Hansjörg Heep

Basaloid squamous cell carcinoma of the esophagus

Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract.

Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities.

In the present study, the expression of cyclin D1, as detected by immunohistochemistry, was compared with other prognostic variables and its prognostic impact was evaluated in a group of 172 patients with squamous cell carcinoma (SCC) of the esophagus who underwent potentially curative resection therapy and in a second group of 38 patients with SCC of the esophagus who were treated by combined modality therapy (radiochemotherapy ± surgery). Expression of cyclin D1 in surgically treated carcinomas correlated negatively with tumor differentiation (p = 0.026) but positively with mitotic activity (p = 0.0199) and nodal status (p = 0.040). There were no significant correlations with pT category. Patients with cyclin D1‐positive carcinomas showed significantly worse overall survival than patients with cyclin D1‐negative carcinomas, both in univariate (p = 0.0016) and in multivariate survival analyses (p = 0.0038). Expression of cyclin D1 in carcinomas with multimodal treatment was correlated with poor response to chemotherapy (p = 0.026) but not with overall survival. We thus consider expression of cyclin D1 to be an important parameter, predicting an unfavorable overall survival of surgically treated esophageal cancer patients. Int. J. Cancer (Pred. Oncol.) 84:86–91, 1999.

Expression of Bcl-2 and amplification of c-myc are frequent in basaloid squamous cell carcinomas of the esophagus

Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare, poorly differentiated variant of typical esophageal squamous cell carcinoma (SCC) characterized by high proliferative activity and frequent spontaneous apoptoses. In the present study, we investigated the expression of the apoptosis-suppressing protein Bcl-2 in 23 BSCC of the esophagus and 23 stage-matched typical esophageal SCC by means of immunohistochemistry. In addition, amplification of the apoptosis- and proliferation-inducing gene c-myc was determined by means of differential polymerase chain reaction. Bcl-2 expression was found significantly more often in BSCC than in SCC (86.9% vs. 17.4%, P < 0.0001). Amplification of c-myc was nearly twice as common in BSCC as in SCC (47.8% vs. 26.1%, not significant). Bcl-2 protein expression together with c-myc amplification was detected in 43.5% of the BSCC but in none of the typical SCC (P < 0.0001). Taken together, our findings indicate that the molecular pathogenesis of esophageal BSCC differs from that of typical SCC and frequently involves coactivation of c-myc and Bcl-2.

Frequent c-myc Amplification in High-Grade Dysplasia and Adenocarcinoma in Barrett Esophagus

Barrett esophagus (BE) is a condition in which the normal squamous epithelium of the esophagus is replaced by a metaplastic columnar epithelium. BE is a premalignant lesion that represents the initial step in a metaplasia-dysplasia-carcinoma sequence. In the present study, amplification of the proto-oncogene c-myc was determined by means of differential polymerase chain reaction analysis of metaplastic specialized epithelium, low-grade dysplasia, high-grade dysplasia, and invasive adenocarcinoma obtained by microscopic dissection of 43 esophagectomy specimens. Amplification of c-myc was found in none of 29 specialized epithelial specimens, none of 23 low-grade dysplasia specimens, 6 of 24 high-grade dysplasia specimens, and 17 of 39 adenocarcinoma specimens. Our data indicate that amplification of c-myc is a late event in the metaplasia-dysplasia-carcinoma sequence in BE. Furthermore, determination of c-myc amplification may help identify high-risk patients who would benefit from intensified endoscopic surveillance or from immediate treatment.

Retinoblastoma-protein (prb) expression and prognosis in squamous-cell carcinomas of the esophagus

The retinoblastoma gene (RB) is a typical tumor‐suppressor gene. Inactivation of RB has been shown in a variety of human cancers, including esophageal squamous‐cell carcinomas. In the present study, samples of normal esophageal squamous epithelium (n = 10), severe squamous‐cell dysplasias (n = 19), carcinomas in situ (n = 14), invasive squamous‐cell carcinomas (n = 172), and 2 continuous esophageal‐carcinoma cell lines were immunohistochemically analyzed for pRb expression. The specificity of immunostaining was tested by Western‐blot analysis of pRb expression in the cell lines. In normal esophageal epithelium, nuclear pRb expression was restricted to the parabasal cell layer, whereas, in a considerable portion of severe dysplasias and carcinomas in situ, pRb over‐expression was found. Among carcinomas, 161 of 172 cases showed pRb expression, as did the 2 esophageal‐carcinoma cell lines, whereas 11 carcinomas were negative. Expression of pRb among carcinomas was not correlated with pT category, pN category or tumor grade. In the univariate survival analysis, patients with pRb‐negative tumors showed lower 2‐year and 5‐year survival rates (27.3%/9.1%) than patients with pRb‐positive tumors (42.8%/25.8%; not significant). In conclusion, pRb protein can be detected by immunohistochemistry in a high percentage of squamous‐cell carcinomas of the esophagus and its precursor lesions. However, expression of the pRb protein has no significant impact on the prognosis. Int. J. Cancer (Pred. Oncol.) 84:618–622, 1999.

Allelic Loss Involving the Tumor Suppressor Genes APC and MCC and Expression of the APC Protein in the Development of Dysplasia and Carcinoma in Barrett Esophagus

Samples of Barrett metaplastic specialized epithelium (SE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) derived from 36 esophagectomy specimens were studied for loss of heterozygosity (LOH) in APC and MCC and for expression of APC protein. Of 18 cases that were heterozygous (informative) for APC, LOH was found in none of 14 SE samples, 2 of 8 LGD samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immunohistochemically, markedly reduced expression of APC protein (< 50% positive cells) was found in 3 of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17 cases informative for the MCC gene, LOH was detectable in 1 of 14 SE samples, none of 7 LGD samples, none of 9 HGD samples, and 4 of 16 CA samples. Allelic loss of APC and/or loss of APC protein expression occurs earlier in the metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC gene. The determination of alterations at APC or MCC would be of limited importance for the surveillance of patients with Barrett esophagus.

Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus

BackgroundThe effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patients remaining survival time, this study aims to provide rationales for pretreating resection candidates.MethodsFrom March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival.ResultsTwo hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 ± 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834.ConclusionsNT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival.

Penile metastasis secondary to follicular thyroid carcinoma.

Penile metastases are rare and are considered to reflect end‐stage malignant disease. The first case of a follicular thyroid carcinoma metastasizing to the penis is described. Local tumor control and probably enhanced survival was achieved by extended surgery of a previous pelvic recurrence and the penile metastasis and this procedure may be justified in selected cases.

Magenhochzugsoperation beim ösophaguskarzinom — Kaum Einschränkung der Lebensqualität

Einleitung: Die subjektive Bewertung eines Operationsergebnisses durch standardisierte Patientenbefragung ist ein wesentlicher Beitrag zur Erfassung der Lebensqualitat nach grosen Eingriffen. Ziel der Untersuchung war die moglichst objektive Erfassung der Lebensqualitat nach Magenhochzugsoperation im Vergleich zu Gesunden. Methodik: Zwischen April 1986 und Marz 2001 resezierte Patienten mit einem Karzinom des osophagus (oSO-Gruppe) wurden retrospektiv erfasst und seit April 2001 prospektiv mit dem QLQ-C30 („allgemeine Lebensqualitat“)- und dem QLQ-OES24 (,osophagusbezogene Lebensqualitat,,)- Fragebogen der EORTC evaluiert. Als Kontrollgruppe dienten Patienten mit einer Struma 1.Grades praoperativ als, Gesunde“. Zielkriterium war die postoperative Lebensqualitat nach den EORTC-Auswertbedingungen (raw score: 1 = positiv - 4 = negativ) sowohl fur den QLQ-30-als auch den QLQ-OES24- Fragebogen festgelegt. Verglichen wurde die postoperative Lebensqualitat mehr als 1 Jahr nach Operation gegenuber den gesunden Kontrollpatienten. Ergebnisse: In der OSO-Gruppe konnten n = 68 Patienten und in der Kontroll-Gruppe n = 23 Patienten ausgewertet werden. Sowohl beim QLQ-C30-Fragebogen als auch beim QLQ-OES24-Fragebogen ergab sich in der oSO-Gruppe gegenuber der Kontroll-Gruppe kein signifikanter Unterschied (Mittelwert + / - SD, range 1 - 4): 2,2 (+ / - 0,74) gegenuber 1,8 (+ / - 0,9) (p = 0,209) fur den QLQ-C30-Fragebogen, 2,3 (+ / - 0,67) gegenuber 1,9 (+ / -0,77 SD) (p = 0,865) fur den QLQ-OES24-Fragebogen. Schlussfolgerung: Die ersten Ergebnisse unserer Studie zeigen eine nur geringgradige statistisch nicht signifikante Einschrankung der allgemeinen Lebensqualitat und der Nahrungsaufnahme mehr als 1 Jahr nach Magenhochzugsoperation.

Kein erhöhtes postoperatives Risiko nach neoadjuvanter Therapie des Ösophaguskarzinoms — Ergebnisse einer Fallkontrollstudie / No Increased Perioperative Complications After Neoadjuvant Therapy of Esophageal Cancer: A Case Control Study

Einleitung: Nach neoadjuvanter Therapie des Plattenepithel-Ca des O sophagus ist ein erhohtes postoperatives Risiko gefurchtet. Ziel der Fallkontrollstudie (Alter, OP-Zeitraum < 1 Jahr) war die exakt definierte Morbiditat und Mortalitat dieser Patienten (n= 18, NT) gegenuber denen nach sofortiger Operation (n= 18, OP) im Stadium T3 zu untersuchen. Ergebnisse (NT vs. OP): Alter: 55 vs. 54 Jahre, Beatmungsdauer: 16 vs. 33 Stunden, Intensivdauer: 6 vs. 7 Tage, pulmonale Komplikationen: 33% vs. 44% n.s., Anastomosen-insuffizienz: 0% vs. 6% n.s., Krankenhausletalitat: 6% vs. 11% n.s., 2-J-ULR: 50% vs. 11%, 5-J-ULR: 17% vs. 11% (log-rank p=0,2451). Schlussfolgerung: Die NT geht nicht mit einer erhohten postoperativen Morbiditat einher. In der Uberlebensanalyse zeigt sich im Median eine Lebensverlangerung allerdings ohne Uberlebensverbesserung nach 5 Jahren. Denkbar ist ein Selektionsvorteil. Ein Effektivitatsnachweis fur die NT fehlt bis heute.