Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

PURPOSE: The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS: Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS: Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION: This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Evidence for increased nitric oxide production after liver transplantation in humans.

To evaluate the role of in vivo-produced nitric oxide (NO) after orthotopic liver transplantation, nitrate, a stable end product of spontaneous NO conversion in blood, was assayed in plasma samples of 32 patients. In 31 patients, nitrate increased from 36 +/- 2 microM to 137 +/- 8 microM within the first 6 postoperative days. In 11 out of 12 patients with an uneventful early postoperative course, nitrate increased from 33 +/- 2 microM to 70 +/- 8 microM, and returned to baseline levels within 2-3 days. In the remaining 20 patients with episodes of rejection and/or infection, the nitrate peak was augmented and prolonged. Ten patients suffering from these events in the later postoperative course showed a second nitrate elevation. In 31 patients, effective plasma levels of cyclosporine were reached 4-5 days after OLT. The patient without significant elevation in plasma nitrate had effective levels already at day 1. After liver resection or coronary bypass grafting, the median nitrate level remained at 21 microM (range 15-36 microM; healthy persons: median 24 microM, range 18-32 microM). After kidney transplantation nitrate was elevated in the early postoperative course. Thus, NO formation appears to be increased after solid organ transplantation, but not after other surgeries. After OLT, the increase appears to occur (a) in response to rejection and/or infection, and (b) 4-6 days after surgery in the absence of overt complications. In the latter case, NO might be involved in subclinical rejection and its production is possibly dependent upon the effectiveness of the immunosuppressive therapy.

Determination of hepatocellular enzymes in effluent of human liver grafts for preoperative evaluation of transplant quality.

In 50 human livers harvested for transplantation, injury was assessed by determination of liver enzymes (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and creatine kinase) and of thrombomodulin in the effluent perfusate after cold ischemia. The results were compared with the morphology and the clinical course after transplantation. Whereas the release of the markers of endothelial cell injury correlated neither with the history of the graft nor with the postoperative course, the release of hepatocellular enzymes into the perfusate did indicate the severity of liver injury, even when biopsy showed normal liver tissue. Seven of 12 livers with high activities of hepatocellular enzymes in the effluent (activity of more than twice the median) showed delayed onset of function or primary nonfunction. In the other 38 livers with enzyme activities below this borderline, no delayed functioning or primary nonfunction was observed. Thus, determination of liver enzyme activities in the effluent makes it possible to identify those livers in which initial nonfunction is very unlikely, a potential that is especially valuable in livers shown by anamnesis or morphology to be of borderline quality.

Value of an extended monoethylglycinexylidide formation test and other dynamic liver function tests in liver transplant donors.

Measuring monoethylglycinexylidide (MEGX) formation after intravenous administration of lidocaine in potential organ donors (MEGX test) has been advocated as a useful test to select donor livers for transplantation, but some groups have demonstrated a low test efficacy. We, therefore, investigated the value of an extended MEGX formation test and the value of other dynamic liver function tests, in selecting suitable human donor livers. In 51 human multi-organ donors, we measured elimination of galactose, indocyanine green, and lidocaine, as well as formation of MEGX, at 15, 30, and 60 min after administration of the test substances. In the early postoperative period, the function of the transplanted liver was then classified as good or poor, as defined by a prothrombin time above or below 65% by day 4 and fibrinogen concentration above or below 300 mg/dl by day 7. Donor characteristics and preservation modalities were very similar between the two groups. Galactose, indocyanine green, and lidocaine metabolism failed to predict good or poor graft function in the early postoperative period. MEGX serum concentrations, however, were significantly higher in the group of donors whose organs functioned well in the recipients, as compared with donors whose organs functioned poorly in the recipients. This was true for MEGX concentrations at 15 min (117+/-9 vs. 90+/-9 ng/ml; P=0.03), 30 min (108+/-8 vs. 86+/-8 ng/ml; P=0.04), and 60 min (100+/-6 vs. 73+/-5 ng/ml; P=0.006). Extending the MEGX formation test from 15 to 60 min improved test efficacy. Maximal MEGX concentration in 9 or up to 12 consecutive blood samples, drawn between 3 and 120 min after lidocaine infusion, was also significantly higher in donors whose organs functioned well, than in donors whose organs functioned poorly (129+/-10 vs. 101+/-10 ng/ml; P=0.03). Although the groups with good and poor organ function differed significantly with respect to their MEGX serum concentrations, and although efficacy of the MEGX test was improved by extending the test from 15 to 60 min, the overlap in individual MEGX serum concentrations was still so wide that it is virtually impossible to predict early graft function only on the basis of the MEGX test in the donor. Therefore, the MEGX test, although of potential scientific interest, does not predict early graft function with an accuracy necessary for clinical use.

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Monitoring of soluble HLA class I size variants after liver transplantation.

To monitor soluble HLA class I (sHLA-I) and their size variants after liver transplantation (LTX) plasma samples from 22 LTX patients were studied by sHLA-I ELISA, SDS-PAGE, and densitometry. Samples collected were classified into three groups: Group 1 comprised samples taken during episodes without complications, group 2 during episodes of cholangitis/cholestasis (CC), and group 3 during episodes of acute rejection (AR). Compared to group 1 (0.27 +/- 0.03 SEM microg/ml) mean sHLA-I increments in groups 2 and 3 were with 0.53 +/- 0.05 SEM microg/ml and 0.47 +/- 0.04 SEM microg/ml increased (p < 0.001). The same samples were studied by SDS-PAGE and the 43, 39, and 35 kD sHLA-I variants were quantified densitometrically. In samples of group 1 ratios of 43 vs. 39 kD bands revealed a mean of 2.1 +/- 0.3, whereas in group 2 and 3 these were only 0.8 +/- 0.1 SEM and 0.9 +/- 0.1 SEM, respectively, (p < 0.001). For the relation between 43 and 35 kD variants a reduced ratio of 1.1 +/- 0.2 SEM was confined to group 3 samples (p < 0.001), as groups 1 and 2 had ratios of 13.4 +/- 2.3 SEM and 8.4 +/- 2.9 SEM, respectively. This indicates that elevated sHLA-I levels during CC or AR are mainly caused by increases of 39 and/or 35 kD sized molecules. Therefore, our study demonstrates, that after LTX the contribution of sHLA-I size variants to total sHLA-I amounts changes drastically during immune activation pointing to different mechanisms of sHLA-I release.

Predictive assays for the therapy of rectum carcinoma.

Cytofluorometric DNA measurements showed that about 55% of rectum carcinoma (129 patients) had tumours with an abnormal DNA content (DNA aneuploidy). For patients with such a tumour the prognosis was worse than for patients with DNA diploid tumours. From the DNA histograms the number of S-phase cells was calculated. In tumours with the stage pT3, which disseminated to lymph nodes or metastasized, a higher number of S-phase cells was found than in tumours with the staging pT3N0M0. In all untreated tumours cells with micronuclei were found. This demonstrated cell loss. In most tumours this effect was considerable. The ratio:number of S-phase cells/number of cells with micronuclei may allow a rough estimate for cell turnover. In patients with a bad prognosis and in those patients who had a local recurrence after resection of the tumour this ratio was high. In 34 patients the parameters were measured before and after preoperative radiotherapy. In some tumours a rapid increase of S-phase cells occurred after irradiation, this effect might express repopulation. In these patients a local recurrence was frequently found. From the data obtained so far a prediction for local recurrences might be possible from the determination of nuclear protein bound SH-groups. The determination of micronuclei indicated that it can be used as a measure for radiation response in tumours. All parameters show a high variability between individual tumours. A further study is useful whether the measured parameters are suitable as predictors.

Percutaneous dilatational tracheostomy--early results and long-term outcome of 326 critically ill patients.

OBJECTIVE: To analyze perioperative and postoperative complications and long-term sequelae following percutaneous dilatational tracheostomy (PDT). DESIGN: A prospective clinical study of patients undergoing PDT. SETTING: Seven intensive care units at a University hospital PATIENTS: 326 intensive care patients (202 male, 124 female; age: 11-95 years) with indications for tracheostomy. INTERVENTIONS: Using tracheoscopic guidance, 337 PDTs were performed according to Ciaglias' method. In 106 decannulated patients, tracheal narrowing was assessed by plain tracheal radiography. RESULTS: Two procedure-related deaths were seen (0.6%). Perioperative and postoperative complications occurred with 9.5% of the PDTs. One of 106 patients, who were followed-up for at least 6 months, showed a clinically relevant tracheal stenosis. Subclinical tracheal stenosis of at least 10% of the cross-sectioned area was recognized in 46 of 106 patients (43.4%). In the univariate analysis, the degree of stenosis was influenced by the age of the patient (p = 0.044), the duration of intubation prior to PDT (p = 0.042) and by the duration of cannulation (p = 0.006). These parameters had no statistical significance in a multiple regression model. CONCLUSION: When performed by experienced physicians, percutaneous dilatational tracheostomy under fiberoptic guidance is a safe method. The risks of early complications and of clinically relevant tracheal stenoses are low. Subclinical tracheal stenoses are found in about 40% of patients following PDT.

Lactic acidosis from thiamine deficiency during parenteral nutrition in a two-year-old boy.

This is a case report of a two-year-old boy who was operated electively for a blind-loop syndrome of the proximal jejunum. Because of the appearance of chylous ascites, parenteral nutrition was carried out postoperatively. The boy developed a severe uncompensated acidosis and paralytic ileus. Relaparotomy on suspicion of ischemic bowel did not explain the cause of the acidosis and ileus. Postoperatively, the child's condition worsened, requiring intensive care. The drastically elevated lactate levels corroborated the eventually suspected diagnosis of a vitamin B1 deficiency syndrome. The administration of thiamine within two hours produced correction of the acidosis without further bicarbonate therapy. In 24 hours circulation was stabilized. Two months post-operatively the boy had completely recovered from the sequelae of his shock event.

[Quality assurance from the viewpoint of the surgeon]. / Qualitätssicherung aus Sicht des Chirurgen.

The problem of global standardization, clinical documentation, and confidentiality of methods in quality control are discussed. It is concluded that conventional methods of quality assurance should be further developed in order to avoid investments into administration tools that have not yet proved any effectiveness worldwide. Future developments should be orientated to achieve benefits for the patient and to promote surgical excellence.

[Mechanical compression anastomosis (AKA-2) of the colon and rectum. Results of a prospective clinical study]. / Die maschinelle Kompressionsanastomose (AKA-2) an Colon und Rectum. Ergebnisse einer prospektiven klinischen Studie.

Based on the highly superior mechanical and functional properties of an experimental sutureless anastomosis performed without any foreign material compared to conventional anastomosis we have introduced a sutureless compression anastomosis (AKA-2) to colorectal surgery and controlled the outcome prospectively. This type of anastomosis was employed in 30 patients with sigmoid and rectal resections for carcinomatous and inflammatory bowel disease. The first 3 patients and further 3 high-risk patients got a protective colostomy. The clinical outcome was uneventful in all patients but 2 with anastomotic fistula. Radiological controls showed no further fistula. The study revealed no negative side effects of the compression anastomosis but the procedure seems to provide considerable advantages by complete mechanical relief of the anastomosis and early epithelial covering of the anastomotic line.

[Surgery in patients with renal failure in emergency and elective interventions]. / Chirurgie bei niereninsuffizienten Patienten unter Notfall- und Elektivbedingungen.

The classification of renal insufficiency into stages of full compensation, compensated and decompensated retention and terminal renal failure is of importance if patients with impaired renal function are to undergo elective and emergency surgery. Furthermore, it should be established whether the renal disease is stable or progressive. Preoperatively, particular attention should be paid to problems of fluid and electrolyte homoeostasis as well as to acid-base balance. Many drugs should be avoided altogether in patients with kidney disease.

[Can "internal intestinal splinting" prevent ileus recurrence? Results of a retrospective comparative study]. / Kann die "innere Darmschienung" das Ileusrezidiv verhindern? Ergebnisse einer retrospektiven Vergleichsstudie.

The high rate of recurrence after the treatment of adhesive obstruction demands special prophylactic treatment. In a 13-year period, 52 out of 95 patients with major adhesions were provided with a long nasointestinal tube for intestinal splinting intraoperatively. The was being left in situ on an average of 6.6 days. After an observation period of at least 36 months a recurrence was seen in 2 of these 52 patients (3.9%; causes: volvulus after 6 months/fibrinous peritonitis on the 6th postoperative day). Amongst the 43 'non-splinted' patients, recurrence of adhesive obstruction was documented in 8 cases (18.6%; causes: adhesions after 0.3-136.9 months). In the course of after-care abdominal complaints were significantly fewer in patients who had been splinted. Complications concerning the nasointestinal tubes did not occur. The rate of perioperative complications was similar in both groups.

[Effect of liver transplantation on general techniques of liver resection]. / Einfluss der Lebertransplantation auf die allgemeinen Techniken der Leberresektion.

The techniques of liver surgery and liver transplantation have benefited from one another. This is demonstrated by the sophisticated methods in modern transplant surgery, such as size reduction, splitting and resection during organ harvesting in living donors. However, techniques of transplantation have also influenced resection procedures by the use of one procedure or another (depending on the stage), as clearly shown by the evaluation of indications (assessment of liver function) in some diseases (Caroli syndrome, Klatskin tumor etc.). The exposure of the abdomen, the exploration of the liver, the knowledge about the tolerance of the liver to ischemia and the techniques of ex situ resection demonstrate the close ties between liver transplantation and liver resection. Standards of the procedure of liver transplantation and resection are explained. Details of techniques, parallels and influences are discussed.

[Methodology in puncture tracheostomy. Technique, indications and contraindications]. / Methodik der Punktionstracheostomie. Technik, Indikationen und Kontraindikationen.

Percutaneous dilatational tracheostomy is a relatively new minimally invasive method for bedside tracheostomy of immobilized adult patients. This procedure is based on the Seldinger technique: after percutaneous puncture of the trachea beneath the cricoid a guidewire is placed into the trachea. Afterwards the wound channel around the wire is dilated until a tracheal cannula can be put in place. The surgeon requires not only precise knowledge of cervical anatomy and manual skills to perform this technique but should also be aware of contraindications and how to proceed if there are technical problems. Based on our personal experience of more than 300 percutaneous dilatational tracheostomies, appropriate recommendations are given.

[Sutureless compression anastomosis of the distal colon and rectum. An expanded report of experiences with a total of 140 patients]. / Die nahtlose Kompressionsanastomose am distalen Colon und Rectum. Ein erweiterter Erfahrungsbericht über insgesamt 140 Patienten.

Based on animal experiments with a sutureless anastomosis, the sutureless compression anastomotic technique (AKA) was introduced to colorectal surgery. The procedure was applied to 140 patients following resections of the distal colon and rectum. The outcome was controlled prospectively. Anastomosis fistulae occurred in 8 out of 140 patients (5.7%). Excluding the 16 patients with a primary protective colostomy the leakage rate was 6.4%. Out of 67 patients with an anastomosis height of 10 cm or less, 6 developed fistulae (8.9%). Excluding the 11 patients with primary colostomy the leakage rate was 10.7%. 3 patients showed clinically inapparent fistulae in the routinely performed gastrografin enema. The clinical application of the compression-anastomotic technique revealed no disadvantage. The technique seems to have advantages due to more areactive anastomosis healing.

[Intra-abdominal melanoma metastases and their prognosis]. / Intraabdominelle Melanommetastasen und ihre Prognose.

Very often in advanced stages of malignant melanoma several organs are involved. In a small number of patients only intraabdominal metastases seem to occur. The analysis of 106 cases found in the literature and 6 cases from our department revealed the small bowel and the stomach as the main site of metastases, giving rise to intestinal bleeding and obstruction. Apart from emergency cases, even in the advanced stage of disease palliative procedures are indicated since the prognosis in individual cases is quite unpredictable, as seen in some cases with a survival time of up to seven years.

[Enlargement surgery of duodenal stenosis caused by chronic pancreatitis with a pedicled open jejunal graft]. / Erweiterungsplastik einer durch chronische Pankreatitis bedingten Duodenalstenose mittels gestielten offenen Jejunumtransplantates.

A method of enlarging localized duodenal stenosis is described in a case of chronic pancreatitis. After incision of the duodenum in the stenosis area, the defect is closed by an open, vascularized jejunum transplant. This method has several advantages over by-pass procedures. The physiological passage of the ingesta is preserved. Other methods such as a pedicle graft from the stomach or the colon may be functionally equally good, but more dangerous.

[Absorbable synthetic mesh in abdominal surgery. Indications, operative procedures and results]. / Resorbierbare Kunststoffnetze in der Abdominalchirurgie. Indikation, Operationsverfahren und Ergebnisse.

Compared to non absorbable mesh, the use of absorbable mesh offers a wider range of surgical indications. Otherwise the complications of implanted non absorbable mesh can be almost avoided. Reporting the experience of 41 own cases in abdominal surgery, indications, surgical technique and complications of absorbable mesh are demonstrated.

[Late pelvic recurrence of rectal cancer]. / Pelvines Spätrezidiv eines Rectumcarcinoms.

We report on a case of late pelvic recurrence of a rectal carcinoma 15 years after primary abdominoperineal resection and radiotherapy (primary stage T2 N0 M0; Dukes B). The origin of the recurrent tumour was undoubtfully proved by histological examination of the palliatively resected recurrent carcinoma.