High-risk Carcinoma Research Articles

Outcome of Rectal and Sigmoid Carcinoma Patients Receiving Adjuvant Chemoradiotherapy in Marmara University Hospital

Adjuvant chemoradiotherapy is the standard treatment in resected stage II/III rectosigmoid carcinoma. We report a retrospective analysis of 33 patients who received adjuvant chemoradiotherapy. Patients received 5-fluorouracil (375mg/m2/day × 5days) and calcium leucovorin (20mg/m2/day × 5days), q4weeks, two courses before and two courses after radiotherapy. The 5-fluorouracil dose was reduced to 225mg/m2/day given continuously as protracted short-term infusion on the first and last 3 days during radiotherapy. Radiotherapy was started at 7th week and 45-50.4 Gy was given to pelvic region. Median age was 63 years. Median follow- up was 38 months starting from the operation date. Four-year local and distant control rates were 78% and 69%, respectively. Four-year disease-free survival and overall survival were 60% and 62%, respectively. Protracted short-term infusion of 5-fluorouracil during pelvic irradiation is a safe treatment modality. Further studies are needed to improve the local control of high-risk rectal and sigmoid carcinomas.

Prognostic Significance of the Deleted in Colorectal Cancer Gene Protein Expression in High-Risk Resected Gastric Carcinoma

The deleted in colorectal cancer (DCC) gene is a candidate tumor suppressor gene that may be associated with differentiation and proliferation of normal cells. Loss of heterozygosity (LOH) of 18q, where the gene is located, and absence of DCC protein expression have been associated with worse prognosis in certain subgroups of patients with colorectal adenocarcinoma. We studied the prognostic significance of loss-of-protein expression in 66 patients with resected gastric cancer with a high probability of relapse (T3, T4, N+). The DCC protein was detected with immunohistochemistry using an anti-DCC monoclonal antibody on paraffin-embedded sections. The DCC protein expression was present in 51 cases (77.3%) and absent in 15 cases (22.7%). Poorly differentiated and signet ring carcinomas had significantly lower expression than more differentiated tumors(p<0.05) as did diffuse-type tumors compared to intestinal and mixed(p<0.01). There was no correlation with proliferation rate, estimated immunohistochemically using an anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Absence of DCC protein was an independent favorable prognostic factor (median survival 57 months vs. 18 months,p=0.0176). The DCC protein expression was correlated with relapse site: all patients with distant metastases were positive for DCC staining, while one-third of patients with local/peritoneal relapse were negative(p<0.01). In conclusion, DCC protein expression seems to be a significant prognostic factor in high-risk resected gastric cancer. Our results support previous data associating the DCC gene with differentiation and indicate that this gene may play a role in the metastatic potential of these tumors. These findings need to be confirmed by future larger studies.

EDITOR'S NOTE: re: randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

EDITOR'S NOTE: re: randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

Current concepts: The use of immunoperoxidase techniques in Mohs micrographic surgery

Mohs micrographic surgery is used for the removal of certain malignant tumors, both ensuring complete excision by histologic examination of margins as well as minimizing normal tissue loss. Recently, several investigators have incorporated the use of immunoperoxidase techniques to aid in the removal of selected high-risk carcinomas, sarcomas, and melanomas. We describe the basic principles of immunoperoxidase and review recent articles in which immunoperoxidase was used as an adjunct to routine hematoxylin-eosin staining in Mohs micrographic surgery. Additionally, we show examples of selected tumors comparing routine hematoxylin-eosin stains and immunoperoxidase. We believe the use of immunoperoxidase can be of significant value in the removal of certain high-risk tumors. In particular, this technique is useful in “unmasking” malignant cells in areas of dense inflammation, identification of some cases of perineural invasion, identification of pagetoid spread in carcinomas and melanomas, and finally in helping to identify subtle margins in dermatofibrosarcoma protuberans. (J Am Acad Dermatol 2000;43:66-71.)

Treatment concept of adenomas of Vater's ampulla

The most common benign ampullary tumors are adenomas (80%). They are considered as premalignant lesions with a transformation rate to carcinoma of up to 30%. From 1 January 1997 to 28 February 1999 we treated 11 patients with adenoma of the ampulla of Vater. An ampullectomy was performed in 10 cases. One poor-risk patient could not be operated on. No operative mortality occurred. In two patients a pT1 adenocarcinoma was diagnosed postoperatively. One of the two patients with a high-risk carcinoma underwent a second operation, a Whipple pancreatoduodenectomy. Nine of 10 patients had no recurrence with a median follow-up of 12 months. One patient died of glioblastoma. We would therefore recommend ampullectomy as the first-line treatment for benign tumors of the ampulla of Vater. In low-risk pT1 carcinoma (G1/G2, L0) and R0 resection, local excision is acceptable. In high-risk pT1 carcinoma (G3 and/or L1) Whipple pancreatoduodenectomy is mandatory.

Adjuvant high-dose chemotherapy supported by peripheral blood stem cell transplantation for high-risk cervical carcinoma.

Cervical carcinoma is a common disease for which the prognosis has not been substantially improved with standard locoregional treatments. Three stage IB patients with untreated cervical carcinoma were treated with high-dose chemotherapy and refrigerated peripheral blood stem cell support using the ICE program (Ifosfamide 10 g/m2 plus mesna at 100% of the ifosfamide dose; Carboplatin at 1.5 g/m2 and Etoposide 2.1 g/m2). Patients received the treatment in an adjuvant setting after radical hysterectomy with pelvic lymph-node dissection and postoperative cisplatin-based standard-dose chemotherapy. All patients underwent postoperative radiotherapy. The treatment was well-tolerated, all patients had rapid hematologic recovery, and the most frequent complications were grade 3 mucositis and neutropenic fever. The three patients are disease-free at 58, 60, and 63 months of follow-up. Our results show that adjuvant high-dose chemotherapy could be effective to reduce the likelihood of relapse in high-risk patients. High-dose chemotherapy deserves a formal evaluation in high-risk cervical cancer.

Basal cell carcinoma. Identification and treatment of the high-risk patient.

Some cutaneous basal cell carcinomas have a significant potential to recur, disfigure, and metastasize. The identification and selection of treatment of these high risk carcinomas is based on a review of studies of recurrence, giant size, metastasis, and mortality. Basal cell carcinomas with any of the following: long duration, location in the mid face or ear, larger than 2 cm, with aggressive histologic subtype, previous treatment, neglected, or a history of radiation exposure, should be considered "high risk." For basal cell carcinomas with this high risk profile, complete excision by margin control or total destruction should be considered.

Serum interleukin-2 and soluble interleukin-2 receptor in gestational trophoblastic diseases.

To investigate serum interleukin-2 (IL-2) and soluble interleukin-2 receptor (SIL-2) levels in gestational trophoblastic diseases (GTD). Sixty-six patients with GTDs and 23 first-trimester healthy pregnant women (controls) participated in this study. According to the World Health Organization scoring system, GTDs were subgrouped into the following groups: 30 hydatidiform mole spontaneous regression (HMSR), 12 postmolar gestational trophoblastic tumors of high risk (PMHR), 14 low-risk choriocarcinomas, and ten high-risk choriocarcinomas. Before treatment, a blood sample from each case was assayed for beta-hCG by radioimmunoassay, IL-2 by IRMA, and SIL-2R by enzyme-linked immunosorbent assay. Follow-up beta-hCG assays were carried out at weekly intervals after treatment for 3 months, then monthly for 1 year. Serum IL-2 levels in all subgroups of GTD were significantly lower than that of controls. Meanwhile, there were concomitant significant elevations of serum SIL-2R, showing mean rises of 3.86-fold, 3.9-fold, twofold, and 6.1-fold for cases of HMSR, PMHR, low-risk choriocarcinoma, and high-risk carcinoma, respectively. All cases of high-risk choriocarcinoma revealed abnormally high SIL-2R values. There was a significant positive correlation between serum beta-hCG and SIL-2R concentrations. The possible causes of IL-2 decreases and SIL-2R increases may indicate a defective immune response in GTDs. The high correlation between SIL-2R level and tumor burden suggests the use of serum SIL-2R assay for disease monitoring: SIL-2R is indirect marker of tumor activity, and it is useful in the differential diagnosis of GTD because a normal value of serum SIL-2R excludes high-risk cases of choriocarcinoma.

138 Controlled clinical trial in high metastatic risk carcinoma of the prostate comparing pelvic radiotheraoy alone to pelvic radiotherapy plus LHRH analogue

138 Controlled clinical trial in high metastatic risk carcinoma of the prostate comparing pelvic radiotheraoy alone to pelvic radiotherapy plus LHRH analogue

455 Correlation and prognostic value of pathological features, biological and clinical data before treatment, in high metastatic risk carcinoma of the prostate

From 1987, 380 patients (pts) with high metastatic risk carcinoma of the prostate (T1/T2 with WHO grade 3, T3/T4 all grades) were treated in a randomized multicentric trial comparing curative radiotherapy alone with radiotherapy plus adjuvant LHRH analogue. The histology is currently reviewed by 2 reference pathologists. The initial PSA value, the UICC T-classification, the WHO histological grade (G) (local and review diagnostic), and the Gleason score (GS) attributed by the reference pathologist (sum of the 2 gleason grades) were investigated as potential prognostic factors for relapse free survival amongst the 175 pts already reviewed by the referees. Local control and survival were not considered in the analysis because too few events have been recorded so far. The median FU was 2 years. The potential prognostic factors were investigated first by univariate analysis, (Kaplan Meier estimate and logrank test), and subsequently in a multivariate model (Cox regression model). The median age was 70 (51–80), the median GS was 7 (2–10), 50% of the pts were G2, 30% were G3, and T1–T2 were only 8.5% of the pts. For histological grade, we found a good concordance between the local and review diagnostic (71% of concordant cases). In the univariate analysis for relapse free survival, G (local diagnostic) was predictive (<i>P</i>=0.001), G (review diagnostic) had a border line prognostic value (<i>P</i>=0.2), and GS had a significant influence (<i>P</i>=0.002). In the multivariate analysis, G only (local diagnostic) remained discriminant for relapse free survival (<i>P</i>=0.02). In conclusion this study confirmed the prognostic values of G and GS. However in the multivariate model GS did not provide any additional information to G. Surprisingly neither the PSA nor the T-class were found to be significant. This could be mainly explained by the selection of pts. The review process will be completed before the presentation and the present analysis will be accordingly updated.

Endoscopic Polypectomy and Management of Colorectal Adenomas with Invasive Carcinoma

Invasive carcinoma is found at histology in 2-5% of colorectal polyps removed under flexible endoscopy. The aim of this study was to confirm that histologically complete endoscopic polypectomy under favorable low-risk conditions is sufficient therapy for pT1 carcinoma, while tumors at or close to the margin of the polypectomy, and histological high-risk criteria, require surgical resection with lymphadenectomy. Eighty-six patients with 87 pT1 carcinomas underwent polypectomy within a twelve-and-a-half-year period. Further treatment prospectively followed the above guidelines. The follow-up was documented. A local tumor residue was found in 5 of 34 patients who had undergone surgical resection for doubtful or incomplete polypectomy. Two patients were found to have nodal disease in the surgical specimen, only one of them harboring a high-risk carcinoma. Two further patients with high-risk carcinomas had tumor progression, despite postpolypectomy resections without local tumor residue or lymph-node infiltration, and died. One patient had a local tumor recurrence on follow-up endoscopy eight weeks after doubtfully complete polypectomy. He underwent resection, and had no further recurrence. No further manifestations of invasive carcinoma occurred after complete polypectomy of 42 patients with low-risk carcinomas. This study supports the view that complete endoscopic polypectomy is an adequate therapy for low-risk carcinoma: A modification of the follow-up regimen, with less frequent endoscopic controls, is justified.

72 Long term outcome of adjuvant whole abdominopelvic radiation therapy for patients with high risk and papillary serous endometrial carcinoma

72 Long term outcome of adjuvant whole abdominopelvic radiation therapy for patients with high risk and papillary serous endometrial carcinoma

Effective Secondary Neoadjuvant Chemotherapy with 5-Fluorouracil and Folinic Acid in a Patient with Cancer of the Colon

Background: Adjuvant chemotherapy of high-risk carcinomas of the colon and rectum has recently been established. However, early chemotherapy is not yet proven to have a positive influence on the resectability and prognosis in patients with synchronous distant metastases. Case Report: We report on a 63-year-old patient who suffered from colon cancer with synchronous hepatic metastases. In August 1992, a left-sided hemicolectomy was performed for pT3, pN1, pM1 (hepar.) G2 cancer of the descending colon. Intraoperatively 2 hepatic metastases were found. Following a postoperative chemotherapy with 5-fluorouracil (5-FU) and folinic acid (FA) (3 cycles) a significant regression of the metastases became evident. In absence of further distant metastases and local recurrence the potentially curative resection of the hepatic metastases was performed successfully by segmentectomy of the segments 4 and 8 in December 1992. The postoperative course was uneventful. The histopathological examination showed complete necrotic and devitalized tumor tissue. For one more year, until September 1993, adjuvant chemotherapy with 5-FU and FA was performed. Until now (December 1994) the patient has remained tumor free. Conclusions: In carcinoma of the colon with synchronous distant metastases the combination of 5-FU and FA might serve as a potentially successful neoadjuvant chemotherapy regimen.

MANAGEMENT OF THE PATIENT WITH AN ABNORMAL PAPANICOLAOU TEST: Recent Developments

Based on available data, virtually all cervical cancers and the majority of their high-grade precursors (Hi-SIL/CIN 2-3) contain sexually transmitted oncogenic HPV types, among these the most common type is HPV type 16. In current practice, the most cost-effective diagnostic and therapeutic means for Hi-SIL/CIN lesions is LEEP. Judgment must be exercised, however, to tailor the depth of electroexcision of cervical cancer precursors, particularly with respect to the low-grade variants, according to the position of their endocervical lesional margin. About half of the low-grade lesions also carry intermediate- to high-risk oncogenic viruses; unfortunately, morphology cannot identify them unless abnormal mitotic figures are present on the histologic sections. When sophisticated, low-cost viral probing tests and perhaps Cervicography become available, it may be pertinent to determine whether a low-grade lesion contains low-risk virus or is associated with a high- to intermediate-risk virus group. Indeed, the former are unlikely to progress to invasion and may, in fact, regress without therapy other than multiple biopsies, whereas the latter carry high-risk carcinoma potential. Treating long-term monogamous men with asymptomatic, subclinical lesions who are partners of HPV-infected women is not considered cost effective, for they do not seem to reinfect each other. Management strategies for patients with HPV infections should not only be therapeutic but also educative, encouraging patients to practice sexual monogamy.

Gastrointestinal Disturbances with Obesity

Steatosis and steatohepatitis are associated with obesity. Despite florid histological changes, patients with non-alcoholic steatohepatitis generally remain asymptomatic, and it usually runs a relatively benign course. An elevated insulin level may be important in the pathogenesis. There is a marked regression of fatty changes after weight reduction. In obese subjects the risk of developing gallstones is increased due to an increased saturation of gallbladder bile with cholesterol and possible gallbladder stasis. During weight reduction with very low calorie diets the incidence in gallstones increases probably because of an increased saturation of bile during the loss of weight. Ursodeoxycholic acid appears to be a promising prophylactic agent. Chenodeoxycholic acid is not useful for these subjects. There is controversy over whether obesity contributes to gastroesophageal reflux and gastric emptying disturbances. There are changes in gastrointestinal peptide plasma levels in obesity but it is not clear if this contributes to its development. The risk for high-risk colorectal adenomas and carcinomas is reported to be increased in obese males. Vertical banded gastroplasty and gastric bypass procedures are nowadays the surgical options for the treatment of obesity. Nutritional deficiencies, particularly of vitamin B12, folate and iron are common after gastric bypass and must be sought and treated. Dumping is another potential complication of this operation. If stenosis and gastric outlet obstruction develop endoscopic dilatation is a good therapeutic option.

New Approaches to Adjuvant Therapy of Colorectal Carcinoma Including Current German Activities

In this review new approaches to adjuvant therapy of colon and rectum carcinomas are reported. Early trials in the 70s using 5-fluorouracil and other monotherapies did not show any advantage for prognosis. The use of combination chemotherapy (e.g. 5-fluorouracil + methyl-CCNU) in several prospective trials suggested a considerable increase of late neoplasia. A statistically significant prolongation of recurrence-free survival and overall survival for patients with high-risk colon carcinoma (Dukes C) was first seen by combination of 5-fluorouracil with levamisole. Data of a first multicenter trial were recently confirmed by a larger series. For rectum carcinoma postoperative radiation therapy, effective for reduction of local recurrences, was included in adjuvant chemotherapy in several studies suggesting a statistically significant advantage of recurrence and overall survival. Recent data and analyses indicate that the combination of 5-fluorouracil and folinic acid, which shows high efficacy in advanced stages of colorectal carcinoma, is effective in the adjuvant setting too. During 1992/1993 in Germany five multicenter, prospective randomized trials were activated to clarify further details of this new prophylactic treatmenl possibility for colorectal carcinoma.

A phase II trial of mitomycin, vincristine, bleomycin, cis-platinum (MOBP) as neuadjuvant therapy in high-risk cervical carcinoma

A phase II trial of mitomycin, vincristine, bleomycin, cis-platinum (MOBP) as neuadjuvant therapy in high-risk cervical carcinoma