Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

Ciliated Hepatic Foregut Cyst: Definitive Diagnosis Is Critical to the Optimal Treatment Pathway.

Background. Ciliated hepatic foregut cyst (CHFC) is a rare, benign cyst of the liver, derived from the embryonic foregut epithelium. Although CHFCs are typically asymptomatic, some present with nonspecific abdominal symptoms. Imaging modalities alone are insufficient for diagnosis, with intrahepatic cholangiocarcinoma included in the differential due to nonspecific imaging features; definitive diagnosis relies on histologic confirmation. These lesions are often benign; however, larger lesions can have malignant transformation into squamous cell carcinoma (SCC), which carries a poor prognosis, thus making a definitive diagnosis, no matter what size, essential. Here, we present a case of CHFC as well as a comprehensive literature review. Given these data, we propose an algorithm for definitive diagnosis.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Neuroendocrine tumors of the rectum: a 10-year review of management.

Neuroendocrine tumors of the rectum constitute approximately 19 per cent of gastrointestinal neuroendocrine tumors (NETs). The histologic characteristics of the tumor seem to be an indicative prognostic factor. Optimal treatment of NETS of the rectum has been widely debated, but more recent studies suggest that treatment depends upon the size. The medical records of 37 patients with NETS of the rectum were retrospectively reviewed. We reviewed their presentation, surgical treatment, pathology, and outcome. All pathological specimens were reviewed. Neuroendocrine tumors of the rectum were classified as either well-differentiated tumors, well-differentiated neuroendocrine carcinoma, or poorly differentiated neuroendocrine carcinoma. Evaluating tumor size, we found 35/37 patients had tumors less than 1 cm, 1 patient had a tumor between 1 and 2 cm, and one had a tumor greater than 2 cm. Pathologic evaluation of the tumors revealed that 35 of the tumors invaded the submucosa only, one invaded the muscularis propria, and one invaded the perirectal adipose tissue. The histopathologic features of the tumors revealed that 34 of the tumors were well-differentiated NETS with benign features, one tumor had invaded the submucosa, with angioinvasion, and two tumors were neuroendocrine carcinoma. Thirty-five patients underwent local excision. Eleven had reexcisions for positive margins. Two patients had local excision for recurrence, and one patient underwent low anterior resection (4 cm). Twelve patients had negative margins, 25 had positive margins. Eleven patients underwent reexcision. Six had no evidence of residual disease, and five had persistent positive margins and were offered no further treatment. Nineteen patients had positive margins and did not have reexcision. They all had tumors < 1 cm. Despite half of the lesions being resected with final pathologic positive margins, we have seen no significant influence on recurrence or overall survival. This raises the question of margin clearance in early lesions.

Hepatic lobe torsion: A rare disease necessitating surgical management.

BACKGROUND: Accessory liver lobes and other congenital liver abnormalities are rare and most often asymptomatic. However, these abnormalities can result in liver torsion, requiring surgical resection. CASE REPORT: We report a case of a 72-year-old woman with hepatic lobe torsion. She presented with an acute onset of chest pain and was discovered to have hypoperfusion of the left lobe of the liver on contrast-enhanced abdominal computed tomography (CT) scan. An exploratory laparotomy revealed left hepatic lobe torsion with irreversible ischemic changes requiring left hepatic lobe resection. CONCLUSION: Even though hepatic torsion is rare, it should be considered in the differential diagnosis for abdominal pain and appropriately imaged so that surgical teams can prepare for the complex surgical procedure.

The use of sentinel lymph node biopsy in ductal carcinoma in situ.

Although ductal carcinoma in situ (DCIS) does not require axillary evaluation, controversy exists regarding the use of sentinel lymph node biopsy (SLNB) in patients with DCIS diagnosed by core needle biopsy (CNB). Advocates of concomitant SLNB and lumpectomy cite the low morbidity of SLNB, the high rate of invasive ductal carcinoma in resected specimens, and the positive nodes found in 1 to 2 per cent of patients with resected DCIS despite finding no invasive component. Opponents of this practice cite the complication risk and the improbability of clinically significant axillary recurrence. We therefore proposed to determine our rate of invasive cancer in DCIS diagnosed by CNB and to determine whether SLNB at first operation would decrease return to the operating room. We retrospectively reviewed patients diagnosed with DCIS by CNB from 2003 to 2008. Standard clinicopathological data were collected and analyzed. In 110 patients, the prevalence of invasive cancer on final resection pathology was 13.6 per cent (15 of 110). Of those patients with invasive cancer, 93 per cent (14 of 15) had high-grade DCIS (P = 0.077) by CNB. Seventeen per cent (14 of 82) of patients with high-grade DCIS had invasive cancer. Of 34 patients with SLNB, three (9%) had positive nodes. Fifteen patients required re-excision to obtain negative margins, including 13 patients with invasive cancer. Five patients (4.5%) were spared additional operative intervention by initially performing SLNB. We suggest using concomitant SLNB when a high clinical suspicion of invasive cancer exists, in the presence of a palpable mass, or when mastectomy precludes future SLNB. Intraoperative margin assessment is needed to avoid return to the operating room.

GIST identified during bariatric surgery: to treat or not to treat?

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare GI tumors that compose 1% of GI tumors. With the rise in obesity, bariatric surgery is becoming an increasingly common procedure and the incidental GISTs in this population have been noted more often than in the general population. OBJECTIVE: We evaluated and characterized the incidental GISTs in our bariatric surgical population. SETTING: The study was completed at a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited academic hospital system. METHODS: All GISTs identified during Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy between January 1, 2005 and December 31, 2016 were evaluated. Typical demographic, clinicopathologic, treatment, follow-up, and outcome data were recorded. RESULTS: Within the 2655 bariatric surgeries at our institution, 17 GISTs were identified (.64%). Mean age was 54 years; 94% of lesions were identified intraoperatively. Lesions were identified in the fundus (29.4%) or body (70.6%), were unifocal, and <1 cm; 94.1% of resections had clear margins. Histology revealed 88.2% spindle cell and 11.8% mixed histology with <5 mitoses/50 fields, portending a low malignancy potential. Follow-up included the bariatric surgeon and oncology consult; 17.6% were recommended by oncology for computed tomography surveillance. No recurrences were recorded. CONCLUSION: We present the largest cohort to date of incidental GISTs in a bariatric population. A diligent intraoperative examination of the serosa in the left-behind portion of the remnant in bypass and the discarded remnant in sleeves allows the bariatric surgeon the opportunity to leave the patient cancer-free after removal of incidental tumor.

Head and neck cancer PEG site metastases: Association with PEG placement method.

BACKGROUND: Many patients with head and neck cancer (HNC) will require feeding tube placement for nutritional support using percutaneous endoscopic gastrostomy (PEG) tube. Rarely, HNC metastases have been reported at the PEG site, a morbidity associated with a poor outcome. METHODS: Along with a case report, an evaluation of PEG placement methods with metastases from the literature was completed along with a statistical analysis of the literature to determine PEG site metastases and method of placement correlations. RESULTS: The incidence of PEG metastases in patients with HNC with the "pull" method is statistically identical to that of patients receiving any other method for PEG placement. CONCLUSIONS: When considering options for the placement of PEG tubes in patients with HNC, the "pull" method should not be considered as a technique which will put patients at risk for PEG site metastases more than any other method of placement.

Predictive genetic profiles for regional lymph node metastasis in primary cutaneous melanoma: a case-matched pilot study.

Melanoma confers an estimated lifetime risk of one in 50 for 2016. Clinicopathologic staging and sentinel lymph node biopsy (SLNB) have been the standard of care for T2 and T3 lesions. Molecular biomarkers identified in the primary lesion suggestive of metastatic potential may offer a more conclusive prognosis of these lesions. Our purpose was to investigate molecular mutations in primary melanoma that were predictive for micrometastasis as defined by a positive sentinel lymph node (SLN) in a case-controlled manner: nine patients with negative SLN and nine with positive SLN. The two cohorts were statistically identical as shown by a t-test for age (P=0.17), race (P=0.18), Breslow depth (P=0.14), Clark level (P=0.33), host response (P=0.17), ulceration (P=0.50), satellite nodules (P=0.17), lymphovascular invasion (P=0.50), and mitotic activity (P=0.09). While no single gene was significantly associated with SLN status, multivariate analysis using classification and regression tree assessment revealed two unique gene profiles that completely represented regional metastases in our cohort as defined by a positive SLN: PIK3CA (+) NRAS (-) and PIK3CA (-) ERBB4 (-) TP53 (+) SMAD4 (-). These profiles were identified in 89% of the patients with positive SLN; none of these profiles were identified in the SLN-negative cohort. We identified two unique gene profiles associated with positive SLN that do not overlap other studies and highlight the genetic complexity that portends the metastatic phenotype in cutaneous melanoma.

Combined treatment of dendritoma vaccine and low-dose interleukin-2 in stage IV renal cell carcinoma patients induced clinical response: A pilot study.

Vaccination using dendritic/tumor cell hybrids represents a novel and promising cancer immunotherapy. We have developed a technology that can instantly purify the hybrids (dendritomas) from the fusion mixture of dendritic cells (DCs) and tumor cells. Our animal studies and a phase I study of stage IV melanoma patients demonstrated that dendritoma vaccination could be conducted without major toxicity and induced tumor cell-specific immunological and clinical responses. In this pilot study, ten stage IV renal cell carcinoma patients were studied. Dendritomas were made from autologous DCs and tumor cells and administered by subcutaneous injection. After initial vaccination, three escalating doses of IL-2 (3, 6, and 9 million units each) were followed within five days. This treatment regimen was tolerated well without severe adverse events directly related to the dendritoma vaccine. Most adverse events were related to IL-2 administration or pre-existing disease. Patient-specific immune responses were evaluated by flow cytometric measurement of interferon-gamma-producing T-cells before and after vaccination in response to stimulation with tumor antigens. Nine out of nine patients eligible for the analysis showed an increase of IFN-gamma-expressing CD4+ T cells after vaccination(s); while five out of eight patients eligible for the analysis showed an increase of IFN-gamma-expressing CD8+ T cells. Clinical responses were documented in 40% of the patients, three with stabilization of disease and one with a partial response documented by a reduction in tumor size. This pilot study demonstrated that dendritoma vaccines could be administered safely to patients with metastatic renal cell carcinoma, while producing both clinical and immunologic evidence of response.

Differential expression of prognostic factors and effect on survival in young (< or =40) breast cancer patients: a case-control study.

The belief that young women develop more aggressive forms of breast cancer than other women is controversial. The purpose of this study was to determine if women 40 years of age and under with breast cancer have more negative prognostic indicators and a higher 5-year mortality than those women over 40 years of age. From January 1998-December 2002, all women with breast cancer were identified from our tumor registry. Women with metastatic disease at presentation were excluded from our study. The women were divided into two groups, women under 40 (cases) and women 40 and over (controls). Seventy-eight cases were identified and matched to 228 controls. These cohorts were matched 3:1 (cases:controls) based on tumor staging. The data collected on each patient included prognostic factors such as tumor size, tumor type, estrogen and progesterone receptors, Her2/neu, and Ki-67. Information on surgical procedure, postoperative therapy, recurrence, and mortality was also gathered. The mean ages for cases and controls were 35 and 59 years, respectively. The rates of modified radical mastectomy were similar in the two groups, but young women were more likely to have breast reconstruction (33.7% vs 9.8%). The rates of breast conservation therapy were actually lower in the group under 40 (32.5% vs 37.6%). Tumors in the 40 and under group were more frequently estrogen receptor negative (33.8% vs 21.9%: P = 0.046) and progesterone receptor negative (50.0% vs 35.5%: P = 0.033). Younger women also experienced a greater prevalence of Ki-67 (P < 0.001) and higher levels of Her2/neu overexpression (P = 0.013). Women over 40 were more likely to receive hormonal therapy (39.7% vs 36.1%). Women over 40 had a lower overall rate of recurrence. A difference in overall survival does exist between these two groups of women, which trends toward significance. The women 40 and under had a lower overall 5-year survival. The reason for this difference remains unclear. Although we demonstrate a higher percentage of younger women with negative biochemical markers, the only factors independently and significantly related to higher mortality were estrogen receptor negativity and tumor stage at presentation.

Effect of lymphatic mapping on the new tumor-node-metastasis classification for colorectal cancer.

PURPOSE: Sensitive detection methods and accurate reporting are necessary to determine the prognostic significance of micrometastases (MM) and isolated tumor cells (ITCs) in lymph nodes that drain colorectal cancers (CRCs). This study examined the role of lymphatic mapping (LM) in the application of the new tumor-node-metastasis (TNM) classification for MM and ITC. PATIENTS AND METHODS: All patients at the John Wayne Cancer Institute underwent LM immediately before standard resection of primary CRC between 1996 and 2001. Sentinel nodes (SNs) were identified using blue dye and/or radiotracer and were examined by hematoxylin-eosin (H&E) staining, cytokeratin immunohistochemistry, and multilevel sectioning. The comparison group comprised 370 patients whose primary CRCs were resected without LM during the same period at the same institution. RESULTS: LM was successfully performed in 115 of 120 (96%) patients and correctly predicted the tumor status of the nodal basin in 110 of 115 (96%) patients. Thirty-seven patients (32%) were lymph node-positive by H&E, ITC and MM were found in 23 patients (29.4%) whose lymph nodes were negative by H&E. Tumor deposits were found in the SN only in 29 patients (50%). Nodal involvement was identified for 14.3%, 30%, 74.6%, and 83.3% of T1, T2, T3, and T4 tumors, respectively, in the study group, and for 6.8%, 8.5%, 49.3%, and 41.8% of T1, T2, T3, and T4 tumors, respectively, in the comparison group. The study group had a higher percentage of nodal metastases (53% v 36%; P <.01) and a higher incidence of MM and ITC (29.4% v 1.9%; P <.0001). The mean number of lymph nodes found in the study group (14) was also significantly more than the number found in the comparison group (10; P <.00001). CONCLUSION: Conventional examination of lymph nodes for CRC is inadequate for the detection of MM and ITC as described in the new TNM classification. Thus, LM and focused SN analysis should be considered to fully stage CRC.

Treatment and outcomes of melanoma with a Breslow's depth greater than or equal to one millimeter in a regional teaching hospital.

Local control and regional lymph node evaluation are the primary treatment goals for cutaneous primary melanoma. Historically, primary lesions were excised with large 3- to 5-cm radial margins. Recent clinical trials have suggested that similar survival and recurrence rates can be achieved with smaller margins of excision. In addition to excision of the primary lesion, the presence or absence of nodal metastasis is the single most powerful predictor of survival in patients with melanoma. Based on the available trials, the standard of care for a melanoma 1 mm or greater in depth is a wide local excision with a 2-cm margin and a sentinel lymph node biopsy (SLNB). The application of this standard in regional teaching hospitals is unknown. We performed a retrospective review of a cancer registry at a teaching hospital in South Carolina. This analysis included all patients who underwent surgery for melanoma at our institution between July 1997 and March 2003. Our single inclusion criterion was that the primary melanoma had to be 1 mm or greater in depth. Only 42 per cent of the patients underwent excision with a radial margin >2 cm, and only 60 per cent of the patients underwent SLNB. As time progressed, the use of SLNB at our institution increased; but, even as late as 2003, some patients did not receive SLNB. Adherence to standards did not appear to have an effect on overall survival. In conclusion, the current standard for the treatment of invasive melanoma greater than or equal to 1 mm in thickness is a 2-cm margin of excision and a SLNB. In this regional teaching hospital, surgical treatment and staging of melanoma did not strictly adhere to the standard.

Management of periampullary adenocarcinoma by pancreaticoduodenectomy at a regional teaching hospital.

BACKGROUND: Periampullary adenocarcinoma (PA) includes: pancreatic, duodenal and ampullary adenocarcinoma; and cholangiocarcinoma. Pancreaticoduodenectomy (PD) is required for cure of PA. Previous studies demonstrated the likelihood of cure increases when a microscopically negative (R0) margin is achieved. Clearance of the superior mesenteric artery (SMA) margin has been identified as the most critical margin in PD. Some authors have emphasized the importance of certain techniques to clear the SMA margin. Neither the degree to which these techniques have been incorporated nor their impact on margin status and survival has been described. We hypothesized that use of techniques focusing on clearing the SMA margin would result in higher R0 resection rates and improved survival after PD in patients with PA. METHODS: A retrospective study was performed on patients from 1/1/1985 until 7/31/2007. Data on patient demographics, clinical presentation, preoperative treatment, operative technique, margins, and postoperative outcomes were collected. Ninety-three patients were identified for inclusion in the study. Three approximately equal groups were created for analysis. RESULTS: The overall survival (OS) for the entire cohort was 19 months and was not different among the groups studied. Margins were microscopically negative in 81% of cases. The percentage of node-positive cases increased during the time period, as did the number of lymph nodes (LNs) examined (P=0.017). The use of pylorus-preserving PD decreased (P=0.001) while resection of the superior mesenteric/portal vein (SMV/PV) increased during the study period. We observed an increase in descriptions of the clearance of the anterior aspect of the aorta and inferior vena cava (IVC), dissection to the right side of the SMA, dissection to the origin of the SMA and intra-operative identification of the SMA margin. Dissecting to the SMA did not change the likelihood of achieving an R0 margin. OS was improved after R0 resections (R0: 21 months vs. R1/2: 10 months) but this difference was not statistically significant (P=0.099). There was no association between margin status and OS. Changes in the pathology reporting of margins were observed, with statistically significant increases in the percentage of cases in which the SMA, common bile duct and pancreatic neck margins were separately reported. However, the SMA margin was separately reported in only 26% of pathology reports. CONCLUSIONS: The operative techniques used in PD at this institution have changed over time. The increasing frequency of dissection to the SMA and identification of the SMA margin by both surgeon and pathologist suggest an increased attention to the SMA margin. This shift did not result in significant improvements in survival or margin status, but it is consistent with the recognition of the importance of the SMA margin. Our analysis has also identified areas of potential improvement in the ways in which operative and pathology reports for PD are generated.

Sentinel node in the era of neoadjuvant therapy and locally advanced breast cancer.

The most important determinant of prognosis for patients with breast cancer is the status of the axillary lymph nodes. Axillary lymph node dissection (ALND) has been performed for over a century to stage the cancer, achieve regional control, and perhaps improve survival. In accordance with tradition, ALND has been performed on all patients with the diagnosis of invasive breast cancer. In the early 1990s, this dogma was challenged because of the significant morbidity associated with ALND (paresthesia, extremity lymphedema) and the fact that greater than 50% of all breast cancers are node negative. A less morbid but highly accurate staging procedure, lymphatic mapping and sentinel lymph node biopsy (SNB) was introduced. Currently, the de facto standard of care in breast cancer is to perform LM and SNB in patients with small tumors and clinically negative axilla. While numerous methodological issues are being raised, the utility of LM and SNB identification continues to expand. In the current review we assess the application of this technique to locally advanced breast cancer (LABC) and neoadjuvant chemotherapy. What role does SNB play in locally advanced disease? Is LM and SNB accurate for patients with advanced disease? What influence do axillary metastases have on further treatment? What is the role of SNB in the planning for neoadjuvant patients? The skillful management of patients with breast cancer lies in the delicate balance between maximizing the efficacy of treatment and minimizing its morbidity and failure.

Combination probe and dye-directed lymphatic mapping detects micrometastases in early colorectal cancer.

Nodal metastasis is the single most important prognostic factor in early colorectal cancer (CRC). Lymphatic mapping can identify sentinel nodes for focused histopathologic examination and thereby improve the nodal staging of CRC; however, the optimal technique for identifying sentinel nodes in CRC is unclear. We hypothesized that a combination of radiotracer and blue dye would more accurately identify tumor-positive sentinel nodes than blue dye alone. Lymphatic mapping was performed in 48 consecutive patients undergoing resection for CRC and in two original patients who underwent sentinel node mapping in 1996. Prior to resection, 1% vital blue dye and radiotracer were injected around the tumor in the subserosal layer. Nodes were designated as sentinel by blue coloration and/or radioactivity. Lymphatic mapping identified at least one sentinel node in 49 patients. Focused examination of multiple sentinel node sections by means of hematoxylin and eosin and immunohistochemical analysis showed that sentinel nodes accurately predicted the status of the nodal basin in 93.8% (46 of 49) of patients. Of the 19 patients with nodal metastases, 11 had macrometastases (>.2 mm), three had micrometastases (between 2 mm and 0.2 mm), and five had isolated tumor cells or clusters (<.2 mm) identified by immunohistochemical analysis only. Patients had significantly fewer blue/radioactive ("hot") nodes than blue-only nodes (1.38 vs. 2.48 per patient; P = 0.0001). It is important to note that nodal metastases were more common in blue/hot nodes than in blue-only nodes (27.3% [19 of 68] vs. 8.8% [11 of 124]; P = 0.005). Dual-agent lymphatic mapping more accurately identifies sentinel node metastases than blue dye alone. In addition, this technique allows a more focused histopathologic examination of these nodes, in conjunction with the revised American Joint Committee on Cancer guidelines, and thereby offers the potential for significant upstaging of CRC.

Identification of an occludin cell adhesion recognition sequence.

The molecular mechanisms by which the tight junction integral membrane protein, occludin promotes cell adhesion and establishes an endothelial monolayer permeability barrier have not been elucidated. In particular, the amino acid sequences of the occludin cell adhesion recognition (CAR) sites have not been determined. Here we demonstrate that a cyclic peptide containing the sequence LYHY, which is found in the second extracellular domain of occludins in all mammalian species, inhibits the establishment of endothelial cell barriers in vitro and in vivo. This cyclic peptide also prevents the aggregation of fibroblasts stably transfected with cDNA encoding occludin. The data suggest that the LYHY motif is an occludin CAR sequence.

Differential expression of thymidylate synthase in colorectal tumors and matched lymph nodes: impact on adjuvant treatment.

Although the expression of thymidylate synthase (TS) in metastatic colorectal cancer (CRC) may be a better predictor of response to 5-fluorouracil chemotherapy than TS expression in primary CRC, this enzyme has not been well studied in tumor-draining regional lymph nodes. We retrospectively examined TS expression in 12 primary CRC lesions (pT3) and matched sentinel lymph nodes. Of the 8 primary tumors that were TS-positive, 50 per cent (4/8) had tumor-positive lymph nodes and 50 per cent (4/8) had tumor-negative nodes. Of the 4 primary tumors that were TS-negative, 75 per cent (3/4) had tumor-positive nodes and 25 per cent (1/4) had tumor-negative nodes [kappa = -0.1386, 95 per cent confidence interval: (-0.4820, 0.2048), P = 0.4284]. Of the 8 TS-positive primaries, 25 per cent (2/8) had TS-positive nodes and 75 per cent (6/8) had TS-negative nodes. Of the 4 TS-negative primaries, 50 per cent (2/4) had TS-positive nodes and 50 per cent (2/4) had TS-negative nodes [kappa = -0.0131, 95 per cent confidence interval: (-0.2958, 0.2696), P = 0.9274]. Two of the three TS-negative primaries that had metastasized to regional lymph nodes were associated with TS-positive lymph nodes. Our findings indicate that expression of TS by a primary CRC does not correlate with nodal metastases or nodal TS expression. Nodal expression of TS may be important in predicting response to 5-fluorouracil when a primary CRC is TS-negative.

What is the risk of diagnostic endoscopic retrograde cholangiopancreatography before cholecystectomy?

Many surgeons prefer to perform endoscopic retrograde cholangiopancreatography (ERCP) before cholecystectomy, specifically in patients at significant risk of having biliary pathology. However, a preoperative diagnostic ERCP, without the use of an endoscopic ultrasound or magnetic retrograde cholangiopancreatoscopy, remains controversial. This is the result of the risk of either performing an unnecessary procedure and/or the development of post-ERCP pancreatitis (PEP). We performed a retrospective review of all surgeon-performed ERCPs at our institution between July 2011 and May 2013. This was done to examine patients who had pericholecystectomy ERCP. We had 550 ERCPs performed at our institution during this time period, 169 of which were pericholecystectomy procedures. We divided the 169 patients who had a diagnostic procedure (Diagnostic group) from those who had known biliary pathology before intervention (Therapeutic group). As a result, 34 patients (20.1%) were placed in the Diagnostic group and 135 patients (79.9%) in the Therapeutic group. Of the 34 Diagnostic patients, four (11.8%) developed PEP. Fifteen (44.1%) had unnecessary procedures, two of which had PEP (2.9%). Of the 135 ERCPs in the Therapeutic group, 18 patients (13.4%) developed PEP. Five of the 11 who had unnecessary procedures developed PEP. Based on the low incidence of complications, diagnostic ERCP has an acceptable rate of pancreatitis and/or unnecessary procedures when performed in highly selected patients and before cholecystectomy when compared with patients undergoing therapeutic ERCP. However, more aggressive use of diagnostic imaging before ERCP should be adopted given the number of unnecessary procedures performed.