William C. Dooley

Pancreaticoduodenectomy for cancer of the head of the pancreas: 201 patients

ObjectiveThis single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. Summary of Background DataIn recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. MethodsTwo hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. ResultsThe overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections: n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, <800 mL intraoperative blood loss, <2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection.

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

OBJECTIVE This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.

Impact of axillary lymph node dissection on the therapy of breast cancer patients.

PURPOSE We studied a series of 283 breast cancer patients retrospectively to determine the actual benefits of axillary lymph node dissection (ALND) for these patients. PATIENTS AND METHODS The records of 283 women with invasive breast cancer treated between 1988 and 1990 were reviewed for histologic status of the axillary lymph nodes, tumor size, DNA content, hormone-receptor values, and actual adjuvant treatments received. RESULTS ALND was of possible therapeutic benefit for the 15% (43 of 283) of patients who had clinically positive nodes. Nodal metastases were found in 86% (37 of 43) of patients in this subgroup. ALND alone determined the indication for standard adjuvant therapy for a group of 31% (88 of 283) of patients who had favorable primary biopsy findings and clinically negative axillary nodes; ALND proved that 13% (11 of 88) of these latter patients had positive nodes. For 54% (152 of 283) of patients who had clinically negative nodes and unfavorable biopsies, ALND played no role in the decision as to whether standard adjuvant therapy was indicated. Only 5% (seven of 152) and 3% (four of 152) of these latter patients received radiation therapy and/or high-dose adjuvant chemotherapy, respectively, because of ALND. CONCLUSION The benefits of ALND vary greatly for different groups of breast cancer patients, and controlled studies may be needed to determine whether ALND is necessary for all breast cancer patients.

Contour abnormalities of the abdomen after breast reconstruction with abdominal flaps: The role of muscle preservation

&NA; The purpose of the present study was to determine whether contour abnormalities of the abdomen after breast reconstruction with abdominal flaps are related to the harvest of the rectus abdominis muscle. Abdominal contour was analyzed in 155 women who had breast reconstruction with abdominal flaps; 108 women had free transverse rectus abdominis muscle (TRAM) flaps, 37 had pedicled TRAM flaps, and 10 had deep inferior epigastric perforator (DIEP) flaps. The reconstruction was unilateral in 110 women and bilateral in 45 women. Three methods of muscle‐sparing were used; they are classified as preservation of the lateral muscle, preservation of the medial and lateral muscle, or preservation of the entire muscle. One of these three methods of muscle‐sparing was used in 91 women (59 percent) and no muscle‐sparing was used in 64 women (41 percent). Postoperative contour abnormalities occurred in 15 woman and included epigastric fullness in five, upper bulge in three, and lower bulge in 10. One woman experienced two abnormalities, one woman experienced three, and no woman developed a hernia. Of these abnormalities, 11 occurred after the free TRAM flap, seven after the pedicled TRAM flap, and none after the DIEP flap. Bilateral reconstruction resulted in 11 abnormalities in nine women, and unilateral reconstruction resulted in seven abnormalities in six women. &KHgr;2 analysis of the free and pedicled TRAM flaps demonstrates that muscle‐sparing explains the observed differences in upper bulge and upper fullness (p = 0.02), with a trend toward significance for lower bulge (p = 0.06). &KHgr;2 analysis of the free TRAM and DIEP flaps does not explain the observed difference in abnormal abdominal contour. Analysis of muscle‐sparing and non‐muscle‐sparing methods demonstrates that the observed difference between the techniques is only explained for a lower bulge after the bilateral free TRAM flap (p=0.04). (Plast. Reconstr. Surg. 109: 91, 2002.)

Hurthle cell neoplasms of the thyroid : are there factors predictive of malignancy?

OBJECTIVE To determine if any preoperative or intraoperative factors can reliably predict malignancy in patients with Hürthle cell neoplasms. SUMMARY BACKGROUND DATA Most experienced surgeons recommend total thyroidectomy for Hürthle cell carcinomas and reserve thyroid lobectomy for Hürthle cell adenomas. However, delineation between Hürthle cell adenoma versus carcinoma often cannot reliably be made either before or during surgery. METHODS Medical records from 57 consecutive patients who underwent thyroid resections for Hürthle cell neoplasms between October 1984 and April 1995 at The Johns Hopkins Hospital were analyzed to determine if any factors were predictive of malignancy. RESULTS Of the 57 patients with Hürthle cell neoplasms, 37 had adenomas and 20 had carcinomas, resulting in a 35% prevalence of malignancy. Patients with adenomas did not differ from those with carcinoma with respect to age, sex, or history of head and neck irradiation. However, patients with Hürthle cell carcinomas had significantly larger tumors (4.0 +/- 0.4 cm vs. 2.4 +/- 0.2 cm, p < 0.005). Furthermore, although the incidence of malignancy was only 17% for tumors 1 cm or less and 23% for tumors 1 to 4 cm, tumors 4 cm or greater were malignant 65% of the time (p < 0.05). Both fine-needle aspiration and intraoperative frozen section analysis had low sensitivities in the detection of cancer (16% and 23%, respectively). With up to 9 years of follow-up, there has been no tumor-related mortality. CONCLUSIONS These data demonstrate that the size of a Hürthle cell neoplasm is predictive of malignancy. Therefore, at the time of initial exploration for large Hürthle cell neoplasms (>4 cm), definitive resection involving both thyroid lobes should be considered because of the higher probability of malignancy.

DNA content and other factors associated with ten‐year survival after resection of pancreatic carcinoma

Background and Objectives: The 5‐year survival rates after resection of pancreatic carcinoma have recently increased and are predicted by tumor size, DNA content, and lymph node metastases at the time of resection. However, whether the 10‐year survival rates have also increased and are similarly predicted by these factors is not known.

Association between extent of axillary lymph node dissection and survival in patients with stage I breast cancer

AbstractBackground: The role of axillary lymph node dissection for stage I (T1N0) breast cancer remains controversial because patients can receive adjuvant chemotherapy regardless of their nodal status and because its therapeutic benefit is in question. The purpose of this study was to determine whether extent of axillary dissection in patients with T1N0 disease is associated with survival. Methods: Data from 464 patients with T1N0 breast cancer who underwent axillary dissection from 1973 to 1994 were examined retrospectively. Kaplan-Meier estimates of overall survival, disease-free survival, and recurrence were calculated for patients according to the number of lymph nodes removed (<10 or ⩾10; <15 or ⩾15), and survival curves compared using the Wilcoxon-Gehan statistic. Cox proportional hazards regression modelling was used to adjust for confounding prognostic variables. Results: Median follow-up time was 6.4 years. Patient groups were similar in age, menopausal status, tumor size, hormonal receptor status, type of surgery, and adjuvant therapy. There was a statistically significant improvement in disease-free survival in the ⩾10 versus <10 nodal groups (P<.01). Five-year estimates of survival were 75.7% and 86.2% for <10 nodes and ⩾10 nodes, respectively; 10-year estimates were 66.1% and 74.3%. There also was a notable improvement in the survival comparison of patients with <15 versus ⩾15 nodes (P⩽.05). These findings were confirmed in the multivariate analysis. Conclusions: These results may reflect a potential for misclassification of tumor stage among patients who had fewer nodes removed. The data, however, suggest that in patients with Stage I breast cancer, improved survival is associated with a more complete axillary lymph node dissection.

Pancreatic Cancer Cell Dna Content Correlates With Long-term Survival After Pancreatoduodenectomy

The DNA content of 47 adenocarcinomas arising in the head of the pancreas from patients who had undergone successful pancreatoduodenectomy was measured. The DNA measurements of each tumor were made without knowledge of the clinical course by absorption cytometry performed on Feulgen-stained nuclei that had been disaggregated from pancreatic cancer tissue blocks. Forty-seven evaluable DNA distributions were obtained from specimens taken between 1975 and 1988. Of the 47 tumors, 19 (40%) were diploid and 28 (60%) were aneuploid cancers. The 19 patients with diploid cancers had a median survival time of 25 months. Median survival of the 28 patients with aneuploid cancers was 10.5 months. This difference was statistically significant (p = 0.003). A multivariate life table regression analysis demonstrated that the ploidy and proliferative index as determined by absorption cytometry were independent prognostic factors, as strong as or stronger than the number of positive nodes and tumor size. Thus cellular DNA content appears to be one of the most important predictors of survival in patients with adenocarcinoma of the head of the pancreas who have successfully undergone a pancreaticoduodenectomy.

Is preoperative angiography useful in patients with periampullary tumors

Ninety patients with periampullary tumors, staged by CT scan and believed to be resectable, were staged further by visceral angiography. Most of these patients (78) had carcinoma of the head of the pancreas. Visceral angiography was normal in 62 patients. Major vessel encasement (17 patients) or occlusion (11 patients) was identified in 28 patients. There were no complications related to angiography. Among the 62 patients with normal angiograms, 48 underwent a pancreaticoduodenectomy, for a resectability rate of 77%. Among the 17 patients with vessel encasement, the resectability rate was 35%. For the 11 patients with vessel occlusion, the resectability rate was 0%. Combined with CT scan, visceral angiography is a useful adjunct in the staging of patients with periampullary tumors. Major vessel occlusion precludes resection, and major vessel encasement makes resection unlikely. If visceral angiography is normal, it is very likely that the tumor will be resectable.

Telomerase Activity and Prognosis in Primary Breast Cancers

PURPOSE Recent studies associate telomerase activity with prognostic factors and survival. We compared quantitative telomerase activity in primary tumors with traditional prognostic factors and outcome in a group of invasive but nonmetastatic breast cancers. PATIENTS AND METHODS Telomerase activity was measured in 203 invasive breast cancers by the quantitative telomeric repeat amplification protocol method. Telomerase expression was compared with 28S rRNA level, tumor content, and clinical variables, including outcome. For clinical correlations, telomerase activity was standardized by two methods: (1) a correction for cellularity using 28S rRNA levels, and (2) a correction for the histologically determined invasive proportion of the specimen. RESULTS Telomerase activity was found in 82% of breast cancers with measurable 28S rRNA levels. Telomerase activity was associated with the proliferative index (P <.01) of the tumor but not with any other prognostic variable. Neither uncorrected nor corrected telomerase activity was associated with relapse-free or overall survival in this study. CONCLUSION Telomerase activity level was associated with the proliferative index of invasive breast cancers, but its measurement in samples from this group of nonmetastatic breast cancer patients did not predict survival.