Spontaneous changes in tumour cell dissemination to bone marrow in colorectal cancer.

AIM: The study aimed to evaluate the incidence of disseminated tumour cells (DTCs) in bone marrow (BM) preoperatively and during follow up and to correlate these with established risk factors in patients with colorectal cancer. METHOD: We prospectively studied BM in 57 patients using the anti-cytokeratin antibody A45-B/B3. RESULTS: The overall detection rate of DTCs was 23% with a similar detection rate through all stages of the disease. No significant association was found between the presence of DTCs and clinicopathological parameters. After a median follow up of 35.4 months, no differences were found in relapse and overall survival between patients with and without DTC preoperatively. In 31 of 45 patients with local disease, we performed a follow-up BM examination after 1 year. In 26% of the patients, the BM status had changed as compared with the preoperative finding. CONCLUSION: This is the first study to report the follow up of DTC in BM in colorectal cancer using the A45-B/B3 antibody. The presence of tumour cells in the preoperative BM had no impact on outcome. The BM status had changed after 12 months in a quarter of patients.

Sacral nerve stimulation in patients with severe constipation.

PURPOSE: Constipation is frequently a multifactorial disease. This study was designed to evaluate the potential effects of sacral nerve stimulation for patients suffering from severe chronic constipation. METHODS: Nineteen patients suffering from pathologic colonic transit time or rectal outlet obstruction were included. Only patients with severe rectal outlet obstruction who needed digital manipulation for defecation or patients suffering from pathologic colonic transit constipation with less than two bowel movements per week were regarded as candidates. A temporary stimulation lead was implanted into the sacral foramen that showed the best muscular response. After an evaluation period, the stimulation electrode was removed. An improvement in constipation (more than 2 bowel movements per week or defecation without digital manipulation, respectively) during the test stimulation, as well as a recurrence of prestimulation constipation symptoms during the following surveillance period of three weeks were prerequisites for implanting the permanent sacral nerve stimulating system. RESULTS: All of the patients showed a positive motor response to acute needle stimulation. After the evaluation period, eight patients (42 percent) reported an improvement of constipation, and permanent systems were implanted successfully. During the median follow-up of 11 (range, 2-20) months, a significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (baseline: median: 23, range, 18-27; 12 months after implantation: median, 8, range, 4-13). After successful sacral nerve stimulation, patients also showed a significant improvement in their quality of life. CONCLUSIONS: Patients suffering from severe constipation are a new challenge for sacral nerve stimulation but further research on pelvic floor function is needed.

Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro.

Toxin A but not toxin B, appears to mediate intestinal damage in animal models of Clostridium difficile enteritis. The purpose of this study was to investigate the electrophysiologic and morphologic effects of purified C. difficile toxins A and B on human colonic mucosa in Ussing chambers. Luminal exposure of tissues to 16-65 nM of toxin A and 0.2-29 nM of toxin B for 5 h caused dose-dependent epithelial damage. Potential difference, short-circuit current and resistance decreased by 76, 58, and 46%, respectively, with 32 nM of toxin A and by 76, 55, and 47%, respectively, with 3 nM of toxin B, when compared with baseline (P < 0.05). 3 nM of toxin A did not cause electrophysiologic changes. Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is approximately 10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficile colitis in man.

Effects of extracellular pH on intracellular pH-regulation and growth in a human colon carcinoma cell-line.

Mechanisms of intracellular pH (pHi) regulation seem to be involved in cellular growth and cell division. Little is known about how extracellular acidosis, known to occur in central regions of solid tumors, or alkaline conditions affect pHi regulation in colonic tumors. pHi changes in the colonic adenocarcinoma cell-line SW-620 were recorded by spectrofluorimetric monitoring of the pH-sensitive, fluorescent dye BCECF, and proliferative activity was assessed by [3H]thymidine uptake. Resting pHi in Hepes-buffered solution was 7.53 +/- 0.01 (n = 36). Both 1 mM amiloride and Na(+)-free solution inhibited pHi recovery from acidification and decreased pHi in resting cells. In HCO3-/CO2-buffered media resting pH1 was 7.42 +/- 0.01 (n = 36). Recovery from acidification was Na(+)-dependent, CI(-)-independent, and only partially blocked by 1 mM amiloride. In the presence of amiloride and 200 microM H2DIDS pHi recovery was completely inhibited. In Na(+)-free solution pHi decreased from 7.44 +/- 0.04 to 7.29 +/- 0.03 (n = 6) and no alkalinization was observed in CI(-)-free medium. Addition of 5 microM tributyltin bromide (an anion/OH-exchange ionophore) caused pHi to decrease from 7.43 +/- 0.05 to 7.17 +/- 0.08 (n = 5). The effects of pH0 on steady-state pHi, pHi recovery from acidification and proliferative activity after 48 h were investigated by changing buffer [CO2] and [HCO3-]. In general, increases in pH0 between 6.7 and 7.4 increased pHi recovery, steady-state pHi and growth rates. In summary, SW-620 cells have a resting pHi > 7.4 at 25 degrees C, which is higher than other intestinal cells. Acid extrusion in physiological bicarbonate media is accomplished by a pHi-sensitive Na+/H+ exchanger and a pHi-insensitive Na(+)-HCO3-cotransporter, both of which are operational in control cells at the resting pHi. No evidence for activity of a CI-/HCO3- exchanger was found in these cells, which could account for the high pHi observed and may explain why the cells continue to grow in acidic tumor environments.

Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.

PURPOSE: The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). PATIENTS AND METHODS: In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. RESULTS: Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. CONCLUSION: IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.

Improving the safety of laparoscopic cholecystectomy: the routine use of preoperative magnetic resonance cholangiography.

BACKGROUND: The aim of this study was to determine the value of routinely performed preoperative magnetic resonance cholangiography (MRC) in detecting common bile duct (CBD) stones in patients stated to undergo elective laparoscopic cholecystectomy. In addition, we used MRC to investigate possible variants of the cystic duct. METHODS: Magnetic resonance cholangiography was performed preoperatively in 773 patients (311 male and 462 female; median age 55 years, range 16-91) who had no clinical signs of cholestasis prior to undergoing elective laparoscopic cholecystectomy. In cases where the MRC was positive for CBD stones, endoscopic retrograde cholangiopancreatiography (ERCP) was then performed. A total of 532 patients were available for continuous postoperatively follow-up (median 54 months, range 36-85). In 462 patients (247 female, and 215 male), MR images were also reviewed for variants of the cystic duct. RESULTS: In 705 patients (91%), MRC was negative for CBD stones. In 64 patients (9%) MRC was positive. Of these patients, 47 (6%) had CBD stones on ERCP. In 12 patients (2%), MRC was false positive. In five cases (0.6%), ERCP had an inconclusive result postoperative follow-up (532 patients, or 69%) revealed evidence of CBD stones in three patients (10.4%) despite a preoperative negative MRC result. Anatomical variants in the course of the cystic duct and its confluence with the common bile duct were found in 27 of 462 patients (6%). CONCLUSIONS: Magnetic resonance cholangiography proved to be a reliable screening technique in the preoperative evaluation of patients with silent CBD stones. Imaging of the course of the cystic duct is possible in a high percentage of cases. Therefore, MRC can be recommended as a screening technique before laparoscopic cholecystectomy.

Downregulation of lymphocyte mitogenesis by breast cancer-associated p43.

Placental isoferritin-associated p43 has proven to induce immune suppression during pregnancy in order to avoid rejection of the fetus' alloantigens by maternal lymphocytes. It has been demonstrated previously that p43 is also synthesized by breast cancer cells and can also be found on the surface of a subpopulation of T cells in women with this disease. Therefore, it was the aim of the present study to investigate if breast cancer-associated p43 has immunosuppressive properties. In 40 women undergoing surgical excision of a suspicious lump in their breast, blood was withdrawn and lymphocytes were isolated. Lymphocyte cultures were incubated with p43 antigen and anti-p43 antibody (CM-H-9). In a second series, lymphocyte mitogenesis was activated by addition of concanavalin A (Con A), Con A + p43 and Con A + anti-p43, respectively. While lymphocytes of breast cancer patients (n = 21) and women with benign breast disease (n = 19) incubated with p43 as well as with anti-p43 antibody did not show any difference in terms of incorporation of [3H]thymidine, activation of lymphocytes by addition of Con A was significantly inhibited after addition of p43 antigen in breast cancer patients compared to women with benign breast disease (P = 0.0178). Analysis of prognostic factors for breast cancer showed that inhibition of lymphocyte mitogenesis was dependent on the degree of tumor differentiation and was significantly higher in well differentiated tumors (GI) compared with more dedifferentiated tumors (GIII). The present study shows that breast cancer-associated antigen p43 is able to induce immune suppression in breast cancer patients but not in women with benign breast disease.

Activated lymphocytes from breast cancer patients express the characteristics of type 2 helper cells--a possible role for breast cancer-associated p43.

P43, a breast cancer-associated antigen, has been repeatedly described as an immunosuppressive factor. The objective of the present study was to investigate whether immune dysregulation induced by p43 affects the profile of cytokines secreted by mitogen-stimulated lymphocytes in breast cancer patients as compared with stimulated lymphocytes in women with benign tumors. The study consisted of 32 women undergoing surgical excision for a suspicious lesion in their breast. Histology revealed malignant breast disease in 20 patients and benign lesions in 10 patients. Lymphocytes isolated from peripheral blood were activated by Conconavalin A (Con A) with and without the addition of p43 and the concentrations of cytokines (IL-2, TNF-alpha, IFN-gamma, IL-4, IL-10 and IL-6) secreted into the culture medium were determined. Lymphocytes of patients with malignant breast disease stimulated with Con A secreted a significantly higher concentration of IL-10 compared with lymphocytes of patients with benign tumors. No significant differences were found between the two groups regarding the levels of IL-2, TNF-alpha, IFN-gamma and IL-4. Cytokine concentrations were analyzed according to the type 1/type 2 cytokine profile (IL-2, TNF and IFN-gamma and IL-4, IL-6 and IL-10, respectively). This analysis revealed no significant differences in IL-2, TNF or IFN-gamma between benign and malignant tumors. However, in the type 2 cytokines, lymphocytes from cancer patients secreted significantly higher levels of IL-4 (27.3 +/- 7.2 U/ml) and IL-10 (44.1 +/- 22.3 U/ml) than did the lymphocytes from patients with benign disease (21.4 +/- 7.3 and 1.8 +/- 0.3 U/ml, respectively). The addition of p43 to the culture medium significantly enhanced the levels of IL-4 secreted by lymphocytes in both groups of patients (malignant disease, from 27.3 +/- 9.2 to 40.7 +/- 6.3 U/ml; benign disease, from 21.4 +/- 7.3 to 28.4 +/- 2.1 U/ml). P43 antigen significantly enhanced the low levels of IL-10 in the benign lymphocytes (from 1.8 +/- 0.4 to 8.4 +/- 1.5 U/ml) while the high levels of IL-10 secreted by the PBL in patients with malignant tumors were not significantly increased (44.1 +/- 22.3 versus 50.1 +/- 12.6 U/ml). The study showed a difference in the immune response of lymphocytes between malignant and benign tumors. When the current results were analyzed according to the type of response, i.e. in terms of whether at least two cytokines of either type 1 or type 2 were elevated, a significant type 2 response was observed in the PBL of patients with malignant breast cancer (IL-10 and IL-4). These results may explain why antitumor response is impaired in patients with breast cancer.

H+ back diffusion stimulating gastric mucosal blood flow in the rabbit fundus.

The effect of barrier breakers on gastric mucosal blood flow (MBF) has been disputed, but the influence of acid back diffusion alone has never been studied. In anesthetized New Zealand white rabbits, intramural pH (pHi) and gastric MBF were measured with an antimony microelectrode and with radioactive microspheres (51Cr, 85Cr, 141Ce), respectively. Innervated fundic pouches were perfused with solutions of varying [H+] at 37 degrees C. In the rabbit, back flux of H+ is linearly dependent on luminal [H+] and in the present studies a direct positive linear correlation was found between luminal [H+] and MBF (r = 0.97 P < 0.001) while pHi remained unchanged up to luminal [H+] of 80 mM. The usual 80% increase in MBF induced by 80 mM HCl was prevented by pretreatment with vasopressin, which decreased pHi and caused gross ulceration. Without vasopressin, [H+] of 120 mM HCl produced gross mucosal ulceration and a decrease in MBF and pHi. Our data suggest that back diffusion of H+ influences MBF in the rabbit. There is an increasing MBF caused by increasing luminal [H+] up to 80 mM, beyond which MBF decreases. When the balance between back diffusion and MBF is disturbed by a vasoconstrictor or a high luminal [H+], pHi decreases and gross ulceration occurs.

The effect of acid perfusion on mucosal blood flow and intramural pH of rabbit duodenum.

To evaluate the role of blood flow for acid tolerance of the duodenal mucosa, we perfused the duodenums of anesthetized rabbits with different concentrations of hydrochloric acid (HCl). Acid perfusion stimulated blood flow to the duodenal wall in a concentration-dependent fashion up to 80 mmol/L HCl (0 mmol/L; 0.44 +/- 0.05, 10 mmol/L; 0.84 +/- 0.14, 50 mmol/L; 1.44 +/- 0.11, 80 mmol/L; 2.03 +/- 0.12, 100 mmol/L; 1.82 +/- 0.07 ml/gm/min X +/- SEM). The pH in the lamina propria of the mucosa, which was measured with antimony microelectrodes was not changed in experiments during perfusion with 50 and with 80 mmol/L HCl in normotension. Acidosis in the lamina propria could be demonstrated only when the duodenum was perfused with 100 and with 80 mmol/L HCl combined with hemorrhagic hypotension. Damage to the mucosa, which developed after 30 and 60 minutes of acid perfusion, also showed a H+-dependent pattern. Reduction of blood flow by hemorrhagic hypotension aggravated the morphologic damage. We conclude that luminal acid stimulates blood flow in the duodenum. The decrease in blood flow induced by hypotension results in a greater susceptibility to mucosal damage.

Failure of cimetidine to prevent gastroduodenal ulceration and bleeding after renal transplantation.

Treatment of renal transplant patients with the H2-antagonist cimetidine has previously been assumed to be of reasonable prophylactic value in controlling the incidence of the postoperative complications of gastric or duodenal ulceration. We attempted to evaluate the performance of the drug in a controlled trial by treating transplant patients with either cimetidine or a placebo. Of the 59 patients accepted for the trial, four had to be excluded eventually because of irregularities in the administration of the drug and, in on case, nonfatal respiratory failure. Six of 27 from the cimetidine group had erosions or ulcers by the third day after surgery and two more had them by the end of the fourth week. Three of 28 placebo patients developed lesions after 3 days and three more developed them after 7 weeks. In the months after transplantation, one cimetidine and two placebo patients developed ulcers. Bleeding occurred three times with cimetidine and twice with the placebo. Renal function was similar in both groups as was the necessity of transplantectomy because of irreversible rejection. We conclude that cimetidine does not lower the incidence of gastroduodenal mucosal lesions and upper gastrointestinal bleeding after renal transplantation, nor does it influence rejection of the allograft.

Postoperative infections in colonic surgery after enteral bacitracin-neomycin-clindamycin or parenteral mezlocillin-oxacillin prophylaxis.

In a prospective randomized, blind trial, three groups of patients undergoing elective colonic surgery were compared for frequency of surgical wound infection, intra-operative wound contamination and other postoperative infections. All patients allotted to the three groups received whole gut irrigation (101 balanced salt solution) by gastric tube on the evening before surgery and were treated as follows. Group A: no antibiotics; Group B: neomycin (1 g/l) + bacitracin (50,000 IU/l) + clindamycin (900 mg/l), contained in the last 31 of irrigation fluid; Group C: mezlocillin (4 g) + oxacillin (2 g) intravenously (iv) at induction of anaesthesia, followed by two identical doses at 8 and 16 h. The rate of postoperative wound infection was highest in A (38 per cent) and much lower in B (3.3 per cent, P less than 0.002) and C (6.9 per cent, P less than 0.004). The difference between B and C was statistically not significant. In A a correlation was established between the degree of wound contamination and the occurrence of wound infection. Intra-operative wound contamination was lowest in B (30 per cent), equal in A (58.1 per cent) and B (55.2 per cent). Other infections were least frequent in group C (four of 29 patients), but were not significantly different to groups B (six of 30) and A (nine of 31). It is concluded that antibiotics together with an effective mechanical preparation considerably reduce the rate of wound infection in colonic surgery.

The gastric mucosal barrier and ulceration.

The gastric mucosal barrier is that property which defends against acid and which impedes diffusion of acid from the lumen into the mucosa. The disappearance of luminal H+ is linearly related to luminal (H+) both in the normal stomach and in stomachs exposed to barrier breakers. The latter invaribaly produce anatomic evidence of surface cellular injury. Strong direct evidence for back diffusion of luminal H+ derives from the recent demonstration of a highly significant correlation between the disappearance of luminal H+ and the pH of the lamina propria measured by an implanted microelectrode. The permeabilities of the antrum and fundus to H+ differ from each other in the same species and in different species. Gastric ulceration does not occur in the absence of luminal acid and is not dependent upon the absolute loss of H+ from the luminal solution. Mucosal ischemia induced by hemorrhage reduces tolerance against ulceration as does inhibition of acid secretion, acidification of the tissue caused by absence of nutrient bicarbonate, inhibition of carbonic anhydrase, and blockade of anion exchange by SITS. A tentative schema is proposed by which defense against luminal acid is accomplished in gastric mucosa.

The multidrug-resistance modifiers verapamil, cyclosporine A and tamoxifen induce an intracellular acidification in colon carcinoma cell lines in vitro.

In this study we have investigated the effects of the multidrug-resistance (MDR) modifiers verapamil (VPM), cyclosporin A (CsA) and tamoxifen (TMX) on the intracellular pH(pHi) of four colon carcinoma-derived cell lines with low P-glycoprotein expression (CaCo-2, HT-29, SW 620 and SW 480). Addition of VPM (1 mu M), CsA (1 microgram/ml) or TMX (2 microM) in HEPES- or bicarbonate/CO2-buffered Ringer's solution was followed by dose-dependent and reversible decreases of the pHi (0.1-0.3 units) of all cell lines, as measured ratiometrically by the changes in the pH-dependent fluorescence of bis(carboxyethyl)carboxyfluorescein (BCECF). Testing the effects of the resistance modifiers on the Na+/H+ antiporter and bicarbonate trans-porters under appropriate buffer conditions and addition of inhibitors (amiloride, DIDS) revealed that the chemomodulator-induced acidification does not interfere with the function of these major pHi-regulating acid-base transporters. The induction of changes in pHi shows no correlation with MDR-reversing activity of the drugs and our data do not support the P-gp-inhibition-mediated accumulation of acidic substrates as underlying mechanism. In addition to the P-gp-directed MDR-reversal, chemomodulator-induced intracellular acidification may enhance the chemosensitivity of the cells especially under alkaline extracellular conditions, and contribute to the decreased efficacy of MDR-modifiers in acidic extracellular environments and to the chemosensitising effect of VPM in P-gp-negative cell lines.

Restoration of anal sphincter function by single-stage dynamic graciloplasty with a modified (split sling) technique.

BACKGROUND: Controlled muscle fiber conversion by electrostimulation makes transformation of fast twitching type II muscle fibers to slow twitching type I fibers possible, which gives skeletal muscles the capacity for tetanic contraction. This phenomenon has been recently applied in the so-called "dynamic graciloplasty" to restore function of an insufficient or excised anal sphincter. This paper describes our results with this method in patients with fecal incontinence or following an abdomino-perineal resection (APR) of the anorectum. METHODS: From April 1992 through April 1997, 28 patients (12 women and 16 men) were treated by dynamic graciloplasty. The median age was 53.5 years (range 16 to 79). Indications were as follows: APR + synchronous restoration of the excised sphincter by graciloplasty (n = 12); total anorectal reconstruction (TAR) following APR in the past (n = 6); Patients with acquired fecal incontinence (n = 4); and Congenital atresia (n = 6). Muscle transposition, implantation of stimulation electrodes and pulse generator were done as a single-stage procedure, the "neosphincter" was wrapped in a modified technique (split-sling technique). Muscle transformation was performed by controlled neuromuscular stimulation during 8 weeks (from 1992 to 1995) and 4 weeks (since 1996), respectively. RESULTS: No postoperative mortality (90 days) was observed in either group. In our early experience, rectal injury occurred in 4 patients as the most prominent complication. Evaluation of the functional outcome showed the best results in patients operated either for congenital of acquired incontinence who achieved a continence for solids and liquids or solids alone, respectively (1 or 2 according to Williams' score) in 90%, while patients following APR showed a satisfying outcome (continence for solids and liquids, solids alone or with occasional episodes for liquids) in only 55.5%. In patients following APR, defecation disorders turned out to be the most prominent functional problem and had to be treated by enemas. CONCLUSION: In this series, we have been able to perform dynamic graciloplasty as a one-stage procedure using a modified muscle wrap (split-sling-technique) thus reducing the time period until continence could be achieved to 7 weeks. We found the appropriate tension of the muscle wrap essential to prevent direct injury to the rectum as it was seen in our early experience. For this reason, we have introduced a modified device to perform intraoperative anal manometry and to measure pressures created by the neosphincter objectively.

Long-term results of modified graciloplasty for sphincter replacement after rectal excision.

OBJECTIVE: Restoration of the anal sphincter by means of electrically stimulated (dynamic) graciloplasty is a new therapeutic option for patients with severe faecal incontinence or those having abdomino-perineal resection (APR) of the anorectum. The present study reviews the outcome of total anorectal reconstruction (TAR) after APR for low rectal cancer or recurrent anal cancer. METHODS: From 1992 to 2000, 35 of 64 patients treated with dynamic graciloplasty had a TAR performed either synchronously (n=26) or as a secondary procedure one to five years after rectal excision (n = 9). RESULTS: The most frequent complication was injury or erosion of the neorectum (n = 9) which, was avoided with increasing surgical experience. Defaecation disorders and consequent incontinence were the most common functional problem and had to be treated with periodical enemas. CONCLUSION: Although sphincter replacement by means of TAR after APR led to poorer functional results than those achieved in patients treated with dynamic graciloplasty for faecal incontinence, TAR remains a valid treatment option for patients who do not tolerate a permanent stoma.

Factors influencing the restitution of the duodenal and colonic mucosa after damage.

Rapid epithelial restitution is an important protective mechanism which enables the gastrointestinal mucosa to reestablish epithelial integrity following superficial injury within hours. In this study we examined the influence of an acidic luminal pH, removal of the necrotic layer, nutrient bicarbonate, calcium and sodium desoxycholate (Na-DOC) on restitution in the rabbit duodenum in vitro and the role of Na-DOC and calcium for rapid restitution of the human colon in vitro. Transmucosal potential difference (PD), short-circuit current (lsc) were measured and resistance against passive ion flux (R) was calculated. Electrophysiological changes paralleled morphological injury but did not necessarily reflect restitution in all experiments. The extent of mucosal injury was assessed by computerized real-time morphometry. 5 hrs after luminal exposure to 10 mH HCl for 10 min residual damage (RD) was 14% in the duodenum. Luminal pH of 3.0 (RD of 30%), removal of necrotic layer at acidic luminal pH (RD of 66%), absence of bicarbonate from the serosal solution (RD of 35% at neutral luminal pH; RD of 96% at acidic luminal pH) and removal of calcium from the serosal solution (RD of 58%) impaired restitution in the duodenum. Continuous postinjury luminal Na-DOC exposure did not influence restitution in the duodenum (RD of 19%). 5 hrs after luminal exposure to 0.5 mM Na-DOC for 10 min RD was 26% in the human colon. Continuous postinjury luminal Na-DOC exposure (RD of 51%) and removal of calcium from the nutrient solution (RD of 65%) impaired restitution in the human colon. Thus we conclude that restitution of the rabbit duodenum in vitro requires a necrotic layer and bicarbonate flux to withstand acidic luminal pH, while restitution is not affected by Na-DOC. In the human colon Na-DOC inhibits restitution. Both the duodenum and colon require calcium for rapid restitution.

Preservation and restoration of sphincter function in patients with rectal cancer.

Radical resection of rectal cancer is the standard treatment for curing this disease. Half of these tumours are located in the rectosigmoid region or the upper third of the rectum and are, therefore, easily resectable with preservation of the sphincter muscles, thus guaranteeing acceptable continence in most patients. However, tumours that originate in the lower parts of the rectum have been accompanied with the need for an abdominoperineal resection and the threat of a permanent colostomy. In the past 20 years, sphincter-saving surgery has become increasingly common in the treatment of tumours of the middle and low rectum due to the knowledge of tumour growth, the use of stapling devices, and the knowledge of the physiology of the pelvic floor and the sphincter muscles, respectively. Recent surgical techniques of resection of the 'ultralow' rectum (intersphincteric resection) and the reconstruction by coloanal anastomosis are reviewed. Functional problems following ultralow resections are emphasized, as well as the possibility of sphincter restoration after abdominoperineal resection by use of dynamic graciloplasty. Taking all surgical options into account, a permanent colostomy for rectal cancer can be avoided in most curatively and electively operated patients.

[A clinical-radiological investigation concerning the accuracy of diatrizoate (Gastrografin) in the demonstration of anastomosis dehiscence and perforation of the gastro-intestinal tract (author's transl)]. / Klinisch-radiologische Untersuchung über die Treffsicherheit des Diatrizoat-(Gastrografin-) Testes zum Nachweis von Anastomosendehiszenzen und Perforationen des Gastrointestinaltraktes

A Gastrografin test is described for diagnosing perforations and dehiscence of anastomoses in the gastro-intestinal tract by carrying out a simple urine analysis. False positive and false negative results can be avoided by obtaining radiographs of urine samples under standard conditions. The accuracy of the method was checked in 97 patients by comparing the results of the urine analysis with radiographic examinations and with the clinical course. From this, it appears that the test is reliable, simple and capable of being used anywhere. The test is therefore recommended a) where there is a lack of radiographic facilities, b) for immobile patients, c) where there is clinical suspicion of a perforation or dehiscence of an anastomosis in the absence of radiographic findings and d) in individual cases where the radiographic changes are positive.

[Clinical significance of prostaglandins in the gastrointestinal tract]. / Klinische Bedeutung der Prostaglandine im Gastrointestinaltrakt.

Endogenous prostaglandins are involved in several gastrointestinal diseases such as peptic ulcer. Crohn's disease, ulcerative colitis and radiation enteritis, although a casual role has not been proven in any condition. At present therapeutic indications are confined to the treatment of peptic ulcer with synthetic analogues at a dosage which inhibits acid secretion.