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Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy.

Objective:To assess the axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases (>0.2 mm to ≤2.0 mm) after breast surgery and SLN procedure without formal axillary lymph node dissection (ALND). Summary Background Data:Under controlled study conditions, the SLN procedure proved to be a reliable method for the evaluation of the axillary nodal status in patients with early-stage invasive breast cancer. Axillary dissection of levels I and II can thus be omitted if the SLN is free of macrometastases. The prognostic value and potential therapeutic consequences of SLN micrometastases, however, remain a matter of great debate. We present the follow-up data of our prospective SLN study, particularly focusing on the axillary recurrence rate in patients with negative SLN and SLN micrometastases. Methods:In this prospective study, 236 SLN procedures were performed in 234 patients with early-stage breast cancer between April 1998 and September 2002. The SLN were marked and identified with 99m technetium-labeled colloid and blue dye (Isosulfanblue 1%). The excised SLNs were examined by step sectioning and stained with hematoxylin and eosin and immunohistochemistry (cytokeratin antibodies Lu-5 or CK 22). Only patients with SLN macrometastases received formal ALND of levels I and II, while patients with negative SLN or SLN micrometastases did not undergo further axillary surgery. Results:The SLN identification rate was 95% (224/236). SLN macrometastases were found in 33% (74/224) and micrometastases (>0.2 mm to ≤2 mm) in 12% (27/224) of patients. Adjuvant therapy did not differ between the group of SLN-negative patients and those with SLN micrometastases. After a median follow-up of 42 months (range 12–64 months), 99% (222/224) of evaluable patients were reassessed. While 1 patient with a negative SLN developed axillary recurrence (0.7%, 1/122), all 27 patients with SLN micrometastases were disease-free at the last follow-up control. Conclusions:Axillary recurrences in patients with negative SLN or SLN micrometastases did not occur more frequently after SLN biopsy alone compared with results from the recent literature regarding breast cancer patients undergoing formal ALND. Based on a median follow-up of 42 months—one of the longest so far in the literature—the present investigation does not provide evidence that the presence of SLN micrometastases leads to axillary recurrence or distant disease and supports the theory that formal ALND may be omitted in these patients.

Transanal endoscopic microsurgical excision of rectal tumors: indications and results.

Transanal endoscopic microsurgery (TEM) allows local excision of rectal tumors located 4 to 18 cm above the anal verge. The technique is not yet generally established because of the necessary special instrumentation and tools, the unusual technical aspects of the approach, and the stringent patient selection criteria. The aim of this prospective, descriptive study was to analyze the currently accepted indications for TEM and to evaluate the use of this procedure for treating rectal cancer. Over a 4-year period 50 patients aged 31 to 86 years (mean 64 years) underwent TEM for treatment of rectal tumors located 12 cm above the anal verge (range 4–18 cm). The local complication rate was 4%. Altogether, 76% of lesions were benign, and 24% were T1 and T2 tumors. Of 12 cancer cases, 4 required reoperation by total mesorectal resection; the other 8 are currently under follow-up management. Over the follow-up period of 30.6 months (range 11–54 months) the recurrence rate of T1 tumors was 8.3%. TEM is a minimally invasive surgical technique that may benefit a small, specific population of patients with rectal tumors. Compared with conventional transanal resection, TEM provides superior exposure of tumors higher up in the rectum (i.e., up to 18 cm from the anal verge). The greater precision of resection combined with low morbidity (10%, relative to that of anterior resection) and short duration of hospitalization (5.5 days) make this technique a reliable and in some cases more effective surgical approach than laparotomy and low anterior resection.RésuméLa microchirurgie transanale endoscopique (MTE) permet une excision locale des tumeurs situées entre 4 et 18 cm au-dessus de la ligne anocutanée. La technique n’est pas encore très répandue en raison du besoin d’une instrumentation et d’outils spécifiques, une technique un peu spéciale, et une sélection stricte des patients. Le but de cette étude prospective, descriptive, a été d’analyser les indications actuelles de cette technique et d’évaluer l’utilisation de ce procédé pour le traitement du cancer du rectum. En quatre ans, nous avons traité 50 patients âgés entre 31 et 86 ans (âge moyen =64 ans) par MTE pour tumeur rectale située à 12 cm (en moyenne) de la marge anale (extrêmes 4–18 cm). Le taux de complications locales a été de 4%. Soixante-six pourcent des lésions étaient bénignes et 24% des tumeurs T1 et T2. Parmi les 12 cas de cancer, quatre ont nécessité une réopération pour excision totale du mésorectum, les huit autres patients sont actuellement sous surveillance. Pendant la période de suivi de 30,6 mois (extrêmes =11–54 mois), le taux de récidive des tumeurs T1 a été de 8,3%. La MTE est une technique chirurgicale mini-invasive qui pourrait être appliquée à un sous-groupe de la population atteint de tumeur rectale. Comparée à la résection transanale conventionnelle, la MTE permet une meilleure exposition des tumeurs du haut rectum, c’est-à-dire jusqu’à 18 cm de la marge anale. Une grande précision dans la résection, combinée à une morbidité basse (par rapport à la résection antérieure) (10%) et une courte hospitalisation (5,5 jours) rendent cette technique fiable, et dans certains cas, plus efficace que la résection antérieure par laparotomie.ResumenLa microcirugía endoscópica transanal (TEM) permite la resección de tumores rectales localizados de 4 a 18 cm por encima del margen anal. Este procedimiento hasta ahora no se ha generalizado debido a la necesidad de desarrollar instrumentos y herramientas especiales, aspectos técnicos inusuales de abordaje y criterios estrictos para la selección de los pacientes. El objetivo de este estudio prospectivo y drescriptivo es analizar las indicaciones actualmente aceptadas para las TEM y evaluar la eficacia de esta técnica en el tratamiento del cáncer de recto. En un periodo de 4 años, 50 pacientes con edades comprendidas entre 31 y 86 años (media =64 años) fueron tratados mediante el procedimiento quirúrgico TEM, por padecer tumores rectales situados a 12 cm por encima del margen anal (rango: 4–18 cm). La tasa de complicaciones locales fue del 4%. En el 76% las lesiones fueron benignas y en el 24% malignas: tumores T1 y T2. De los 12 casos de cáncer, 4 requirieron una reintervención con resección total del mesorrecto; los otros 8 están actualmente controlados y sometidos a tratamiento. Tras un periodo de seguimiento de 30.6 meses (rango: 11–54 meses) la tasa de recidivas de tumores T1 fue del 8.3%. La TEM es una técnica quirúrgica mínimamente invasiva que puede ser muy útil en un número reducido y escogido de pacientes con cáncer de recto. Comparada con la resección transanal convencional, la TEM permite la exposición de tumores del alto recto i.e. hasta 18 cm de los márgenes del ano. La gran precisión de la resección, junto con la baja morbilidad (en comparación con la resección anterior) 10% y la corta hospitalización (5.5 días) hace que esta técnica sea, fiable y, en algunos casos, más eficaz que la laparotomía con resección anterior baja del recto.

Selective axillary surgery in breast cancer patients based on positron emission tomography with 18F-fluoro-2-deoxy-D-glucose: not yet!

We prospectively evaluated 31 patients with invasive breast cancer. Preoperative positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) for detection of axillary lymph node metastases was compared with the histopathologic status of the sentinel lymph node (SLN). Sensitivity of PET imaging was 43%, specificity and negative predictive value were 94 and 67%, respectively. The smallest metastasis detected by PET measured 3 mm in diameter. The results of this study suggest that detection of small axillary lymph node metastases is limited by the currently achievable spatial resolution of PET imaging. Selective axillary surgery in breast cancer patients based on 18F-FDG PET is yet not possible.

Tissue Microarray Evaluation of Melanoma Antigen E (MAGE) Tumor-Associated Antigen Expression: Potential Indications for Specific Immunotherapy and Prognostic Relevance in Squamous Cell Lung Carcinoma

ObjectiveTo evaluate MAGE tumor-associated antigen (TAA) expression in an extensive panel of normal and neoplastic tissues. Summary Background DataTAAs of the MAGE family represent targets of active specific immunotherapy. Limited-size studies indicate that they are expressed in normal testis and tumors of different histologies. High-throughput tissue microarray (TMA) technology and MAGE TAA-specific monoclonal antibodies now allow us to comprehensively evaluate their expression in large numbers of tissues and to address clinical correlations. MethodsA TMA containing 3,520 samples from 197 different tissues and a non-small-cell lung cancer TMA including 301 specimens were stained using the MAGE TAA-specific monoclonal antibody 57B. For patients with squamous cell carcinoma of the lung, the dichotomous result (positive vs. negative) of MAGE TAA staining was used as a predictor variable along with other covariates in proportional hazard regression analysis of tumor-specific survival. ResultsMAGE TAAs are expressed with frequencies ranging between 22.7% (larynx) and 50% of cases (lung) in squamous cell carcinomas from different anatomic areas and in large cell carcinomas of the lung (37.9%). The authors provide here the first description of MAGE TAA expression in basalioma (48.1%). To investigate the clinical significance of MAGE expression in a frequently positive tumor type, a non-small-cell lung cancer, TMA was then studied. In this TMA 43.2% of tumors were 57B positive. In patients with squamous cell carcinoma, MAGE TAA positivity was significantly correlated with a shorter tumor-specific survival in the proportional hazard regression analysis model. ConclusionsThese data suggest novel potential therapeutic indications in different types of cancers. In lung squamous cell carcinoma, the significant association of MAGE TAA expression with poor prognosis suggests that patients with 57B-positive tumors may benefit from early, specific immunotherapy procedures.

Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo.

A specific cellular immune response directed against a panel of three defined tumor-associated antigen (TAA) epitopes was induced in metastatic melanoma patients by a prime-boost strategy taking advantage of an innovative recombinant vaccinia virus as evaluated by quantitative assessment of cytotoxic T lymphocytes (CTLs) with corresponding specificity. The immunization protocol consisted of the administration of psoralen-UV-treated and replication-incompetent recombinant vaccinia virus encoding the three immunodominant HLA-A*0201-restricted epitopes Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) together with two costimulatory molecules, B7.1 and B7.2, in the context of systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. Boosts were subsequently applied with corresponding synthetic nonapeptides and GM-CSF. Specific CTL induction was assessed by tetramer staining and CTL precursor (CTLp) frequency evaluation. Within 12 days of injection of the recombinant vector, cytotoxic T cell responses specific for engineered epitopes were detectable in three of three patients. During the vaccination treatment, antigen-specific CTLp frequencies exceeding 1:10,000 peripheral CD8(+) T cells could be observed. Tetramer staining also revealed significant increases in specific CD8(+) T cell numbers. We conclude that active specific antitumor vaccination can raise a concurrent and specific cellular immune response against a panel of molecularly defined antigens, thereby increasing the chance of an immune hit against neoplastic cells with heterogeneous antigen expression. Data from this study emphasize the potency of a recombinant vaccinia virus vector encoding multiple minigenes and costimulatory molecules in the context of exogenously administered GM-CSF. Clinical effectiveness of this immunologically active protocol should therefore be explored in appropriately selected groups of patients.

New technique for pouch-anal reconstruction after total mesorectal excision

PURPOSE: Surgical options in metachronous or recurrent rectal cancer after anterior or low anterior resection are limited and frequently result in abdominoperineal rectal extirpation sacrificing the sphincter or in straight coloanal reconstruction. Decreased capacity and distensibility in straight coloanal reconstruction after proctectomy correlate well with increased daily stool frequency, urgency, and incontinence. A new technique for coloanal pouch reconstruction using the ileocecal segment is proposed. METHODS: A pedunculated ileocecal segment was rotated 180° counterclockwise and placed between the sigmoid colon and anal canal. Ileal end of the pouch was then anastomosed end-to-end with the transected sigmoid colon and proximal end of the ileum with distal end of the ascending colon. Functional results and defecation quality of a 67-year-old woman are described 6 and 12 months after ileocolonic interposition pouch replacing the tumorbearing rectum. RESULTS: Twelve months postoperatively, the patient is free of disease with an excellent defecation quality, has full anal continence without soiling, is having two solid stools in 24 hours. Functional control revealed normal anal sphincter pressure and large rectal capacity and compliance. Neither outlet obstruction nor incomplete evacuation have been observed. CONCLUSION: The ileocecal interposition pouch (cecum pouch) represents an alternative technique for coloanal reconstruction in low rectal cancer, recurrent rectal cancer, or metachronous low rectal cancer with intact sphincter function. This new method presents some attractive features compared with techniques presently in use.

Nonoperative treatment of splenic rupture in malaria tropica: review of literature and case report.

In many parts of the world malaria still is a major medical problem. Heavy international and transcontinental traveling carries malaria to non-endemic areas. Practicing physicians must be aware of the common, but also the rare and severe complications of malaria. During malaria changes in splenic structure can result in asymptomatic enlargement or complications such as hematoma formation, rupture, hypersplenism, ectopic spleen, torsion, or cyst formation. An abnormal immunological response may result in massive splenic enlargement. Spontaneous rupture of the spleen is an important and life threatening complication of Plasmodium vivax infection, but is rarely seen in Plasmodium falciparum malaria. The ability to properly diagnose and manage these complications is important. Spleen-conserving procedures should be the standard whenever possible especially in patients with a high likelihood of future exposure to malaria.

Parathyroidectomy in primary hyperparathyroidism: Preoperative localization and routine biopsy of unaltered glands are not necessary

BACKGROUND An assessment was made of operative risk and outcome after parathyroidectomy for primary hyperparathyroidism. METHODS A retrospective study was conducted in a single center university hospital in Switzerland. The 173 patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0 years). No routine preoperative localization methods were used for primary neck exploration. Parathyroidectomy was performed under general anesthesia. No routine use was made of intraoperative biopsy of glands whose macroscopic appearance was normal. The 173 patients underwent 179 operations (170 primary and 9 secondary interventions). Resection of a single gland was performed in 127 cases (73.4%) and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands) was performed in 10 cases (5.8%). RESULTS Of 170 patients with primary intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients (3.5%) underwent early reexploration. Three additional patients underwent late secondary procedures. These nine secondary operations were successful in seven patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia was noted in 163 of 171 patients (95.3%). Persistent and recurrent hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively. Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS Our surgical strategy for treatment of primary hyperparathyroidism has proved to be safe with a favorable outcome in more than 95% of patients. This was possible without the routine use of preoperative localization studies and intraoperative biopsy of macroscopically normal glands. Routine biopsy of normal-appearing glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients.

OBJECTIVE The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND). METHODS Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen. RESULTS The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019). CONCLUSIONS This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.

Single-layer end-on continuous suture of colonic anastomoses

The single-layer end-on continuous suture technique for intestinal anastomoses on mobile intraperitoneal bowel segments is at least as safe and probably safer than a corresponding single-layer interrupted suture technique. Although the evaluation of this technique included a substantial number of surgeons who were performing their first anastomosis or who contributed only a single one to the series in a teaching university setting, there were no instances of clinical leak among 143 consecutive colonic anastomoses. Furthermore, 27 percent of the operations were performed as emergencies, thus optimal bowel preparation was lacking. The anastomosis time is distinctly shorter than the time needed for an interrupted single-layer technique, and contamination of the operative field is reduced to a minimum. The anastomosis is extremely simple, comfortable to perform, and reliable.