Adenocarcinomas of the upper third of the rectum and the rectosigmoid junction seem to have similar prognosis as colon cancers even without radiotherapy, SAKK 40/87.

PURPOSE: To investigate the prognosis of adenocarcinomas of the upper third of the rectum and the rectosigmoid-junction without radiotherapy. METHODS: Patients from a multicenter randomized controlled trial from 1987-1993 on adjuvant chemotherapy for R0-resected colorectal cancers with stage I-III disease were retrospectively allocated: cancers of the lower two-thirds of the rectum (11 cm or less from anal-verge, Group A, n = 205), of the upper-third of the rectum and rectosigmoid-junction (>11-20 cm from anal-verge, Group B, n = 142), and of the colon (>20 cm from anal-verge, Group C, n = 378). The total mesorectal excision (TME) technique had not been introduced yet. The adjuvant chemotherapy turned out to be ineffective. None of the patients received neoadjuvant or adjuvant radiotherapy. RESULTS: The patients had a regular follow-up (median, 8.0 years). The 5-year disease-free survival (DFS) rate was 0.54 (95%CI, 0.47-0.60) in Group A, 0.68 (95%CI, 0.60-0.75) in Group B, and 0.69 (95%CI, 0.64-0.74) in Group C. The 5-year overall survival (OS) rate was 0.64 (95%CI, 0.57-0.71) in Group A, 0.79 (95%CI, 0.71-0.85) in Group B, and 0.77 (95%CI, 0.73-0.81) in Group C. Compared with Group C, patients in Group A had a significantly worse OS (hazard ratio [HR] for death 2.10) and a worse DFS (HR for relapse/death 1.93), while patients in Group B had a similar OS (HR 1.12) and DFS (HR 1.07). CONCLUSIONS: Adenocarcinomas of the upper third of the rectum and the rectosigmoid-junction seem to have similar prognosis as colon cancers. Even for surgeons not familiar with the TME technique, preoperative radiotherapy may be avoided for most rectosigmoid cancers above 11 cm from anal-verge.

Surgical experiences with 191 implanted venous Port-a-Cath systems.

The introduction of totally implantable catheter device has provided a simple, permanent and safe access to the vascular system. They have greatly improved the quality of life of the patients involved, whose activities, daily hygiene and bodily attractiveness remain practically unrestricted. To gain the greatest freedom from complications in the use of fully implantable catheter devices, the following requirements are important in to our experience: 1. Experience with only one kind of catheter system, irrespective of whether it is claimed to be the best, the simplest, or the cheapest. Various companies offer a variety of totally implantable catheter devices. Every system has its advantages and its disadvantages. However, each system also requires a considerable degree of surgical experience and experience in postoperative care and management to keep the complication rate as low as possible. Frequent changing to other systems does not enlarge the experience obtained. 2. The experience of the surgical team. In Basel catheter systems are implanted by three surgeons only. We are convinced that this contributes to our relatively low rate of complications. Brothers et al. (1988) also show that the rate of complications is inversely related to the experience of the surgeon involved. 3. The experience, commitment and training of the nursing staff responsible for the care and maintenance of the implanted catheter device. This care and maintenance of the implanted catheter device should start immediately after the surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastro-intestinal metastases as first clinical manifestation of the dissemination of a breast cancer.

Of 1192 patients treated for breast cancer, four had extrahepatic gastro-intestinal metastases as first clinical manifestation of the tumour dissemination. One woman presented with gastric metastases mimicking a linitis plastica. Another had metastases localized to the rectum also mimicking a linitis plastica. Two women had peritoneal and retroperitoneal metastases that caused, in one case, a right hydronephrosis. Histology of the four primary tumours showed invasive lobular carcinoma (ILC) mixed with invasive ductal carcinoma in two. However, ILC exclusively was found at the site of the gastro-intestinal metastases involving the serosal layer (two cases) and extending to the submucosa (one case) or to the mucosal stroma (one case). Thus, when a women with previous history of invasive lobular breast cancer experiences gastro-intestinal symptoms, particular attention should be paid to the large and deep biopsy of lesions to ascertain the histological type and whether oestrogen or progesterone receptors differ from those of the primary breast lesion. Since survival is extremely variable (one woman is alive 7 years after the discovery of gastro-intestinal metastases), treatment including surgery, hormonal manipulation and chemotherapy with the expectation of a cure is often justifiable, particularly if no other extensive metastases are present.

Adjuvant portal liver infusion with 5-fluorouracil and mitomycin in colorectal cancer. SAKK.

Between 1981 and 1987, 533 patients from 9 institutions were entered in a randomized trial to assess the value of adjuvant perioperative portal infusion with Fluorouracil and Mitomycin as compared to radical surgery alone. Analysis of 469 evaluable patients at a median follow-up of 5.8 years revealed 110 recurrences in the control and 94 recurrences in the infusion group. Estimated 5-year disease-free survival was 52% and 61% respectively (hazard ratio: 1:0.75; 95% confidence interval 0.57-0.99; p = 0.046). Overall survival was 59% in the control and 69% in the infusion group (p = 0.048). Adjuvant portal infusion did not influence the occurrence of liver metastases but reduced the overall recurrence rate.

Hematological toxicity of adjuvant portal liver infusion with fluorouracil, mitomycin and heparin.

Adjuvant perioperative liver infusion chemotherapy with fluorouracil, mitomycin and heparin caused mild but significant myelosuppression in the first two postoperative weeks. This was associated with a slightly increased bleeding tendency. Mortality was not increased. Future trials might combine chemotherapy with hematopoietic growth factors in order to minimize myelosuppression.

Early hematological toxicity of adjuvant perioperative intraportal and intravenous chemotherapy with fluorouracil, mitomycin and heparin in colorectal cancer. Swiss Group for Clinical Cancer Research.

BACKGROUND: From 1987 to 1993 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III adjuvant trial in patients with colorectal adenocarcinoma with the objective of comparing intraportal versus intravenous perioperative chemotherapy. PATIENTS AND METHODS: Patients younger than 75 years had a curative en bloc resection of their cancer and were then randomized into three arms: 1. adjuvant perioperative portal liver infusion with fluorouracil, mitomycin and heparin, 2. adjuvant subclavian intravenous infusion with the same regimen and 3. no adjuvant treatment. The hematological toxicity was evaluated by hemoglobin determination and leucocyte and thrombocyte counting before and during ten days after surgery. RESULTS: Hemoglobin showed a median decrease of 22% in the control group. This decrease is aggravated significantly by 3% through the chemotherapy. Leucocytes showed a median decrease of 7% in the control group. Perioperative chemotherapy caused a significantly higher median drop; 23% when given into the liver through the portal vein and 34% when given systemically through a subclavian catheter. Thrombocytes revealed a median decrease of 25% in the control group. Chemotherapy was not associated with a significant additional drop. CONCLUSIONS: Adjuvant perioperative chemotherapy with fluorouracil, mitomycin and Heparin as given in this study is associated with a significant mild drop in hemoglobin and leucocytes during the first 10 postoperative days. If drug dose increases are planned in future trials the addition of hematopoietic growth factors might be considered.

[Following curative resection of colorectal cancer, portal chemotherapy especially benefits non-transfused patients]. / Nach kurativer Resektion colorectaler Carcinome wirkt die portale Chemotherapie vor allem beim nicht-bluttransfundierten Patienten.

After curative resection of colorectal cancer, immediate short-term postoperative intraportal adjuvant chemotherapy reduces the relative risk of recurrence and death in the non-transfused patient significantly, when compared to transfused patients without chemotherapy. This is demonstrated in a multivariate analysis using the Cox model on a group of 469 patients who have been intraoperatively randomized to receive either intraportal chemotherapy for 7 days or no further treatment. The transfused patients with chemotherapy and those receiving neither transfusions nor chemotherapy had a relative risk of recurrence and death situated in between the two groups mentioned above, not statistically different from either of them. In the setting of this study, 7 days postoperative intraportal chemotherapy seems particularly effective in the non-transfused patients.

[Status of portal perfusion in colorectal cancer. Swiss Study Group for Clinical Cancer Research]. / Stellenwert der portalen Perfusion beim colorectalen Carcinom. Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK).

533 patients with diagnosis of operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C (MMC) and 5-Fluorouracil (5-FU) starting immediately after operation, or no adjuvant treatment. Of these, 505 (94%) were evaluable. Over the median follow-up of 8 years, the adjuvant therapy reduced the risk of recurrence by 22% (Hazard ratio = 0.78%, 95% CI 0.61-0.99; P = 0.045). The relative reduction of relapse on death was similar in all subgroups (i.e. nodal status, localization). However, adjuvant portal chemotherapy proved to be most efficient in the subgroups of patients with tumor involvement of the regional lymph nodes (Dukes C) and of patients with colon cancer. Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (i.e. local relapses, liver metastases and/or other distant metastases) in the treated group, rather than to liver relapses alone. We conclude therefore, that part of significant benefit obtained for patients with operable colorectal carcinoma treated with a single course of adjuvant chemotherapy via the portal vein might be due to the additional systemic effects of the portal chemotherapy and further study of perioperative treatment with and without prolonged chemotherapy appears worthwhile.

[Colorectal cancers: adjuvant therapy and after care (including tumor markers)]. / Kolorektale Karzinome: adjuvante Therapie und Nachsorge (inklusive Tumormarker).

Perioperative adjuvant treatment after radical surgery for colorectal cancer has proven to be possible without an increase of postoperative complications and postoperative mortality. In overcoming this surgical fear, a number of randomized studies, all of them investigating the role of adjuvant treatment, have been initiated. Preliminary results of these trials show, some of them already statistically significant, an advantage of the adjuvant treated patient group. Unless these results have been confirmed, adjuvant treatment should only be given in well designed, randomized clinical trials. Only these trials can prove the effectiveness of adjuvant therapy in radical surgery of colorectal neoplasms. In addition, these studies should be used to define the group of patients who really benefit of adjuvant treatment. The main goal of follow up methods after surgery for colorectal cancer should be the detection of asymptomatic and still treatable tumor recurrences. For this reason, frequent clinical investigations and frequent CEA level determinations seem to be the most important components at this time.

Morbidity in surgery: impact of the 50-hour work-week limitation in Switzerland.

PRINCIPLES: Work-hour regulations for residency programmes in Switzerland, including a 50-hour weekly limit, were set in on 1 January 2005. Patient safety was one of the major arguments for the implementation. As the effect of the restriction of residency work hours on patient care in Switzerland has not yet been evaluated on objective data, the aim of the present study was to assess its impact by comparing the patients' morbidity and mortality before (2001-2004) and after (2005-2008) the implementation. METHODS: Retrospective analysis of records of the Spitalzentrum Biel AG, a large referral center classified according to the Swiss Medical Association, collected in the database of the Association for Quality Assurance in Surgery (AQC), a prospective database of consecutive patients undergoing surgical procedures in Switzerland. A selection of 2,686 patients with common surgeries, operated on by residents, was performed. RESULTS: There were 1,259 (46.9%) patients meeting our inclusion criteria who were admitted during the period before introduction of work-hour limitation and 1,427 (53.1%) patients after introduction. The in-hospital mortality and postoperative surgical complication rate were significantly higher after the reform (p <0.05 and p <0.01, respectively). No significant differences could be found concerning the overall intraoperative (p = 0.61) and postoperative medical complication frequencies (p = 0.08). CONCLUSIONS: The work-hour limitation implemented in Switzerland was not associated with surgical patient safety measure improvement for common surgeries (i.e., morbidity and mortality rate). Further research on a nationwide basis is needed to assess the value of the higher surgical complication and mortality rate.

Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial.

BACKGROUND AND AIMS: The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349-353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival. MATERIALS AND METHODS: Stages I-III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m(2) plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m(2) given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3). RESULTS: The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015). CONCLUSIONS: The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer.

[Breast saving treatment of breast cancer: 10 questionable aspects]. / Brusterhaltende Behandlung des Mammakarzinoms: 10 Fragezeichen.

Conservative treatment of breast cancer includes all those techniques by which a sizable amount of the gland is left behind after tumor resection, where the axilla is partially cleared and radiotherapy follows surgery. Thus, the subcutaneous mastectomy as a means of treating breast cancer does not fall into this category. Conservative treatment of breast cancer is a well-established technique as long as some basic principles concerning indication, technical details and general therapeutic plans are respected. Among many questions that have arisen from this kind of treatment, 10 are discussed. Among those is the fact of leaving behind vital carcinoma cells within breast tissue, the question of radiation-induced malignant tumours and other radiation sequelae, advantages and drawbacks of a simultaneous combination of radio- und chemotherapy, the quality of life, questions of follow-up and especially technical aspects in relation to the more radical quadrant resection or the cosmetically more advantageous tumorectomy. Considering all these aspects and open questions, conservative treatment of breast cancer has nevertheless to be regarded as the treatment of choice, at least for T1-lesions, as long as some clearly defined conditions are fulfilled. The aim of this multimodality treatment must be to achieve a cosmetic result better than that to be expected by reconstructive surgery after amputation of the breast, as long as the same survival figures can be obtained as after amputation.

Intraportal chemotherapy for colorectal hepatic metastases.

One-third of colorectal cancer patients suffer from liver metastases on initial diagnosis. Overt liver metastases appear to be the first site of relapse for 40% to 50% of the patients with operable disease. The fact that tumor cells can be discovered in the mesenteric blood during surgery may indicate that circulating tumor cells give rise to metastases. Experimental investigations have shown that metastatic tumors reaching a diameter of 5 to 7 mm are predominantly perfused by the arterial route, which explains the unsuccessful attempts to treat established liver metastases through the portal vein. However, because metastases in the liver presumably arise via blood flow through the portal vein, adjuvant intraportal chemotherapy might permit ready access of the drug to small liver deposits in a way that systemic chemotherapy might not. The interest in portal adjuvant cytotoxic liver infusion in radically resected colorectal cancer patients is based on an early publication by Taylor, who in 1979 reported on a significant reduction of the incidence of liver metastases in a group of patients randomly assigned to perioperative adjuvant portal infusion with 5-fluorouracil. Based on these results, several groups initiated prospective randomized trials comparing intraportal infusion of various regimens to surgery alone. Results of most of these trials have been published during the last few years. All but one demonstrate improved overall survival and disease-free survival and a reduction of the incidence of liver recurrences in the adjuvant-treated patient group. Ongoing meta-analyses of the randomized trial data may confirm this tendency soon.

[What is the value of tumor debulking and intraperitoneal cytostasis]. / Sind Tumor-Debulking und intraperitoneale Zytostase sinnvoll.

Local recurrences of intraperitoneal malignancies are mainly localized at the primary tumor site and the peritoneal surface. Surgical procedures alone are neither able to further reduce the development of local recurrence nor to treat the already established recurrent disease. In this situation intraperitoneal chemotherapy as an "adjuvant" treatment modality could be thought helpful. Experimental and clinical trials have shown that high doses of cytotoxic agents can be applied to the abdominal cavity with less systemic side effects. While the recent published data are not promising for gastrointestinal malignancies, they seem to be more encouraging for ovarian cancer.

[Indications-related and technical errors and their consequences in breast saving treatment]. / Indikatorische und technische Fehler und ihre Konsequenzen bei brusterhaltender Behandlung.

Conservative treatment becomes an established procedure for small breast cancer worldwide. Randomized and non-randomized studies have shown equal prognostic results compared with the more radical operative treatment. This large-scale therapy only can be worthwhile, if the cosmetic results are better than breast reconstruction after mastectomy. Therefore a rigorous indication, a standardized technical procedure and a well-functioning team of interdisciplinary cooperation is required. Out of 500 conservatively treated patients we controlled a random sample of 134 relative to the cosmetic result. The results were related to our standard technique.

[Value of subtotal stomach resection in stomach cancer]. / Stellenwert der subtotalen Magenresektion beim Magencarcinom.

The controversy about the extent of resection of gastric cancer has been lasting for decennies. The extreme viewpoints may have become less divergent recently although controlled data are still lacking. As gastrectomy has generally become safer, a somewhat broader indication for it is justified. Subtotal resection is still justified for cancer of the antrum of the intestinal type (Laurén-classification) without evidently involved distant nodes and as long as a clear margin can be expected, furthermore in some advanced disease situations and finally in high risk patients, especially with severe cardiopulmonary handicaps.