Unresectable Group Research Articles

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of 5-fluorouracil (250 mg/m 2/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of 5-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 15 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy.

What prognostic factors are important in duodenal adenocarcinoma?

Survival of patients with adenocarcinoma of the duodenum depends on the ability to perform a complete resection and the tumor stage Retrospective case series. Tertiary care referral center. A cohort of 101 consecutive patients (mean age, 62 years), undergoing surgery for duodenal adenocarcinoma from January 1, 1976, through December 31, 1996. Patients with ampullary carcinoma were specifically excluded. Mean duration of follow-up was 4 years. Surgery was curative in 68 patients (67%) and palliative in 33 patients (33%). Of the curative group, 50 patients (74%) underwent radical surgery, ie, 30 (60%), pancreaticoduodenectomy; 15 (30%), pylorus-preserving pancreaticoduodenectomy; and 5 (10%), total pancreatectomy. A more limited resection procedure was used in 18 patients (26%) involving a segmental duodenal resection in 15 (83%) and a transduodenal excision in 3 (17%). patient survival, and correlation with patient and tumor variables using univariate and multivariate analysis. Actuarial 5-year survival for the curative group was 54%. Only 1 patient in the unresected group survived beyond 3 years. Nodal metastasis (P = .002), advanced tumor stage (P<.001), positive resection margin (P = .02), and weight loss (P<.001) had a significant negative impact on survival in multivariate analysis. Tumor grade, size, and location within the duodenum had no impact on survival. Patient age and tumor depth of invasion influenced survival in univariate analysis, but lost their prognostic significance in multivariate analysis. Metastasis to lymph nodes, advanced tumor stage, and positive resection margins are associated with decreased survival in patients with duodenal adenocarcinoma. An aggressive surgical approach that achieves complete tumor resection with negative margins should be pursued. Pancreaticoduodenectomy is usually required for cancers of the first and second portion of the duodenum. Segmental resection may be appropriate for selected patients, especially for tumors of the distal duodenum.

Management of symptomatic malignant melanoma of the gastrointestinal tract.

Melanoma metastatic to the gastrointestinal (GI) tract is asymptomatic or presents with pain, bleeding, or obstruction. To determine whether surgery influences outcomes, we reviewed our experience with this patient population. Medical records of patients with metastatic melanoma to the GI tract were reviewed. Patients were divided into four groups, i.e., complete resection, partial debulking, unresectable, or unexplored. Analysis was performed using the Kaplan-Meier method. Fifty patients with melanoma metastatic to the GI tract were identified (40 men and 10 women; mean age, 44 years). Presenting symptoms included pain (62%), bleeding (28%), and obstruction (18%). Diagnosis was confirmed using contrast studies (38%), endoscopy (20%), or computed tomography (30%). Thirty-six patients (61%) underwent a total of 39 operations. Seventeen patients underwent complete resection, whereas 14 underwent partial debulking. Five patients had unresectable lesions, and 14 patients did not undergo exploration because of medical contraindications. The operative mortality rate was 2.5% (1 of 39). The mean survival times for the unexplored and unresected groups were similar (4.1 months). Patients who underwent partial resection exhibited a longer mean survival time (8.9 months) than did patients in the unresected group (P < .001). The complete-resection group demonstrated a mean survival time of 23.5 months, which was significantly longer than that for patients who underwent less than complete resection (P < .0001). Metastatic melanoma to the GI tract can result in significant morbidity and death. Surgical resection can be performed safely. Patients for whom all sites of disease are completely resected experience significant improvements in survival times, compared with patients who undergo less than complete resection. For selected patients, surgical treatment of metastatic melanoma involving the GI tract is appropriate therapy.

Isolated liver metastases from neuroendocrine tumors: does resection prolong survival?

Background: Neuroendocrine tumors commonly metastasize to the liver. Although surgical resection is considered a treatment option for patients with localized metastases confined to the liver, the longterm survival benefit of liver resection has not been clearly demonstrated. We examined the survival of patients undergoing liver resection for this disease. Study Design: Between 1984 and 1995, we evaluated 38 patients with liver-only metastases from neuroendocrine tumors, including 21 carcinoid, 13 islet cell, and 4 atypical neuroendocrine neoplasms. Data from a combined prospective and retrospective database and a tumor registry were analyzed. Of these patients, 15 underwent complete resection of all known disease. The remaining 23 patients, who also had disease confined to the liver, had comparable tumor burden but were believed to be unresectable. The longterm survival rates of these two groups were compared. Results: Patients who underwent liver resection did not differ from those who were unresectable with regard to age, pathology, primary tumor site, serum alkaline phosphatase levels, or percentage of the liver involved. All resections were complete, leaving no residual disease, and consisted of lobectomy (n = 3), segmentectomy (n = 1), and wedge resections (n = 11). There were no operative deaths. Patients who underwent hepatic resection had a significantly longer survival than unresected patients. Although median survival had not been reached in resected patients, the median survival in the unresectable group was 27 months. Patients who underwent liver resection had a higher 5-year actuarial survival (73% versus 29%). Conclusions: Hepatic resection in selected patients with isolated liver metastases from neuroendocrine tumors may prolong survival. This conclusion was reached by comparing our resected group with an unresectable group with similar tumor burden.

Survival After Combined Modality Therapy for Pancreatic Cancer

Twenty consecutive patients with unresectable, locally advanced pancreatic cancer were treated with split courses of radiotherapy (RT) and simultaneous multidrug chemotherapy consisting of 5 fluorouracil, continuous infusion, streptozotocin, and cisplatin. A separate, retrospective study identified a group of 28 contemporary patients with less advanced pancreatic cancers, all of which were successfully resected. The survival rate of the two groups were similar over the first 2 years, although it initially favored the unresectable group. This pattern of survival among patients treated with combined modality therapy provides a basis for new studies. At the two clinical extremes, these include treatment of unresectable tumors previously considered ineligible for this treatment and initial treatment before resection of stage I tumors.

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584.

We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival.

High dose preoperative irradiation for cancer of the rectum, 1976–1988

Two hundred twenty patients with adenocarcinoma of the rectum have been treated in a program using high dose (>4000 cGy) preoperative irradiation followed by radical surgical resection. The patients were staged on the basis of pretreatment clinical mobility of the cancers. Seventy-four patients had mobile cancers, 49 had partial fixation (tethered), 85 patients had total tumor fixation, and 12 patients had a frozen pelvis (unresectable). Patients were treated with high energy photons using a four field box technique with total doses ranging from 4000 to 6000 cGy. The overall incidence of local recurrence was 15% ( 32 220 ). Patients with fixed and unresectable tumors had a higher incidence of local recurrence, 20% (21/97) as compared with patients with mobile and partially fixed tumors, 10% ( 13 123 ). Local recurrence by pathological stage of disease was 6% for patients with Stages O, A, B1 versus 20% for patients with Stages B2 and C cancer. Overall 5-year survival of the total group was 67%. The 5-year survival by clinical stages of disease was 87% for mobile tumors, 74% for partially fixed tumors, 70% for fixed tumors, and 22% for the unresectable group. The 5-year survival by pathological stages of disease was 90% for those with Stage O, A, B1 and 71, 75, and 47%, respectively, for Stages B2, Cl, and C2 disease.

Relationship between intestinal permeability to [51Cr]EDTA and inflammatory activity in asymptomatic patients with Crohn's disease

The relationship between intestinal permeability to an oral dose (100 mu Ci) of [51CR]EDTA and the inflammatory activity of Crohn's disease was studied in 63 adult patients (32 unresected and 31 resected) who underwent 162 evaluations. The results of the [51CR]EDTA test were compared with the serum levels of the acute-phase reactant proteins (APRP) and with the result of the [111In]leukocyte scanning, respectively, as an indirect and direct method to assess intestinal inflammation. In a group of healthy adult controls, the upper normal value for the 24-hr urinary [51CR]EDTA excretion was 3.61 (97.5% percentile) and the mean coefficient of variation was 21%. Sensitivity and specificity of the [51CR]EDTA test in identifying active inflammation expressed by increased serum levels of APRP were, respectively, 97% and 54% in the unresected group and 68% and 52% in the resected group of patients. The low specificity of the test was due to the presence of increased [51CR]EDTA urinary excretion in about half the cases with normal serum levels of APRP. The [111In]leukocyte scanning was performed in a subgroup of 11 patients (three unresected and eight resected) with normal serum levels of APRP, six with increased and five with normal [51CR]EDTA urinary excretion. All six patients with increased intestinal permeability had a positive 111In image of mild to moderate degree of activity. A positive 111In scan was present in two of the five patients with normal permeability; these were two resected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of squamous-cell carcinoma of the head and neck with cisplatin and 5-fluorouracil.

Seventy patients with squamous-cell carcinoma of the head and neck were treated with a 24-hour infusion of cisplatin, followed by a 5-day continuous infusion of 5-fluorouracil (5-FU). Among 31 patients without prior treatment, stage III (six patients) and IV (25 patients), there were seven complete responses (CRs) and 19 partial responses (PRs) for an overall response rate of 84%. In the group of 30 patients with recurrent disease after surgery and/or radiotherapy, there were five CRs and ten PRs (total response rate of 50%). Among nine patients who failed prior chemotherapy, there were two CRs and one PR. Performance status and stage had minor effects on response frequency. The projected survival in the no prior treatment group was 59% at 22 months while the median survival of the recurrent cancer group was nine months. Compared to our previous study using cisplatin-vincristine-bleomycin (COB) chemotherapy, our present regimen has a higher CR rate (P less than .008). Durations of response and survival in the present study appear to be longer in the unresectable group and the recurrent cancer group. Toxicity was generally mild. The use of dexamethasone, diphenhydramine, droperidol, and perphenazine as antiemetics prophylactically resulted in 28% of treatment cycles associated with vomiting. This compares favorably with our previous 79% incidence of vomiting. This regimen appears to be more effective than our previous regimen and can be given with less toxicity.

Carcinoma of the lung in patients under 40 years of age

Bronchogenic carcinoma in the young population (40 years of age or less) is reported to present in an advanced stage and to have a virulent course. Between 1969 and 1979, 101 patients (65 men and 36 women) presented with cancer of the lung. Their mean age was 36.2 +/- 3.9 years (range 18 to 40 years). Eighty-seven percent had a history of cigarette smoking. Fifty percent of the patients had a strong familial history of malignancy of several organs. The interval between onset of symptoms and diagnosis was 4.01 +/- 3.48 months (3.56 +/- 3.34 for the surgically treated group and 4.16 +/- 3.53 for the nonoperated or unresectable group). Diagnosis was made at bronchoscopy in 32 patients, during thoracotomy in 30 patients, during nodal biopsy in 28 patients, and on cytologic examination of the sputum in 9 patients. The most common cell types were adenocarcinoma in 39 patients, squamous carcinoma in 29 patients, and oat cell carcinoma in 18 patients. Eighty-six patients (the majority) presented in stage III, whereas 9 were in stage I and 6 were in stage II. Twenty-seven patients (26.7 percent) underwent resection for cure, whereas 18 patients were inoperable at surgery. Eighteen of the surgical patients had adjuvant radiotherapy, and chemotherapy, immunotherapy, or both. The average length of survival for the nonresected patients was 7.12 +/- 5.9 months (range 1 to 36 months) and the actuarial survival was 1.5 percent at 36 months. The survival for the surgically managed patients was 56.1 +/- 52.6 months (range 3 to 168 months) or 48 percent at 36 months. At 46 to 168 months after treatment, the only survivors were 13 patients who were surgically managed. Stage III patients had longer survival after surgery (24.1 +/- 24.6 months to 7.09 +/- 5.90 months; range 3 to 74 months and 1 to 36 months, respectively). The survival at 5 years for patients with stage I disease was 78.8 percent, stage II disease 66.6 percent, and stage III disease, 3.6 percent. Early diagnosis and aggressive surgical management are necessary to improve the survival of patients with bronchogenic carcinoma under 40 years of age.

Primary carcinoma involving the temporal bone: analysis of twenty-five cases.

Twenty-five patients with primary carcinoma involving the temporal bone were reviewed. Pain and discharge were the most common complaints. A history of previous otitis media was found in 64% of the patients. On clinical and radiological assessment, 18 cases were deemed surgically resectable and 7 unresectable. Analysis of treatment revealed 3 groups of patients: an unresectable group of 7 patients treated by primary radical radiation therapy in which there were no long-term survivors; another group received primary radiotherapy with surgery reserved for residual or recurrent disease--4 of this group of 12 survived 4 years or longer; and the remaining group had primary surgery with radical postoperative radiation therapy--4 of this group of 6 patients survived 4 years or longer despite incomplete surgical removal of tumor in all except 1 patient. The results and possible reasons for failure are discussed.