Molecular analysis of sentinel lymph nodes in patients with breast cancer using one-step nucleic acid amplification (OSNA): Does not lead to overtreatment in the current era of de-escalating axillary management.

PURPOSE: OSNA is a molecular technique for sentinel lymph node (SN) analysis in breast cancer. Compared to histology, OSNA may yield more (micro)metastases and thereby result in more axillary lymph node dissections or radiotherapy. We investigated whether axillary treatments increase when using OSNA, applying current guidelines for de-escalating axillary management. METHODS: All patients treated for cT1-3N0 breast cancer in our hospital between December 2013 and February 2016 were included. In 148 prospectively included patients (January 2015-February 2016), SN's were examined with OSNA. In a retrospective cohort of 123 patients (December 2013-December 2014), SN's were examined with conventional histology. Outcomes were: number of macro and micrometastases, amount of patients receiving axillary dissection or irradiation, number of patients receiving adjuvant systemic therapy. Data were analyzed using Mann-Whitney and Pearson Chi-square test. P < 0.05 was considered statistically significant. RESULTS: 230 SN's from 123 patients were examined with conventional histology. 229 SN's from 148 patients were evaluated with OSNA. Amount of macrometastases was equal between groups (histology 17.9% versus OSNA 16.2%, p = 0.715). We found significantly more micrometastases when using OSNA (histology 11.4% versus OSNA 25.0%, p = 0.004). Total number of axillary lymph node dissections was comparable in both groups (histology 12.2%, OSNA 12.2%, p = 0.993), as well as number of axillary radiations (histology 8.9%, OSNA 11.5%, p = 0.493). Also, the number of patients receiving adjuvant systemic therapy was similar between conventional histology and OSNA (histology 53.7% versus OSNA 58.1%, p = 0.462). CONCLUSION: OSNA analysis for SN in breast cancer is a highly sensitive technique, detecting more micrometastases than standard histology. When applying current guidelines, OSNA analysis does not lead to overtreatment with more axillary dissections or irradiation.

Is young age a risk factor for chronic postoperative inguinal pain after endoscopic totally extraperitoneal (TEP) repair?

PURPOSE: A generally known risk factor for developing chronic postoperative inguinal pain after inguinal hernia repair is young age. However, studies discussing young age as a risk factor are mainly based on open repairs. The aim of this study was to determine if young adults (age 18-30) are also more prone to experience chronic postoperative inguinal pain after totally extraperitoneal (TEP) inguinal hernia repair, compared to older adults (age ≥ 31). METHODS: A prospective study was conducted in a high-volume TEP hernia clinic in 919 patients. Patients were assessed using the Numeric (Pain) Rating Scale, Inguinal Pain Questionnaire and Carolina Comfort Scale preoperatively, at 3 months, 1 year and 2 years after TEP mesh repair. The primary outcome was clinically relevant pain in young adults compared to older adults at 3 months follow-up. Secondary outcomes were pain 1 and 2 years postoperatively, the impact of pain on daily living, foreign body feeling and testicular pain. Furthermore, age categories were analyzed to determine potential age-dependent risk factors. RESULTS: Follow-up was completed in 867 patients. No significant difference was found between young adults and older adults for clinically relevant pain at 3 months follow-up (p = 0.723). At all follow-up time points, no significant differences were found for clinically relevant pain, any pain, mean pain scores, the Inguinal Pain Questionnaire and the Carolina Comfort Scale. The subgroup analyses showed no age-dependent risk factor. CONCLUSIONS: Young age is not associated with a higher risk of chronic postoperative inguinal pain after endoscopic TEP hernia repair.

Pain after totally extraperitoneal (TEP) hernia repair might fade out within a year.

BACKGROUND: The incidence of chronic pain after endoscopic hernia repair varies between 1 and 16 %. Studies regarding the course of pain in time after the operation are scarce. METHODS: 473 male patients ≥18 years of age, scheduled for totally extraperitoneal (TEP) hernia repair (Prolene® mesh) between March 2010 and August 2012 were requested to record pain symptoms preoperative, and 1 day, 1 week, 6 weeks, 3 months and 1 year postoperatively and visit the outpatient department 3 months and 1 year postoperatively for a standardized interview and physical examination. RESULTS: Preoperatively, 25 % (n = 114) of the patients had moderate-to-severe pain (NRS 4-10). Six weeks postoperatively, 3 % (n = 12) of the patients still experienced moderate-to-severe pain. Three months after TEP, only 3 patients (0.6 %) had moderate-to-severe pain, while 83 patients (18 %) experienced mild pain. One year after TEP, 39 patients experienced mild pain (8 %) and 3 patients moderate pain (0.7 %), no patients experienced severe pain after 1 year. Patients with moderate-to-severe pain preoperatively had a higher risk of pain persisting until 3 months and 1 year postoperatively (p = 0.03). In most patients who had pain 3 months postoperatively and were pain-free 1 year after TEP, pain 'faded out' at 4-6 months postoperatively. Two patients had a not-painful recurrent hernia, diagnosed 2 and 5 months after TEP repair. CONCLUSION: Moderate-to-severe pain after TEP hernia repair is self-limiting, with less than 1 % of the patients reporting moderate pain 1 year postoperatively.

Three-month results of the effect of Ultrapro or Prolene mesh on post-operative pain and well-being following endoscopic totally extraperitoneal hernia repair (TULP trial).

BACKGROUND: Recurrence rates after inguinal hernia repair have been reduced to a few per cent, since mesh repair has become standard of care. Lightweight meshes reduce post-operative pain and stiffness in open anterior repair, but for endoscopic repair, the discussion about this benefit is ongoing. This study was done to analyse the effects of lightweight mesh versus heavyweight mesh following endoscopic totally extraperitoneal (TEP) hernia repair. METHODS: In a single-centre double-blindly randomized clinical trial, 950 patients with unilateral primary inguinal hernia were randomized to undergo endoscopic TEP using either an Ultrapro(®) or a Prolene(®) mesh. Data were collected by validated questionnaires at day 1, day 7, after 6 weeks and after 3 months, and clinical assessment was performed after 3 months. The presence of groin pain after 3 months, defined as an NRS score >3, was evaluated as the primary outcome measure. Secondary outcomes were foreign body feeling and the impact of pain and foreign body feeling on daily activities. RESULTS: At 3-month follow-up, the incidence of pain (NRS 4-10) was 2 versus 0.9 % in the lightweight and heavyweight mesh group, respectively (p = 0.17). Pain interfered with daily activities in 1.7 % of the lightweight and 1.5 % of heavyweight group. In the lightweight group, 20 % of patients reported a foreign body feeling versus 18 % in the heavyweight group (p = 0.62). No differences between the groups were observed regarding time to return to work, interference with sports and sexual activities, testicular pain and ejaculatory pain. Severe preoperative pain (OR 2.01, 95 % CI 1.21-3.35, p = 0.01) was the only independent predictor of any post-operative pain after 3 months. CONCLUSION: Three months after TEP inguinal repair, there were no significant differences between lightweight and heavyweight mesh use regarding the incidence of pain, foreign body feeling or any other endpoint.

One-stop endoscopic hernia surgery: efficient and satisfactory.

BACKGROUND: One-stop surgery offers patients diagnostic work-up and subsequent surgical treatment on the same day. In the present study, patient satisfaction and efficiency from an institutional perspective were evaluated in patients who were referred for one-stop endoscopic inguinal hernia repair. METHOD: In a high-volume inguinal hernia clinic, all consecutive patients referred for one-stop surgical treatment, were registered prospectively. An instructed secretary screened patients for eligibility for the one-stop option when the appointment was made. Totally extraperitoneal hernia repair under general anaesthesia was the preferred operative technique. Patient's satisfaction, successful day surgery and institutional efficiency were evaluated. RESULTS: Between January 2010 and January 2012 a total of 349 patients (17 % of all patients in the hernia clinic) were referred for one-stop hernia repair. Mean age was 47.5 years and 96.3 % were males. Three hundred thirty-six patients underwent hernia surgery on the same day (96.3 %). In thirteen patients (3.7 %) no operative repair was done on the day of presentation due to an incorrect diagnosis (n = 7), a watchful waiting policy for asymptomatic hernia (n = 3), rescheduling due to a large scrotal hernia, and there were two "no shows". Following hernia repair 97 % of the patients were discharged on the same day, while ten patients required hospitalization. Based on the questionnaires the main satisfaction score among patients was 9.0 (8.89-9.17 95 % CI) on a scale ranging from 0 to 10. CONCLUSION: One-stop hernia surgery is feasible and satisfactory from an institutional as well as from a patient's perspective.

Is there an end of the "learning curve" of endoscopic totally extraperitoneal (TEP) hernia repair?

BACKGROUND: An important challenge of totally extraperitoneal (TEP) hernia repair is the learning curve. The European guidelines suggest that the learning curve ranges between 50 and 100 procedures, with the first 30-50 being critical. Others suggest that optimal outcomes are achieved after 200 or more TEP procedures. METHODS: All TEP repairs performed between 2005 and 2009 were included in this study. The effect of (surgeon) expertise on perioperative complications, conversion to open anterior repair, and operative time was assessed to evaluate the extent of the learning curve of TEP repair. RESULTS: Intraoperative complications occurred in <1 % of the 3,432 patients and postoperative complications were observed in 243 (7 %) patients. With a median follow-up of 2 years after TEP, 19 patients (0.55 %) had a recurrence. During the study period, at the end of which all four surgeons had treated 900-1,000 patients, intraoperative complications and recurrences did not decline. On the other hand, the median operative time decreased from 30 to 20 min (p < 0.001). The conversion rate (1.6-0.2 %, p = 0.018) and postoperative complication rate (11.6-4.2 %, p < 0.001) also declined. The decline was observed for all four surgeons, irrespective of their initial expertise with TEP. The largest decrease in the conversion rate was seen after at least 250 TEP procedures; the postoperative complication rate and operative time showed a linear and significant decline throughout the study period. A more or less "steady state" was observed after approximately 450 procedures per surgeon. CONCLUSIONS: Even after more than 400 individually performed TEP procedures, there is progress in reducing the conversion rate, the incidence of short-term postoperative complications, and operative time, indicating a rather long learning curve.

Selecting patients during the "learning curve" of endoscopic Totally Extraperitoneal (TEP) hernia repair.

BACKGROUND: Totally Extraperitoneal (TEP) hernia surgery is associated with little postoperative pain and a fast recovery, but is a technically demanding operative procedure. Apart from the surgeon's expertise, patient characteristics and hernia-related variations may also affect the operative time and outcome. METHODS: Patient-related factors predictive of perioperative complications, conversion to open anterior repair, and operative time were studied in a cohort of consecutive patients undergoing TEP hernia repair from 2005 to 2009. RESULTS: A total of 3,432 patients underwent TEP. The mean operative time was 26 min (SD ± 10.9), TEP was converted into an open anterior approach in 26 patients (0.8 %), and perioperative complications were observed in 55 (1.6 %) patients. Multivariable regression analysis showed that a history of abdominal surgery (OR 1.76, 95 per cent confidence interval 1.01-3.06; p = 0.05), and the presence of a scrotal (OR 5.31, 1.20-23.43; p = 0.03) or bilateral hernia (OR 2.25, 1.25-4.06; p = 0.01) were independent predictive factors of perioperative complications. Female gender (OR 5.30. 1.52-18.45; p = 0.01), a history of abdominal surgery (OR 3.96, 1.72- 9.12; p = 0.001), and the presence of a scrotal hernia (OR 34.84, 10.42-116.51, p < 0.001) were predictive factors for conversion. A BMI ≥ 25 (effect size (ES) 1.78, 95 % confidence interval 1.09-2.47; p < 0.001) and the presence of a scrotal (ES 5.81, 1.93-9.68; p = 0.003), indirect (ES 2.78, 2.05- 3.50, p < 0.001) or bilateral hernia (ES 10.19, 9.20-11.08; p < 0.001) were associated with a longer operative time. CONCLUSION: Certain patient characteristics are, even in experienced TEP surgeons, associated with an increased risk of conversion and complications and a longer operative time. For the surgeon gaining experience with TEP, it seems advisable to select relatively young and slender male patients with a unilateral (non-scrotal) hernia and no previous abdominal surgery to enhance patient safety and 'surgeon comfort'.

Female 'groin' hernia: totally extraperitoneal (TEP) endoscopic repair seems the most appropriate treatment modality.

BACKGROUND: About 30% of all female 'groin' hernias are femoral hernias, although often only diagnosed during surgery. A Lichtenstein repair though, as preferred treatment modality according to guidelines, would not diagnose and treat femoral hernias. Totally extraperitoneal (TEP) hernia repair, however, offers the advantage of being an appropriate modality for the diagnosis and subsequent treatment of both inguinal and femoral hernias. TEP therefore seems an appealing surgical technique for women with groin hernias. METHODS: This study included all female patients ≥ 18 years operated for a groin hernia between 2005 and 2009. RESULTS: A total of 183 groin hernias were repaired in 164 women. TEP was performed in 85% of women; the other 24 women underwent an open anterior (mesh) repair. Peroperatively, femoral hernias were observed in 23% of patients with primary hernias and 35% of patients with recurrent hernias. There were 30 cases (18.3%) of an incorrect preoperative diagnosis. Peroperatively, femoral hernias were observed in 17.3% of women who were diagnosed with an inguinal hernia before surgery. In addition, inguinal hernias were found in 24.0% of women who were diagnosed with a femoral hernia preoperatively. After a follow-up of 25 months, moderate to severe (VAS 4-10) postoperative pain was reported by 8 of 125 patients (6.4%) after TEP and 5 of 23 patients (21.7%) after open hernia repair (P = 0.03). Five patients had a recurrent hernia, two following TEP (1.4%) and three following open anterior repair (12.5%, P = 0.02). Two of these three patients presented with a femoral recurrence after a previous repair of an inguinal hernia. CONCLUSION: Femoral hernias are common in women with groin hernias, but not always detected preoperatively; this argues for the use of a preperitoneal approach. TEP hernia repair combines the advantage of a peroperative diagnosis and subsequent appropriate treatment with the known good clinical outcomes.

Impairment of sexual activity before and after endoscopic totally extraperitoneal (TEP) hernia repair.

BACKGROUND: In patients with inguinal hernias, sexual activity may be impaired due to hernia-related pain. Surgical repair may improve these complaints but can also lead to similar symptoms as a long-term complication of the operation. Endoscopic hernia repair is associated with less postoperative pain and earlier return to normal activities, but its effect on pain-related sexual function is unknown. In this study, the incidence and effect of pain related to sexual activity are evaluated before and after endoscopic totally extraperitoneal (TEP) hernia repair. METHODS: A hospital-based questionnaire study of pain-related sexual dysfunction was conducted in November 2009 in 500 male patients ≥18 years, who underwent TEP repair of a primary hernia between March 2006 and December 2008. The response rate was 77.2%. RESULTS: Pain of any severity during sexual activity was reported by 124 patients (32.1%) preoperatively and 35 patients (9.1%) postoperatively. Only 2.3% of the 262 patients with no history of preoperative pain experienced moderate to severe (VAS 4-10) pain postoperatively. Pain impaired sexual function in 63 patients (16.3%) preoperatively and in 18 patients (4.7%) postoperatively. The majority of patients who reported pain during sexual activity preoperatively (n = 102, 82.3%) had no pain postoperatively. The frequency of moderate to severe painful sexual activity decreased from 21.2% (preoperatively) to 3.4% after TEP repair (P < 0.001), and the frequency of moderate to severely impaired sexual function decreased from 6.0 to 1.0% (P < 0.001). The preoperative presence of pain during sexual activity and chronic non-hernia-related pain syndromes were predictive for the occurrence of postoperative pain. CONCLUSION: Painful sexual activity, present in one third of patients with inguinal hernias, improved in the majority of patients following TEP hernia repair. Postoperatively, moderate to severe painful sexual activity occurred in 2.3% of the patients with no history of preoperative complaints.

A comparison between 1.36% and 3.86% glucose dialysis solution for the assessment of peritoneal membrane function.

OBJECTIVE: To assess peritoneal membrane function with respect to fluid transport, parameters of low molecular weight solute transport, and estimations of the function of peritoneal water channels, comparing the results from a 1.36%/1.5% glucose solution with those from a 3.86%/4.25% solution in standardized peritoneal function tests. DESIGN: The study was performed in 40 stable continuous ambulatory peritoneal dialysis (CAPD) patients [median age 50 years (range: 22-74 years); duration of CAPD 9 months (range: 2-45 months)] who underwent two standard peritoneal permeability analyses (SPAs) within 1 month. One SPA used 1.36% glucose; the other, 3.86% glucose. Mass transfer area coefficients (MTACs) and dialysate-to-plasma (D/P) ratios were compared for the two solutions. Also, two different methods of estimating aquaporin-mediated water transport were compared: the sieving of sodium (3.86% glucose) and the difference in net ultrafiltration (deltaNUF), calculated as NUF 3.86% SPA - NUF 1.36% SPA. RESULTS: Median NUF in the 1.36% glucose SPA was -46 mL (range: -582 mL to 238 mL); in the 3.86% SPA, it was 554 mL (range: -274 mL to 1126 mL). The median difference in NUF for the two SPAs was 597 mL (range: 90-1320 mL). No difference between the two solutions was seen for the MTAC of creatinine (11.4 mL/min for 1.36% vs 12.0 mL/min for 3.86%) and absorption of glucose (64% vs 65%, respectively). Also, D/P creatinine was not different: 0.77 (1.36%) and 0.78 (3.86%). However, the ratio of dialysate glucose at 240 minutes and at 0 minutes (Dt/D0) was 0.34 (1.36%) and 0.24 (3.86%), p < 0.01. Values of D/P creatinine from the two glucose solutions were strongly correlated. The intra-individual differences were small and showed a random distribution. Patient transport category was minimally influenced by the tonicity of the dialysate. The minimum D/P Na+ (3.86%) was 0.884, and it was reached after 60 minutes. After correction for Na+ diffusion, D/P Na+ decreased to 0.849 after 120 minutes. The correlation coefficient between the diffusion-corrected D/P Na+ and the deltaNUF was 0.49, p < 0.01. An inverse relationship was present between MTAC creatinine and D/P Na+ (p < 0.01) This correlation can be explained by the rapid disappearance of the osmotic gradient owing to a large vascular surface area. Such a correlation was not present between MTAC creatinine and deltaNUF. CONCLUSIONS: We conclude that a standardized 4-hour peritoneal permeability test using 3.86%/4.25% glucose is the preferred method to assess peritoneal membrane function, including aquaporin-mediated water transport. The D/P Na+ after correction for Na+ diffusion is probably more useful for the assessment of aquaporin-mediated water transport than is deltaNUF obtained with 3.86%/4.25% and 1.36%/1.5% glucose-based dialysis solutions.

Peritoneal transport characteristics with glucose polymer based dialysate.

Dialysate fluids containing glucose polymers as osmotic agent are different from the conventional solutions, because they are iso-osmotic to plasma and produce transcapillary ultrafiltration (TCUF) by colloid osmosis. To investigate the effects on fluid and solute kinetics, a comparison was made between a 7.5% glucose polymer based dialysate (icodextrin) and 1.36% and 3.86% glucose based dialysate in 10 stable CAPD patients. In each patient three standard peritoneal permeability analyses (SPA) were done with the osmotic agents and concentrations mentioned above. Dextran 70 was added to the glucose solutions to calculate fluid kinetics. In the glucose polymer SPAs fluid kinetics were calculated from the dilution and disappearance of dextrin. The TCUF rate with icodextrin was closer to that obtained with 3.86% glucose than to 1.36% glucose. Extrapolation of the fluid profiles revealed sustained ultrafiltration with icodextrin. TCUF increased linearly in time in the icodextrin tests, whereas a hyperbola best described the glucose profiles. The effective lymphatic absorption rate with icodextrin was similar to the glucose based solutions. Mass transfer area coefficients of low molecular weight solutes with icodextrin were also similar to the values obtained with glucose, as was D/P creatinine. A positive correlation was present between the MTAC creatinine and the TCUF rate with icodextrin (r = 0.66, P = 0.05), which was absent in the glucose SPAs. This suggests that in patients with a larger effective peritoneal surface area, more ultrafiltration can be achieved by glucose polymer solutions. Clearances of beta 2-microglobulin (beta 2m) were higher with icodextrin than with 3.86% glucose and 1.36% glucose dialysate (P < 0.05). No differences were found for the larger serum proteins albumin, IgG and alpha 2-macroglobulin. Initial D/PNa-->was higher (0.96) with icodextrin than with the glucose based solutions (0.92), due to the higher Na+ concentration of icodextrin, and it remained unchanged during the dwell. In contrast, D/PNa+ of 1.36% glucose increased during the dwell, whereas D/PNa+ decreased with 3.86% glucose until 60 minutes, followed by a subsequent increase. The ultrafiltration coefficient (UFC) of the total peritoneal membrane was assessed using 3.86% glucose (0.18 +/- 0.04 ml/min/mm Hg), and the UFC of the small pores was assessed using icodextrin (0.06 +/- 0.008 ml/min/mm Hg). The difference between these represented the UFC through the transcellular pores, which averaged 50.5% of the total UFC, but with a very wide range (0 to 85%). An inverse relation existed between the duration of CAPD treatment and the total ultrafiltration coefficient (r = -0.68, P < 0.04), which could be attributed to a lower UFC of the transcellular pores in long-term patients (r = -0.66, P < 0.05), but not to the UFC of the small pores (r = -0.48, NS). The TCUFRo-60 min through the transcellular pores correlated with the sodium gradient, corrected for diffusion, in the first hour of the dwell (r = 0.69, P < 0.04), indicating that both parameters indeed measure transcellular water transport. It can be concluded that the glucose polymer solution induced sustained ultrafiltration and had no effect on peritoneal membrane characteristics. In addition, the results of the present study support the hypothesis that the glucose polymer solutions exerts its osmotic pressure across intercellular pores with radii of about 40 A. This leads to increased clearances of low molecular weight proteins such as beta 2m that are transported through these pores without sieving of Na+. The latter, as found during 3.86% glucose dialysate, is probably caused by transcellular water transport. The transcellular water transport accounted for 50% of the total ultrafiltration with glucose based dialysis solutions. It was lower in long-term CAPD patients.

The standard peritoneal permeability analysis: a tool for the assessment of peritoneal permeability characteristics in CAPD patients.

Peritoneal transport characteristics in CAPD patients are often assessed by the peritoneal equilibration test (PET), which uses a four hour dwell with glucose 2.27% dialysate. From the test, the dialysate/plasma ratio of creatinine (D/PCr), the dialysate/initial dialysate ratio of glucose (D/Do) and net ultrafiltration (NUF, drained minus instilled volume) are calculated. The standard peritoneal permeability analysis (SPA) is a modification and extension of the PET: glucose 1.36% dialysate is used, to which dextran 70 (1 g/liter) is added for the calculation of fluid kinetics. Mass transfer area coefficients (MTAC's) of low molecular weight solutes, clearances of proteins and the change in intraperitoneal volume (delta IPV) can be assessed. In this study the SPA was analyzed, and a comparison with the PET was made. A total number of 138 SPA's was analyzed in 86 different clinically stable patients. Normal values were calculated for both SPA and PET parameters in the same tests. Median (ranges) of comparable transport parameters from SPA and PET were: MTACCr, 10.4 ml/min (5.7 to 19.3); glucose absorption, 61% (35 to 87); delta IPV, 9.5 ml (-761 to 310); D/PCr, 0.76 (0.53 to 1.14); D/D0, 0.37 (0.13 to 0.56); NUF, -75 ml (-675 to 450). The agreement between SPA and PET was analyzed using the method of Bland and Altman. A fairly good agreement was present between NUF and delta IPV. Systematic errors were found when D/PCr and MTACCr were compared: D/P overestimated MTAC mainly in the low range, whereas in the high range values were underestimated. A similar pattern was seen for the transport parameters of glucose. In 40 patients negative net ultrafiltration was present, and possible reasons for this were assessed. In 9 patients no reason could be identified. It can be concluded that the SPA provides useful and extensive information on peritoneal transport parameters. Compared to the PET, the SPA has better discriminative power for the transport of glucose and creatinine.