Zwi Steiger

Combined modality therapy for esophageal squamous cell carcinoma

Of 55 patients with esophageal squamous cell carcinoma, 30 with localized disease were treated with a combined modality for curative intent. Treatment consisted of mitomycin C (10 mg/m2 day 1) and continuous infusion 5‐FU (1000 mg/m2 day, days 1–4, 29–32) (CT), radiation (XRT) (3000 rad, days 1–21) with nutritional support, and surgery (days 49–64). Surgery consisted of celiotomy, esophagectomy and esophagogastrostomy ± postoperative ventilatory support. Postoperative CT plus an additional 2000 rad XRT was restricted to patients with histologic positive tumor. Since five resected patients with subclinical metastatic tumor had an inferior survival equal to 25 patients treated essentially for palliation, pretreatment celiotomy seems warreanted to identify patients with an inferior prognosis. Of 18 resected patients without disseminated tumor evaluable for this combined modality: six were tumor free, three had intramural and nine transmural tumor; the median survival is 76 weeks and five of six living patients are disease free at 95–190 weeks; and local recurrence occurred in two and in two of seven unresected patients. Since toxicity was minimal except for postoperative pneumonitis (13%) and local recurrence low (13%), two courses of chemotherapy and 5000 rad XRT perhaps obviates the need for resection.

Chemo/radiation with and without surgery in the thoracic esophagus: the wayne state experience

Wayne State University was the site of one of the initial experiences with combination chemotherapy, radiation, and surgery for carcinoma of the thoracic esophagus. This review analyzes all the patients seen with thoracic esophageal carcinoma from 1980 to 1984 inclusive, plus an additional 22 patient pilot study. The great majority of patients seen were treated with combination radiation and chemotherapy, which may have a greater applicability than dose esophagectomy. Eighty-nine patients completed planned preoperative treatment consisting of (5-FU cisplatin and radiation therapy). Of these patients, 39 patients refused or were not offered surgery, and 4 patients are still alive and well several years from treatment initiation. Fifty patients underwent esophagectomy. Twelve of this patients were free of tumor at esophagectomy, and 4 of these are still alive and well several years from treatment. One patient with residual tumor in the esophagectomy specimen alone is still alive. Because of disappointing results and surgical mortality risk, 22 patients were entered on the pilot study, increasing the tumor dose of 5,000 cGy, and increasing chemotherapy to 4 courses. Six patients are still alive in this small series. Since the results of radiation and chemotherapy combination approximates that of best prior trials of radiation therapy alone, a randomized study has been initiated comparing these treatment plans to determine if the combination of radiation and chemotherapy is superior to radiation alone.

Analysis of adenocarcinoma in barrett's esophagus utilizing a staging system

Based on a retrospective review of nine patients with adenocarcinoma in a Barretts esophagus and the reports of similar cases in the literature, a staging system for this malignancy was devised. A progression of changes could be identified that corresponded to the stages. These changes consisted of dysplasia progressing to carcinoma in situ and invasive malignancy with metastases. Stage III disease carried the same grim prognosis as a similar stage of squamous cell carcinoma of the esophagus. Earlier stages of adenocarcinoma of the esophagus appeared to have a better prognosis. White men with symptoms of reflux esophagitis, esophageal strictures, and/or hiatal hernias who have Barretts esophagus extending proximal to the distal 10 cm of the esophagus appear to have a propensity to develop adenocarcinoma of the esophagus. Consideration should be given to antireflux surgery and close follow‐up by periodic esophagoscopy and biopsy of the esophagus in these patients. If neoplasia is found, the thoracic esophagus should be totally removed with the stomach or left colon anastomosed to the cervical esophagus. Because of the poor prognosis of Stage III disease, postoperative chemotherapy should be considered. Cancer 55:1353‐1360, 1985.

A universal method for the mutational analysis of K-ras and p53 gene in non-small-cell lung cancer using formalin-fixed paraffin-embedded tissue.

The p53 tumor suppressor gene has been found to be altered in almost all human solid tumors, whereas K-ras gene mutations have been observed in a limited number of human cancers (adenocarcinoma of colon, pancreas, and lung). Studies of mutational inactivation for both genes in the same patients sample on non-small-cell lung cancer have been limited. In an effort to perform such an analysis, we developed and compared methods (for the mutational detection of p53 and K-ras gene) that represent a modified and universal protocol, in terms of DNA extraction, polymerase chain reaction (PCR) amplification, and nonradioisotopic PCR-single-strand conformation polymorphism (PCR-SSCP) analysis, which is readily applicable to either formalin-fixed, paraffin-embedded tissues or frozen tumor specimens. We applied this method to the evaluation of p53 (exons 5–8) and K-ras (codon 12 and 13) gene mutations in 55 cases of non-small-cell lung cancer. The mutational status in the p53 gene was evaluated by radioisotopic PCR-SSCP and compared with PCR-SSCP utilizing our standardized non-radioisotopic detection system using a single 6-μm tissue section. The mutational patterns observed by PCR-SSCP were subsequently confirmed by PCR-DNA sequencing. The mutational status in the K-ras gene was similarly evaluated by PCR-SSCP, and the specific mutation was confirmed by Southern slot-blot hybridization using 32P-labeled sequence-specific oligonucleotide probes for codons 12 and 13. Mutational changes in K-ras (codon 12) were found in 10 of 55 (18%) of non-small-cell lung cancers. Whereas adenocarcinoma showed K-ras mutation in 33% of the cases at codon 12, only one mutation was found at codon 13. As expected, squamous cell carcinoma samples (25 cases) did not show K-ras mutations. Mutations at exons 5–8 of the p53 gene were documented in 19 of 55 (34.5%) cases. Ten of the 19 mutations were single nucleotide point mutations, leading to amino acid substitution. Six showed insertional mutation, and three showed deletion mutations. Only three samples showed mutations of both K-ras and p53 genes. We conclude that although K-ras and p53 gene mutations are frequent in non-small-cell lung cancer, mutations of both genes in the same patients samples are not common. We also conclude that this universal nonradioisotopic method is superior to other similar methods and is readily applicable to the rapid screening of large numbers of formalin-fixed, paraffin-embedded or frozen samples for the mutational analysis of multiple genes.

Cardiac tamponade due to an iatrogenic pericardialdiaphragmatic hernia

Because of its ease, safety, and effectiveness, surgeons are increasingly using the subxiphoid approach to drain pericardial effusions and to insert epicardial pacemakers. Although we could find no previous reports of iatrogenic pericardial-diaphragmatic hernias in the literature, experience with a recent patient who developed this problem after a subxiphoid pericardial drainage suggests that it may become much more frequent. Physicians should strongly suspect this complication in patients with a triad of previous subxiphoid pericardial incision and signs of bowel obstruction and tamponade.

Combined pectoralis flap and gastric pull‐up for pharyngeal reconstruction

The gastric transposition flap, “gastric pull‐up,” is one of the standard techniques of reconstruction after total laryngopharyngectomy. Under certain circumstances, this method may provide insufficient tissue for a tension‐free closure. In these circumstances, the surgeon could either close under tension, risking the viability of the flap and probable fistula; create a pharyngostome; or recruit additional tissue. In this article, we describe the use of the pectoralis major myocutaneous flap in combination with the gastric pull‐up for reconstruction.

Improved surgical palliation of advanced carcinoma of the esophagus.

Fifty-four patients with far-advanced carcinoma of the esophagus were operated on between the years 1974 and 1976. No attempts were made to resect the lesion. The stomach was used fifty-three times to bypass the lesion and the right colon was used once. In twenty-eight patients the stomach was placed substernally and the anastomosis was done in the neck. Twenty-five patients had the anastomosis to the esophagus done in the chest. The thirty day operative mortality was 7.4 per cent and the average survival was five months. These figures compared favorably with a group of thirty-five patients with far-advanced carcinoma of the esophagus seen between the years 1971 and 1973 and handled with a variety of modalities. In this group the thirty day mortality was 31.4 per cent (11/35) and the average survival was three and a half months.