The presence of leukaemia‐associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia

Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia‐associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P < 0.05, estimated risk ratio of 1.6, 95%CI, 1.0–2.6) in a multivariate analysis. In conclusion, our data show the presence of LAP in AML is an independent predictor for response to induction chemotherapy and risk of relapse and should be considered for counselling patients and planning therapy.     

Simultaneous defecography and peritoneography in defecation disorders

A number of physiologic and radiologic investigations are used in investigating defecation disorders. Defecography is one important part of these investigations. However, a correct diagnosis of an enterocele is sometimes difficult despite use of contrast media in the rectum, vagina, and small bowel. PURPOSE: This study was undertaken to ascertain if it was technically possible to perform simultaneous defecography and peritoneography in an effort to improve the diagnostic possibilities in patients with defecation disorders. METHODS: Twelve patients with defecation disorders and an unexplained widening of the rectovaginal space at defecography were investigated. Contrast medium was introduced intraperitoneally, after which conventional defecography was performed. RESULTS: All investigations were carried out without complications and demonstrated the peritoneal outline in all patients. Simultaneous defecography and peritoneography differentiated between an enterocele and a pathologically deep pouch of Douglas—a peritoneocele. Three types of peritoneocele were visualized: vaginal peritoneocele, septal peritoneocele, and rectal peritoneocele with or without enterocele. Combinations of the three types were also found. Eight of the 12 patients had rectal intussusception or rectal prolapse. All of these eight patients had a rectal peritoneocele. CONCLUSIONS: Simultaneous defecography and peritoneography can be performed without technical difficulties or complications. Peritoneal outlines and pouches can, therefore, be studied directly during the act of defecation. An unexplained widening of the rectovaginal space at defecography can be clarified as a peritoneocele, with or without an enterocele. Peritoneocele can be of three different types: rectal, septal, or vaginal.Supported by grants from Marianne and Marcus Wallenbergs Stiftelse, Kjell and Märta Beijers Stiftelse, and Karolinska Institutet's research funds.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Results of rectocele repair

PURPOSE: This study was designed to evaluate the results of rectocele repair and parameters that might be useful in selecting patients for this operation. METHODS: Twentyfive patients with symptom-giving rectoceles were prospectively evaluated with a standardized questionnaire, physical examination, defecography, colon transit studies, anorectal manometry, and electrophysiology. Patients underwent posterior colporrhaphy and perineorrhaphy. They were followed postoperatively (mean, 1.0 year) with the same questionnaire, physical examination, defecography, anorectal manometry, and electrophysiology. RESULTS: Constipation had improved postoperatively in 21 of 24 constipated patients (88 percent). At postoperative follow-up 13 patients (52 percent) had no constipation symptoms, 8 (32 percent) had occasional symptoms, and 4 (16 percent) had symptoms more than once per week. Four patients with rectocele at preoperative defecography, but not at physical examination, had favorable outcomes following surgery. The majority of patients not using vaginal digitalization preoperatively had improved with respect to constipation. All patients with pathologic transit studies had various degrees of constipation postoperatively. Constipation was not improved in two of five patients with preoperative paradoxic sphincter reaction. CONCLUSIONS: Rectocele is one cause of constipation that can be treated with good results. Preoperative use of vaginal digitalization is not mandatory for a good postoperative result. Defecography is an important complement to physical examination. Patients with pathologic transit study might have a less favorable outcome of rectocele repair with respect to constipation. More studies about the significance of paradoxic sphincter reaction in these patients are indicated.Poster presentation at the XVth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Singapore, July 2 to 6, 1994.     

Internal rectal intussusception seldom develops into total rectal prolapse

PURPOSE: This study was designed to analyze how often internal rectal intussusception develops into total rectal prolapse. METHODS: Repeated investigations with defecography were performed in 312 patients because of persisting symptoms. In 79 patients who had a rectal intussusception at the first defecography, results of the second defecography and the patients' records were studied. RESULTS: A total of 38 patients had not undergone any surgical treatment of rectal intussusception or rectal prolapse between the first and second defecographies. One of these patients had a rectal prolapse at the second defecography, and another developed a clinical prolapse after the second defecography. CONCLUSIONS: The present study demonstrates that the risk of developing a rectal prolapse in patients with rectal intussusception is small. This risk should, therefore, not be used as an indication for surgery.     

Paradoxical sphincter reaction is influenced by rectal filling volume

PURPOSE: Paradoxical sphincter reaction is frequently found in constipated patients but sometimes also in incontinent patients and in asymptomatic subjects. Its significance in defecation disorders has, therefore, been debated. The aim of the present study was to investigate whether paradoxical sphincter reaction is influenced by rectal filling volume. PATIENTS AND METHODS: Eighteen patients with defecation disorders and paradoxical sphincter reaction shown by electromyography were reinvestigated with an extended electromyographic investigation while in the lying position and while in the sitting position, with 50-ml, 100-ml, and 150-ml water-filled rectal balloons. RESULTS: All 18 patients showing paradoxical sphincter reaction in the first investigation also showed the reaction at the second investigation in the lying position with a 0-ml volume of rectal contents. In the sitting position, with a volume of 150 ml of rectal contents, the increase in electromyographic activity disappeared in seven patients (39 percent) and no longer showed paradoxical sphincter reaction. Electromyography showed decreased activity in one patient and unchanged activity in six patients during straining. A closing reflex was seen after completed straining in all of these seven patients. CONCLUSIONS: The present study demonstrates that paradoxical sphincter reaction diagnosed by electromyography is influenced by the rectal filling volume and might diminish when the rectum is filled with contents. The conventional electrophysiologic technique in the diagnosis of paradoxical sphincter reaction might, therefore, overdiagnose this condition.     

Effect of delivery on anal sphincter morphology and function

PURPOSE: Anal sphincter injury is a serious complication of childbirth, which may result in persistent anal incontinence. Occult injuries, visualized with endoanal ultrasonography, have previously been reported in up to 35 percent of females in a British study. The aim of the present study was to study anal sphincter morphology and function before and after delivery in primiparous females in the United States. METHODS: Thirty-eight primiparous patients (mean age, 31 years) were evaluated with endoanal ultrasonography, anal manometry, and pudendal nerve terminal motor latency during pregnancy and after delivery. Bowel function before and after delivery was recorded according to set questionnaires. Cesarean section was performed in three patients. RESULTS: Clinical sphincter tears, requiring primary repair, occurred in 15 percent of the patients. After delivery endoanal ultrasonography revealed disruptions in the external anal sphincter in six patients, but no patient had disruption in the internal anal sphincter. One patient had slight scarring in the external sphincter. Of the seven patients with pathologic findings at endoanal ultrasonography, the left pudendal latency increased after delivery (P<0.05), and manometric results were reduced. Three of these seven patients had a third-degree or fourth-degree tear during delivery. All investigations were normal in the three patients who underwent cesarean section. CONCLUSIONS: The present study demonstrates a significant frequency of sphincter injuries (20 percent) after vaginal delivery. Obstetricians should be aware of this risk and explicitly inquire about incontinence symptoms at follow-up after delivery.Health East Foundation and Mead Johnson Pharmaceutical Inc. provided economic support, enabling participating volunteers to receive a stipend and baby supplies on completion of their tests.Dr. Mellgren was supported by grants from Health East Foundation and Karolinska Institutet Research Funds. Dr. Zetterström was supported by grants from Karolinska Institutet Research Funds.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998. Poster presentation at the XVIIth Biennial Congress of the International Society Of University Colon and Rectal Surgeons, Malmö, Sweden, June 7 to 11, 1998.     

Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer

AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated. METHODS: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics. RESULTS: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.     

Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome

The purpose of the present study was to investigate substitutions in the D-loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty-two cases of SIDS and 133 controls were investigated and the D-loop sequences were recorded in the base-pair range 16 055-16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D-loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D-loop than the controls ( p = 0.088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.     

Glucose metabolism and insulin secretion in children with cyanotic congenital heart disease

The aim of the study was to reveal differences in carbohydrate metabolism in children with cyanotic congenital heart diseases (CHD). Thirteen children with diseases of these kinds were investigated with regard to glucose tolerance and insulin secretion and comparisons were made with healthy controls of the same age. Investigations included an intravenous glucose tolerance test, insulin response to the glucose load in plasma and insulin secretion rate. The results reveal lower fasting glucose levels and signs of a higher insulin secretion rate in the relatively few patients in the CHD group where C-peptide measurements were performed, but no differences in glucose tolerance. The reasons for the differences are unclear, but the chronic increases in circulating catecholamines in combination with the impaired nutritional status of these children with CHD are probably the most important factors. We conclude that these divergences in carbohydrate metabolism should be emphasized in the care of children with CHD.