Sentinel lymph node biopsy in rectal cancer--not yet ready for routine clinical use.

BACKGROUND: The value of sentinel node biopsy in visceral cancers is uncertain. We evaluated the feasibility and utility of radiocolloid lymphatic mapping and selective lymph node sampling in patients with rectal cancer. METHODS: Forty-eight patients with rectal cancer were investigated. Thirty-seven patients had already undergone preoperative radiochemotherapy for locally advanced tumors. Eleven patients underwent primary surgery. An endoscopic injection of 1 mL technetium 99m-sulfur-colloid into the peritumoral submucosa was performed 15 to 17 hours before surgery. Ex vivo identification of the nuclide-enriched "sentinel lymph nodes" (SLNs) was performed using a hand-held gamma-probe. The selected SLNs were then carefully and systematically examined using serial sections and immunohistochemistry. RESULTS: One or more SLNs were found in 46 of the 48 patients. The SLN detection rate was 96%. Sixteen of the 48 patients had lymph node metastases (35%). In 7 of the 16 patients, the SLNs correctly represented the nodal status. In 9 of the 16 patients, the SLN was tumor-free whereas non-SLN harbored metastases. This result represents a sensitivity of only 44%, and a false-negative rate of 56%. Further analysis showed that the method correctly predicted the nodal status only in the small subgroup of 5 patients with early cancer without preoperative radiation. In 4 patients, juxtaregional lymph nodes were excised on the basis of intraoperative radiocolloid detection, leading to upward staging in 1 patient. CONCLUSIONS: Sentinel lymph node biopsy using the radiocolloid technique with ex vivo lymph node identification shows a relatively high detection rate; however, the sensitivity in patients with locally advanced/irradiated rectal cancer is low. Nevertheless, the detection of juxtaregional metastases can improve staging in some patients. Further studies should focus on patients with early rectal cancers where the data were more promising.

Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas.

Despite some success in the treatment of colorectal carcinomas, novel rational therapies targeting specific cancer-related molecules are under development and urgently needed. These approaches need careful preclinical evaluation in models that closely mirror the clinical situation. Therefore, we established a panel of 15 xenotransplantable tumours directly from fresh surgical material. We showed that both the histology and expression of tumour-associated markers (Epithelial Cell Adhesion molecule (EpCAM), E-cadherin, carcinoembryonic antigen (CEA)) could be maintained during passaging in nude mice. Xenotransplanted tumours were characterised for chemosensitivity and revealed a response rate of 5/15 (33%) for 5-fluorouracil (5-FU), 15/15 (100%) for irinotecan and 8/14 (57%) for oxaliplatin. 5 patients out of 15 were treated with cytostatics because of synchronous metastases. The response to chemotherapy in these patients coincided very closely with the response of the individual xenografts. All of the xenografts expressed the proliferation marker Ki67 and the nuclear enzyme, Topoisomerase IIalpha (Topo IIalpha) at the protein level. Most of the xenografts also expressed the tumour suppressor, p53 (9/14) and the nuclear enzyme Topoisomerase Ialpha (Topo Ialpha) (13/14) at the protein level. Interestingly, the presence of a K-ras mutation in codon 12 (5/15 xenografts) coincided with a low response rate towards oxaliplatin. This observation needs further confirmation using a larger number of tumours. In conclusion, we were able to establish transplantable xenografts suitable to mimic the clinical situation. These well characterised models are useful tools for the preclinical development of novel therapeutic approaches and for investigating translational research aspects.

Sentinel node biopsy in anal cancer - a promising strategy to individualize therapy.

BACKGROUND: In order to individualize the therapy in patients with anal cancer, we evaluated the applicability of the sentinel lymph node (SLN) concept for the staging of inguinal lymph nodes in these patients. PATIENTS AND METHOD: SLN mapping using the radiocolloid technique was performed in 12 patients with histopathologically proven anal cancer. Mean age of the 4 male and 8 female patients was 62 years (range: 37-83 years). All patients underwent injection of (99m)Tc-colloid (Nanocis) in 4 portions around the tumor followed by scintigraphy after 17 h and selective lymph node biopsy in case of nuclide enrichment. The nuclide-enriched lymph node was intraoperatively identified by a hand-held gamma-camera. Histopathological assessment of the harvested SLNs included serial sections and immunohistochemical staining. RESULTS: Enrichment of radiocolloid in lymph nodes was seen in 10 of the 12 patients (detection rate: 83%). SLN biopsy was performed in 9 patients, one patient refused the SLN biopsy (SLNB). 4 patients revealed tumor-infiltrated sentinel lymph nodes including one patient with bilateral biopsy, who showed metastases unilaterally. The remaining 5 patients had no evidence of metastases in the excised SLNs. CONCLUSION: It is feasible to evaluate the nodal status of the groin in patients with anal cancer using the radiocolloid technique. Preliminary results indicate a refined diagnostic work-up for anal cancer patients, potentially improving the results of clinical and sonographical examinations. Further application of the method may lead to an individualized treatment of patients with anal cancer.

Surgical oncology in the interplay of surgical and nonsurgical disciplines.

Advances in surgical tumor therapy are founded on a very close interaction between different surgical subspecialties as well as the inclusion of surgical into modern multimodality treatment concepts. The ongoing development of surgical techniques, e.g. microsurgical flap transfers or pouch reconstructions of intestinal reservoirs, has increasingly enabled organ- and function-preserving surgery. In addition, new materials (e.g. modular tumor endoprosthesis) has supported this development. The broad application of the sentinel node technique in melanoma and breast cancer and also in gastrointestinal tract cancers opens new concepts of diagnosis and therapy for lymphatic metastasized tumors. Locally advanced tumors can be treated in neoadjuvant protocols to increase the resectability rate and the probability for local control as a prerequisite for long-term survival. Especially for metastatic disease, interventional treatment techniques such as laser-induced thermotherapy (LITT) or photodynamic therapy have added valuable options to surgical treatment.

Seromuscular spiral cuff perineal colostomy: an alternative to abdominal wall colostomy after abdominoperineal excision for rectal cancer.

Seromuscular spiral cuff perineal colostomy may be an alternative to abdominal wall colostomy after abdomino-perineal excision. We present our initial experience with the procedure in 13 patients operated upon between March 1993 and December 1997. Patients undergoing abdomino-perineal excision for rectal cancer, under 65 years of age, without severe concomitant disease, and strongly motivated to comply with an intensive postoperative physiotherapy were selected. The neosphincter procedure comprised a pull-through of a sufficient length of well-vascularized colon, 12 cm of which was then cleared of fat. In this segment, the seromuscular layer was separated from the mucosa, cut into a longitudinal sheet and wrapped in spirals around the colon at its perineal insertion. One patient died from pulmonary embolism. A second patient suffered from ischemic necrosis of the distal colon and lost his neosphincter. Minor complications included one stenosis, corrected by surgery, and one iatrogenic lesion on rectoscopy at another institution. No patients experienced local recurrence, while four patients presented distant metastases. Initially, all patients suffered from incontinence. After 6 months, 6 of 11 evaluable patients showed total and 5 showed partial continence.

Local excision of rectal cancer through windowed specula: long-term results.

Transanal local excision of rectal cancer has been advocated as a curative option in patients with early rectal cancer and for patients unsuitable for radical surgery. We report our long-term experience with an easy-to-use and inexpensive technique based on windowed specula. From 1982 to 1994, 137 patients with rectal cancer were treated by local excision with curative intention. An R0 resection was possible in 74% of all patients and in 80% of the patients with a tumor surface of less than 9 cm2. Ninety patients with a follow-up of more than 3 years (T1: n = 50, T2: n = 30, T3: n = 14) were evaluated for survival. Seventy-four of these 90 patients are currently alive. The cause of death is known for all 16 deceased patients. In 4, death was tumor-related; 3 of these patients had a component of local failure. In 6 of 8 patients with local recurrence, a radical reresection was possible. The rate of recurrence increased with T category and with tumor grade. There has been one recurrence in a patient with a T1G1 cancer. The instrumentation enables adequate local excision of rectal cancers of less than 9 cm2 surface area. In this group of patients including a considerable number with T2 and T3 cancers, only 3 died of tumor-related causes with a component of local failure, which compares well with mortality rates above 4% for abdominoperineal excision. Comparison with international data on radical surgery shows that the overall survival is not reduced by local transanal excision for early rectal cancer.

[Perioperative clinical pathomorphologic evaluation of pararectal lymph node status and its contribution to definitive decision for local excision of rectal cancer]. / Perioperative klinisch-pathomorphologische Beurteilung des pararektalen Lymphknotenstatus und ihr Beitrag zur definitiven Entscheidung für eine lokale Exstirpation des Rektumkarzinoms.

On the basis of 669 patients with rectal carcinoma, who underwent radical surgery, we evaluated by means of discriminant statistics the prognostic value of 7 factors concerning lymph node involvement. By stratifying for important prognostic factors (level of differentiation, lymphocytic stromal reaction, depth of tumour infiltration) we have revealed 3 different groups: I--no or rare lymph node metastases; II--more frequent metastases but confined to "N1", and III--numerous distant metastases classified as "N2-3". On the basis of these results the final decision for local extirpation of the tumour with curative intention is made easier.

[Iatrogenic diagnostic delay in rectal cancer]. / Zur iatrogenen Diagnoseverzögerung beim Rektumkarzinom.

From a case material of 151 rectal carcinoma patients it has been established that the duration of anamnesis from the first consultation of the doctor to the onset of treatment was in 40 percent of the cases longer than 3 months, and in 17 percent of the cases, longer than 6 months. Only 36 percent of the patients with clinically manifest disease underwent diagnosis within a month following the first consultation of the doctor; in 37 and 15 percent of the cases, diagnosis was made only after 3 and 6 months, respectively. The causes of iatrogenic delay of diagnosis are analyzed and demonstrated by typical examples.

[The metastasis of rectal cancer]. / Metastazirovanie raka priamoi kishki.

Eight hundred and eighty-six cases of rectal cancer diagnosed and reported to the National Cancer Registry in 1980 were submitted to obduction. Metastases were identified in 46.8%. Liver, lung and bones were affected in 38.7%, 16.1 and 3.5% of cases, respectively. Pattern of metastatic spread was determined by histology, with adenocarcinoma giving rise to blood-borne metastases, mucinous adenocarcinoma producing mostly lymphogenic metastases and signet-ring cell carcinoma spreading in either way. Isolated liver involvement was established in 9% of patients showing liver metastases at radical surgery. The parameter reached 22% when cases of presacral recurrence were excluded. A histologically oriented scheme is suggested to assure complete diagnostic coverage of metastases and to develop a concept for the treatment of liver secondaries. Targeted intraperitoneal and endolymphatic application of cytotoxic agents for the treatment of liver metastases aimed at reduction of extrahepatic dissemination is discussed.

[Status of local excision of local deep rectal cancers with curative intention]. / Stellenwert der lokalen Exstirpation von kleinflächigen, tiefsitzenden Rektumkarzinomen mit kurativer Zielstellung.

103 cases have been analyzed retrospectively to define the indication for local extirpation of small and deep-seated rectum carcinomas with curative purpose. While pedunculated carcinomatous adenomas can be removed by endoscopic loop extraction, the non-sessile polypous carcinomas have to be radically extirpated by excision from intestinal wall resection is a promising procedure. Here, the transanal access by means of a funnel-shaped, lateral fenestrated glass speculum as introduced by Dewey yields better results than the rectotomia posterior.

[Effect of regional centralized treatment on chances of survival in rectal cancer in East Germany]. / Untersuchung zum Einfluss der regional zentralisierten Behandlung auf die Uberlebenschancen beim Rektumkarzinom in der DDR.

Based on cases of rectum-carcinoma reported to the National Cancer Registry a population based method is demonstrated to measure the influence of a regional-centralized treatment on the relative survival rates for cancer patients. This new approach use a centralization-index, characterizing the centralization of treatment activities in single countries. It is shown, that the end results in regions with a high index are much better than that in other regions.

[Incidence of isolated metastatic organ involvement in rectal cancer in an autopsy sample]. / Zur Häufigkeit des isolierten metastatischen Organbefalls beim Rektumkarzinom im Obduktionsgut.

From the rectum carcinoma cases diagnosed and reported to the National Cancer Registry in 1980, 886 were submitted to obduction. Metastases were detected in 46.8% of the autopsy material. Affected were the liver in 38.7%, the lung in 16.1%, and the skeleton in 3.5% of the obducted cases. The pattern of metastases depended on the histological picture of the carcinoma: with adenocarcinomas, haematogenic metastases, and with mucigenic adenocarcinomas, lymphogenic metastases were predominant; the signet-ring-cell carcinomas develop their pronounced metastatic potency in either way. The isolated liver affection could be established in 9% of all liver metastatic patients who underwent radical operation, and in 22% following exclusion of a presacral recurrence, respectively. A histologically oriented scheme is proposed to complete the spreading diagnostics and to establish a therapeutic concept for liver metastases, and an additional, targeted, systematic intraperitoneal and endolymphatic application of cytostatic substances in the treatment of liver metastases to reduce the extrahepatic metastatic rate is discussed.

[Adjuvant postoperative irradiation of rectal cancer in a risk group]. / Adjuvante postoperative Bestrahlung beim Rektumkarzinom in einer Risikogruppe.

The results of the pilot study carried out in 1985 are described. The group with high risk of recurrence is clearly distinguishable by means of prognostic factors. The adjuvant postoperative supervoltage therapy on the former rectum lodge (2 x 5.0 Gy per week up to a total dose of 45.0 Gy) failed to increase the survival rate. The tendency towards reduction of the recurrence rate, 56% vs. 70%, was levelled by post-radiogenic side effects.

[The necessity for a stratification of patients with radically resected rectal cancer]. / Zur Notwendigkeit einer Stratifikation der radikal operierten Rektumkarzinompatienten.

In contrast to the increasing incidence of rectal tumours the treatment results have reached a plateau. For their improvement it is necessary to exhaust all treatment modalities currently available. One approach might be centralized therapy at specialized hospitals (to use capacities and abilities located there) and another approach is the use of adjuvant treatments in certain patients. To secure optimal results of adjuvant treatments the patients should be stratified for some acknowledged prognostic factors.

[Methods of standardizing relative survival rates using rectal cancer in East Germany as an example]. / Methoden zur Standardisierung von relativen Uberlebensraten am Beispiel des Rektumkarzinoms in der DDR.

Statistical analyses concerning survival of cancer patients are mostly based on the concept of relative survival rates, which besides the crude survival rates, calculated by the life-table-method, take into account the influence of other (competing) causes of death. But the use of relative survival rates by no means a full reduction of the influence of age. Methods for standardization of such rates will be presented and demonstrated on the data of the National Cancer Registry in GDR for rectum cancer in 1980.

[The surgical treatment of patients with rectal cancer in the GDR]. / Khirurgicheskoe lechenie bol'nykh rakom priamoi kishki v GDR.

The National Registry of the GDR filed 3286 cases of rectal cancer in 1980: life-time entries--92.7% and post mortem--7.3%. At least one surgical procedure was performed in 82.4% of cases, radical--41.9% of life-time cases. An analysis of data on radical resectability versus age and stage showed that radical surgery application may be extended by 15-20%.

[Arguments for regional centralized treatment of stomach cancer. A statistical study of national results]. / Argumentation für eine regionale zentralisierte Behandlung beim Magenkarzinom. Eine statistische Untersuchung von nationalen Resultaten.

An analysis was made of therapeutic results obtained from 6,220 cases of primary gastric carcinoma and from 1,308 cases of radical surgery, as listed in the 1976 National Cancer Record of the GDR. Results were examined relative to the number of radical operations per annum. Involved in the above treatment of gastric carcinoma were 237 surgical wards throughout the GDR. Numbers of radical operations were between one and four per annum in 56.1 per cent of all wards (Group I), between 5 and 19 in 40.5 per cent (Group II), and 20 or more in only 3.4 per cent (Group III). Radical removability accounted for 13.2 per cent of all cases in Group I, 28.2 per cent in Group II, and 38.5 per cent in Group III. Better therapeutic results relative to the number of radical operations per annum were reflected in the following absolute five-year survival rates: 3.4 per cent in Group I, 6.8 per cent in Group II, and 10.6 per cent in Group III. These findings are likely to support the advisability of regional centralisation of treatment for stomach carcinoma.

[Subtotal distal gastrectomy in antral carcinoma: following Billroth I or II?]. / Subtotale distale Magenresektion beim Antrumkarzinom: nach Billroth I oder II?

In 1976, the National Cancer Registry of the GDR registered 488 cases with radical distal gastrectomy for carcinoma of the gastric antrum. 78.7% of them were treated with Billroth-II and 21.3% with Billroth-I. There were no striking differences regarding the postoperative lethality with 15.1% and 14.4% respectively. With 31.2% and 29.0% the 5-year survival was similar for both surgical methods, too. These results indicate the possibility of performing the Billroth-I-gastrectomy in distal gastric cancer if the principles of surgical oncology are carefully observed.

[Chemoembolization of the hepatic artery combined with intraportal cytostatic infusion--a new concept in the regional chemotherapy of liver metastases]. / Chemoembolisation der A. hepatica kombiniert mit intraportaler Zytostatikum-Infusion--ein neues Konzept für die regionale Chemotherapie von Lebermetastasen.

At present international the regional cytostatic chemotherapy for hepatic metastases is used by the intraarterial way. Newest methods are the technically very pretentious intraarterial perfusion with venous hemofiltration and the chemo-embolization of the hepatic artery requiring meanwhile an adjuvant systemic chemotherapy because the chemo-embolization influences only the arterially supplied part of the metastases. By the combination of the transumbilical intraportal chemotherapy formerly developed in the Central Institute for Cancer Research Berlin-Buch with the intraarterial chemo-embolization it is possible to reduce considerably the technical expenditure and to increase the regional concentration of cytostatics simultaneous avoiding the load of the whole organism. The bases of this new method and the technical procedure are discussed.