A survey of patient satisfaction after day case surgery.

A prospective survey of patients attending day case surgery was undertaken to determine patient satisfaction. In an eight-week prospective study, patients undergoing procedures in the day surgical unit were asked to fill in two questionnaires, the first before surgery and the second two weeks after surgery. One hundred and eighty-nine patients were recruited into the study; of these, 98 (52.4%) returned correctly completed forms. Most of the patients believed the information given them before surgery was adequate and the standard of care in the day unit was high. Only five patients needed to see their general practitioner because of continued problems. Twenty-one patients felt they were discharged too early. Our current practice in day case surgery inevitably leads to some patients being discharged early. Facilities must be provided for some patients to stay longer in the day unit. Day case surgery did not result in an unacceptable increase in the workload for GPs, nor did it compromise the quality of patient care.

Detection of circulating tumour cells and nodal metastasis by reverse transcriptase-polymerase chain reaction technique.

BACKGROUND: In the search for occult metastases in lymph nodes or circulating tumour cells, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed to detect tumour-specific splice variants of the transcript of the CD44 gene. The assay was highly sensitive and could detect ten tumour cell per 10(5) leucocytes. METHODS: RNA was purified from peripheral blood (n = 24) and regional lymph nodes (n = 14) from patients with colorectal cancer. Complementary DNA was made and amplified using primers specific for the CD44 gene. Southern blotting with exon-specific probes was used to enhance the sensitivity. RESULTS: Tumour cells were detected in peripheral blood samples in four patients and lymph nodes in nine, in one of whom conventional histology had not detected tumour cells. CONCLUSION: This technique may be useful in the early diagnosis of primary or metastatic tumours, in assessing prognosis and in detecting residual disease after treatment.

Expression of CD44 splice variants in colorectal cancer.

BACKGROUND: The CD44 gene codes for a family of heavily glycosylated cell surface proteins that have been linked with tumour metastasis. The aim of the study was to analyse the expression of CD44 messenger RNA in colorectal cancer. METHODS: The expression of CD44 variants 2 and 7 in colorectal tumour samples was compared with that in normal colon and lymphocytes from 59 patients using reverse transcription-polymerase chain reaction followed by blot hybridization with exon-specific probes, and a nested polymerase chain reaction. RESULTS: All samples of tumour and metastatic tissue showed complex overexpression of many alternatively spliced products of the CD44 gene. Normal colon, liver and lymphocytes predominantly expressed the standard form of the CD44 molecule (CD44S) with low levels of two or three variants hybridizing to exons v2 and v7. CONCLUSION: Deranged CD44 gene activity in colorectal cancer cells is confirmed. The analysis of CD44 gene expression may provide a promising marker for the early detection of colonic tumours.

The exfoliation of free malignant cells in the peritoneal cavity during resection of colorectal cancer.

The presence of free malignant cells in the peritoneal cavity following potentially curative resection of colorectal cancer may be responsible for some cases of local recurrence. Twenty-six patients (age 58-88 years, male:female 12:14) undergoing colorectal cancer surgery were studied to determine frequency of occurrence of tumour cells in the peritoneal cavity using an immuno-magnetic cell separation technique. Peritoneal washings were collected after opening the peritoneal cavity and also prior to closure. A murine monoclonal antibody specific for epithelial cells was added to the peritoneal washings followed by magnetic labelled goat-antimouse antibody. The labelled tumour cells were retrieved by passing through the magnetic activated cell sorter (MACS). Tumour cells were detected in peritoneal washings from 11 patients (preresection only n = 0, post-resection only n = 6, and both n = 5). Five of these 11 patients had potentially curative surgery. This study supports the use of MACS in detecting free malignant cells in the peritoneal cavity.

Detection of circulating tumour cells with the magnetic activated cell sorter.

A technique has been developed for the detection of tumour cells in blood with the magnetic activated cell sorter (MACS). Colonic carcinoma cell lines and disaggregated primary tumours were used to establish optimal conditions of separation. A murine monoclonal antibody specific for epithelial cells was added to the suspension of leucocytes and tumour cells, followed by magnetic labelled goat antimouse antibody. The labelled tumour cells were retrieved by passing this suspension through a MACS separation column in a strong magnetic field. Tumour cells were detected at a dilution of 10 cells per ml blood. Tumour cells were identified in mesenteric blood in three of 24 patients undergoing surgery for colorectal cancer. This study supports the use of the MACS to detect circulating tumour cells.

Lymphocytes infiltrating colorectal cancer have low proliferative capacity but can secrete normal levels of interferon gamma.

Significant numbers of infiltrating mononuclear cells are commonly observed in solid tumours, although their role in restricting tumour growth is not clear. Tumour-infiltrating lymphocytes (TIL) from 38 patients with colorectal cancer, in parallel with peripheral blood lymphocytes (PBL), were assayed to determine their ability to proliferate in response to concanavalin A (ConA), interleukin-2 (IL-2), ConA+IL-2, phorbol 12-myristate 13-acetate (PMA)+ionomycin ionomycin (IOM), and staphylococcal enterotoxin B(SEB). These reagents were selected to give a range of weak to strong proliferative responses either via or independent of the T cell receptor. Proliferation of TIL was significantly lower than that of PBL in all cultures: ConA (P < 0.001), IL-2 (P = 0.002), ConA+IL-2 (P < 0.001), PMA+IOM (P < 0.001), SEB (P = 0.002). In addition to the low proliferative capacity of TIL, production of cytokines by TIL may also play a role in control of tumour growth. We have assayed IFN gamma production in the supernatants from 16 paired TIL and PBL cultures, and tumour necrosis factor alpha (TNF alpha) in 6 paired cultures. TNF alpha concentrations were significantly lower in TIL cultures than in PBL cultures stimulated with ConA (P < 0.05), but no different in control or IL-2 stimulated cultures. IFN gamma levels did not significantly differ between PBL and TIL cultures, indicating that despite the restricted proliferative capacity of TIL, these cells remain capable of secreting significant amounts of IFN gamma.

Reduction in incidence of glove perforation during laparotomy wound closure by 'no touch' technique.

Intact surgical gloves provide an efficient barrier against the HIV and Hepatitis B viruses but glove perforations are common, particularly during mass closure of laparotomy wounds. Attempts to develop gloves immune to perforation have failed. A series of 100 consecutive laparotomy wounds were randomised to mass closure by either the 'hand in' technique currently favoured by many surgeons, or a 'no touch' technique manipulating the wound edges with instruments only. The two groups were similar with regard to grade of surgeon and assistant, proportion of routine and emergency cases, and proportion of clean or dirty cases. The wound lengths in each group were similar, and the time taken to close the abdominal wall was similar in both groups. Although a similar number of perforated gloves occurred in each group while the operative procedure was being performed ('hand in', 9 of 50 vs 'no touch', 12 of 50; P = 0.62); a significantly reduced number of glove perforations occurred in the 'no touch' group during wound closure ('hand in', 16 of 50 vs 'no touch', 3 of 50, P = 0.0017). No touch closure of the abdominal wall may provide protection to surgeons against blood-borne viruses such as HIV and hepatitis B.

Evidence of clonal variants of Helicobacter pylori in three generations of a duodenal ulcer disease family.

Nine members of a family with a high incidence of duodenal ulcer disease were studied by interview, examination of hospital records, endoscopy, and antral biopsy. Helicobacter pylori was confirmed by CLO test, histology and culture. DNA extraction from pure isolates of H pylori was possible in six family members and strain typing was performed by restriction fragment length polymorphism. DNA restriction digestion was followed by vacublotting and then DNA hybridisation, using a cDNA probe complimentary to H pylori rRNA cistrons. Eight of the nine family members were H pylori positive by CLO test and histology. Five had duodenal ulcer disease. Three family members (one from each generation) harboured clonal variants of a single parent strain of H pylori but only two had duodenal disease. The other three members harboured different strains. Intrafamilial clustering of clonal variants of H pylori occurs in some duodenal ulcer disease families. Family members however, may develop duodenal disease irrespective of the colonising strain.

Safety of early pain relief for acute abdominal pain.

OBJECTIVES: (a) to determine the efficacy of papaveretum in treating pain when administered early to patients presenting with acute abdominal pain and (b) to assess its effect on subsequent diagnosis and management. DESIGN: Prospective, randomised, placebo controlled study. SETTING: Walsgrave Hospital, Coventry. SUBJECTS: 100 consecutive patients with clinically significant abdominal pain who were admitted as emergencies to a surgical firm. INTERVENTIONS: Intramuscular injection of up to 20 mg papaveretum or an equivalent volume of saline. OUTCOME MEASURES: Pain and tenderness scores, assessment of patient comfort, accuracy of diagnosis, and management decisions. RESULTS: Median pain and tenderness scores were lower after papaveretum (pain score 8.3 in control group and 3.1 in treatment group, p < 0.0001; tenderness score 8.1 in control group and 5.1 in treatment group, p < 0.0001). Forty eight patients were deemed to be comfortable after papaveretum compared with nine after saline. Incorrect diagnoses and management decisions applied to two patients after papaveretum compared with nine patients after saline. CONCLUSION: Early administration of opiate analgesia to patients with acute abdominal pain can greatly reduce their pain. This does not interfere with diagnosis, which may even be facilitated despite a reduction in the severity of physical signs. These patients should not be denied effective treatment.

Postoperative nausea is relieved by acupressure.

One hundred and sixty-two general surgical patients were prospectively randomized to one of three treatments for postoperative nausea and vomiting: (1) acupressure using elasticated bands containing a plastic button to apply sustained pressure at the P6 (Neiguan) point above the wrist, (2) control dummy bands without the pressure button and (3) antiemetic injections of prochlorperazine with each opiate given and as required. All patients received papaveretum injections as required for pain, and additional prochlorperazine injections were prescribed if nausea was not controlled in groups 1 and 2. The severity of nausea was assessed using a linear analogue scale and was significantly (P = 0.002) reduced by acupressure on both days 1 and 2, in comparison to both controls and drug treated patients. The incidence of postoperative vomiting, and the need for unplanned antiemetic injections was also reduced by acupressure but this was not statistically significant. Acupressure can work and should be investigated in other clinical situations.

Hepatic recovery after biliary decompression of experimental obstructive jaundice.

Obstructive jaundice was produced in 11 dogs by common bile duct ligation for 4 weeks, then biliary decompression was performed by bilioenteric anastomosis. Animals were regularly studied over the 2 months after decompression by the following methods: (1) serum biochemistry was monitored; (2) light microscopic changes in serial liver biopsies were graded; (3) the respiratory characteristics of isolated hepatic mitochondria, obtained by open liver biopsy, were studied using an oxygen micro-electrode system; (4) in vivo handling of an hepatobiliary imaging agent (diisopropyl iminodiacetic acid) was studied by dynamic liver scintiscanning. None of these liver assessments were normalized after 7 to 10 days of biliary decompression. Our study suggests that biliary decompression of patients with extrahepatic biliary obstruction requires long periods of time to enable major recovery of the abnormal liver function induced by biliary obstruction.

DISIDA kinetics measure liver function in dogs.

We have investigated the ability of 99Tcm-disofenin (DISIDA) kinetics to measure liver function. Two approaches have been used: first, quantitative analysis of serial liver images, and second, clearance estimation from whole blood concentration-time data. Graded liver dysfunction was produced in 11 dogs over three months by common bile duct ligation and surgical relief of biliary obstruction one month later. The kinetic analysis of serial liver images showed clear abnormalities during biliary obstruction, with calculated rates of liver uptake falling in stages from 11.09 to 5.15 cts s-1 (p less than 0.001), and rates of elimination from the liver from 8.8 to 1.6 x 10(-4) cts s-1 (p less than 0.0001). These parameters paralleled the deterioration and recovery of liver function through the experimental period, and had not fully recovered 7 weeks after relief of biliary obstruction (10.5 and 6.2 x 10(-4) cts s-1 respectively). Serial blood sampling after injection of DISIDA permitted calculation of whole blood disposition rates (for hepatic clearance). Mean values fell from 256 to 67 ml min-1 with chronic biliary obstruction (p less than 0.001), and returned to almost normal (206 ml min-1) 10 days after surgical relief of biliary obstruction. It is clear that the gradual nature of recovering liver function was more sensitively identified by image analysis than serial blood data. Serial liver biopsies showed marked changes following biliary obstruction. These improved over a period of 7 weeks following its relief, when there was still considerable residual abnormality. This work supports the view that hepatic abnormalities caused by biliary obstruction do not recover quickly following its relief. DISIDA kinetics can quantitate both major and minor degrees of hepatic dysfunction, and may prove to be a valuable method to quantitative liver function.

Lymphocyte function in obstructive jaundice.

Sepsis is a major factor in the high mortality and morbidity after surgery for obstructive jaundice. Several studies have suggested that reticuloendothelial function is depressed, but changes in lymphocyte function are poorly understood. A model of obstructive jaundice has been produced by chronic common bile duct ligation in eight dogs. In vitro lymphocyte studies were performed both at 2 and 3 weeks duration of jaundice and compared with simultaneous healthy control subjects. Icteric animals showed no abnormality of natural killer cell function. Relative numbers of T and B lymphocytes and their subsets were unchanged. T lymphocyte responses to three mitogens were not significantly reduced in jaundiced animals. Serum immunoglobulin levels were unchanged compared to those before surgery apart from a significant rise in immunoglobulin A. No evidence of circulating immunosuppressive factors was found by mitogen testing on normal lymphocytes in the presence of pooled serum from jaundiced animals, normal serum, or normal serum with added bilirubin. Our study does not suggest that impairment of lymphocyte function contributes significantly to the dangers of sepsis in obstructive jaundice.

A randomised comparison of two postoperative fluid regimens.

Postoperative paralytic ileus follows all significant gastrointestinal surgery. Its duration is variable and has led to a variety of empirical and time-consuming oral fluid regimens. We have compared a traditional method of fluid administration with an unstructured, simpler, patient-determined approach. A series of 102 patients on a general surgical ward who required intravenous fluids on the day after surgery were randomised by a closed envelope system to one of two protocols and followed prospectively. Of these, 12 patients were erroneously randomised or unable to fulfil trial requirements. The first, 'regulated' group (n = 41) received hourly aliquots of oral fluid as determined by twice daily ward rounds according to ward routine. The second, 'unregulated' group (n = 49) were given a jug of water and instructed to drink as desired. Patients in the regulated group received less of their postoperative fluids by the oral route at all stages of recovery but there were no significant differences in the mean durations of intravenous therapy, nasogastric intubation or hospital stay. Postoperative complication and mortality rates were also similar. Patients who underwent gastric or duodenal procedures (n = 14) showed a similar pattern of results. We conclude that 'patient-determined' regulation of postoperative oral fluid intake is safe and effective and may greatly simplify ward management.

Pharmacokinetic studies of DISIDA disposition. II. Clinical studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained clearly discriminated 9 normal subjects from 7 patients with severe liver disease causing jaundice--1233 mls/min vs 384 mls/min (P less than 0.002). Nine subjects with liver disease of insufficient severity to cause jaundice also had clearly abnormal DISIDA disposition--642 ml/min (P less than 0.05 for difference to controls). The time activity curves from all subjects showed biexponential elimination of blood activity, with a rapid (T1/2 = 3.8 min) and a slow disposition phase (T1/2 = 75 min) in normals. These curves were fitted by computer to the timed rate of hepatic uptake, simultaneously obtained by gamma imaging over the liver. It was not possible to satisfactorily fit these using a model which assumed distribution of a single compound within two body compartments. However, another which assumed the administration of two radioactive agents satisfactorily fitted the two types of data. This conclusion is consistent with our animal experiments which indicate the existence of two compounds in injected DISIDA with contrasting high and low hepatic extraction efficiency (Fraser et al. 1988). A pharmacokinetic approach to DISIDA disposition can yield quantitative information which discriminates different degrees of liver dysfunction, but the mechanisms involved are more complicated than previously thought, so that further study should permit very precise quantification.

Pharmacokinetic studies of DISIDA disposition. I. Animal studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced by chronic bile duct ligation (256 vs 58 ml/min, P less than 0.001). Blood levels of radioactivity fell in a biexponential fashion characterized by rapid and slow disposition phases, whose half times were 2.4 and 58 min in normal animals. On 3 occasions, plasma was obtained from 1 animal by exsanguination 35 min after the administration of DISIDA and rapidly transfused into a 2nd animal. The whole blood pharmacokinetics of the second (recipient) animal showed a predominance of the slow disposition phase and a small rapid phase. The hepatic extraction ratio of blood radioactivity was measured in 3 dogs and was high (75%-90%) early after injection of DISIDA, but fell rapidly to remain around 10%. These experiments suggest the presence of two different species in the radiopharmaceutical studied, each being removed from the blood stream by the liver, but at different rates. The contribution of renal clearance to overall whole blood pharmacokinetics was negligible, since three nephrectomized dogs displayed similar pharmacokinetics to normals. Whole blood DISIDA pharmacokinetics are more complex than previously thought but appear to be capable of providing an accurate measure of liver function.

Prolonged bandaging is not required following sclerotherapy of varicose veins.

Following sclerotherapy of varicose veins, 158 limbs of 154 patients were randomized to be bandaged with either crepe or Coban for 6 weeks each, or with Coban for 3 days only. Objective assessment of vein eradication and subjective evaluation of symptoms 3 months after completion of treatment showed no clear differences between these regimens. Significantly more discomfort was experienced with Coban than crepe when used for 6 weeks. It is suggested that, following sclerotherapy, 3 days is an adequate period of bandaging when using Coban. Such a policy would considerably reduce the inconvenience to patients during treatment.