Results of surgery for perforated gastroduodenal ulcers in a Dutch population.

OBJECTIVE: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment. PATIENTS AND METHODS: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality. RESULTS: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class. CONCLUSIONS: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment.

Intra-operative parathyroid hormone measurements - experience of a non-academic hospital.

BACKGROUND: Surgery is the treatment of choice for symptomatic primary hyperparathyroidism. The majority of research concerning intra-operative parathyroid hormone (ioPTH) measurements is conducted in university hospitals. Whether ioPTH measurements are feasible and useful in predicting the presence of remaining hyperfunctioning parathyroid tissue in a non-academic hospital remains uncertain. METHODS: Data were collected on all patients with biochemically proven and surgically treated primary hyperparathyroidism treated at the Reinier de Graaf Hospital from August 2002 to December 2007. RESULTS: Sixty-five patients were included. The mean pre-operative serum calcium level was 2.78 mmol/l (range 2.28 - 3.80 mmol/l, normal range 2.20 - 2.65 mmol/l) and the mean serum parathyroid hormone level 17.0 pmol/l (range 4.0 - 90.3 pmol/l, normal range 1.0 - 5.5 pmol/l). All patients were operated on for primary hyperparathyroidism, using ioPTH measurements during their first operation. Sensitivity and specificity rates of ioPTH measurements were 98% and 89%, respectively. The ioPTH test accurately indicated incomplete removal of all hyperfunctioning parathyroid tissue in 8 patients (12%). Five patients (8%) were re-explored immediately, of whom 4 were successfully treated in this single operative session. One patient was operated on successfully the next day. Two patients were operated on with a successful result during a second admission. In all the ioPTH measurements there was 1 false-positive result (1.5%) and 1 false-negative result (1.5%). The mean postoperative calcium value for the successfully treated patients was 2.34 mmol/l (range 2.14 - 2.71 mmol/l, normal range 2.20 - 2.65 mmol/l). The mean postoperative PTH level for the successfully treated patients was 3.76 pmol/l (range 0.40 - 7.1 pmol/l). CONCLUSION: Our data suggest that ioPTH measurements are feasible and useful in a non-academic hospital.

Surgeon-performed ultrasound as preoperative localization study in patients with primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy is the treatment of choice for single-gland primary hyperparathyroidism. However, the exact location of the abnormal gland has to be established. Sestamibi scintigraphy, computed tomography and ultrasound (US) are commonly used modalities. We describe our experience in a non-academic center with surgeon-performed US (S-US) of the neck as preoperative localization study in patients with primary hyperparathyroidism (PHPT). METHODS: Patients with a biochemically proven diagnosis of PHPT and preoperative S-US were included. Data were recorded prospectively. Perioperative gland location was compared to the preoperative S-US to determine sensitivity, specificity and accuracy rates. RESULTS: Two of the 50 patients who underwent S-US were not subjected to surgery. In 85% of the patients analyzed by S-US, the appropriate abnormal gland(s) were identified. In 11%, no gland was identified, but abnormal glands were found during surgery. Sensitivity of S-US in our hospital is 85%, with a positive predictive value of 97%. CONCLUSIONS: We achieved a satisfactory sensitivity rate. S-US provides anatomic information to the surgeon which enables a more detailed operation planning, and it is a valuable diagnostic modality for patients with PHPT in our opinion. We hope that our data encourage other centers to implement this technique as well.

Validation of 70-gene prognosis signature in node-negative breast cancer.

PURPOSE: The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530-536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. METHODS: We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). RESULTS: The 5-year OS was 82 +/- 5% in poor (48%) and 97 +/- 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P = 0.021). The 5-years DMFP was 78 +/- 6% in poor and 98 +/- 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 +/- 5% and 94 +/- 3% (HR 10.7; 95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 +/- 6% in poor and 86 +/- 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. CONCLUSION: The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.

Helicobacter genotyping and detection in peroperative lavage fluid in patients with perforated peptic ulcer.

INTRODUCTION AND OBJECTIVES: Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are present in patients with PPU and which genotype is dominant in this population. The secondary aim was to study the possibility of determining the H. pylori status in a way other than by biopsy. MATERIALS AND METHODS: Serum samples, gastric tissue biopsies, lavage fluid, and fluid from the nasogastric tube were collected from patients operated upon for PPU. By means of PCR, DEIA, and LIPA the presence of the "cytotoxin associated gene" (cagA) and the genotype of the "vacuolating cytotoxin gene" were determined. RESULTS: Fluid from the nasogastric tube was obtained from 25 patients, lavage fluid from 26 patients, serum samples from 20 patients and biopsies from 18 patients. Several genotypes were found, of which the vacA s1 cagA positive strains were predominant. Additionally, a correlation was found between the H. pylori presence in biopsy and its presence in lavage fluid (p=0.015), rendering the latter as an alternative for biopsy. Sensitivity and specificity of lavage fluid analysis were 100% and 67%, respectively. CONCLUSION: This study shows the vacA s1 cagA positive strain is predominant in a PPU population. The correlation found between the H. pylori presence in biopsy and its presence in lavage fluid suggests that analysis of the lavage fluid is sufficient to determine the H. pylori presence. Risks associated with biopsy taking may be avoided.

[Abscess formation due to lost stones during laparoscopic cholecystectomy]. / Abcesvorming door verloren stenen bij een laparoscopische cholecystectomie.

Two women aged 79 and 69 years presented with abdominal pain at 15 and 38 months respectively after a laparoscopic cholecystectomy. In both cases perforation of the gallbladder had occurred with spillage of bile and gallstones. A CT-scan carried out at presentation showed signs of an abdominal abscess. The origin of the abscess was initially unknown. The first patient was operated on immediately. In the second patient a drain was placed in the abscess under ultrasound guidance. During operation gallstones were seen in the abscess cavity in both patients. Both patients recovered well. Although perforation of the gallbladder with spillage of gallstones during laparoscopic cholecystectomy often occurs, the incidence of major postoperative complications is low. However, in some cases reoperation is necessary. Removal of all spilled stones is therefore indicated to prevent complications. If abdominal symptoms persist after laparoscopic cholecystectomy, an abscess due to spilled gallstones should be considered. Ultra-sound or CT are the most sensitive means of for tracing spilled gallstones or abscesses.

[Very slight chance of other metastases in axillary nodes of breast cancer patients with a small sentinel node metastasis without extranodal tumor growth]. / Zeer geringe kans op andere kliermetastasen in de oksel bij borstkankerpatiënten met een kleine schildwachtkliermetastase zonder extranodale tumorgroei.

OBJECTIVE: To determine in patients with mammary carcinoma and a sentinel node metastasis whether pathological parameters of the sentinel node metastasis and the primary tumour might have predictive value with respect to the presence of metastases in other axillary nodes. DESIGN: Prospective. METHOD: The study group consisted of the first 100 consecutive patients with a sentinel node metastasis, who subsequently underwent a complete axillary dissection. The patients with metastases in the non-sentinel nodes were compared to those without such metastases regarding the size of the largest sentinel node metastasis and the presence of extranodal tissue invasion near any such node, and size, and type of the primary tumour. RESULTS: The median size of the metastases in the sentinel lymph node in the two groups was 3 mm versus 13 mm respectively (p < 0.001) and the frequency of extranodal tissue invasion 3% versus 74% respectively (p < 0.001); the combination of these factors strongly predicted the presence of non-sentinel lymph node metastases in the axilla (94% area under the receiver operating characteristics curve). None of the 30 patients with a micrometastasis < or = 2.0 mm in the sentinel lymph node had metastases in the non-sentinel axillary lymph nodes. Metastases were present in the non-sentinel axillary lymph nodes in 29 of the 31 patients with extranodal tissue invasion near the sentinel node. CONCLUSION: In breast cancer patients with a sentinel lymph node metastasis < or = 2.0 mm and without extranodal tumour growth a complete axillary lymph node dissection might be unnecessary as the risk of additional metastases was very small.

[Important prognostic significance of a sentinel-node biopsy in patients with malignant melanoma]. / Belangrijke prognostische betekenis van schildwachtklierbiopsie bij patiënten met maligne melanoom.

OBJECTIVE: To determine the prognostic significance of sentinel-node biopsy in patients with malignant melanoma (unlike the United States, a sentinel-node biopsy is still not routinely performed on melanoma patients in the Netherlands, as the outcomes of prospectively randomised clinical trials are being awaited). DESIGN: Retrospective. METHODS: Between 1996 and 2001 a sentinel-node biopsy and a re-excision of the scar of the diagnostic biopsy were performed on all melanoma patients who had a Breslow thickness > or = 1 mm or a Clark level > or = IV. At operation the sentinel node was identified with a gamma probe and patent blue. It was removed and sent for pathological investigation for the presence of melanoma cells. If the sentinel node was tumour positive, a dissection of the regional lymph-node basin was performed. Subsequently, these patients were put forward for the European Organisation for Research and Treatment of Cancer (EORTC) peginterferon alfa(2b) adjuvant treatment study. RESULTS: A sentinel-node biopsy was performed in 61 lymphnode basins in 57 patients (18 male and 39 female; median age: 45 years (range: 9-80)). The median Breslow thickness of the melanomas was 2.2 mm (range: 0.7-13 mm). In 10 of the 61 cases histological examination of the sentinel node demonstrated tumour cells. In 2 additional cases tumour cells were demonstrated only by immunohistochemical studies or complete dissection of the node. Eight regional lymph-node basins were dissected, two of which contained additional metastases. The median follow-up was 36 months (range: 1-68). During follow-up 12 of the 57 patients were found to have metastases, in 8 of these patients the sentinel-node biopsy contained tumour cells. The negative predictive value of a tumourless sentinel node with respect to the later occurrence of distant metastases was 92%. CONCLUSION: The patients with a tumour-positive sentinel node had a poorer prognosis with respect to distant metastases than patients with a tumour-negative node. This is the main reason for performing sentinel-node biopsy: to predict the prognosis of the disease. Therefore sentinel-node biopsy should be incorporated into the treatment of patients with malignant melanoma.

Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.

PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.

[Less operations required due to perioperative frozen section examination of sentinel nodes in 275 breast cancer patients]. / Minder operaties vereist door peroperatief vriescoupeonderzoek van schildwachtklieren bij 275 patiënten met mammacarcinoom.

OBJECTIVE: To determine the reliability of a peroperative frozen section examinations of sentinel lymph nodes in mammary carcinoma. DESIGN: Retrospective. METHOD: In the Reinier de Graaf Hospital and Diagnostic Centre SSDZ Delft, the Netherlands, the results of frozen section from sentinel lymph node investigations of mammary carcinomas from 1997-2000 were compared with the final pathological results. If axillary dissection had been performed on these patients, the histopathological findings of the dissected lymph nodes were also studied. RESULTS: Frozen sections were made of 287 sentinel lymph nodes from 275 patients. A tumour was found in the sentinel lymph nodes of 64 patients and these patients immediately underwent a complete axillary lymph node dissection. For 31 of these patients a tumour was also found in the other lymph nodes. In 29 of these 31 patients, histological examination had shown extranodal extension. The frozen sections from the sentinel nodes of the remaining 211 patients were considered negative. However, in 13 of these patients, the paraffin sections of the sentinel node nevertheless showed a tumour and the remaining axillary lymph nodes were removed in a second operation. In the last 89 patients studied, the sentinel lymph nodes were cut at four levels and stained immunohistochemically at one level for cytokeratins. Accordingly micrometastases were found in the sentinel lymph nodes of 4 of the 13 patients with (false-)negative frozen sections. False-positive results did not occur. CONCLUSION: The major advantage of the sentinel node method in breast cancer is that for women without metastasis present in the sentinel node, axillary dissection is avoided. By means of a peroperative examination of frozen sections, 83% of the patients with a metastasis in the sentinel lymph node (or about one quarter of all patients) were spared from having a second operation for axillary dissection at a later stage.

Determining laser dosimetry for consistent retinal photocoagulation.

Laser photocoagulation is used extensively by ophthalmologists to treat retinal disorders such as diabetic retinopathy, macular degeneration, and retinal tears. Currently, the procedure is performed manually and suffers from several drawbacks that a computer-assisted system could help alleviate. These drawbacks include the tedious nature of the procedure for both the patient and the physician and also the extreme criticality of the task. A system is under development that will rapidly and safely place multiple therapeutic lesions at desired locations on the retina in a matter of seconds. This system provides real-time, motion-stabilized lesion placement for typical clinical irradiation times on the order of 100 ms. Considerable work has been accomplished on stabilizing the irradiating laser on the retinal surface. Various tracking systems have been designed, prototypes implemented, and tested in vivo on laboratory animals [1]. Our efforts have most recently concentrated on developing a system to monitor lesion growth in real time and turn off the laser when the desired lesion parameters have been achieved. This subsystem employs dynamic lesion reflectance as an indirect measure of lesion depth. Our goal has been to establish a correlation between the measurable lesion reflectance parameter with the actual lesion depth. Once this correlation is established, these parameters will be used to generate a control signal for the irradiation time of the laser. The goal is to optimize the therapeutic effect, without over- or under-exposing the tissue. The result is consistent lesion formation over any part of the non-homogeneous retinal tissue.

Improved healing of extraperitoneal intestinal anastomoses in the early phase when surrounded by omentum.

BACKGROUND: The extra-anatomical position of a cervical oesophagogastrostomy is a reason for impaired anastomotic healing, but transposition of the omentum that is covered with mesothelial cells may be a way to improve that. METHOD: This hypothesis was tested in a rat model. An end-to-end jejuno-jejunostomy was placed subcutaneously in group I (n = 29), subcutaneously surrounded by omentum in group II (n = 29) and intra-abdominally surrounded by omentum in group III (n = 20). After 3, 7 or 14 days, the rats were sacrificed and bursting pressure (BP) of the anastomosis or jejunum was measured and the hydroxyproline (HP) level was determined. RESULTS: In group I 5/29, in group II 2/29 and in group III 0/20 rats died following anastomotic leakage (nonsignificant) and were excluded from other measurements. BP was decreased after 3 days in group I (60+/-9 mm Hg) compared with group II (101+/-8 mm Hg) and group III (107+/-11 mm Hg) (p = 0.002). After 7 days, BP in groups I (122+/-10 mm Hg) and II (132+/-10 mm Hg) were lower as compared with group III (230+/-8 mm Hg) (p<0.001). Differences in HP levels were not statistically significant between the groups after 3, 7 and 14 days. CONCLUSION: The healing of intestinal anastomoses in an extraperitoneal position is improved in the early phase only when surrounded by omentum.

Deriving irradiation control parameters for laser photocoagulation on the retina.

Laser photocoagulation is used extensively by ophthalmologists to treat retinal disorders such as diabetic retinopathy and retinal breaks. Currently, the procedure is performed manually and suffers from several drawbacks that a computer-assisted system could help alleviate. Such a system is under development that will rapidly and safely place multiple therapeutic lesions at desired locations on the retina in a matter of seconds. This system provides real-time, motion-stabilized lesion placement for typical clinical irradiation times (100 ms). When performing laser photocoagulation on the retina, the dynamic reflectance of the lesion formed by the laser may be used as a control signal. Using digital filtering and estimation techniques on the sampled reflectance signal, the latency time and growth rate are determined. These parameters are used to derive a control signal for the irradiation time of the laser. The goal is to optimize the therapeutic effect, without overexposing the tissue. The result is consistent lesion formation over any part of the retina.

Impaired healing of extraperitoneal intestinal anastomoses.

BACKGROUND: The extra-anatomical position of a cervical oesophagogastrostomy might be a reason for impaired anastomotic healing. METHODS: This hypothesis was tested in a rat model. Jejunal resection with an end-to-end jejunojejunostomy was placed intra-abdominally in group 1 (n = 24) and subcutaneously in group 2 (n = 30). Jejunum without anastomosis was placed subcutaneously in group 3 (n = 12). After 3, 7 or 14 days the rats were killed; the bursting pressure of the anastomosis or jejunum was measured and the hydroxyproline level was determined. RESULTS: Two of 24 rats in group 1 and eight of 30 in group 2 died following anastomotic leakage (P not significant) and were excluded from other measurements. Bursting pressure was decreased after 3 days in group 1 (mean(s.e.) 62(10) mmHg) and group 2 (57(10) mmHg) compared with that in group 3 (204(17) mmHg) (P < 0.001). After 7 days, it was in the normal range in group 1 (200(14) mmHg), but lower in group 2 (104(15) mmHg) compared with that in group 3 (230(8) mmHg) (P < 0.001). Differences in hydroxyproline levels were not statistically significant between the groups after 3, 7 and 14 days. CONCLUSION: Healing of jejunojejunostomies is impaired in an extraperitoneal position compared with an intra-abdominal position.

Extended lymph-node dissection for gastric cancer.

BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. METHODS: Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. RESULTS: Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS: Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cancer.

A method to control irradiation time for laser photocoagulation of the retina--Part II.

When performing laser photocoagulation of the retina, the dynamic reflectance of the lesion formed by the laser may be used as a control signal. Using digital filter and estimation techniques on the sampled reflectance signal, the latency time and growth rate of the lesion reflectance are determined. These parameters are then used to estimate the absorption coefficient of the irradiated tissue. From these estimates, the irradiation time of the laser can be accurately determined so that optimum therapeutic effect may be obtained, without overexposing the tissue. The result is consistent lesion formation over any part of the retina. This paper is a follow up to [4] and provides details of the experimental setup and signals acquisition.

Hybrid tracking system for retinal photocoagulation prototype II.

Laser photocoagulation has been employed extensively by ophthalmologists to treat retinal diseases and disorders such as diabetic retinopathy, macular degeneration, and retinal tears. Treatment is a manual task requiring the physician to carefully place therapeutic lesions on the retina while avoiding critical vision anatomy. We have developed a hybrid tracking system using two retinal tracking modalities: a digital imaging-based subsystem and an analog tracking subsystem to stabilize the irradiating laser on the retina. We have also investigated a lesion parameter control subsystem to provide uniform therapeutic lesions.