropenia. We conclude that fludarabine is effective in T‐LGL, may be given safely despite severe neutropenia and induces durable treatment‐free remissions.
Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients
Authors: Parry‐Jones Nilima , Matutes Estella , Gruszka‐Westwood Alicja M. , Swansbury G. John , Wotherspoon Andrew C. , Catovsky Daniel
Published: March 2003

Summary. Splenic lymphoma with villous lymphocytes (SLVL) is a low‐grade B‐cell lymphoma defined in the World Health Organization classification as the leukaemic form of splenic marginal zone lymphoma. Presenting features and response to therapy have been described, but information on prognostic factors is scanty. Clinical, laboratory and follow‐up data were collected on 129 patients with SLVL to determine features predicting disease behaviour and survival. Diagnosis was made on clinical, morphological and immunophenotypic features and, where available, bone marrow and spleen histology. Median age was 69 years (range 39–90 years) and male:female ratio, 0·9. The majority had splenomegaly, but lymphadenopathy and hepatomegaly were rare. Median Hb was 11·8 g/dl, white blood cell count was 16 × 109/l and platelet count was 145 × 109/l; 27% of patients had monoclonal protein in serum and/or urine. While 27% of patients remained untreated, 10% transformed to high‐grade lymphoma. Median follow‐up was 61 months and median survival was 13 years, with 72% of patients alive at 5 years. Cox regression analysis showed that increasing age, anaemia, thrombocytopenia and lymphocytosis > 16 × 109/l were independent adverse predictors of overall survival. However, only anaemia and lymphocytosis > 16 × 109/l remained highly significant independent prognostic factors when only deaths due to lymphoma were analysed. Splenectomized patients fared better than those receiving chemotherapy only (P = 0·001 for SLVL deaths). We conclude that SLVL is mainly a disease of the elderly with a relatively benign course but, when treatment is required, splenectomy is beneficial.
Acute basophilic leukaemia: eight unsuspected new cases diagnosed by electron microscopy
Authors: Shvidel Lev , Shaft Dina , Stark Batia , Shtalrid Mordechai , Berrebi Alain , Resnitzky Peretz
Published: March 2003

Summary. We report eight new patients with de novo acute basophilic leukaemia (ABL) diagnosed by electron microscopy (EM) in 184 patients with poorly differentiated AML who were selected for ultrastructural analysis between the years 1989 and 2002. Morphology by light microscopy, cytochemistry, immunophenotyping and cytogenetics did not enable an accurate diagnosis in any of these patients. In almost all the patients, the blasts showed reactivity for HLA‐DR and CD34. EM studies demonstrated the presence of basophilic granules in the leukaemic blasts. These granules were membrane bound and their contents varied in appearance from uniformly electron dense to partially speckled or electron lucent. Theta granules were present in only three patients and no mast‐cell type granules were observed. By light microscopy, the myeloperoxidase reaction was positive in three patients in an unusual coarse granular pattern. Ultrastructural demonstration of peroxidase in the granules, nuclear membrane and profiles of endoplasmic reticulum was observed in all eight patients. The reaction in the granules showed a particular speckled pattern. The outcome was unfavourable in six of our eight patients. As a definitive diagnosis of ABL may be made only by EM, we suggest including such studies as an integral part of the diagnostic work‐up of acute leukaemia cases that lack differentiation markers.
Adrenal-sparing surgery for phaeochromocytoma
Authors: Neumann H P H , Bender B U , Reincke M , Eggstein S , Laubenberger J , Kirste G
Published: March 2003

Background

Adrenalectomy is the current treatment for phaeochromocytoma. Consequently, patients with bilateral adrenal phaeochromocytoma become steroid dependent. An adrenal-sparing surgical technique was introduced in 1985. The results of this treatment have been reviewed.

Methods

Since 1985, 39 patients with adrenal phaeochromocytoma (16 men and 23 women, aged 10–76 years) have been treated. Thirty-three patients had unilateral and six had bilateral phaeochromocytomas. Seven of the former 33 had a contralateral adrenal tumour resected previously. All 39 patients were re-evaluated biochemically and clinically for ipsilateral recurrence.

Results

Adrenal-sparing surgery was performed successfully in 37 of the 39 patients. In one, adrenal-sparing resection was impossible anatomically and total adrenalectomy was necessary. Another patient with bilateral tumours had retroperitoneal haemorrhage and became steroid dependent. None of the remaining 12 patients who had bilateral adrenal surgery required steroid replacement. Adrenocortical function was normal in eight and mildly impaired in two of the ten patients who had evaluation by adrenocorticotrophic hormone stimulation. After a mean follow-up of 73 months, one patient with von Hippel–Lindau disease developed a recurrence in the ipsilateral adrenal gland. Genetic testing revealed that 26 of the 39 patients, including half of those with a unilateral tumour, had hereditary phaeochromocytoma.

Conclusion

Adrenal-sparing surgery is safe and effective, and may become the treatment of choice in patients with hereditary phaeochromocytoma.
Audit of methods of laparoscopic cholecystectomy
Authors: Chitre V V , Studley J G N
Published: March 2003

Background

The operation of laparoscopic cholecystectomy began the modern era of laparoscopic surgery. Refinements in technique continue to appear. The techniques currently favoured by British surgeons have been reviewed.

Methods

A questionnaire-based survey was carried out among surgeons with a special interest in minimal access surgery. The data collected were entered into a database and analysed. Current literature relating to surgical technique was reviewed.

Results

Many aspects were evaluated and the results have shown that there is no uniform approach. It is interesting that only 30·8 per cent of surgeons use the open (Hasson) technique for peritoneal access. In addition, the use of intraoperative cholangiography continues to vary, with 65·8 per cent using the technique in selected cases. Fascial repair is not undertaken by 12·2 per cent of surgeons.

Conclusion

Some trends are clearly discernible. There is a greater willingness than previously to perform intraoperative cholangiography, but the consensus seems to be against performing it in all cases. Similarly, British surgeons seem to be largely unimpressed by the dangers of the Veress needle; the Hasson technique has not been widely adopted. The need to prevent port-site herniation seems to be generally accepted, with most surgeons performing fascial repair.
Outcome of primary radiocephalic fistula for haemodialysis
Authors: Golledge J , Smith C J , Emery J , Farrington K , Thompson H H
Published: March 2003

Background

Patient characteristics may help select the most appropriate type of permanent vascular access for haemodialysis. The aim of this study was to assess the influence of patient-related variables on the outcome of radiocephalic fistulas.

Methods

Over 3 years 107 consecutive patients underwent formation of a radiocephalic fistula for permanent haemodialysis access. Patients receiving prosthetic, ulnar, brachial or secondary fistulas were excluded. Patients were followed prospectively until access failure, transplantation or death, or for a minimum of 6 months (median follow-up 24 months).

Results

Primary patency was 69 per cent at 12 months and 56 per cent at 24 months. Endovascular and surgical intervention led to limited improvement in secondary patency to 63 per cent at 24 months. Regression analysis showed that fistula failure was more common in women (P = 0·02), diabetics (P = 0·03) and young patients (P = 0·02). By life-table analysis, primary and secondary patency were significantly better (P = 0·01) for men and non-diabetics, while the outcome was similar for all age groups.

Conclusion

One-third of radiocephalic fistulas fail irreversibly within 2 years. Failure is more likely in women and diabetic patients.
Treatment of colorectal liver metastases
Authors: Geoghegan J G , Scheele J
Published: March 2003

Background

Surgical resection is the only potentially curative treatment for colorectal liver metastases, with 5-year survival rates approaching 40 per cent. However, at present only 20–25 per cent of such lesions are deemed resectable. This review examines developments in neoadjuvant and adjuvant treatments of colorectal liver metastases that aim to improve the results of surgical management of this disease.

Methods

A literature review was undertaken based on a Medline search from 1970 to May 1998.

Results

Further evolution in surgical technique is unlikely to lead to a dramatic increase in the resectability rate of colorectal liver metastases. Recent developments in neoadjuvant and adjuvant chemotherapy schedules, together with a range of interventional radiological procedures and interstitial lytic techniques, show promise in terms of extending the limits of resectability and decreasing recurrence rates associated with these lesions. Using multimodality regimens 5-year survival rates of 40 per cent are now being reported for lesions that were initially considered irresectable.

Conclusion

Patients with colorectal liver metastases should be assessed in units that can offer all the specialist techniques necessary to deliver optimum care. Incorporation of newer neoadjuvant and adjuvant treatments into management strategies should occur in the setting of randomized trials.
Evaluation of positron emission tomography with 2-[18F]fluoro-2-deoxy-d-glucose for the differentiation of chronic pancreatitis and pancreatic cancer
Authors: Imdahl A , Nitzsche E , Krautmann F , Högerle S , Boos S , Einert A , Sontheimer J , Farthmann E H
Published: March 2003

Background

The clinical presentation of patients with pancreatic cancer may resemble the clinical picture of chronic pancreatitis. A definitive preoperative diagnosis is not always obtained in patients with a history of chronic pancreatitis despite the use of modern imaging techniques. Operative strategy therefore remains unclear before operation in these patients.

Methods

Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-d-glucose (FDG) was introduced recently into clinical oncology because of its ability to demonstrate metabolic changes associated with various disease processes. The impact of FDG-PET on the differentiation of chronic pancreatitis and pancreatic cancer was investigated. FDG-PET was performed in 48 patients with chronic pancreatitis (n = 12), acute pancreatitis (n = 3) and pancreatic cancer (n = 27), and in controls (n = 6). Histological examination was undertaken in all cases except controls. The FDG-PET results were obtained without knowledge of results of other imaging procedures. The results were then compared with those of computed tomography, ultrasonography, endoscopic retrograde cholangiopancreaticography, operative findings and histology. PET images were analysed semiquantitatively by calculating a standard uptake value (SUV) 90 –120 min after application of the tracer.

Results

Cut-off values were validated as follows: SUV greater than 4·0 for pancreatic cancer, SUV of 3·0 – 4·0 for chronic pancreatitis, and SUV of less than 3·0 for controls. Sensitivity and specificity of PET imaging were 0·96 and 1·0 for pancreatic cancer, and 1·0 and 0·97 for chronic pancreatitis. In five cases only FDG-PET led to the correct preoperative diagnosis.

Conclusion

The results give further evidence that FDG-PET is an important non-invasive method for the differentiation of chronic pancreatitis and pancreatic cancer. Delayed image acquisition in the glycolysis plateau phase permits improved diagnostic performance. This imaging technique is extremely helpful before operation in patients with an otherwise unclear pancreatic mass, despite its costs.
Three-dimensional endoanal sonography in assessing anal canal injury
Authors: Gold D M , Bartram C I , Halligan S , Humphries K N , Kamm M A , Kmiot W A
Published: March 2003

Background

Instrument design limits endosonography of the anal canal to the axial plane, with no capability for longitudinal imaging or measurement. Using three-dimensional reconstructions, the relationship between the radial and linear extent of an anal sphincter tear has been explored, and sex differences in anal canal and sphincter length have been established.

Methods

Three-dimensional reconstructions were performed in 20 controls and 24 patients with faecal incontinence found to have 25 external and five internal sphincter defects. The radial and linear extent of any sphincter tear was measured. In controls the length of the sphincters was compared with the total anal canal length, and the maximum and mean internal sphincter thickness was compared.

Results

The radial angle of an internal or external sphincter defect was significantly related to its length (R2 = 96·8 per cent and R2 = 84·4 per cent respectively; both P< 0·001). The anal canal was longer in men than in women (mean(s.d.) 32·6(5·3) versus 25·1(3·4) mm; P< 0·001). The internal anal sphincter was also longer in men (25·6(6·3) versus 19·8(4·0) mm; P< 0·02), but the mean internal sphincter length as a percentage of total anal canal length did not differ (78·3 versus 78·7 per cent; P not significant). The anterior external anal sphincter was longer in men than in women (32·6(5·3) versus 15·3(2·8) mm; P< 0·001), and formed a greater percentage of total anal canal length (100 versus 62·9 per cent; P< 0·001).

Conclusion

Multiplanar imaging has revealed a direct relationship between the length of a sphincter tear and its radial extent as shown on axial scanning. Marked sex differences in sphincter configuration have been demonstrated. In women the shorter anterior sphincter length highlights the risk of complete sphincter disruption with extensive tears.
Evaluation of pylorus-preserving pancreatoduodenectomy with the Imanaga reconstruction by hepatobiliary and gastrointestinal dual scintigraphy
Authors: Hishinuma S , Ogata Y , Matsui J , Ozawa I
Published: March 2003

Background

Following pylorus-preserving pancreatoduodenectomy (PPPD), most surgeons use gastrointestinal reconstruction with an end-to-side duodenojejunostomy placed distally to the pancreatojejunostomy and choledochojejunostomy. In contrast, the authors have consistently used PPPD with the Imanaga reconstruction (PPPD-Imanaga) which consists of end-to-end duodenojejunostomy, end-to-side pancreatojejunostomy and choledochojejunostomy, performed in that order. In this study, the movement of bile and food after PPPD-Imanaga was evaluated to document the functional advantages of this method.

Methods

Twenty-four patients who had undergone PPPD-Imanaga were subjected to hepatobiliary and gastrointestinal dual scintigraphy. The interval between operation and scintigraphy ranged from 28 days to 67 months. Six of the 24 patients underwent repeated dual scintigraphy for the observation of temporal changes in gastrointestinal function.

Results

The incidence of biliogastric reflux and bile stasis in the jejunal loop was markedly decreased at times later than 2 months after operation. Delay of gastric emptying and bile evacuation, sometimes accompanied by stasis in the jejunal loop, affected the mixing status of bile and food at 1 h after the beginning of imaging. A majority of the patients, however, had a satisfactory mixing status at 2 h.

Conclusion

The Imanaga reconstruction appears to be a recommendable procedure following PPPD, in light of the bile and food movement achieved in the gastrointestinal tract.
Surgery may be curative for patients with a localized perforation of rectal carcinoma
Authors: Kagda F H Y , Nyam D C N K , Ho Y H , Eu K W , Leong A F P K , Seow-Choen F
Published: March 2003

Background

Perforation at the time of operation adversely affects the prognosis of rectal cancer. These procedures have been termed ‘palliative’ or ‘non-curative’. The long-term outcome of generalized perforations may be different from that of localized or contained perforations. Although the oncological results may be compromised when the tumour is perforated, results in cases where the perforation is contained may not be as bad as previously thought. An attempt was made to examine the intermediate and long-term results for locally contained perforated rectal cancers.

Methods

Some 848 patients with rectal cancer were operated on between March 1989 and December 1995. Of these, 42 (5 per cent) had a locally contained perforation of the rectum. Median follow-up was 23 (range 12–74) months.

Results

The survival of patients with locally contained tumour perforation who underwent resection without macroscopic residual disease (40 per cent at 5 years) was significantly better than that of patients with metastatic disease at the time of surgery (zero at 4 years) (P < 0·01). The survival of patients in whom the tumour was inadvertently perforated during operation was similar to that of patients with locally contained spontaneous tumour perforations. The incidence of local recurrence in these perforated cases was low provided that a wide tumour clearance was achievable at the time of operation. Operative mortality and morbidity rates were not significantly different but the incidence of postoperative wound infection was marginally higher among patients with perforation.

Conclusion

If clear margins can be obtained at the time of operation the prognosis of locally contained perforated rectal cancers is good and approaches that of a potentially curative resection.
Laparoscopy extends the indications for liver resection in patients with cirrhosis
Authors: Abdel-Atty M Y , Farges O , Jagot P , Belghiti J
Published: March 2003

Background

Clinical or biological evidence of liver failure is usually considered a contraindication to open liver surgery as it is associated with a prohibitive risk of postoperative death.

Methods

This report describes three patients who had resection of a superficial hepatocellular carcinoma suspected either to be ruptured, or at high risk of rupture, using the laparoscopic approach. All three patients had intractable ascites, in two superimposed on active hepatitis. Surgery was per- formed under continuous carbon dioxide pneumoperitoneum with intermittent clamping of the hepatic pedicle.

Results

Intraoperative blood loss was between 100 and 400 ml; no blood transfusion was required. The postoperative course was uneventful except for a transient leak of ascites through the trocar wounds. Duration of in-hospital stay was 6–10 days. Liver function tests had returned to preoperative values within 1 month of surgery in all patients.

Conclusion

The laparoscopic approach may enable liver resection in patients with cirrhosis and evidence of liver failure that would contraindicate open surgery.
Oral nifedipine reduces resting anal pressure and heals chronic anal fissure
Authors: Cook T A , Humphreys M M Smilgin , Mortensen N J McC
Published: March 2003

Background

Topical preparations have been used in the treatment of anal fissure. However, they are not universally successful and there is confusion over the site and dose of application. This study assessed the effectiveness of oral nifedipine in reducing resting anal pressure and on fissure healing.

Methods

Anal manometry was performed on eight healthy volunteers and 15 patients with chronic anal fissure before and after oral administration of nifedipine 20 mg. Nifedipine was taken twice daily. Fissure healing was assessed over an 8-week period and pain scores were monitored.

Results

Oral nifedipine produced an initial reduction in maximum resting anal pressure (MRP) of 35 per cent (P < 0·001) and of 28 per cent after 5 days (P < 0·001) in healthy volunteers. A reduction in MRP of 36 per cent (P < 0·001) was observed in patients with fissure. Pain scores were significantly reduced during the treatment period. Healing was complete in nine patients after 8 weeks and a further three were asymptomatic. Ten patients experience flushing and four had mild headaches. There were no episodes of postural hypotension or incontinence.

Conclusion

Oral nifedipine reduces resting anal pressure. It is well tolerated and offers an alternative treatment for chronic anal fissure.
Emerging trends in the management of the impalpable testis
Authors: Flett M E , Jones P F , Youngson G G
Published: March 2003

Background

The management of the impalpable undescended testis is controversial. The study examines emerging trends in the management of this problem.

Methods

Two groups of boys were treated consecutively and recorded prospectively from 1974 to 1984 and from 1990 to 1998 inclusive. A consistent policy of using the preperitoneal approach for impalpable testis was adopted during both time intervals but during the second study period examination under anaesthesia and diagnostic laparoscopy were introduced to ascertain testicular presence and location.

Results

Some 919 boys were treated for cryptorchidism during the study period. Ninety boys in the first group (23 per cent) underwent preperitoneal explorations for impalpable testes. Anorchia was present in 18 and orchidectomy was performed in two boys. Thirty boys in the later group (5 per cent) were diagnosed as having impalpable testes. Fifteen boys underwent successful preperitoneal orchidopexy, anorchia was present in 11 and four underwent orchidectomy, carried out for high intra-abdominal testes.

Conclusion

Examination under anaesthesia and subsequent laparoscopic assessment for all impalpable testes has reduced the need for preperitoneal exploration for the impalpable undescended testis. In this large series, division of the testicular vessels in order to secure scrotal placement of the testis was required in one instance only.
Endoscopically assisted, minimally invasive parathyroidectomy
Authors: Gauger P G , Reeve T S , Delbridge L W
Published: March 2003

Background

Despite the success of open parathyroid exploration, minimally invasive alternatives have been emerging. This study reports an experience with endoscopically assisted, minimally invasive parathyroidectomy and evaluates its current role in patients undergoing surgery for hyperparathyroidism.

Methods

One hundred consecutive patients requiring surgery for hyperparathyroidism were evaluated. Endoscopic parathyroidectomy was offered based on the absence of coexisting nodular thyroid disease, previous neck surgery or irradiation, suspicion of parathyroid hyperplasia, or other anatomical or medical contraindications. Some 24 of 100 patients fulfilled the criteria and underwent endoscopic parathyroidectomy. Unequivocal localization to a single site by a technetium-99m-radiolabelled sestamibi scan allowed removal of the adenoma through a 25-mm suprasternal incision while being guided by a surgical telescope.

Results

There were no statistically significant differences in operating time or the mean size of resected adenomas between patients undergoing endoscopic and open parathyroidectomy. Four patients required conversion to an open procedure. Two patients developed temporary recurrent laryngeal nerve paresis and one had persistent hyperparathyroidism.

Conclusion

Although endoscopic parathyroidectomy is technically feasible, its applicability is limited to a minority of patients undergoing operation for hyperparathyroidism. The potential for higher complication and failure rates makes optimism for the procedure appropriately guarded.
Long-term results of a randomized clinical trial between laparoscopic hernioplasty and Shouldice repair
Authors: Leibl B J , Däubler P , Schmedt C-G , Kraft K , Bittner R
Published: March 2003

Background

At present only short-term follow-up data are available to compare endoscopic and conventional hernia surgery. This paper presents data from a randomized study 6 years after initial recruitment.

Methods

In 1993 a randomized comparative study of transabdominal preperitoneal (TAPP) and Shouldice repair was commenced. Endpoints were rate of recurrence, late complications, complaints and patient satisfaction.

Results

The rate of recurrence in the TAPP group was one (2 per cent) of 48 patients and in the Shouldice group two (5 per cent) of 43. Only five patients in the Shouldice and three in the TAPP group reported slight discomfort in the inguinal region at 6-year follow-up. In neither group was chronic pain syndrome observed. Altogether, 46 (96 per cent) of 48 patients in the TAPP group and 35 (81 per cent) of 43 of those having the Shouldice procedure stated complete satisfaction with the hernia repair.

Conclusion

Long-term evaluation demonstrated greater satisfaction with the result of the repair in the endoscopic group. The difference between the groups in the recurrence rate was not significant, because of the small numbers. The TAPP method appears to be an effective surgical alternative in patients with inguinal hernia.
Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids
Authors: Misra M C , Parshad R
Published: March 2003

Background

Patients with acute bleeding from internal haemorrhoids often have to be referred by the general practitioner to the surgeon for definitive treatment with invasive outpatient procedures. At the initial consultation, patients frequently seek postponement of immediate surgery to a more convenient time. Effective and rapid non-invasive control of acute bleeding could be of practical use in scheduling surgery to a time convenient to both patient and surgeon.

Methods

In a 90-day randomized, double-blind study treatment with a micronized purified flavonoid fraction (MPFF) was compared with placebo, in 100 outpatients who presented for treatment of acute internal haemorrhoids of less than 3 days' duration. The primary endpoint was cessation of bleeding on the third day of treatment.

Results

Of 50 patients randomized to each group, acute bleeding ceased by the third day in 40 (80 per cent) who received MPFF compared with 19 (38 per cent) who had placebo (P < 0·01). Mean(s.d.) duration of acute bleeding from onset to cessation of 4·9(1·6) days was 2·1 (95 per cent confidence interval 1·2–2·9) days less than that in patients receiving placebo (P < 0·01). Continued treatment in patients with no bleeding prevented a relapse in 30 of 47 patients, compared with 12 of 30 receiving placebo (P < 0·05).

Conclusion

Patients with acute internal haemorrhoids treated with MPFF had rapid cessation of bleeding and a reduced risk of relapse. This could be of value in the more convenient timing of treatment with invasive outpatient procedures.
Perioperative blood transfusions, with or without allogeneic leucocytes, relate to survival, not to cancer recurrence
Authors: van de Watering L M G , Brand A , Houbiers J G A , Klein Kranenbarg W M , Hermans J , van de Velde C J H
Published: March 2003

Background

Perioperative blood transfusions are reported to be related to cancer recurrence and reduced survival. Different underlying mechanisms have been proposed, and allogeneic leucocytes in transfused blood have been suggested to contribute to this phenomenon.

Methods

Packed red cells without buffy coat (PC group) were compared with filtered, leucoreduced, red cells (LD group) in a randomized trial of 697 patients with colorectal carcinoma. Five-year survival and cancer recurrence rates were determined, with special emphasis on the location of recurrence.

Results

The intention-to-treat analysis showed a survival rate of 63·6 per cent in the PC group and 65·3 per cent in the LD group (P = 0·69), with recurrence rates of 27·8 and 27·9 per cent respectively. The observational analysis showed a significant difference in survival between transfused and non-transfused patients (59·6 versus 72·9 per cent; P < 0·001). The difference in cancer recurrence rate between transfused and non-transfused patients was not statistically significant (29·8 versus 24·3 per cent; P = 0·13). Local recurrences were more frequent in transfused than non-transfused patients (11·9 versus 7·6 per cent; P = 0·09).

Conclusion

Leucocyte depletion of perioperative transfused blood has no effect on long-term survival and/or cancer recurrence. Perioperative blood transfusions are associated with impaired survival, but not with cancer recurrence. The slight increase in local recurrence rate in transfused patients appears to be related to complicated, in particular rectal, surgery.
Electrolytic ablation as an adjunct to liver resection: experimental studies of predictability and safety
Authors: Wemyss-Holden S A , Dennison A R , Finch G J , de la M Hall P , Maddern G J
Published: March 2003

Background

Combined liver resection and local ablation may offer the only chance of cure to patients with liver metastases who are presently deemed unresectable because of a single awkwardly placed metastasis. By definition, such a metastasis is often close to a major vein. An ablative technique is needed that is both predictable and safe in such a circumstance.

Methods

Electrolytic liver lesions were created in 21 pigs using platinum electrodes, connected to a direct current generator. Both electrolytic ‘dose’ and electrode separation were varied to produce different sized lesions. The ‘dose’ was correlated with the volume of necrosis and any vascular damage was determined histologically.

Results

There was a significant (P < 0·001) correlation between the electrolytic ‘dose’ and the volume of liver necrosis. For a given ‘dose’ the volume of necrosis was less when the electrodes were together, rather than separated. Liver enzymes were only transiently deranged. There were no significant vascular injuries.

Conclusion

Predictable and reproducible necrosis is produced by electrolysis in the pig liver. The treatment appears to cause little or no damage to immediately adjacent liver or major vascular structures and, when combined with resection, may offer the chance of a cure to many patients who are currently unresectable.
Effect of venous ulcer exudates on angiogenesis in vitro
Authors: Drinkwater S L , Smith A , Sawyer B M , Burnand K G
Published: March 2003

Background

Angiogenesis, the formation of new from existing capillaries, is an important mechanism in venous ulcer healing. The aim of this study was to determine whether venous leg ulcer wound exudates stimulate or inhibit angiogenesis.

Methods

Fluid exudate was obtained from 16 venous ulcers over a 4-h interval. Five of the ulcers had not healed after more than 1 year of compression bandaging, and five were rapidly healing ulcers. As a control, acute wound fluids were collected from subcutaneous drains in seven patients. Vascular endothelial growth factor (VEGF) at 2 ng/ml acted as a positive control. Tubules stained with an antiendothelial antibody were quantified using an image analysis system. The extent of angiogenesis was expressed as the ratio of the mean tubule length in the test wells over that in blank control wells.

Results

Venous ulcer exudates significantly inhibited angiogenesis (mean (95 per cent confidence interval) 0·72 (0·48 to 0·96)) compared with acute wound fluids (2·48 (0·86 to 4·10)) (P < 0·002) and VEGF (1·47 (1·32 to 1·61)) (P = 0·01). Exudates from the five non-healing venous ulcers inhibited angiogenesis (0·31 (0·15 to 0·46)) significantly more than exudates from the five rapidly healing venous ulcers (0·93 (0·21 to 1·65)) (P = 0·03).

Conclusion

Fluid exudate from venous ulcers, in particular those that healed slowly, inhibited experimental angiogenesis in this study.
The colorectal adenoma–carcinoma sequence
Authors: Leslie A , Carey F A , Pratt N R , Steele R J C
Published: March 2003

Background

It is widely accepted that the adenoma–carcinoma sequence represents the process by which most, if not all, colorectal cancers arise. The evidence supporting this hypothesis has increased rapidly in recent years and the purpose of this article is to review this evidence critically and highlight its clinical significance.

Methods

Medline searches were used to identify recent key articles relating to the adenoma–carcinoma sequence. Further pertinent articles were obtained by manual scanning of the reference lists of identified papers.

Results

The evidence supporting the adenoma–carcinoma sequence can be classified as epidemiological, clinicopathological and genetic. The most recent and largest body of data relates to molecular genetic events and their cellular effects; however, many other approaches, such as cytogenetics, molecular cytogenetics and cytometry, have also yielded valuable information.

Conclusion

Recent work continues to support the adenoma–carcinoma sequence, but there is a paucity of data on the interrelationship between different genetic mutations and on the relationship between molecular and other types of genetic abnormalities. The clinical utility of the observations described has yet to be fully realized and global genetic analysis of colorectal tumours may prove to be central in rational adenoma management.
Cohort study in South and West England of the influence of specialization on the management and outcome of patients with oesophageal and gastric cancers
Authors: Bachmann M O , Alderson D , Edwards D , Wotton S , Bedford C , Peters T J , Harvey I M
Published: March 2003

Background

To evaluate specialization in National Health Service (NHS) cancer care, volume–outcome relationships were examined.

Methods

This was a cohort study of 1512 patients with oesophageal or gastric cancer in 23 acute NHS hospitals. Outcomes were survival time and operative (30 day) mortality. Multiple regression analysis was performed, adjusted for diagnoses, prognoses and treatments.

Results

For oesophageal cancer, the operative mortality rate decreased by 40 per cent (odds ratio 0·60 (95 per cent confidence interval (c.i.) 0·36 to 0·99 per cent); P = 0·047) for each increase of ten patients in doctors' annual surgical caseloads, and the risk of death decreased by 8 per cent (hazard ratio 0·92 (95 per cent c.i. 0·85 to 0·99); P = 0·021) for each increase of ten patients in doctors' annual caseloads. For gastric cancer, the operative mortality rate decreased by 41 per cent (odds ratio 0·59 (95 per cent c.i. 0·32 to 1·07)) for each increase of ten patients in doctors' annual surgical caseloads, and the risk of death decreased by 7 per cent (hazard ratio 0·93 (95 per cent c.i. 0·89 to 0·98); P = 0·009) for each increase of ten patients in hospitals' annual caseloads. Patients of higher-volume doctors were more likely to receive most investigations and treatments, independently of presenting features.

Conclusion

The study supports concentration of services for oesophageal and gastric cancers. Specialization of doctors and their teams is at least as important as specialization of hospitals.
Identifying patients for blood conservation strategies
Authors: van Klei W A , Rheineck Leyssius A T , Grobbee D E , Moons K G M
Published: March 2003

Background

Generally, only the type of operation is used to estimate the need for perioperative homologous blood transfusion. This study quantified the extent to which the estimation could be improved if, in addition, simple patient characteristics were taken into account.

Methods

Retrospective data on 24 509 consecutive adult surgical patients were used to derive and validate three models to predict perioperative homologous transfusion. The first model was a univariable model with type of operation as the only predictor. The second and third models were a full and a simplified multivariable logistic regression model. The performance of the multivariable models was tested in two validation sets: in similar patients who had operations in the same general hospital (internal validation) and in patients who had operations in a university hospital (external validation). The areas under the receiver–operator characteristic (ROC) curve were compared with that found in the derivation set.

Results

There were no important differences in characteristics between the derivation and validation sets. The ROC area of the model including surgery only was 0·92 (99 per cent confidence interval (c.i.) 0·91 to 0·94) and that of the full and simplified multivariable models 0·95 (99 per cent c.i. 0·94 to 0·96) and 0·94 (99 per cent c.i. 0·93 to 0·95) respectively. The latter two were significantly different from the first one. In the external validation set the ROC area of the simplified model was 0·84 (95 per cent c.i. 0·83 to 0·86). Patients who had a preoperative haemoglobin level lower than 13 g/dl and underwent major invasive surgery had the highest risk (43 per cent) of transfusion.

Conclusion

A simple algorithm using type of operation and haemoglobin concentration was effective in identifying patients likely to need perioperative homologous blood transfusion.
Nitric oxide enhances experimental wound healing in diabetes
Authors: Witte M B , Kiyama T , Barbul A
Published: March 2003

Background

Diabetes is characterized by a nitric oxide deficiency at the wound site. This study investigated whether exogenous nitric oxide supplementation with the nitric oxide donor molsidomine (N-ethoxycarbomyl-3-morpholinyl-sidnonimine) could reverse the impaired healing in diabetes.

Methods

Wound healing was studied by creating a dorsal skin incision with subcutaneous polyvinyl alcohol sponge implantation in diabetic and non-diabetic rats. Half of each group was treated with molsidomine. Collagen metabolism was assessed by wound breaking strength, hydroxyproline (OHP) content, RNA expression for collagen type I and III, and matrix metalloproteinase (MMP) 2 activity in wound sponges. Wound fluid, plasma and urinary nitric oxide metabolite levels, and the number of inflammatory cells were assessed.

Results

OHP content and wound breaking strength were significantly increased by molsidomine. MMP-2 activity in wound fluid was decreased in diabetes and upregulated by nitric oxide donors. The impaired inflammatory reaction in diabetes was unaffected by nitric oxide donor treatment and ex vivo nitric oxide synthesis was no different between wound macrophages from control and diabetic animals, suggesting that the nitric oxide deficiency in the wound is due to a smaller inflammatory reaction in diabetes.

Conclusion

The nitric oxide donor molsidomine can at least partially reverse impaired healing associated with diabetes.
All-comers policy for laparoscopic exploration of the common bile duct
Authors: Thompson M H , Tranter S E
Published: March 2003

Background

Laparoscopic exploration of the common bile duct is associated with substantial variation in results suggesting that different patient populations are being reported. This report observes the results in a defined population and on an intention-to-treat basis.

Methods

All patients with suspected bile duct stones who were fit for surgery from April 1994 were offered laparoscopic bile duct exploration. There were 224 patients of mean age 56 years, of whom 174 were women. Endoscopic sphincterotomy was used in 149 patients deemed unfit for surgery. All data were recorded prospectively and checked at the time of discharge. Patients were followed up after 6 months and beyond after the operation.

Results

Stones were removed transcystically in 56 patients, transductally in 158 and by flushing in nine. The duct clearance rate was 96 per cent overall, 98 per cent for transcystic and 94 per cent for transductal exploration. Intracorporeal lithotripsy safely reduced the failure rate of exploration from seven of the first 28 to four of the subsequent 196 procedures. Biliary complications occurred in 16 per cent of procedures in which a T tube was used but only 4 per cent if the duct was closed by suturing. Conversion to open operation for severe gallbladder inflammation was necessary in 6 per cent of patients. There were no deaths, bile duct injuries or pancreatitis but complications occurred in 19 per cent, associated with use of T tubes and advancing age. Laparoscopic duct exploration succeeded in seven patients after previous cholecystectomy.

Conclusion

Laparoscopic bile duct exploration is effective and safe when used for all patients. For young and fit patients it should replace endoscopic sphincterotomy.
Role of proliferation and apoptosis in net growth rates of human breast cancer cells (MCF‐7) treated with oestradiol and/or tamoxifen
Authors: Budtz P. E.
Published: March 2003

Abstract. Studies on growth regulation in vitro to a large extent rely on comparison of growth curves. However, these do not discriminate between the relative contributions of the mitotic rate and the apoptotic rate to the net growth rate. In the present study, differential effects of 17β‐oestradiol (E2, 10−8 M) and/or tamoxifen (TAM, 10−6 M) on proliferation and apoptosis have been examined and related to growth curves of a subline of the human breast cancer cell line MCF‐7 adapted to grow at low serum concentrations. Counting of cells and scoring of labelling and apoptotic indices were performed at the start of the experiment and 3, 6 and 9 days after changing the experimental media. The results demonstrate that apoptosis in this subline is constitutively expressed, that E2 protects (at least partly) against apoptosis and stimulates proliferation, resulting in an increased (net) growth rate and final cell pool size, and that TAM has a weak cytostatic effect and stimulates apoptosis strongly, resulting in a decreased (net) growth rate and final cell pool size. When E2 and TAM are added simultaneously to the medium, the cytotoxic effect of TAM is partly counterbalanced by the protective role of E2, resulting in a reduced apoptotic rate that, however, is at a higher level than in cultures grown with E2 only. As the cytostatic role of TAM is partly abolished by E2, the combined effect of E2 and TAM results in a final (net) growth rate and cell pool size intermediary to cells grown with E2 or TAM alone.
Heat shock‐induced arrests in different cell cycle phases of rat C6‐glioma cells are attenuated in heat shock‐primed thermotolerant cells
Authors: Kühl N. M. , Kunz J. , Rensing L.
Published: March 2003

The response kinetics of rat C6 glioma cells to heat shock was investigated by means of flow cytometric DNA measurements and western blot analysis of HSP levels. The results showed that the effects on cell cycle progression are dependent on the cell cycle phase at which heat shock is applied, leading to either G1 or G2/M arrest in randomly proliferating cells. When synchronous cultures were stressed during G0 they were arrested with G1 DNA content and showed prolongation of S and G2 phases after release from the block. In proliferating cells, HSC70 and HSP68 were induced during the recovery and reached maximum levels just before cells were released from the cell cycle blocks. Hyperthermic pretreatment induced thermotolerance both in asynchronous and synchronous cultures as evidenced by the reduced arrest of cell cycle progression after the second heat shock. Thermotolerance development was independent of the cell cycle phase. Pre‐treated cells already had high HSP levels and did not further increase the amount of HSP after the second treatment. However, as in unprimed cells, HSP reduction coincided with the release from the cell cycle blocks. These results imply that the cell cycle machinery can be rendered thermotolerant by heat shock pretreatment and supports the assumption that HSP70 family members might be involved in thermotolerance development.
Gadd45 mutations are uncommon in human tumour cell lines
Authors: Campomenosi P. , Hall P. A.
Published: March 2003

GADD45 is an evolutionarily conserved gene that encodes a small acidic, nuclear protein and is an example of a p53 responsive gene. Gadd45 protein has been shown to interact with PCNA and also p21waf1. It has been implicated in growth arrest, DNA repair, chromatin structure and signal transduction. The confusing biochemical data has been clarified by the demonstration that Gadd45 null mice have a phenotype strikingly similar to that of p53 null mice, being tumour prone and showing marked genomic instability. We have tested the hypothesis that mutations in the GADD45 coding region might substitute for p53 abnormalities in tumour cell lines where p53 is wild type. After generating cDNA from mRNA in a panel of 24 cell lines we sequenced the GADD45 cDNA and have demonstrated that no mutations can be observed, even in the p53 wild type cell lines. Such data suggest that Gadd45 mutations are uncommon in human cancer. From this we postulate that, despite the phenotype of the GADD45 null mouse, GADD45 is unlikely to be the key mechanistic determinant of the tumour suppressor activity of the p53 pathway.

Note on nomenclature: We have employed GADD45 to designate the gene and Gadd45 to designate the encoded protein. This gene has also be denoted GADD45α elsewhere in the literature.
The child's voice in child and family social work decision making: the perspective of a guardian ad litem
Authors: Head Ann
Published: March 2003

This article shows how the voice of the child has come to prominence in decision making, against the background of changes in emphasis between family rights and child protection viewpoints, reflected in 20th‐century legislation on family matters. It argues that the role of the guardian ad litem, the historical development of which is charted, is central to the evaluation of the child's views; these are not always straightforward and they must be viewed in tandem with a professional assessment of the child's best interests. The article concludes that the child's voice cannot be the deciding factor in decision making; adults cannot abrogate their responsibility to make reasoned decisions, based both on children's wishes and feelings and on other factors which children, in their immaturity, cannot appreciate.