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Locally advanced unresectable pancreatic adenocarcinoma is characterized by poor survival despite chemotherapy and conventional radiation therapy (RT). Recent advances in real-time image-guided stereotactic radiosurgery (SRS) have made it possible to treat these cancers in two to four fractions followed by systemic chemotherapy.The aims of this study includes the following: (1) obtain local control of the disease; (2) improve the survival of these unresectable patients; (3) evaluate the toxicity of SRS; and (4) report results of the largest series from a single center.Pancreatic SRS involves delivery of high doses of accurately targeted radiation given non-invasively in two to four fractions. We treated 85 consecutive patients with locally advanced and recurrent pancreatic adenocarcinoma from February 2004 to November 2009. Age range: 36-88 years, median 66 years; sex: 50 males, 35 females; race: 79 Caucasian, five African American, one Asian; histology: 80 adenocarcinoma, three islet cell, two other. Pre-SRS staging: T(3-4) 85; N(+) 16, N(x) 57, N(0) 12; M(0) 64, M(1) 21. All patients were unresectable at the time of SRS. Seventy-one had no prior surgical resection, and 14 had local recurrence after prior surgical resection. Twenty-nine patients had progression of disease after prior conventional RT. Location of the tumor: head, 57; body and tail, 28. Pre-SRS chemotherapy was given in 48 patients. All patients received gemcitabine-based chemotherapy regimen after SRS. Median tumor volume was 60 cm(3). PET/CT scans done in 55 patients were positive in 52 and negative in three patients. Average maximum standard uptake value was 6.9. Pain score on a scale of 1-10 was: 0-3 in 54, 4-7 in 18, and 8-10 in 13 patients. SRS doses ranged from 15 to 30 Gy with a mean dose of 25.5 Gy delivered in 3 days divided in equal fractions. Mean conformality index was 1.6, and mean isodose line was 80%.Tumor control: complete, partial, and stable disease were observed in 78 patients for the duration of 3-36 months with median of 8 months. Pain relief was noted in majority of patients lasting for 18-24 weeks. Most of the patients died of distant disease progression while their primary tumor was controlled. Overall median survival from diagnosis was 18.6 months and from SRS it was 8.65 months. For the group of 35 patients with adenocarcinoma without prior surgical resection or RT and no distant metastases, the average and 1-year survival from diagnosis was 15 months and 50%, respectively, and from SRS it was 11.15 months and 30.5%, respectively.A total of 19 (22.37%) patients developed grades III/IV GI toxicity including duodenitis, 12 (14.1%); gastritis, 11 (12.9%); diarrhea, three (3.5%); and renal failure was noted in one (1.2%). Three patient had both gastritis and duodenitis. Toxicity was significantly more prevalent in the first 40 patients compared with the last 45 patients (32.5 vs 13.9%).SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.

Malignant melanoma is increasing in frequency at a rapid rate in the United States. Metastatic disease is chemoresistant with DTIC considered the most active single agent. CI-980 is a synthetic mitotic inhibitor that blocks the assembly of tubulin and microtubules. It has shown cytotoxic activity against a broad spectrum of murine and human tumor cell tines. CI-980 can cross the blood brain barrier, is effective when given orally or parenterally, and is active against multidrug resistant cell lines overexpressing P-glycoprotein. In this trial, patients with disseminated melanoma with measurable disease, SWOG performance status of 0-1, no prior chemotherapy or immunotherapy for metastatic disease, and adequate hepatic and renal function, were enrolled. Treatment with CI-980 was given by 72 h continuous i.v. infusion at a dose of 4.5 mg/m2/day, days 1-3 every 21 days. Twenty-four patients were registered on this study with no patients ineligible. They ranged in age from 33-78 with performance status of 0 in 15 patients and 1 in 9 patients. Nineteen patients had visceral disease with 12 having liver involvement. There were no confirmed responses. The overall response rate was 0% (95% CI 0%-14%). The median overall survival is eleven months (95% CI 4-14 months). The most common toxicities were hematologic and consisted of leukopenia/granulocytopenia and anemia, with nausea/vomiting and malaise/fatigue/weakness also frequent. CI-980 administered at this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.

Angiosarcoma is a rare and aggressive tumor of the thyroid gland, mainly seen in the Alpine regions. We present such a case with literature review. We present the case of a 60-year-old man with cough, dyspnea, and hemoptysis along with slow increase in the size of his long-standing goiter. Computed tomography of the neck showed a large thyroid mass and chest imaging revealed multiple pulmonary nodules. Fine needle aspiration cytology and tru-cut biopsy of the thyroid were notable for poorly differentiated malignant cells. Diagnosis of angiosarcoma of the thyroid was made after total thyroidectomy. Patient died of continued hemoptysis and respiratory failure 3 weeks after admission. We searched the literature for previous case reports using Pubmed and Ovid. Forty-seven reported cases were identified and our case was added to make a database of 48 cases. Demographic and tumor characteristics were analyzed. Angiosarcoma was found to be more common in females and at age of 60 or above. Results were consistent with previously reported series of 14 and 17 cases from Austria. This review provides information on various characteristics angiosarcoma of the thyroid which can be used as baseline data for future reference and research studies for this cancer.

Internal mandibular fixation after resection of advanced oral cavity carcinoma with mandibulectomy has a significant complication rate. We placed the Joe Hall Morris (JHM) external mandibular appliance in 29 patients undergoing mandibulectomy for advanced oral cavity carcinoma. Fourteen patients received postoperative radiation therapy (RT). Three of 29 patients (10%) had complications associated with the JHM appliance: one patient had a broken connecting bar, a second had loosening of a single pin, and a third had loss of fixation requiring complete replacement of the appliance. Complications not associated with the appliance occurred in 8 patients (28%) including mandibular exposure (1), orocutaneous fistula (2), partial flap dehiscence (4), and flap necrosis (1). Oral continence was maintained in 26 patients, and occlusion was normal in 27. The appliance was removed in 12 weeks to 6 months in all patients. The JHM appliance allows for a reliable and rapid immediate fixation of the mandible with acceptable functional and aesthetic results, and no delay or interference with postoperative radiotherapy. Since the life expectancy of these patients is short, most do not require subsequent permanent fixation after removal of the appliance.

Twenty-eight patients with inflammatory carcinoma of the breast were managed initially by induction chemotherapy consisting of 3 courses of a combination of cyclophosphamide, doxorubicin hydrochloride, and 5-fluorouracil. Twenty-two showed a partial response, and 21 underwent mastectomies. Histopathologic examination of the surgical specimens revealed no residual tumor in 2 breasts, but all 21 patients had residual metastases in their axillary lymph nodes. Postoperatively, they received the same chemotherapy. The other six patients who failed to respond to induction chemotherapy received radical radiation therapy followed by a combination chemotherapy regimen that consisted of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone. Any patient in whom chemotherapy failed during the follow-up period was treated by radiation therapy and/or a combination of mitomycin-C and vinblastine as necessary. At the time of diagnosis, 17 patients who had no evidence of distant metastasis, i.e., stage III B disease, had disease-free survival ranging from 5 to more than 84 months, with a median of 30 months, and an overall survival of 7 to more than 120 months with a median of 32 months. The 5-year survival rate was 18%. The other 11 patients who had distant metastases, i.e., stage IV disease, had an overall survival ranging from 4 to 14 months. The results of this approach of initial systemic chemotherapy followed by local-regional cytoreductive therapy, then systemic therapy, might suggest some survival benefits in patients with stage III disease.

Hepatic resection results in significant morbidity and mortality primarily related to intraoperative blood loss. Intermittent vascular inflow occlusion (VO) and low central venous pressure (CVP) during hepatectomy have been used to reduce blood loss. To determine the benefit of VO and low CVP, we reviewed the outcomes of 168 consecutive patients who underwent liver resection. The results of 78 patients who had undergone hepatic resection between 1993 and 1998 with the use of VO and low CVP (post-VO/CVP) were compared to the previous 90 patients who had undergone hepatectomy without VO and low CVP (pre-VO/CVP) between 1979 and 1992. Hepatectomies were performed for metastatic disease (65%), hepatoma (20%), and benign tumors (15%). Resections included 18 trisegmentectomies, 67 lobectomies, and 83 segmental resections. Patients in both groups were similar with regard to extent of resection. Post-VO/CVP patients had significantly lower median estimated blood loss (725 ml vs. 2300 ml, P0.001), less postoperative morbidity (10.3% vs. 22. 2%, P = 0.038), lower in-hospital mortality (2.6% vs. 10%, P = 0. 050), fewer days in the intensive care unit (1.6 +/- 0.1 days vs. 5. 6 +/- 1.2 days, P = 0.003), and shorter overall length of stay (8.0 +/- 0.5 days vs. 15.0 +/- 1.6 days, P0.001) than pre-VO/CVP patients. These data suggest that VO and low CVP during liver resection may improve patient outcomes.

A variety of malignancies, including hematologic malignancies, Kaposi's sarcoma, as well as adenocarcinomas and squamous cell carcinoma have been reported in association with acquired immune deficiency syndrome. Tumors of the umbilical area are unusual and can represent lesions of urachal origin. These may require extensive resection and are associated with a poor prognosis. We describe here a case of a young woman with AIDS who developed a squamous cell carcinoma of the umbilicus which suggests more than a casual relationship between these two conditions.

Thirty-two patients with histologically proved metastatic malignant melanoma of the brain were evaluated. Intracranial surgery was performed in 19 and was considered not indicated in 13 patients. Following intracranial surgery, satisfactory improvement in neurologic deficits was observed in 14 (74%) patients. The median survival after occurrence of brain metastases was 5–6 months (1 – 15 months) for the surgical group; and for the nonsurgical group, patients with multiple brain metastases and multiple visceral involvement did not survive beyond a median of 1 month (range 0.5–6 months). Intratumor hemorrhage with substantial intracerebral hematoma was present in 7 (41%) out of 17 craniotomies. The overall incidence of intratumor hemorrhage found at autopsy was 59% for the entire series. Among ail the cases with intratumor hemorrhage, only 2 patients who received chemotherapy after craniotomy developed thrombocytopenia with fatal intracranial hemorrhage. The latter cause-and-effect correlation could not be assessed in the other patients. As a result of this retrospective study, we have observed that patients with malignant melanoma and evidence of single brain metastasis without multiple visceral involvement seemed to benefit more from palliative surgery. Moreover, intratumor hemorrhage was a frequent occurrence and should be considered in the differential diagnosis of a patient with malignant melanoma and rapid deterioration of neurologic deficits.

Ocular melanoma is the most common malignant tumor of the eye and accounts for 70 to 80 percent of all extracutaneous melanomas. Its biologic behavior differs from that of its cutaneous counterpart. To elucidate this, 62 patients with histologically proven melanoma of eye (58 uveal tract and 4 conjuntiva) at Roswell Park Memorial Institute from 1945 to 1977 were studied. The prominent contradistinctions from other head and neck melanomas were (1) a very high percentage of patients had either locally advanced or systemic disease at diagnosis, although the eye is the most sensitive organ; (2) regional lymph node involvement was absent even in the late stages of disease; (3) hematogenous spread involved single organs, most commonly the liver and the lung; (4) local recurrence was rare; (5) most recurrences occurred evenly in first 10 years after treatment; (6) regional resection, chemotherapy or both are advocated for distant metastases since they are confined to a single organ and are amenable to it; and (7) despite hematogenous spread and advanced disease at diagnosis, the overall prognosis of ocular melanoma is comparable to that of cutaneous melanoma.

One hundred fifty-two patients with squamous cell carcinoma of the larynx were studied. The disease free survival and overall survival rates were correlated to 12 variables. Seven of them seemed to affect survival. Poor prognosis was related to (1) advanced stage of disease at diagnosis, (2) cord fixation and massive local invasion, (3) ulceration of the primary tumor, (4) lymph node metastases at diagnosis, (5) glottic lesions had a poorer prognosis than supraglottic ones, (6) locoregional recurrences, and (7) male gender. However, most of these significant differences were in disease-free survival, and only primary tumor staging; lymph node status; and locoregional recurrences affected overall survival. On the other hand, the other five variables showed no effect on either disease-free or overall survival rates. These included age, race, cell differentiation, type of recurrence, and the initial definitive therapeutic modality.

Preoperative pulmonary function test results in 258 patients who underwent pulmonary resection for bronchogenic carcinoma were studied in relation to postoperative mortality from cardiopulmonary complications. Poor outcome of surgery was related to the maximal breathing capacity value below 59 per cent of the predicted normal, age over sixty-nine years, and abnormal electrocardiographic findings. Combinations of these factors were associated with a very high mortality (56 per cent). This group of patients needs further evaluation on an individual basis to identify the risk of pulmonary resection. A formula to predict the risk of surgery based on the maximal breathing capacity value is suggested. Values for one second forced expiratory volume and vital capacity were of no use in predicting the outcome of surgery.

The effect of known chemotherapeutic programs in patients with breast cancer who developed metastasis during or after adjuvant chemotherapy with L-PAM plus 5-FU (PF) were studied. Thirteen patients failed while receiving adjuvant therapy at 3-22 months from the time therapy started. Three patients failed 6-28 months after 2 years of therapy. Thirteen patients received PF followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) at the time of progression on PF. Of these, ten received Adriamycin and vincristine (AV) at the time of progression on CMF. The response to CMF was 7%. No patient responded to AV after progression on CMF. Two of three patients treated with AV after failure on PF did respond, but both for only 6 months. This suggests that adjuvant therapy may render the tumor less responsive to further chemotherapy. Since most patients failed while on adjuvant therapy, this may indicate a poor prognosis regardless of the agents used.

Fifteen malignant melanomas were subjected to chromosomal analysis, in order to determine whether the number of chromosomes in a tumor cell could be correlated to a clinical prognosis. The protocol involved a direct technique which utilized a Colcemid blockade of spindle formation in mitosis to allow study of metaphase chromosomes. The direct method was chosen to reveal chromosome changes in the tumor cell in situ rather than changes in the cultured cell. Two tumors yielded chromosome spreads which could be counted and correlated with a clinical prognosis. Failure to obtain other adequate chromosome spreads were accounted for by the presence of tissue necrosis and the absence of viable tumor cells.

Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

Forty-one 67Ga images were obtained for 33 patients with a diagnosis of soft-tissue sarcoma or chondrosarcoma. Tumor was detected in 27 cases of soft-tissue sarcoma; 25 (93%) of these were found on the Ga scans. The overall accuracy of scanning was 95.1%. All patients with positive scans had tumor present. In soft-tissue sarcoma patients the scan detected the tumor in 39 out of 45 sites. Ga scintigraphy was found to be useful in the initial evaluation and follow-up of these patients. If the Ga citrate scan is positive at multiple sites, the possibility of tumor being present is 100% with a false negative rate of 16%.

To evaluate an effective, cell-cycle-specific combination chemotherapy which could be administered on an outpatient basis, COMB of Maryland (Cytoxan, Oncovin, methotrexate and bleomycin) was used in 20 patients with stage IV squamous cell carcinoma of head and neck origin. All patients had unresectable but measurable disease. Nine patients had distant metastases. Prior to this chemotherapy, 15 (75%) patients underwent radiation therapy, 12 (60%) had radical surgery, and 3 (15%) were administered other chemotherapeutic drugs. The distribution of the primary site of tumor was identical to the overall distribution of squamous cell carcinoma of head and neck found in this country. Drug dosages were: Cytoxan 100 mg/m2 p.o. days 1-14, Oncovin 1 mg/m2 IV days 1 and 8, methotrexate 25 mg/m2 IV days 1 and 8, and bleomycin 15 units/m2 IM days 1 and 8. This cycle was repeated every four weeks. Two (10%) patients had complete response and 7 (35%) had partial response, thus giving the total response rate of 9 (45%). Seven (35%) patients had static disease and 4 (20%) had progression of disease. Duration of response was from 8 to 26+ weeks with a median duration of 17+ weeks. Response rate was statistically related to performance status and previous chemotherapy. However, it was not related to age, sex, site of origin, previous radiation therapy, or differentiation of the tumor. Increased survival (P < 0.01) was seen in responders (median 16+ weeks) as compared to nonresponders (9 weeks). Hematologic toxicity was seen in 9 (45%) patients, resulting in one chemotherapy-related death. Overall, this chemotherapy has been well tolerated on an outpatient basis. Although 15 (75%) patients received prior radiation therapy, the results were comparable to those obtained by other, more toxic combination chemotherapeutic regimens.

Hepatic dearterialization by ligation of the main hepatic artery followed by local intraarterial chemotherapy was performed in 24 patients with clinically isolated but unresectable hepatic metastasis after local resection of carcinoma of the colon. Computed tomography of the abdomen and laboratory parameters were used both to stage and follow-up these patients. Computed tomography changes following dearterialization and chemotherapy of the liver are described. Computed tomography is a valuable technique for both staging and follow-up this group of patients.

Adequate flow cytometric DNA analysis comparing primary and concurrent metastatic squamous cell carcinoma of the head and neck has not been done in the past. The purpose of this study was to define any differences between the primary and concurrent metastasis of each patient with respect to flow cytometric parameters and histologic grade. Paraffin-embedded archival specimens from 28 patients with primary and metastatic tumors were prepared into nuclei and analyzed by flow cytometry using human lymphocyte standards. The mean DNA index was 0.82 for primary tumors and 0.83 for the metastases. Aneuploidy was found in 68 percent of primary tumors and in 82 percent of metastases. The percentage of cells in the proliferative fraction was 40.4 in the primary tumors and 24.5 in the metastases. A direct correlation was found between the differentiation of the primary and metastatic tumors. No survival difference was discovered among the flow cytometric parameters and histologic grade. We conclude that there is no difference between the primary and concurrent metastasis in squamous cell carcinoma of the head and neck with regard to DNA index, aneuploidy, or histologic grade.