Francis E. Rosato

Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy

Background. One thousand seventy patients treated conservatively for Stages I and II breast cancer between the years 1982 and 1994 were reviewed. The median follow‐up was 40 months with a maximum follow‐up of 152 months.

Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas.

PURPOSE To evaluate the effectiveness of combined intraoperative radiation therapy (IORT) and perioperative chemotherapy in the management of unresectable pancreatic cancer. MATERIALS AND METHODS Forty-nine patients with localized unresectable adenocarcinoma of the pancreas were treated in a multimodality program of initial IORT and perioperative chemotherapy (fluorouracil [5-FU]/leucovorin) followed by combined external-beam radiation (40 to 55 Gy) and continued chemotherapy. Patients were evaluated for toxicity, pattern of failure, and survival. The follow-up times of these patients range from a minimum of 12 months to a maximum of 62 months, with a median of 28 months. RESULTS The incidence of perioperative mortality was 0%. Early postsurgical morbidity (grade 3/4) was observed in seven of 49 patients (14%) and late treatment-related morbidity (grade 3/4) in eight of 43 patients (19%) alive beyond 6 months. Morbidity was primarily gastrointestinal (GI), with no hematologic toxicities observed. The median survival time in the total group of patients is 16 months, with a 2-year survival rate of 22% and a 4-year survival rate of 7%. Freedom from local progression of disease was achieved in 71% of patients. CONCLUSION The patients who undergo IORT with electrons and treated with perioperative chemotherapy (5-FU leucovorin) followed by additional external-beam radiation and chemotherapy appear to have improved survival, with few early or late complications. Dose escalation of external-beam radiation and chemotherapy may further improve local control of disease and survival of patients.

Multimodality therapy of localized unresectable pancreatic adenocarcinoma

Eighty‐eight patients with localized unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital between 1974 and 1981. Four treatment regimens were used which were sequential modifications of the technique based on the experience in the preceeding group of patients. Each treatment changed the course of the disease, and as patterns of failure were identified, the treatment was altered to deal with them. Initially, all patients were treated with external beam radiation. Subsequently, Iodine‐125 implantation was added to improve local control; low‐dose preoperative radiotherapy to reduce the risk of peritoneal seeding; and adjuvant chemotherapy to reduce the risks of distant metastases. The addition of 125I implantation increased the local control from 22% to 81%, but did not increase the median survival, which was unchanged from 7 months. The addition of adjuvant chemotherapy increased the median survival from 7 months to 14 months, but had no impact on the control of the pancreatic tumor. Adjunctive chemotherapy and low‐dose preoperative radiotherapy appear synergistic in reducing the risk of peritoneal seeding. The combination of 125I implantation, external beam radiation, and adjunctive chemotherapy is safe and effective. This regimen produces excellent local control with acceptable morbidity. This regimen produced a 30% survival at 18 months. The patterns of failure among these patients suggest future modifications of the technique.

Radiotherapy of unresectable pancreatic carcinoma: A six year experience with 104 patients☆☆☆

Abstract From 1974 to 1980, 104 patients with unresectable carcinoma of the pancreas were seen in the Department of Radiation Therapy at Thomas Jefferson University Hospital. Sixty-six patients were accepted for definitive therapy. Of these, 48 patients received precision high dose radiotherapy to a dose of 6800 rad on the 45 MeV Betatron, using either photons alone or mixed photon and high energy electron beams. Eighty-nine percent of the patients completed treatment as per the protocol. Relief of symptoms was obtained in 65 % of patients. Median survival was 10 months. In spite of the high doses employed, 67 % of the patients had evidence of recurrent tumor in the treatment volume at the time of death. In view of the high incidence of local failure with precision high dose therapy alone, a protocol using Iodine-125 implantation to supplement the external beam therapy was developed in 1978. Since then, 18 patients with disease confined to the region of the pancreas were treated with the combination of Iodine-125 implantation and precision high dose therapy. Eighty-five percent of the patients completed treatment. Follow-up ranges from eight to 22 months. None of the patients completing the treatment protocol have developed local recurrence of tumor. These results are presented together with details of the treatment technique, normal tissue reactions and implications for future approaches to the treatment of localized unresectable cancer of the pancreas.

Improved staging of liver tumors using laparoscopic intraoperative ultrasound

Intraoperative ultrasound has been shown to provide significant assistance in operative staging and management of patients with liver tumors during open surgery. The availability of the 5.0–7.5 Mhz semiflexible ultrasound transducer with gray‐scale, color and spectral Doppler capabilities can provide similar information laparoscopically.

Combined modality treatment of localized unresectable adenocarcinoma of the pancreas

Since 1978, 86 patients with unresectable localized adenocarcinoma of the pancreas have been treated with a combined modality program using radioactive iodine 125-Implantation, external beam radiation, and systemic chemotherapy. Three treatment approaches were used with sequential modifications of the technique based on the course of disease and patterns of failure. Group 1 was comprised of 13 patients treated with a combination of implantation followed by a planned external radiation dose of 5000 to 6000 cGy delivered in 6 weeks. Group 2 included patients treated as in Group 1 followed by adjuvant chemotherapy. The most recent group of 54 patients, Group 3, has been treated since 1981 with implantation into the tumor of radioactive Iodine 125 seeds (12000 cGy minimal peripheral dose), perioperative chemotherapy (5-FU, Mito-C), and external beam irradiation (5000-5500 cGy) followed by further chemotherapy. Incidence of perioperative mortality has been reduced from 31% (10/32) in Groups 1 & 2 to 7% (4/54) in Group 3. Clinical local control of tumor has been excellent in all three groups (84%). Analysis of the Group 3 results indicate that the problem of distant metastasis, in spite of adjuvant chemotherapy, still remains overwhelming (64%)--especially to the liver--and requires development of more effective regimens. Median survival in the three groups of patients is 5.5, 11.3, and 12.5 months. The 2-year survival is 0, 15, and 22%, retrospectively in the three groups.

Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas

From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri-operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.

Use of an endothelial monolayer on a vascular graft prior to implantation: temporal dynamics and compatibility with the operating room

The temporal sequence of events was examined from initial contact of endothelial cells (ECs) to Dacron until the establishment of a monolayer. Cultured human adult ECs were radiolabeled, seeded onto Dacron, and adherence was quantified after vigorous washing. Firm adherence of 70% of the seeded ECs was seen by 2 hours to untreated Dacron, by 30 minutes to Dacron pretreated with a combination of interstitial type I/III collagen and an amnion-derived basement membrane (Type IV) collagen surface, and by 10 minutes to plasma-coated Dacron. Parallel samples were examined morphologically by scanning electron microscopy (SEM) to evaluate the adherence of ECs to surfaces. ECs seeded onto plain Dacron exhibited limited adherence, while cells on plasma-treated Dacron exhibited limited cell-cell associations. On basement membrane-treated Dacron, by 30 minutes the ECs exhibited a flat attenuated morphology, completely covering the graft surface. This time-frame is compatible with most vascular procedures, making an immediately endothelialized graft feasible.

Changing site distribution patterns of colorectal cancer at Thomas Jefferson University Hospital.

Analyzed data from an earlier reported experience with colorectal cancer at Thomas Jefferson University Hospital, compared with findings observed and analyzed from 1959 to 1977 indicate a changing pattern of distribution of colorectal cancers. These changes lead to therapeutic conclusion that fiberoptic flexible sigmoidoscopy is the preferred diagnostic tool.

The consequences of a major bile duct injury during laparoscopic cholecystectomy

Bile duct injury is perhaps the most feared complication of laparoscopic cholecystectomy. The focus of this study was on the immediate and short-term outcome of patients who have undergone repair of major bile duct injuries with respect to hospital stay, perioperative interventions, and reoperations. The records of patients who underwent surgery at three academic hospitals in Philadelphia (Hospital of the University of Pennsylvania, Thomas Jefferson University Hospital, and Graduate Hospital) from 1990 to 1995 for repair of a major biliary injury following laparoscopic cholecystectomy were reviewed. A major biliary injury was defined as any disruption (including ligation, avulsion, or resection) of the extrahepatic biliary system. Small biliary leaks not requiring surgery were excluded. Thirty-two patients sustained major bile duct injuries. The injury was recognized immediately in 10 patients. The remaining 22 patients had pain (59%), jaundice (50%), and/or fever (32 %) as the symptom heralding the injury. Bismuth classification was as follows: 13% of patients were class I, 63% were class II, 7% were class III, 7% were class IV,, and 10% were class V. Biliary reconstruction included a Roux-en-γ hepaticojejunostomy in 30 patients and two were primary repairs. There was one postoperative death from multiorgan system failure. The mean length of hospital stay after repair was 17 ± 8 days. Over a mean follow-up period of 11.5 ± 10.5 months, 11 patients (38%) required 19 emergency readmissions, most commonly for cholangitis. Five patients (17%) required postoperative balloon dilatation for biliary stricture. At follow-up 18 patients (62.0%) remain asymptomatic with normal liver function values, eight (28%) are experiencing episodic cholangitis, and three (10%) are asymptomatic with persistently elevated liver function values. The consequences of a major biliary tract injury following laparoscopic cholecystectomy include a complex operative repair resulting in a lengthy postoperative stay with an increased risk of death, an excessive number of perioperative diagnostic and therapeutic studies, frequent readmissions (often as emergencies), and a lifelong risk of restricture. The “cost” to these patients remains enormous.