Required distal mesorectal resection margin in partial mesorectal excision: a systematic review on distal mesorectal spread.

BACKGROUND: The required distal margin in partial mesorectal excision (PME) is controversial. The aim of this systematic review was to determine incidence and distance of distal mesorectal spread (DMS). METHODS: A systematic search was performed using PubMed, Embase and Google Scholar databases. Articles eligible for inclusion were studies reporting on the presence of distal mesorectal spread in patients with rectal cancer who underwent radical resection. RESULTS: Out of 2493 articles, 22 studies with a total of 1921 patients were included, of whom 340 underwent long-course neoadjuvant chemoradiotherapy (CRT). DMS was reported in 207 of 1921 (10.8%) specimens (1.2% in CRT group and 12.8% in non-CRT group), with specified distance of DMS relative to the tumor in 84 (40.6%) of the cases. Mean and median DMS were 20.2 and 20.0 mm, respectively. Distal margins of 40 mm and 30 mm would result in 10% and 32% residual tumor, respectively, which translates into 1% and 4% overall residual cancer risk given 11% incidence of DMS. The maximum reported DMS was 50 mm in 1 of 84 cases. In subgroup analysis, for T3, the mean DMS was 18.8 mm (range 8-40 mm) and 27.2 mm (range 10-40 mm) for T4 rectal cancer. CONCLUSIONS: DMS occurred in 11% of cases, with a maximum of 50 mm in less than 1% of the DMS cases. For PME, substantial overtreatment is present if a distal margin of 5 cm is routinely utilized. Prospective studies evaluating more limited margins based on high-quality preoperative magnetic resonance imaging and pathological assessment are required.

Variations in respiratory rate do not reflect changes in tidal volume or minute ventilation after major abdominal surgery.

Monitoring of postoperative pulmonary function usually includes respiratory rate and oxygen saturation measurements. We hypothesized that changes in postoperative respiratory rate do not correlate with changes in tidal volume or minute ventilation. In addition, we hypothesized that variability of minute ventilation and tidal volume is larger than variability of respiratory rate. Respiratory rate and changes in tidal volume and in minute ventilation were continuously measured in 27 patients during 24 h following elective abdominal surgery, using an impedance-based non-invasive respiratory volume monitor (ExSpiron, Respiratory Motion, Waltham, MA, US). Coefficients of variation were used as a measure for variability of respiratory rate, tidal volume and minute ventilation. Data of 38,149 measurements were analyzed. We found no correlation between respiratory rate and tidal volume or minute ventilation (r2 = 0.02 and 0.01). Mean respiratory rate increased within the first 24 h after abdominal surgery from 13.9 ± 2.5 to 16.2 ± 2.4 breaths/min (p = 0.008), while tidal volume and minute ventilation remained unchanged (p = 0.90 and p = 0.18). Of interest, variability of respiratory rate (0.21 ± 0.06) was significantly smaller than variability of tidal volume (0.37 ± 0.12, p < 0.001) and minute ventilation (0.41 ± 0.12, p < 0.001). Changes in postoperative respiratory rate do not allow conclusions about changes in tidal volume or minute ventilation. We suggest that postoperative alveolar hypoventilation may not be recognized by monitoring respiratory rate alone. Variability of respiratory rate is smaller than variability in tidal volume and minute ventilation, suggesting that adaptations of alveolar ventilation to metabolic needs may be predominately achieved by variations in tidal volume.

Locoregional recurrences after transanal total mesorectal excision of rectal cancer during implementation.

BACKGROUND: Transanal total mesorectal excision (TaTME) has been proposed as an approach in patients with mid and low rectal cancer. The TaTME procedure has been introduced in the Netherlands in a structured training pathway, including proctoring. This study evaluated the local recurrence rate during the implementation phase of TaTME. METHODS: Oncological outcomes of the first ten TaTME procedures in each of 12 participating centres were collected as part of an external audit of procedure implementation. Data collected from a cohort of patients treated over a prolonged period in four centres were also collected to analyse learning curve effects. The primary outcome was the presence of locoregional recurrence. RESULTS: The implementation cohort of 120 patients had a median follow up of 21·9 months. Short-term outcomes included a positive circumferential resection margin rate of 5·0 per cent and anastomotic leakage rate of 17 per cent. The overall local recurrence rate in the implementation cohort was 10·0 per cent (12 of 120), with a mean(s.d.) interval to recurrence of 15·2(7·0) months. Multifocal local recurrence was present in eight of 12 patients. In the prolonged cohort (266 patients), the overall recurrence rate was 5·6 per cent (4·0 per cent after excluding the first 10 procedures at each centre). CONCLUSION: TaTME was associated with a multifocal local recurrence rate that may be related to suboptimal execution rather than the technique itself. Prolonged proctoring, optimization of the technique to avoid spillage, and quality control is recommended.

ANTECEDENTES: La escisión total del mesorrecto por vía transanal (Transanal Total Mesorectal Excision, TaTME) se ha propuesto como abordaje quirúrgico en pacientes con cáncer de recto medio e inferior. La técnica TaTME se ha introducido en los Países Bajos mediante un proceso de formación estructurado que incluye la supervisión. Este estudio evaluó el porcentaje de recidiva local durante la fase de implementación de TaTME. MÉTODOS: Se recogieron los resultados oncológicos de los primeros 10 procedimientos realizados mediante TaTME en cada uno de los 12 centros participantes como parte de una auditoría externa de implementación del procedimiento. Se reunió una cohorte más amplia de pacientes procedentes de 4 centros para analizar los efectos de la curva de aprendizaje. El criterio de valoración principal fue la presencia de recidiva locorregional. RESULTADOS: La cohorte de implementación de 120 pacientes tuvo una mediana de seguimiento de 21,9 meses. Los resultados a corto plazo incluyeron una tasa del margen de resección circunferencial positivo del 5% y una tasa de fuga anastomótica del 17,4%. La tasa global de recidiva local en la cohorte de implementación fue del 10% (12/120) con un intervalo medio de recidiva de 15,2 (DE 7) meses. El patrón de recidiva local fue multifocal en 8 de 12 casos (67%). En la cohorte ampliada (n = 266), la tasa global de recidiva fue del 5,6% (4,0%, excluyendo a los primeros 10 pacientes). CONCLUSIÓN: TaTME se asoció con un porcentaje de recidiva local multifocal que puede relacionarse con una ejecución subóptima, más que con la técnica en sí. Se recomienda una supervisión prolongada, la optimización de la técnica para evitar la diseminación tumoral, así como un control de calidad.

Sentinel node staging in colon carcinoma: value of sentinel lymph node biopsy with radiocolloid and blue staining.

BACKGROUND: Nodal staging accuracy is important in the prognosis and selection of patients for chemotherapy. This prospective study aims to assess the feasibility and accuracy of the sentinel lymph node procedure (SNP) using radiocolloid and blue dye in colon carcinoma. METHODS: In 56 patients, lymphatic mapping was accomplished by means of intraoperatively injecting patent blue and nanocoll subserosally around the tumour. Sentinel nodes (SNs) were harvested ex-vivo. Nodes were stained with H&E. If lymph nodes were interpreted as negative for metastatic tumour, serial sectioning and immunohistochemical staining were performed. RESULTS: At least one SN was detected in 49 of 53 patients (92.5%). Three patients were excluded because of preoperatively detected metastases. Overall, 121 SN were harvested with a mean of 2.2 SN/patients. Eighteen patients had tumour positive nodes. In four patients, pathological nodes were palpable during operation and were excluded. The SN was histologically negative in 2 of 14 patients with positive nodes (false-negative rate 14.3%). In 5 of 14 patients with positive nodes, the SN was the exclusive site of regional nodal metastasis. Four patients were upstaged by immunohistochemical staining (28.6%). The negative predictive value was 93.9% and the overall accuracy 95.6%. Scintigraphy was done in 17 patients. In three patients the SN was detected only by this modality. DISCUSSION: The SN biopsy with the combined technique proved a feasible technique with a steep learning curve. It can change the initial staging from stage II to stage III colon carcinoma. Scintigraphy can improve the success rate of the technique.

Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects.

The discovery of bone morphogenetic proteins marks a major step forward in the understanding of bone physiology and in the development of advanced methods in skeletal surgery. The cornerstones for successful growth-factor therapy in skeletal surgery remain biomechanical stability and biological vitality of the bone providing an adequate environment for new bone formation. Knowledge of the biological characteristics, mechanisms of action, and methods of delivery of growth factors will become essential for skeletal surgeons. The current clinical application of bone morphogenetic proteins is safe and efficacious as a result of a well-regulated cascade of events leading to bone formation. Clinical trials have not yet determined whether different clinical indications each require a specific bone-tissue-engineering format or if a single pathway for stimulating bone-healing with growth factors is sufficient.

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture.

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.

The reliability of plain radiography in experimental fracture healing.

OBJECTIVE: To investigate the reliability of radiographs in the evaluation of healing of closed fractures. DESIGN: A closed midshaft tibial fracture was created in 40 goats and stabilized with an external fixator. The animals were assigned to four groups: no injection, injection of 1 mg osteogenic protein-1 (OP-1), 1 mg OP-1 with collagenous carrier, or carrier alone. Radiographs were performed weekly until the animals were killed after 2 and 4 weeks. Healing was evaluated using radiographs, biomechanical testing, and histological examination. All radiographs were examined by two independent observers. Interobserver agreement was calculated and radiographic scores were compared with mechanical and histological scores using regression analysis. RESULTS: Regression analysis showed poor correlation between radiographic scores and biomechanical and histological data. Correlation coefficients varied between 0.39 and 0.63. Good agreement between the observers was seen in only three parameters: visibility of the fracture line, weightbearing ability, and a combined healing parameter. CONCLUSION: Plain radiography provides poor parameters for monitoring the fracture healing process.

Biomechanical and histological aspects of fracture healing, stimulated with osteogenic protein-1.

Fracture healing could be stimulated with osteoinductive bone morphogenetic proteins (bmp's), such as osteogenic protein-1 (OP-1), but little is known about its effectiveness in stimulation of fracture healing. In this study, biomechanical and histological aspects of fracture healing after an injection of OP-1 in the fracture gap were investigated. In 40 goats, a closed fracture was created in the left tibia. The fractures were stabilized with an external fixator and the animals were assigned to four different groups: no injection, injection of 1 mg OP-1, injection of 1 mg OP-1 with collagenous carrier material, and injection of carrier material alone. Twenty-one animals were sacrificed after 2 weeks and 19 after 4 weeks. Biomechanical testing was perfomed on both explanted tibiae. Four longitudinal samples of the fracture were sawn, processed for histology, and examined by two observers. Biomechanical evaluation showed a higher stiffness and strength at 2 weeks after injection of OP-1. Histological evaluation showed normal fracture healing patterns in all animals without adverse effects of the given injections. These data show that fracture healing can be accelerated with a single injection of OP-1, eventually resulting in normally healed bone.

Evaluation of strength of healing fractures with dual energy Xray absorptiometry.

Dual energy xray absorptiometry was investigated as a method for evaluation of the strength of closed tibial fractures. In 40 goats, a closed midshaft fracture was created in the left tibia. The fractures were stabilized with an external fixator. After 2 weeks (n = 21) and after 4 weeks (n = 19), both tibias were explanted and, using dual energy xray absorptiometry, bone mineral density and bone mineral content were measured in a 1 cm region. With nondestructive bending tests, area ratio and stiffness index were determined and torsional strength and torsional stiffness were determined with a torsional test to failure. Linear regression analysis was used to calculate the squared correlation coefficients for the relations between dual energy xray absorptiometry and the outcome of the mechanical tests. The squared correlation coefficients for the relation between bone mineral density and torsional strength, torsional stiffness, and area ratio and stiffness index were 0.72, 0.76, 0.64, and 0.72, respectively. The squared correlation coefficients for the relation between bone mineral content and these mechanical parameters were 0.72, 0.77, 0.63, and 0.77, respectively. The results using dual energy xray absorptiometry indicate the strength of healing closed fractures. Additional research is required to investigate specific aspects of this technique.

Resorbable calcium phosphate particles as a carrier material for bone marrow in an ovine segmental defect.

Resorbable calcium phosphate ceramics are only osteoconductive; therefore, their combination with osteogenic substances may lead to stimulation of bone healing. In the present study this combination, using autologous bone marrow, was investigated. In 31 sheep, a 3-cm tibial segmental defect was created and stabilized with an intramedullary nail. The animals were divided into four groups: empty defects (group 1, n = 7), and defects filled with 10-mL dense resorbable calcium phosphate particles (group 2, n = 8), with 10-mL particles soaked in bone marrow (group 3, n = 8), or with 10-mL autologous bone (group 4, n = 8). On evaluation after 12 weeks, significantly higher values were seen in group 3 than in group 2 for callus volume (p = .016), bone mineral density ratio (p = .03), bone mineral content ratio (p = .04), torsional strength (p = .005), and torsional stiffness (p = .01). For all end points, the outcome of group 3 was lower than that of group 4. In the histology, there was direct contact between newly formed bone and remnants of the particles. There were no signs of inflammatory reactions. Although a stimulatory effect of bone marrow was seen, the combination of resorbable calcium phosphate particles with bone marrow does not provide an alternative for autologous bone grafting.

New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy x-ray absorptiometry.

An appropriate animal model is required for the study of treatments that enhance bone healing. A new segmental long bone defect model was developed for this purpose, and dual energy x-ray absorptiometry was used to quantify healing of this bone defect. In 15 sheep, a 3-cm segmental defect was created in the left tibia and fixed with an interlocking intramedullary nail. In seven animals, the defect was left empty for the assessment of the spontaneous healing response. In eight animals serving as a positive control, autologous bone grafting was performed. After 12 weeks, healing was evaluated with radiographs, a torsional test to failure, and dual energy x-ray absorptiometry. The mechanical test results were used for the assessment of unions and nonunions. Radiographic determination of nonunion was not reliably accomplished in this model. By means of dual energy x-ray absorptiometry, bone mineral density and content were measured in the middle of the defect. Bone mineral density was 91+/-7% (mean +/- SEM) and 72+/-6% that of the contralateral intact tibia in, respectively, the autologous bone-grafting and empty defect groups (p = 0.04). For bone mineral content, the values were, respectively, 117+/-18 and 82+/-9% (p = 0.07). Torsional strength and stiffness were also higher, although not significantly, in the group with autologous bone grafting than in that with the empty defect. Bone mineral density and content were closely related to the torsional properties (r2 ranged from 0.76 to 0.85, p < or = 0.0001). Because interlocking intramedullary nailing is a very common fixation method in patients, the newly developed segmental defect model has clinical relevance. The interlocking intramedullary nail provided adequate stability without implant failure. This model may be useful for the study of treatments that affect bone healing, and dual energy x-ray absorptiometry may be somewhat helpful in the analysis of healing of this bone defect.

The influence of hydroxyapatite granules on the healing of a segmental defect filled with autologous bone marrow.

Hydroxyapatite(HA) ceramics are frequently used as a bone graft substitutes for the filling of bony defects. The addition of autologous bone marrow to HA ceramics does improve defect healing. There is conflicting evidence in the literature whether autologous bone marrow transplantation alone is as effective as the combination of HA ceramics and bone marrow combined. It was the purpose of this study to identify the role of additional HA ceramic granules on the healing of a sheep tibia segmental defect filled with autologous bone marrow. After permission of the local animal rights committee was obtained, a 3 cm segmental defect in the midshaft of 31 adult sheep was stabilized with an unreamed tibia nail. The animals were divided into 4 groups according to the mode of defect filling: HA plus autologous bone marrow (HA + MAR) (n = 8), autologous bone marrow (MAR) (n = 9), empty defect (DEF) (n = 6), cancellous bone graft (CAN) (n = 8). After three months follow up animals were sacrificed and analysed for the key parameters of union and maximum torque at failure. One nonunion was present in each of the HA + MAR, MAR, and CAN groups. Four of the six animals in the DEF group developed a nonunion. Maximum torque at failure was reported as percentage of the intact contralateral tibia: HA + MAR 39% +/- 24%, MAR 26% +/- 17%, DEF 22% +/- 13%, CAN 41% +/- 20%. The difference between the groups was statistically significant, but appeared to be relevant. We conclude from our data, that HA ceramics do improve healing of a segmental defect in the sheep tibia filled with autologous bone marrow. The results of this combination are comparable to cancellous autograft.

Quantification of fracture healing with three-dimensional computed tomography.

Quantitative methods are necessary for an objective evaluation of fracture healing. Three-dimensional computed tomography (CT) for the measurement of callus volume and density could be such a method and was investigated in an animal model. In 23 goats a closed tibial fracture was created and stabilized with a cast. The animals were killed at 2, 4 and 6 weeks for radiographical, CT and biomechanical analysis. From the CT scans a three-dimensional reconstruction of the callus was made to measure its volume and mean density. At 2 weeks the callus volume had already reached its maximum. In contrast, callus density, torsional strength and torsional stiffness increased over time (P < 0.0001, analysis of variance, ANOVA). Multiple regression analysis showed that the callus volume was not related to the torsional properties. However, callus density was a significant explanatory variable for both torsional strength (R2 = 0.72, P < 0.0001) and torsional stiffness (R2 = 0.82, P < 0.0001). Therefore, callus density as measured by three-dimensional CT is a predictor of the extent of fracture consolidation. CT with three-dimensional reconstruction of the callus seems a valid technique for the quantification of fracture healing.