Herbert Chen

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

BACKGROUNDnNeuroendocrine 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.nnnSTUDY DESIGNnBetween 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.nnnRESULTSnPatients 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%).nnnCONCLUSIONSnHepatic 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.

Clinically Significant, Isolated Metastatic Disease to the Thyroid Gland

n= 5), esophageal adenocarcinoma (n= 1), pulmonary squamous cell carcinoma (n= 1), gastric leiomyosarcoma (n= 1), lingual squamous cell carcinoma (n= 1), and parotid gland carcinoma (n= 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 ± 6.0 years (range 0–19.5 years). Total thyroidectomy (n= 5) or lobectomy (n= 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.

Follicular lesions of the thyroid. Does frozen section evaluation alter operative management

OBJECTIVEnThe authors determined the usefulness of frozen section (FS) evaluation in the operative management of follicular lesions of the thyroid.nnnSUMMARY BACKGROUND DATAnFine-needle aspiration (FNA) cannot reliably discriminate between benign and malignant follicular lesions of the thyroid. Accordingly, FS evaluation is used routinely to guide intraoperative management.nnnMETHODSnOne hundred twenty-five consecutive patients with follicular thyroid lesions who underwent surgical exploration at the Johns Hopkins Hospital were reviewed.nnnRESULTSnFrozen sections were categorized in 104 of 120 patients (87%) as follicular lesion, defer to permanent section, rendering no useful clinical information. In only 4 of 120 patients (3.3%) did FS evaluation correctly modify the operative procedure. Notably, in six cases (5.0%), an incorrect FS evaluation misled the surgeon, resulting in four misguided operations.nnnCONCLUSIONnFrozen section evaluation is of minimal diagnostic value for follicular thyroid lesions, rendering no additional information 87% of the time; it prolongs the operation, increases costs, and leads to misguided interventions. Until a more definitive diagnostic tool exists for follicular thyroid lesions, FS evaluation could be omitted, resection of the lobe with the nodule could be performed, and the definitive operative management could be based on the final permanent histology.

Parathyroidectomy in Maryland: Effects of an endocrine center

BACKGROUNDnSurgery for hyperparathyroidism is associated with high cure rates and low morbidity and mortality when performed by experienced surgeons. We wanted to determine whether referral of patients with hyperparathyroidism to an endocrine surgery center has an impact on patient outcomes and costs.nnnMETHODSnData from 901 patients who underwent parathyroidectomy recorded in the Maryland inpatient discharge database between 1990 and 1994 at 52 hospitals were compared with 169 consecutive patients who underwent surgical exploration by one surgeon (R.U.) at the Johns Hopkins Hospital.nnnRESULTSnAlthough in 47 of 52 hospitals fewer than 10 parathyroidectomies were performed each year, in these hospitals four of five related deaths occurred before patient discharge. The percentage of parathyroidectomies in Maryland performed by one endocrine surgeon has increased from 8% in 1990 to 21% in 1994 and is associated with a 97% cure rate and no mortality. Moreover, while hospital length of stay (LOS) in the state has decreased from 7 to 3.1 days, LOS for the high-volume provider has declined to a mean of 1.3 days.nnnCONCLUSIONSnPatients with hyperparathyroidism are increasingly referred to an endocrine surgery center, which results in a high cure rate, low morbidity, no mortality, and a shorter LOS. Improved surgical outcomes and lower costs depend on an experienced surgeon and argue for the referral of these patients to endocrine surgery centers.

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

OBJECTIVEnTo determine if any preoperative or intraoperative factors can reliably predict malignancy in patients with Hürthle cell neoplasms.nnnSUMMARY BACKGROUND DATAnMost 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.nnnMETHODSnMedical 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.nnnRESULTSnOf 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.nnnCONCLUSIONSnThese 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.

Parathyroidectomy in the Elderly: Do the Benefits Outweigh the Risks?

Abstract. Although the incidence of hyperparathyroidism (HPT) in the elderly exceeds 1.5%, limited resources and co-morbidity inhibit referral for parathyroidectomy. To determine the risks and benefits of surgery, we examined the outcomes of elderly patients who underwent exploration for primary HPT. Data from 211 consecutive patients who underwent parathyroidectomy by one surgeon at the Johns Hopkins Hospital between August 1990 and May 1996 were recorded prospectively. Of these patients, 184 had primary HPT. Demographic and outcome data of elderly patients (> 70 years of age) (n= 36) were compared to those from younger patients (< 70 years of age) (n= 148). Preoperative symptoms of mental impairment, bone disease, and fatigue were more common in elderly patients (p < 0.05), and nephrolithiasis was more frequent in younger patients (p < 0.025). Elderly patients presented with more advanced disease, manifested by higher preoperative parathyroid hormone levels (301.9 ± 63.3 vs. 169.2 ± 14.3 pg/ml, p < 0.05). The cure rate (94.4%), morbidity (5.5%), and mortality (0%) in the elderly were indistinguishable from those of their younger cohorts (98%, 1.4%, and 0%, respectively). In conclusion, the more advanced disease seen in the elderly suggests that they are referred for surgery with a higher threshold than younger patients. Although several series of parathyroidectomy in elderly patients have reported high morbidity rates, significant mortality, and long length of stay (LOS), we found that parathyroidectomy in these patients can be performed with high cures, low morbidity, no mortality, short LOS, and high patient satisfaction. These data suggest that the benefits of surgery outweigh its risks and argue for a lower threshold for referral of elderly patients with primary HPT for surgical treatment.

Hepatic resection using intermittent vascular inflow occlusion and low central venous pressure anesthesia improves morbidity and mortality

Hepatic resection results in significant morbidity and mortality primarily related to intraoperatiye blood loss. Intermittent yascular inflow occlusion (VO) and low central venous pressure (CVP) during hepatectomy have been used to reduce blood loss. To determine the benefit or 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 1908 with the use of VO and low CAT (post-VO/CAP) were compared to the previous 90 patients who had undergone hepatcctomy without VO and low CAP (pre-VO/CVP) between 1979 and 1992. Hepatectomies were performed for metastatic disease (65%), hepatoma (20%), and benign minors (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, P <0.001), 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, P <0.001) than pre-VO/CVT patients. These data suggest that VO and low CAP dunnc liver resection may improve patient outcomes.

Effective long-term palliation of symptomatic, incurable metastatic medullary thyroid cancer by operative resection

OBJECTIVEnTo evaluate the short- and long-term consequences of palliative reresection of specific symptomatic lesions in patients with widely disseminated (incurable) medullary thyroid cancer (MTC).nnnSUMMARY BACKGROUND DATAnAlthough reoperative neck microdissections can normalize calcitonin levels in patients with metastatic MTC confined to regional lymph nodes, there is no curative therapy for widely metastatic disease. However, these patients frequently have prolonged survival, but often with debilitating symptoms.nnnMETHODSnBetween October 1981 and January 1997, 16 patients (mean age, 46 +/- 3 years; 10/16 female) underwent 21 palliative reoperations for unresectable MTC at the Johns Hopkins Hospital. All patients had significant symptom(s) or impending compromise of vital structures by a discrete lesion and had unequivocal preoperative evidence of a total disease burden that was unresectable.nnnRESULTSnThe mean interval from initial thyroidectomy to palliative surgery was 5.8 +/- 1.5 years. All patients had significant tumor burdens as evidenced by preoperative calcitonin values ranging from 900 to 222,500 pg/mL (nL < or = 17 pg/mL). The palliative operations consisted of reoperative neck dissection/mass excision (11), mediastinal mass resection (4), esophagectomy (1), liver trisegmentectomy (1), sigmoidectomy (1), bilateral simple mastectomies (1), pituitary resection (1), and subcutaneous mass excisions (1). All but two of the operative specimens contained MTC. There was no perioperative mortality. The long-term morbidity rate was limited to one recurrent laryngeal nerve injury. All patients had initial relief of the index symptom(s) after the palliative surgery, followed by a median actuarial symptom-free survival rate of 8.2 years.nnnCONCLUSIONSnPatients with widely metastatic MTC often live for years, but many develop symptoms secondary to tumor persistence or progression. Judicious palliative, reoperative resection of discrete, symptomatic lesions can provide significant long-term relief of symptoms with minimal operative mortality and morbidity. In selected patients with metastatic MTC lesions causing significant symptoms or physical compromise, palliative reoperative resection should be considered despite the presence of widespread incurable metastatic disease.

Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid

BACKGROUNDnAlthough fine-needle aspiration (FNA) is 90% sensitive in the detection of papillary carcinoma (PC) of the thyroid, its specificity has been reported as low as 52%. Consequently, patients who have an FNA suspicious for PC may undergo operation for a benign process. The ribonucleoprotein telomerase has been noted to be activated in a wide variety of carcinomas. We examined 30 PCs for telomerase activity to determine whether this would be a useful adjunct to FNA in the diagnosis of lesions suspicious for PC.nnnMETHODSnStandard telomere repeat amplification protocol assays were performed on fresh frozen tissue samples from 30 PCs, 3 benign nodules, and 10 normal thyroids.nnnRESULTSnTelomerase activity was documented in 20 of 30 (67%) of the PCs, 0 of 3 benign nodules, and 0 of 10 normal thyroids. In all, 11 of the 20 PCs had FNA cytology that was nondiagnostic of PC, and 2 of the benign nodules had FNA that was suspicious for PC.nnnCONCLUSIONSnThe telomerase assay appears useful in the distinction of benign from malignant thyroid lesions that have FNA suspicious for but not diagnostic of PC. On the basis of these findings, a prospective trial examining telomerase activity in FNAs suspicious for thyroid cancer has been initiated.

Differentiation of medullary thyroid cancer by C-Raf-1 silences expression of the neural transcription factor human achaete-scute homolog-1

BACKGROUNDnHuman achaete-scute homolog-1 (hASH1), a fetal neural transcription factor, is highly expressed in neuroendocrine tumors such as medullary thyroid cancer (MTC). Although hASH1 probably plays a part in the growth and development of these tumors, its precise role and mechanism are unknown.nnnMETHODSnTo further elucidate the function and regulation of hASH1 in neuroendocrine tumor differentiation, we used a model of MTC tumor differentiation mediated by the ras/raf-1 signaling pathway. The MTC TT cells alone or transduced with a beta-estradiol activatable raf-1 construct (TT: delta Raf-1:ER) were treated with beta-estradiol or carrier. Northern analysis and nuclear run-off assays were performed to determine the hASH1 messenger RNA (mRNA) levels and transcription rate, respectively.nnnRESULTSnThe TT: delta Raf-1:ER cells treated with beta-estradiol underwent marked biochemical and morphologic changes, including cell rounding, increase in calcitonin transcription, loss of RET proto-oncogene expression, and cessation of cell growth. During this differentiation process expression of hASH1 mRNA was silenced. Nuclear run-off experiments revealed that this decrease in steady-state hASH1 mRNA by raf-1 activation resulted predominantly from transcriptional inhibition.nnnCONCLUSIONSnSilencing of hASH1 in parallel with loss of RET is associated with development of a mature C-cell differentiation pattern. Mechanisms leading to transcriptional silencing of hASH1 may be crucial in regulating the proliferative capacity or differentiation status of MTC. Downstream targets of hASH1 could play a role in C-cell proliferation and progression to MTC.