George I. Salti

Primary hyperparathyroidism in the 1990s. Choice of surgical procedures for this disease.

Many advances have occurred in recent years in the diagnosis, localization, and treatment of primary hyperparathyroidism. Several different operative choices for primary hyperparathyroidism also have been proposed--a unilateral approach versus the standard bilateral parathyroid exploration. The unilateral approach is based on the concept that if an enlarged parathyroid gland and a normal gland are found on the first side of the neck that is explored, then this is an adenoma and the second side should not be explored. Only if both glands on the initial side are recognized to be abnormal is the second side explored. The theoretical advantages of this unilateral approach are a decrease in operative morbidity rates--hypoparathyroidism and nerve injuries--and a decrease in operative time. Furthermore, proponents argue that if persistent hyperparathyroidism occurs, the second side can be easily explored because it was previously untouched. In the hands of several expert parathyroid surgeons, excellent results have been achieved. However, the unilateral approach has a number of disadvantages. It places considerable pressure on the surgeon and pathologist, for they have only one parathyroid gland other than the large one to examine. There is a significant potential risk of missing double adenomas or asymmetric hyperplasia because the second, ipsilateral parathyroid gland may appear normal or near normal in these conditions. This could lead to an increased incidence of persistent or recurrent hyperparathyroidism. Furthermore, a significant reduction of operative time may be questioned, especially when the time for performing special fat stains, which often are performed with unilateral explorations, is added. Finally, even if the intent is to perform a unilateral exploration, a bilateral exploration will be necessary about half of the time. The authors strongly recommend a bilateral parathyroid exploration for all patients undergoing an initial parathyroid operation. In cases of adenoma, bilateral visualization of normal parathyroid glands and careful biopsy of only one of them will minimize hypoparathyroidism. This operative approach will lead to better results, especially for the less experienced parathyroid surgeon.

Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells

The present study was undertaken to determine if (a) genistein induces topo II-mediated DNA damage in HT-29 colon cancer cells; and (b) if this damage is required to induce apoptosis. DNA damage was evaluated using the comet assay. Apoptosis was determined by the ethidium bromide/acridine orange staining technique. DNA breakage was noted within 1 h of treatment. Apoptosis was only induced with high concentrations (>/=60 microM) of genistein. Marked inhibition of HT-29 cell growth was evident at concentrations ranging from 60 to 150 microM. This was associated with a cell cycle arrest at G(2)/M. Similar findings were obtained in SW-620 and SW-1116 colon cancer cell lines. Aclarubicin, a topo II antagonist, reduced genistein-induced DNA breaks but did not reduce apoptosis. These data suggest that, in colon cancer cells, topo II serves as the enzymatic target of genistein. Furthermore, topo II-mediated DNA cleavage is not required for the induction of apoptosis.

Role of sentinel lymph node biopsy in patients with thin (<1 mm) primary melanoma.

Background: Thin melanomas have become increasingly prevalent, and lesions ≤1 mm in thickness are frequently diagnosed. They are considered highly curable when treated solely with wide local excision, with reported 5-year disease-free survivals of 95% to 98%. However, thin Clark level III and IV melanomas may have increased potentials for metastasizing and late recurrences because of dermal lymphatics located at the interface of the papillary and reticular dermis. We have addressed this controversial area by reviewing the outcomes of patients with invasive thin melanomas.Methods: We performed 266 sentinel lymph node biopsy procedures, using both radioisotope and blue dye, over a 5-year period. Sixty-five of the 266 invasive melanomas were thin and were treated by wide local excision and sentinel lymph node biopsy.Results: Two (3%) of the 65 thin melanomas were found to have a positive sentinel lymph node. In melanomas thinner than .75 mm, no positive sentinel lymph node was found. Therefore, only 3% of patients may benefit from tumor upstaging by sentinel lymph node biopsy.Conclusions: The occurrence of regional lymph node metastases in thin melanomas is rather low. Our data suggest that sentinel lymph node biopsy may not justified in patients with melanoma <.75 mm thick.

Predicting residual lymph node basin disease in melanoma patients with sentinel lymph node metastases

BACKGROUND The incidence of residual occult disease in nonsentinel lymph nodes (NSLN) after a positive sentinel lymph node (SLN) biopsy in patients with melanoma is relatively low. The purpose of this study is to identify factors that may be predictive of occult NSLN metastases after positive SLN biopsy. METHODS Fifty-six consecutive melanoma patients with positive sentinel nodes who subsequently underwent complete lymph node dissection (CLND) were evaluated. RESULTS Only the number of positive SLN predicted the status on NSLN by univariate (P = 0.008) and multivariate (P = 0.028) analyses. None of the other variables (characteristics of SLN metastases, number of draining nodal basins, age, sex, thickness, Clark level, ulceration, number of mitoses/mm(2), histological subtype, and location of the primary) significantly predicted CLND results. CONCLUSIONS Identifying patients with residual lymph node basin disease remains difficult. Thus, lymph node dissection should be performed in all patients after positive sentinel node biopsy.

The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery.

Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: evidence for a potential role as a chemopreventive agent.

Melanoma transformation progresses in a multistep fashion from precursor lesions such as congenital naevi. Exposure to ultraviolet (UV) light promotes this process. Betulinic acid (BA) was identified by our group as a selective inhibitor of melanoma that functions by inducing apoptosis. The present study was designed to investigate the effect of BA and UV-C (254 nm) on cultured congenital melanocytic naevi (CMN) cells, using the single-cell gel electrophoresis (comet) assay to detect DNA damage. Exposure to UV light induced a 1.7-fold increase in CMN cells (P = 0.008) when compared with controls. When a p53 genetic suppressor element that encodes a dominant negative polypeptide (termed GSE56) was introduced into the CMN cells, the transfected cells were more sensitive to UV-induced DNA breakage. This suggests that p53 can protect against UV-induced DNA damage and subsequent melanoma transformation. Pretreatment with BA (3 μm) for 48 h resulted in a 25.5% reduction in UV-induced DNA breakage in the CMN cells (P = 0.023), but no changes were observed in the transfected cells. However, Western blot analysis revealed no changes in the p53 or p21 levels in BA-treated cells, suggesting that BA might mediate its action via a non-p53 pathway. These data indicate that BA may have an application as a chemopreventive agent in patients with congenital naevi.

History of the Recurrent Laryngeal Nerve: From Galen to Lahey

During the second century A.D., Galen described a nerve that came from the brain on each side of the neck, went down toward the heart, and then reversed course and ascended to the larynx and caused the vocal cords to open. He called these “reversivi” (or recurrent nerves) and stated that he was the first to discover “these wonderful things.” Demonstrating before the elders of Rome, he showed that cutting the recurrent laryngeal nerve in the neck caused a live pig to stop squealing—an extraordinary feat. Because of Galen’s fame and influence, this nerve retained great importance in dissections by later anatomists and surgeons before and throughout the Renaissance. This paper documents many of these anatomical findings and highlights the importance of a careful, delicate, recurrent laryngeal nerve dissection during thyroidectomy, as popularized by Dr. Frank Lahey in 1938.

Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy

BACKGROUND The number of nodal basins and the number of lymph nodes containing regional metastases are important prognostic factors in patients with truncal malignant melanoma. Because the lymphatic drainage pattern of truncal melanoma often includes more than 1 basin, we designed a study to evaluate whether: (1) patients with dual-basin drainage were at an increased risk of lymph node metastases identified by sentinel lymph node (SLN) biopsy; and (2) the histologic status of an individual basin reliably predicted the status of the other draining basin in patients with dual-basin drainage. METHODS The records of 269 consecutive patients with melanoma, who were treated primarily with intraoperative lymphatic mapping and SLN biopsy between 1997 and 2002, were reviewed. Of these patients, 122 had primary truncal melanomas. All patients underwent preoperative lymphoscintigraphy, which established the number and location of draining nodal basins. The chi-square and Fishers exact tests of relevant clinicopathologic factors determined which factors were predictive of the presence of a pathologically positive SLN. RESULTS At least one SLN was identified in all patients. Dual-basin drainage was present in 39 (32%) patients, and a pathologically positive SLN was found in 12 (31%) of these patients. By chi-square and Fishers exact tests, dual-basin drainage was not a significant independent risk factor for the presence of at least 1 pathologically positive SLN (P =.846). Tumor thickness (P <.001), Clark level (P =.003), and tumor ulceration (P =.003) were significant independent risk factors for the presence of at least 1 pathologically positive SLN. SLN pathology in one basin did not predict the histology of the other basin in 7 (18%) of 39 patients with dual-basin drainage. CONCLUSIONS Dual-basin drainage is not independently associated with an increased risk of nodal metastases in patients with truncal melanoma. Because the histologic status of an individual basin did not reliably predict the status of the other draining basins in patients with dual-basin drainage, it is important to adequately identify and completely assess all nodal basins at risk, as defined by lymphoscintigraphy, in patients with truncal melanoma.

Application of topoisomerase assays in the evaluation of natural products as antitumor agents

Initially, DNA topoisomerase (topo) inhibitors found clinical applications as antibiotics and cancer chemotherapeutic agents. Recently, we demonstrated that plant flavonoids that inhibit mammalian topo I or topo II might be useful as cancer chemopreventive agents (Constantinou et al., 1995b). Phytochemicals can inhibit DNA topoisomerases in different ways; depending on the mode and the type of enzyme, these can be classified as topo I poisons, topo II poisons, topo I antagonists, or topo II antagonists. Correctly classifying topo inhibitors is critical because it provides an important lead as to whether the plant agent can be useful in chemoprevention or in chemotherapy. We outline below a strategy that was designed to identify and classify topo I and II inhibitors.

Delayed presentation of major complications in patients undergoing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy following hospital discharge

Peritoneal surface malignancy is increasingly treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). This is associated with potentially high morbidity. We analyzed the incidence of delayed major complications following CRS plus HIPEC.