George L. Nardi

Coffee and Cancer of the Pancreas

Abstract We questioned 369 patients with histologically proved cancer of the pancreas and 644 control patients about their use of tobacco, alcohol, tea, and coffee. There was a weak positive associ...

Carcinoma of the pancreas: Review of MGH experience from 1963 to 1973—Analysis of surgical failure and implications for radiation therapy

A retrospective study was done of all patients who were seen for definitive treatment of adenocarcinoma of the pancreas at the Massachusetts General Hospital from 1963 to 1973. There were a total of 145 patients. Thirty‐one patients were treated with radical surgery, with a 16% operative mortality, a 5‐year crude survival rate of 15%, and a local recurrence rate of 50%. Sixty‐two patients were treated with a palliative procedure with a 5‐year crude survival of 5%. Fifty‐two patients were treated with biopsy alone, with no 5‐year survivors. In addition, there were 35 patients who did not have a radical surgical procedure performed only because of the extent of the local disease. It is proposed that postoperative irradiation may reduce the incidence of local failure after radical surgery, and that preoperative radiation therapy or radiation therapy alone would be an appropriate treatment of those patients in whom the local extent of disease is initially too far advanced to perform radical surgery.

Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma.

Since 1978 we have used electron beam intraoperative radiation therapy (IORT) to deliver higher radiation doses to pancreatic tumors than are possible with external beam techniques while minimizing the dose to the surrounding normal tissues. Twenty-nine patients with localized, unresectable, pancreatic carcinoma were treated by electron beam IORT in combination with conventional external radiation therapy (XRT). The primary tumor was located in the head of the pancreas in 20 patients, in the head and body in six patients, and in the body and tail in three. Adjuvant chemotherapy was given in 23 of the 29 patients. The last 13 patients have received misonidazole (3.5 mg/M2) just prior to IORT (20 Gy). At present 14 patients are alive and 11 are without evidence of disease from 3 to 41 months after IORT. The median survival is 16.5 months. Eight patients have failed locally in the IORT field and two others failed regionally. Twelve patients have developed distant metastases, including five who failed locally or regionally. We have seen no local recurrences in the 12 patients who have been treated with misonidazole and have completed IORT and XRT while 10 of 15 patients treated without misonidazole have recurred locally. Because of the shorter follow-up in the misonidazole group, this apparent improvement is not statistically significant. Fifteen patients (52%) have not had pain following treatment and 22 (76%) have had no upper gastrointestinal or biliary obstruction subsequent to their initial surgical bypasses and radiation treatments. Based on the good palliation generally obtained, the 16.5-month median survival, and the possible added benefit from misonidazole, we are encouraged to continue this approach.

Iodine‐125 implant and external beam irradiation in patients with localized pancreatic carcinoma. A comparative study to surgical resection

Twelve patients with biopsy‐proven clinically localized ductal pancreatic cancers (less than 7 cm in greatest diameter) judged unsuitable for resection were treated by bypass surgery, an Iodine‐125 implant (20–39 mCi), and postoperative irradiation (4000–4500 rads). The potential problems of significant bleeding, pancreatic fistula, or pancreatitis were not experienced. A local recurrence developed in one patient and two recurred in regional lymph nodes. The projected median survival of the group is 11 months with four of the 12 patients still surviving. For purposes of comparison all patients with pancreatic ductal carcinoma treated by radical resection during a similar time were evaluated. All ten have died with a median survival of six months. Twelve of 22 (55%) of the combined implanted and resected groups have developed distant metastasis. Further pursuit of intraoperative techniques of irradiation in combination with adjuvant multidrug chemotherapy seems indicated in an attempt to prolong patient survival which is now limited by hematogenous metastases. Cancer 45:709‐714, 1980.

Intraoperative irradiation for unresectable pancreatic carcinoma

Twelve patients with localized, unresectable, pancreatic carcinoma were treated with a combination of external photon beam and intraoperative electron beam irradiation. Eleven tumors arose in the head and one in the body of the pancreas. Chemotherapy was administered to six of the 12 patients. Of the 11 patients who received both intraoperative and external beam irradiation, four are alive without evident disease. The median survival is 15+ months. This pilot study demonstrates the feasibility of combining external beam and intraoperative therapy in a general hospital setting with no operative deaths, a brief postoperative stay, and no wound infections. The late complications of irradiating gastric antrum and duodenum are discussed.

Intraoperative irradiation: A pilot study combining external beam photons with “boost” dose intraoperative electrons

Intraoperative “boost” dose electron beam therapy given in combination with 4500‐5000 rad (45–50 Gray) external beam irradiation has been demonstrated as a practical therapeutic modality at the MGH. This procedure has been employed thus far in 58 patients; the results in the initial 36 are analyzed in detail in this paper. Thirty‐four of the 36 patients had locally advanced lesions—unresectable, recurrent, or residual disease. Results achieved to date are in full agreement with our expectations: high radiation doses have been delivered to the primary intra‐abdominal and pelvic tumors, excluding the sensitive structures from irradiation. This has been accomplished by a truly multidisciplinary effort comprising surgery, anesthesiology, OR nursing, administration, engineers, physicists, therapy technologists, and radiation therapists. Although follow‐up is not yet sufficient to judge ultimate efficacy, acute and chronic severe morbidity is low and local control is good. There is justified enthusiasm for continuing the procedure.

The role of misonidazole combined with intraoperative radiation therapy in the treatment of pancreatic carcinoma

We tested the efficacy of the hypoxic cell sensitizer misonidazole in conjunction with intraoperative electron beam radiation therapy (IORT) and external beam irradiation in patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas. Misonidazole was delivered intravenously (IV) at a dose of 3.5 g/m2 in conjunction with IORT of 1,500 to 2,000 cGy to the pancreas. Additional external beam radiation as administered to 4,960 cGy. The study was based on the premise that the effect of misonidazole would be maximized when a high dose of the drug was administered and, thus, high hypoxic cell sensitization could be obtained when using a high single dose of radiation where the hypoxic fraction would be expected to dominate in the survivors. In a nonrandomized study of 41 patients treated with misonidazole and 22 without, the 1-year local control was 67% and 55%, and 1-year survival was 50% and 77%, respectively. Although there was a bias towards larger tumors in the patients treated with the sensitizer, we were unable to demonstrate an advantage to misonidazole in this clinical situation.

Transduodenal Sphincteroplasty: 5–25 Year Follow-up of 89 Patients

Between 1957 and 1977, 95 patients underwent transduodenal pancreatic sphincteroplasty (TPS) for a diagnosis of recurrent pancreatitis. Five to twenty-five year follow-up was obtained for 89 patients (94%) and was analyzed by life-table method. Short-term successful outcome was defined as relief of symptoms (e.g., pain) for one to three years; long-term successful outcome was defined as those patients who remained symptom-free at time of last follow-up. Operative mortality was 4.2% (4 patients). Fifty-six patients (66%) had a successful short-term outcome. Of these, 13 patients had recurrence of symptoms: 7 occurred at 4 years, 5 at 5 years and 1 at 6 years. Preoperative factors associated with poor short-term outcome were previous upper abdominal surgery (X2 = 5.67, p < 0.05) and frequent diarrhea (X2 = 6.18, p < 0.05). Preoperative factors associated with poor long-term outcome were previous upper abdominal surgery (X2 = 7.82, p < 0.01), heavy alcohol intake (X2 = 4.71, p < 0.05), narcotic use (X2 = 5.68, p < 0.05) and frequent diarrhea (X2 = 4.8, p < 0.05). Morphine Prostigmin Test (MPT) was performed preoperatively in 78 patients (82%). A significantly greater proportion of patients with a rise in serum pancreatic enzymes secondary to MPT (MPT+) had a successful long-term outcome compared with those without such a rise (MPT-) (61% v 41%, X2 = 5.13, p < 0.05). Furthermore, of the patients with a successful short-term outcome, 88% with MPT+ remained long-term symptom-free compared to 38.5% with MPT- (X2 = 8.36, p < 0.01). We conclude that TPS can be a successful operation for acute recurrent pancreatitis. Previous upper abdominal operations, signs of more advanced pancreatic disease, preoperative narcotic use and alcohol abuse, were associated with a worse outcome and probably associated with chronic recurrent pancreatitis. Preoperative use of MPT, coupled with accurate clinical history, defined groups with different short- and long-term prognosis after TPS.

Papillitis and Stenosis of the Sphincter of Oddi

Diagnosis may be established by a careful history, elevation of serum alkaline phosphatase, amylase, or lipase, the presence of increased fats or undigested muscle fibers in the stool, and a positive morphine-Prostigmin evocative test. Successful operation must be guided by preoperative pancreatography and depends on an adequate sphincteroplasty to both the common duct and the duct of Wirsung.

Aneuploidy in pancreatic insulinomas does not predict malignancy.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow‐up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas.