Colon cancer: survival after curative surgery.

Several new aspects have evolved during the past years concerning factors that influence survival in surgically and medically treated colon cancer patients that are relevant to the treating team for the treatment strategy and patient's choice. The 5-year-survival rates dependent on UICC stages/substages (I: 68%-100%, II: 58%-90%, III: 33%-76%, IV: <5%-9%) show remarkable variations between published reports, surgical hospital units, individual surgeons, and continents (USA vs Europe). Those variations may be due to surgical techniques, training status, hospital and individual case volume, and, also, referral patterns and statistical evaluation methods. Survival times and cure rates are significantly improved by adjuvant chemotherapy in UICC III and in substages of UICC II (e.g. UICC II B) by 5%-12%, when compared with surgical controls. In three recently published trials standard adjuvant chemotherapy was further improved by increased survival rates, e.g. from 59% to 71% in stage III and IIB patients. Molecular and genetic factors, such as thymidylate synthase (TS), microsatellite instability (MSI) or loss of chromosome 18q/"DCC" might have an independent impact on prognosis in the spontaneous course, and TS could help to better select patients for adjuvant chemotherapy.

Modeling the ponto-medullary respiratory network.

The generation and shaping of the respiratory motor pattern are performed in the lower brainstem and involve neuronal interactions within the medulla and between the medulla and pons. A computational model of the ponto-medullary respiratory network has been developed by incorporating existing experimental data on the medullary neural circuits and possible interactions between the medulla and pons. The model reproduces a number of experimental findings concerning alterations of the respiratory pattern following various perturbations/stimulations applied to the pons and pulmonary afferents. The results of modeling support the concept that eupneic respiratory rhythm generation requires contribution of the pons whereas a gasping-like rhythm (and the rhythm observed in vitro) may be generated within the medulla and involve pacemaker-driven mechanisms localized within the medullary pre-Botzinger Complex. The model and experimental data described support the concept that during eupnea the respiration-related pontine structures control the medullary network mechanisms for respiratory phase transitions, suppress the intrinsic pacemaker-driven oscillations in the pre-BotC and provide inspiration-inhibitory and expiration-facilitatory reflexes which are independent of the pulmonary Hering-Breuer reflex but operate through the same medullary phase switching circuits.

[Rectal carcinoma. Optimizing therapy by local excision]. / Rektumkarzinom. Optimierung der Therapie durch lokale Exzision.

The results of local excision and radical surgery in patients with T1-carcinomas of the rectum were compared. In a retrospective study (1.1.1985-1.7.1997) the results obtained in 107 patients with T1-rectal carcinoma ("low risk" T1: n = 83, "high risk" T1: n = 24) undergoing local excision or radical surgical therapy were compared. The complication rate in patients undergoing local excision was 3.3% (2/60) and ranged at 19% (9/47) in the group treated with radical surgery. Two out of 47 patients (4.2%) died after radical resection; there were no deaths after local excision. With regard to the actuarial 5-year survival rate, in the group with "low risk" T1 carcinoma no difference was observed between patients treated with local excision (79%) or radical resection (81%) (p = 0.72). In patients with "high risk" T1 carcinoma lymph node metastases were identified in 4 out of 11 patients undergoing radical resection (36%). 4 out of 13 patients with "high risk" T1 carcinoma treated by local excision developed recurrences, while none of the patients undergoing primary radical surgery had a recurrence. This underlines the necessity of radical surgery in "high risk" T1-carcinomas. Local excision for the treatment of "low risk" T1-carcinoma is associated with a significantly lower complication rate than the performance of a radical surgical therapy. There is no difference in five-year-survival between local and radical surgical therapy in patients with "low risk" T1 carcinoma.

[Risk of malignant degeneration of preoperatively-classified benign large sessile rectal polyps. A comparison with adenoma size]. / Das Entartungsrisiko präoperativ als benigne eingestufter breitbasig aufsitzender Rektumpolypen. Ein Vergleich mit der Polypengrösse.

From January 1986 to December 1995 307 patients with preoperatively as benign classified rectal polyps underwent transanal endoscopic microsurgery or transanal excision at the Hospital of General and Abdominal Surgery, Johannes Gutenberg-University Mainz. Mean polyp size was 3.9 cm in diameter. Postoperatively in 233 patients (75.9%) a benign rectal adenoma was found. In 69 patients (22.5%) with the preoperative diagnosis "benign rectal adenoma" the postoperative histologic result was a carcinoma. No residual polyps were encountered on snare excision in 5 patients (1.6%) with inconclusive evidence of surgical margin involvement. The mean size of malignant polyps was 3.4 cm and significantly below the mean size of benign polyps (4.1 cm, p = 0.009). Especially in polyps with a size to 1 cm and from 1 to 2 cm in diameter the part of malignant rectal polyps was unexpected high (8/15 polyps, 53.3%, respectively 16/37 polyps, 43.3%. Patients with preoperatively as benign classified large sessile rectal polyps had a high risk of malignancy even when polyp's size was small. Therefore in toto excision has to be done also in small polyps.

Follow-up after transanal endoscopic microsurgery or transanal excision of large benign rectal polyps.

METHODS: Between January 1986 and December 1995, 238 patients with benign rectal polyps underwent either transanal endoscopic microsurgery (n = 226) or transanal excision (n = 12) at the Clinic of General and Abdominal Surgery, Johannes Gutenberg-University, Mainz. RESULTS: Mean polyp size was 4.2 cm; 89.1% of polyps measured more than 2 cm in diameter. In 89.1% of cases, histological analysis revealed polyps containing tubulovillous or villous adenomas. Synchronous colonic polyps were detected in 12.5% of patients. Follow-up data are available on 222 patients (94%). At follow-up examination, 169 of the 193 surviving patients (87.6%) were recurrence free. Seven of 193 patients (3.6%) had developed neoplastic colonic polyps and, in 17 patients (8.8%), metachronous polyps were detected. CONCLUSIONS: Transanal endoscopic microsurgical polypectomy was furthermore demonstrated to be a low-risk procedure with a low recurrence rate for the complete resection of large rectal polyps. At a follow-up rate of 61.1 %, the incidence of metachronous carcinoma ranged at 3.1%, which is markedly below the rate of 8-18% for tubulovillous or villous adenomas larger than 1 cm in diameter cited in the literature.

Comparison of results after transanal endoscopic microsurgery and radical resection for T1 carcinoma of the rectum.

BACKGROUND: We compared the results of transanal endoscopic microsurgery and radical surgery in patients with T1 carcinomas of the rectum. METHODS: We performed a retrospective study (1985-96) to compare the results obtained in 103 patients with T1 rectal carcinomas (low-risk T1, n = 80; high-risk T1; n = 23) undergoing transanal endoscopic microsurgery and radical surgical therapy. RESULTS: The complication rate in patients undergoing local excision was 3.4% (two of 58); it was 18% (eight of 45) in the group treated with radical surgery. Two of 45 patients (3.8%) died after radical resection; there were no deaths after local excision. With regard to the actuarial 5-year survival rate, no difference was observed in the group with low-risk T1 carcinoma between patients treated with local excision (79%) and those who had radical resection (81%) (p = 0.72). In patients with high-risk T1 carcinoma, lymph node metastases were identified in four of 11 patients undergoing radical resection (36%). Four of 12 patients with high-risk T1 carcinoma treated by local excision developed recurrences, whereas none of the patients undergoing primary radical surgery had a recurrence. CONCLUSIONS: Transanal endoscopic microsurgery for the treatment of low-risk T1 carcinomas is associated with a significantly lower complication rate than radical surgical therapy. There is no difference in 5-year survival between local and radical surgical therapy in patients with low-risk T1 carcinoma.

[Influence of the number of dissected lymph nodes on local recurrence of rectal carcinomas. A staging effect]. / Der Einfluss der Zahl der dissezierten Lymphknoten auf die Lokalrezidivrate rectaler Carcinome. Ein Stagingeffekt.

In 386 patients with rectal carcinoma of UICC stage I-III operated on between 1 January 1985 and 31 December 1995 we investigated the influence of the number of dissected lymph nodes on tumor stage and local recurrence retrospectively. We found a significant correlation between the number of lymph nodes dissected and the number of detected lymph node metastases. Following this result we found an increase in UICC stage III (P = 0.013) and pTx pN2 tumors (P = 0.000) in correlation with the number of dissected lymph nodes. Significantly lower rates of local recurrence were found only in UICC stage I and UICC stage II. Overall and in a multivariate analysis the number of dissected lymph nodes had no influence on local recurrence. It was shown that lower local recurrence rates in UICC stage I and II did not depend on therapeutic benefit but on stage migration because of more exact tumor staging. The influence of other surgical factors, especially total mesorectal excision, remains to be discussed.

[Lymph node dissection, stage migration and perioperative risk in rectal carcinoma]. / Lymphknotendissektion, Stadienverschiebung und perioperatives Risiko beim Rectumcarcinom.

In 348 patients with an initial diagnosis of rectal carcinoma operated on between 1985 and 1994 we investigated the quality of lymph node dissection, its influence on the perioperative risk and tumor staging. The same histopathological work-up was carried out in all cases. Whether resections or extirpations were performed, the number of dissected lymph nodes increased from 5.3 and (1985/1986) to 16.7 and 17.3 (1991/1992) and to 15.8 and 17.3 (1993/1994) respectively. Neither the type of operation nor the surgeon's experience had a significant influence on the number of lymph nodes dissected. The increase in the number of lymph nodes dissected had no negative effect on the length of the operation, the amount of blood infused during the operation or the perioperative risk. We found a significant correlation between the number of lymph nodes dissected and the number of lymph node metastases (P = 0.02) and between an increase in UICC stage III (P = 0.005) and pN2 tumors (P = 0.000) and an increase in the number of lymph nodes dissected. Central lymph node dissection by high ligation of the inferior mesenteric artery did not increase the perioperative risk in spite of the fact that in recent years we have observed more patients with multiple diseases.

[Prognostic factors in local recurrence rate after surgical therapy of rectal carcinomas]. / Prognostische Faktoren der Lokalrezidivrate nach operativer Therapie von Rektumkarzinomen.

From January 01, 1985 to December 31, 1993 515 patients with primary rectal cancer underwent operative treatment at the hospital of general and abdominal surgery of the university of Mainz. In 294 patients with conventional surgical treatment and R0-resection of the tumor we investigated the influence of tumor-, patient- and therapeutic factors on local tumor recurrence. At a univariate analysis the following factors were significant: UICC-staging (p = 0.001), pT-classification (p = 0.001), pN-classification (p = 0.013) and localisation of the tumor (p = 0.013). These results could be verified for the pT-classification and pN-classification in a multivariate analysis. The significant influence of operative treatment (p = 0.034), blood transfusion (p = 0.018) and preoperative raised CEA (p = 0.026) depended on significant differences of UICC - staging and tumor - localisation of the different groups. Grading, sex and age had no influence. Inspite of a shift of local resurrence from 13% to 50% (0% to 42.9% for resections, respectively 6.7% to 55.4% for exstirpations) we could not find a significant influence of the surgeon. This fact depended on the dividing of a small number of cases on a lot of surgeons. In our opinion the influence of the surgeon or of different hospitals on local recurrence should be investigated in further studies.

[Local excision of rectal carcinoma]. / Lokale Exzision beim Rektumkarzinom.

From January 1985 till December 1994 109 patients with rectal carcinoma were treated by local excision, in 36 patients a radical operation was performed afterwards. In the assessment of tumor infiltration endosonography was superior to rectal-digital examination. In 34 patients with local excised "low risk" T1-carcinomas and tumor free margins no local recurrence was observed. Two of ten patients with local excised "low risk" T1-carcinoma and no adequate margin of healthy tissue developed a local recurrence. Regarding our results the local excision of "low risk" T1-carcinomas seems justified, if final histological workup reveals an adequate margin of healthy tissue.

[DNA content of the tumor cell. A new prognostic parameter in hepatocellular carcinoma?]. / DNA-Gehalt der Tumorzelle. Ein neuer prognostischer Parameter beim hepatozellulären Karzinom?

Hepatocellular carcinoma is a heterogeneous disease with considerable differences in malignant behaviour. Some relevant factors for prognosis are known. In this study we analysed DNA ploidy as a potential prognostic parameter. With DNA image cytometry we were able to differentiate between diploid, hypotriploid, triploid, hypertriploid, tetraploid and aneuploid tumours. The best prognosis was for patients with diploid, hypotriploid and tetraploid tumours with a median survival time of 41 months in contrast to 3 months for patients with triploid, hypertriploid or aneuploid tumours. There was a strong correlation between histomorphological parameters and the DNA content. The DNA content of tumour cells may be considerable clinical relevance in hepatocellular carcinoma regarding the decision as to whether or not to perform a resection. In patients with prognostically unfavorable parameters adjuvant oncological therapy may improve the prognosis.

[Does the surgeon modify risk of local recurrence in rectal carcinoma?]. / Beeinflusst der Chirurg das Lokalrezidivrisiko beim Rektumkarzinom?

Investigating long-term operative results of nine surgeons, we found a variation in the local recurrence rate of 13% to 50%. Operative quality should not only be verified by investigating the perioperative risk, but also by investigating the local recurrence rate or prognosis.

[Immunoscintigraphy with MAb B72.3 for preoperative detection of lymph node metastases of colorectal carcinoma]. / Die Immunszintigraphie mit MAb B72.3 zum präoperativen Nachweis von Lymphknotenmetastasen colorectaler Carcinome.

From April 1, 1992 to December 31, 1993 we investigated 30 patients with suspected primary colorectal carcinoma or questionable tumor relapse by immunoscintigraphy prospective with the monoclonal antibody MAb B72.3 in order to detect the tumor and especially regional lymph node metastases. All the patients underwent surgical treatment. The diagnosis was based on surgery and biopsy. The diagnostic sensitivity of immunoscintigraphy in detecting the tumor was 76%, the specificity 94% (predictive value positive [PVP] 95%) and 43%, respectively 85% in detecting lymph node metastases (PVP 60%). The diagnostic sensitivity in detecting rectosigmoid tumors was 79 and 60% in detecting lymph node metastases of rectosigmoid carcinoma (PVP 60%). The specificity was 90%. It could be shown, that the detection of metastases in singularly lymph nodes smaller than 1 cm was not possible and often a final decision could not be done. We conclude, that the benefit of this method in detection of lymph node metastases compared to basic diagnostic, expenses and costs is doubtfully.

Trisomy 12 in chronic lymphoid leukemias--a metaphase and interphase cytogenetic analysis.

Trisomy 12 has been shown to be one of the most common chromosome abnormalities in chronic lymphoid leukemias of B-cell origin, and some studies suggested that it predicts poor overall survival. We have prospectively studied 42 patients with B-cell chronic lymphocytic leukemia (B-CLL) and three patients with B-prolymphocytic leukemia (B-PLL) for the incidence of trisomy 12 and other chromosome 12 aberrations applying fluorescence in situ hybridization (ISH) and conventional G-banding analysis. Dual-color hybridization experiments using centromere-12-specific DNA probes were performed for interphase cytogenetics. A subset of patients (n = 11) was analyzed using a DNA library for painting of chromosome 12. The incidence of trisomy/partial trisomy 12 was 18% (8/45 patients; 6/42 with B-CLL and 2/3 with B-PLL) by fluorescence ISH, and 11% (5/45 patients; 4/42 with B-CLL including one patient with partial trisomy 12q13-qter, and 1/3 with B-PLL) on G-banding analysis. Four patients with trisomy 12 were detected by ISH alone. One of these patients only had 4.5% interphase cells with three fluorescence signals indicating the presence of a small subclone with trisomy 12. On G-banding analysis, three of the four patients had a normal karyotype, and one patient had no analyzable metaphases. In conclusion, fluorescence ISH to interphase nuclei is a sensitive method for detecting trisomy 12 in patients with chronic lymphoid leukemias.

High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetics.

Inactivation of the retinoblastoma tumor-suppressor gene (RB-1) has been associated with tumorigenicity in various human malignancies. In chronic lymphoid leukemias of B-cell origin (B-CLL) an involvement of RB-1 has been suggested based on cytogenetic data. We examined RB-1 and its chromosomal locus 13q14 in 35 cases of B-CLL by dual-color in situ hybridization to interphase nuclei and by G-banding analysis of metaphase chromosomes. In one patient (pt) a monosomy 13, and in three other pts deletions involving or encompassing band 13q14 were detected by conventional cytogenetic analysis. In contrast, in situ hybridization to interphase nuclei showed a monoallelic RB-1 deletion in 11 cases (31%). One pt showed a translocation with the breakpoint in 13q1?4 on G-banding, but on in situ hybridization analysis the RB-1 signals were not affected. Our data show that RB-1 deletions can be diagnosed accurately by in situ hybridization on the one-cell level. The frequency of RB-1 deletions detected in this study is significantly higher than previously assumed in B-CLL, and seems to be in the same range as in retinoblastoma.

[Diagnosis and therapy of cecal diverticulitis]. / Diagnose und Therapie der Zökumdivertikulitis.

Acute pain in the lower right side of the abdomen caused by caecal diverticulitis is very rare and hardly to distinguish from acute appendicitis. Therefore it is usually diagnosed intraoperatively. We report our experience with 12 patients, who received surgical treatment from 1984 to 1991. The diagnosis was made not before operation in 11 cases. Because of a severe inflammation of the caecal wall we performed an ileocaecal resection in 10 cases, in 2 cases it was necessary to perform a right hemicolectomy because of additional diverticulitis of the ascending colon. The surgical resection of the inflammatory mass was followed by an uncomplicated postoperative healing in all cases.