Volume-outcome relationship of liver surgery: a nationwide analysis.

BACKGROUND: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. METHODS: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien-Dindo grade IIIA or higher) and 30-day or in-hospital mortality. RESULTS: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20-69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. CONCLUSION: Hospital volume and postoperative outcomes were not associated.

ANTECEDENTES: La asociación entre el volumen hospitalario y los resultados de la cirugía hepática no está clara. Según la recomendación actual de las guías holandesas se requiere un volumen mínimo de 20 procedimientos anuales por centro. El objetivo de este estudio fue analizar la asociación entre el volumen hospitalario con los resultados postoperatorios en la auditoría hepatobiliar obligatoria holandesa a nivel nacional. MÉTODOS: Se realizó un estudio a nivel nacional en los Países Bajos. Se incluyeron todas las resecciones hepáticas registradas en la auditoría hepatobiliar holandesa entre 2014 y 2017. El volumen anual del centro se calculó y se clasificó en categorías de 20 procedimientos por año. Los objetivos principales fueron la morbilidad de mayor grado (Clavien-Dindo grado IIIA o superior) y la mortalidad hospitalaria o la mortalidad a los 30 días. RESULTADOS: Se realizaron un total de 5.590 resecciones en 34 centros con una mediana (rango intercuartílico) de volumen anual de 35 procedimientos (20-69). La tasa global de morbilidad mayor fue del 11% y la mortalidad del 2%. La mortalidad fue de 1,9% después de la resección por metástasis hepáticas colorrectales (colorectal liver metastases, CRLM), 1,2% para no CRLM, 0,4% para tumores benignos, 4,9% para carcinoma hepatocelular, y 10,3% para tumores biliares. Los centros de mayor volumen realizaron más resecciones hepáticas mayores y más resecciones por carcinoma hepatocelular y cáncer biliar. En el análisis multivariable después de ajustar por factores de riesgo conocidos de eventos adversos, no se observó ninguna asociación entre el volumen hospitalario y la morbilidad o mortalidad mayor. CONCLUSIÓN: No hubo asociación entre el volumen hospitalario y los resultados postoperatorios de la cirugía hepática en los Países Bajos.

Supervised automated microscopy increases sensitivity and efficiency of detection of sentinel node micrometastases in patients with breast cancer.

AIMS: To investigate the practicality and sensitivity of supervised automated microscopy (AM) for the detection of micrometastasis in sentinel lymph nodes (SLNs) from patients with breast carcinoma. METHODS: In total, 440 SLN slides (immunohistochemically stained for cytokeratin) from 86 patients were obtained from two hospitals. Samples were selected on the basis of: (1) a pathology report mentioning micrometastases or isolated tumour cells (ITCs) and (2) reported as negative nodes (N0). RESULTS: From a test set of 29 slides (12 SLN positive patients, including positive and negative nodes), 18 slides were scored positive by supervised AM and 11 were negative. Routine examination revealed 17 positive slides and 12 negative. Subsequently, automated reanalysis of 187 slides (34 patients; institute I) and 216 slides (40 patients; institute II) from reported node negative (N0) patients showed that two and seven slides (from two and five patients, respectively) contained ITCs, respectively, all confirmed by the pathologists, corresponding to 5.9% and 12.5% missed patients. In four of the seven missed cases from institute II, AM also detected clusters of four to 30 cells, but all with a size < or = 0.2 mm. CONCLUSIONS: Supervised AM is a more sensitive method for detecting immunohistochemically stained micrometastasis and ITCs in SLNs than routine pathology. However, the clinical relevance of detecting cytokeratin positive cells in SLNs of patients with breast cancer is still an unresolved issue and is at the moment being validated in larger clinical trials.

[Negative sentinel node in breast cancer patients a good indicator for continued absence of axillary metastases]. / Negatieve schildwachtklier bij borstkankerpatiënten goede indicator voor het uitblijven van okselmetastasen.

OBJECTIVE: To determine the prevalence of axillary recurrences in sentinel-node-negative patients with breast cancer who had no axillary dissection. DESIGN: Follow-up study. METHOD: The first one hundred consecutive sentinel-node-negative patients with a minimal follow-up of 36 months (median 47) were included in this study. All patients underwent sentinel-node biopsy using the triple technique. During the first year after the operation patients were seen on a 3-monthly basis and thereafter every 6 months. RESULTS: Intensive pathological examination of the harvested sentinel nodes revealed no (micro)metastases in any patient. One patient developed an axillary recurrence after 24 months. Three out of the 100 patients developed distant metastases during follow-up; 2 of them died as a result of these metastases. One patient was treated for a local mammary recurrence. In terms of survival the sentinel-node procedure did not appear to be disadvantageous: the 3-year survival rate in our study was 98% for node-negative patients, compared to 88-94% quoted in the literature for node-negative patients after axillary dissection. This apparent improvement may be due to better staging of breast-cancer patients through the use of the sentinel-node procedure (stage migration). CONCLUSION: The triple technique was a reliable method for identifying the sentinel node in breast-cancer patients. Compared to the historical data on node-negative breast cancer, the sentinel-node procedure improved the prognosis of node-negative breast-cancer patients. This effect was probably due to the more accurate staging of breast-cancer patients using the sentinel-node procedure.

Predictive factors for metastatic involvement of nonsentinel nodes in patients with breast cancer.

BACKGROUND: The potential morbidity of an axillary lymph node dissection in patients with breast cancer can be avoided in patients with a negative sentinel node (SN). HYPOTHESIS: It may be possible to identify a subset of patients with a positive SN and without metastases in the remaining axillary lymph nodes. DESIGN: Case-control study. SETTING: Both primary and referral hospital care. PATIENTS: Data were studied for 255 consecutive patients with stage T1 or T2 breast cancer who had a successful identification of the SN. INTERVENTIONS: In patients with a positive SN, histological examination of all non-SNs that were negative by routine examination was the same as that for SNs (multiple sectioning and immunohistochemical analysis). MAIN OUTCOME MEASURES: The incidence of non-SN metastases was correlated with the surface area and number of SN metastases and primary tumor characteristics. A micrometastasis was defined as less than 1 mm(2). RESULTS: Of 255 patients, the SN appeared to be positive in 93 (36%). Subsequent axillary lymph node dissection revealed positive non-SNs in 46 patients (49%). Patients with a single positive SN and patients with metastases less than 1 mm(2) in the SN had significantly less non-SN involvement than patients with more than 1 positive SN (40% vs. 78%) and patients with macrometastases (27% vs. 49%). CONCLUSIONS: The incidence of non-SN metastases seemed to be related to the number of positive SNs and the size of SN metastases. However, in the group of patients with a positive SN, it was not possible to identify a subset of patients without non-SN metastases.

Pathologic analysis of sentinel lymph nodes.

The sentinel lymph node (SLN) procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative SLN predicts the absence of tumor metastases in the other regional lymph nodes with a high degree of accuracy. This means that in case of a negative SLN, regional lymph node dissection is no longer necessary. Besides saving patients the significant morbidity associated with lymph node dissection, it will also save costs. Crucial for the success of the SLN procedure is the screening of the SLN for metastases by the pathologist. To this end, several techniques are available such as standard histo- and cytopathological techniques, immunohistochemistry, flow cytometry, and molecular biological techniques. In this paper, the value of these methods for detecting SLN metastases is discussed. Some of these techniques have also appeared to be quite useful for intraoperative evaluation of SLNs. The standard protocol for detection of SLN metastases consists of extensive histopathological investigation including stepped sections stained with hematoxylin and eosin (HE) and immunohistochemistry. Intraoperative frozen section analysis and imprint cytology of SLNs have been shown to be reasonably reliable for detecting breast cancer metastases in SLNs. Further studies are necessary to establish the role of multiparameter flow cytometry and sophisticated molecular biological techniques such as reverse transcription polymerase chain reaction (RT-PCR) in detecting SLN metastases.

Sentinel node investigation in breast cancer: detailed analysis of the yield from step sectioning and immunohistochemistry.

AIMS: To evaluate in detail the extent to which step sectioning and immunohistochemical examination of sentinel lymph nodes (SNs) in patients with breast cancer reveal additional node positive patients, to arrive at a sensitive yet workable protocol for histopathological SN examination. METHODS: This study comprised 86 women with one or more positive SN after a successful SN procedure for clinical stage T1-T2 invasive breast cancer. SNs were lamellated into pieces of approximately 0.5 cm in size. One initial haematoxylin and eosin (H&E) stained central cross section was made for each block. When negative, four step ribbons were cut at intervals of 250 microm. One section from each ribbon was stained with H&E, and one was used for immunohistochemistry (IHC). RESULTS: When taking the cumulative total of detected metastases at level 5 as 100%, the percentage of SN positive patients increased from 80%, 83%, 85%, 87% to 88% in the H&E sections through levels 1 to 5, and with IHC these values were 86%, 90%, 94%, 98%, and 100%. Three of nine patients in whom metastases were detected at levels 3-5 only had metastases in the subsequent axillary lymph node dissection. CONCLUSIONS: Multiple level sectioning of SNs (five levels at 250 microm intervals) and the use of IHC detects additional metastases up to the last level. Although more levels of sectioning might increase the yield even further, this protocol ensures a reasonable workload for the pathologist with an acceptable sensitivity when compared with the published literature.

The implementation of the sentinel node biopsy as a routine procedure for patients with breast cancer.

BACKGROUND: The sentinel node procedure for breast cancer allows for accurate staging of the axilla while the axillary node dissection can be avoided in patients with no sentinel node metastasis. This study describes those patients in whom an axillary dissection is performed, depending on the outcome of the sentinel node procedure, with particular emphasis on the use of strict criteria for the procedure and its practical limitations. METHODS: Preoperative lymphoscintigraphy was performed in 115 consecutive patients. The sentinel nodes were located with the use of a gamma probe and blue dye. Axillary dissection was performed at the same time when the sentinel node procedure was positive by frozen section or not successful by the criteria used. RESULTS: The sentinel node procedure was successful in 106 patients, with the sentinel node being both radioactive and blue in 94% of these patients. The frozen section was positive in 21 of 37 patients with sentinel node metastases. Axillary dissection could be avoided in 69 patients. CONCLUSIONS: The triple technique (with the use of lymphoscintigraphy, the gamma probe, and the blue dye) gives a high success rate of the sentinel node procedure, even when strict criteria for a successful sentinel node procedure are used. Palpation of the open axilla for metastatic nonsentinel nodes is advocated.

Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer.

AIMS: The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN. METHODS AND RESULTS: Seventy-four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1-2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty-one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not. CONCLUSIONS: Intraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.