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.

Pancreatic necrosis: CT manifestations.

Pancreatic necrosis is a potential sequela of acute pancreatitis, which pathologically represents a collection of devitalized tissue. Appropriate therapeutic planning requires definition of this irreversibly damaged gland, the presence of which is not consistently diagnosed on the basis of clinical and laboratory data. Over an 18-month period, 22 patients with pancreatic necrosis were studied by one or more computed tomographic (CT) examinations. Retrospective analysis showed the findings to vary with the developmental stage of the necrotizing process. During the acute phase, there was considerable morphologic overlap of necrosis and pancreatic phlegmon. Typical findings were seen in the subacute and chronic stages and included diffuse enlargement of the gland with largely decreased central density. A thick, smooth surrounding rim produced a characteristic saclike configuration. CT-guided aspiration for culture material was performed in four patients with suspected superinfection. Negative gram stain and culture results in two patients allowed surgery to be performed on a more elective basis.

Hepatic echinococcal cyst: successful percutaneous drainage.

Percutaneous needle aspiration of hydatid cysts has long been discouraged because of potential complications, such as anaphylactic shock and the spread of daughter cysts. We used this procedure with successful results, however, in the treatment of a woman with a recurrent hepatic hydatid cyst. The cyst was drained percutaneously using radiologic imaging guidance and then lavaged through a catheter using silver nitrate and hypertonic saline solutions. One year after drainage, all liver function test results remain normal. Although surgical drainage is normally the treatment of choice for hepatic Echinococcus disease, percutaneous catheter drainage may be an alternative therapy for patients who cannot undergo 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.

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 less than 0.05) and frequent diarrhea (X2 = 6.18, p less than 0.05). Preoperative factors associated with poor long-term outcome were previous upper abdominal surgery (X2 = 7.82, p less than 0.01), heavy alcohol intake (X2 = 4.71, p less than 0.05), narcotic use (X2 = 5.68, p less than 0.05) and frequent diarrhea (X2 = 4.8, p less than 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 less than 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 less than 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.

The role of canal-neck interaction for the perception of horizontal trunk and head rotation.

The present report considers the conscious perception of passive horizontal rotations of the trunk, the head, or both, by human observers. It examines in particular how this perception depends on the interaction of canal and neck afferents. Three sets of sinusoidal stimulations (0.2 Hz) were applied to subjects (Ss): Rotations of (1) whole body (pure labyrinthine stimuli, lambda), of (2) only the trunk with the head stationary in space (pure neck stimuli, nu), and of (3) both head and trunk, each with an amplitude and a direction of its own, giving rise to various in-phase and counter phase combinations of lambda and nu.--The Ss were to estimate the magnitude of their turning sensations (psi). In doing so, they were to concentrate either on the rotation of their trunk in space (TS) or of their head in space (HS), or of the head relative to the trunk (HT). The TS and HS turning sensations induced by pure lambda-stimuli were essentially the same as to magnitude and direction. Pure nu-stimulation also led to TS and HS turning sensations. However, the former had the direction of the trunk-to-head (T delta S) deflection, the latter that of the head-to-trunk deflection. The nu-induced HS turning sensation represented an illusion, since the head remained stationary in space. When the lambda- and nu-stimuli were combined, the interaction could be described by a linear summation of their effects. The estimates of TS turning followed the equation psi HS approximately lambda-nu, thus well reflecting the actual TS rotation. The estimates of HS could be described by psi HS approximately lambda+k nu; the term k nu represents the "nu-illusion" contaminating the HS turning sensation. The estimates of HT turning were roughly proportional to nu alone and, therefore, close to the actual HT rotation. We conclude that humans may derive a rather faithful information about trunk rotation from the combined activation of canal and neck afferents, but that the sensation of passive head rotation is contaminated by an (illusionary) contribution from neck afferents. These additive and subtractive modes of interaction have parallels in postural reflexes as well as in neuronal responses that are known from cat.

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.

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.

Acute pancreatitis: analysis of factors influencing survival.

Of patients with acute pancreatitis (AP), there remains a group who suffer life-threatening complications despite current modes of therapy. To identify factors which distinguish this group from the entire patient population, a retrospectiva analysis of 519 cases of AP occurring over a 5-year period was undertaken. Thirty-one per cent of these patients had a history of alcoholism and 47% had a history of biliary disease. The overall mortality was 12.9%. Of symptoms and signs recorded at the time of admission, hypotension, tachycardia, fever, abdominal mass, and abnormal examination of the lung fields correlated positively with increased mortality. Seven features of the initial laboratory examination correlated with increased mortality. Shock, massive colloid requirement, hypocalcemia, renal failure, and respiratory failure requiring endotracheal intubation were complications associated with the poorest prognosis. Among patients in this series with three or more of these clinical characteristics, maximal nonoperative treatment yielded a survival rate of 29%, compared to the 64% survival rate for a group of patients treated operatively with cholecystostomy, gastrostomy, feeding jejunostomy, and sump drainage of the lesser sac and retroperitoneum.

Hereditary pancreatitis. Nonspecificity of aminoaciduria and diagnosis of occult disease.

Hereditary pancreatitis appears in many different ways and in a variety of age groups, spanning both pediatric and adult medicine. The variable expression of hereditary pancreatitis is emphasized by the difficulty in diagnosing it in a patient obviously at risk because of a severely affected father and son. The morphine prostigmine test and hypotonic duodenogram were most helpful. Aminoaciduria previously associated with this disorder is coincidental or nonspecifically related to acute pancreatic inflammation. The increased risk for pancreatic carcinoma (about 20%) is emphasized by the concern for that complication in the proband's grandfather.