The value of a dedicated multidisciplinary expert panel to assess treatment strategy in patients suffering from colorectal cancer liver metastases.

BACKGROUND: For patients with colorectal cancer liver metastases (CRLM), local treatment is the only treatment with curative intent. The majority of patients with CRLM are however evaluated in multidisciplinary teams of colorectal cancer specialists often lacking expertise in local treatment of liver tumors. The aim of this study was therefore to assess the value of a dedicated multidisciplinary panel consisting of hepatobiliary surgeons and interventional radiologists for patients suffering from liver-only CRLM. METHODS: Patients diagnosed with liver-only CRLM in 2016 were identified in a tertiary referral hospital, and two of the referring hospitals in the Netherlands. Diagnostic imaging was independently reviewed by a panel of four hepatobiliary surgeons and two interventional radiologists to re-evaluate treatment strategy retrospectively. If two or more panelists assessed all lesions eligible for resection and/or ablation, patients were deemed eligible for local treatment with curative intent. Interrater reliability between hepatobiliary surgeons was assessed through intraclass correlation coefficient (ICC) and weighted Cohen's kappa. RESULTS: Diagnostic imaging of 61 patients with liver-only metastases were reviewed. Local treatment strategies appeared feasible in 40/61 (65.6%) patients. Five out of 25 patients (20.0%) initially assigned to systemic therapy were deemed eligible for upfront local treatment with curative intent (p = 0.015). In this subgroup, interrater reliability between hepatobiliary surgeons was substantial (ICC: 0.704, 95% CI: 0.536-0.838, n = 25). CONCLUSION: Assessment of treatment strategy by a dedicated multidisciplinary panel including liver experts may result in an increased number of patients eligible for potentially curative treatment and reduce undertreatment of patients suffering from liver-only CRLM.

(99M)Technetium-sestamibi scintimammography in non-palpable breast lesions found on screening X-ray mammography.

OBJECTIVE: The sensitivity and specificity of (99m)Tc-sestamibi scintimammography in patients with non-palpable breast lesions diagnosed by screening mammography and the value of (99m)Tc-sestamibi to detect axillary lymph node metastases was determined. METHODS: Between September 2000 and December 2003, 103 females with non-palpable breast lesions were included for further evaluation. X-ray mammography was repeated and 99mTc-sestamibi scintimammography performed within one-week. Anterior, and left and right lateral images were obtained. The scintimammography was analysed by 2 experienced observers who were blinded to the clinical, pathological, and radiological results. The sensitivity and specificity of scintimammography to diagnose non-palpable lesion(s), including the axillary regions, was compared with histopathology, clinical, and radiological follow up. RESULTS: Two patients (one non-small lung cancer and one non-Hodgkin's disease) were excluded. Both showed (99m)Tc-sestamibi avid lesions in the breast and axillary region. In the remaining 101 patients, 37 true positive (TP), 4 false positive (FP), 52 true negative (TN), and 8 false negative (FN) breast carcinomas were found. The specificity was 92.8%, sensitivity 82.2%, positive predictive value (PPV) 90.2%, and negative predictive value (NPV) 86.6%. (99m)Tc-sestamibi scintimammography showed axillary lesions in 5/15 (33%) patients with axillary lymph node metastasis. CONCLUSION: In patients with non-palpable lesions diagnosed by screening- X-ray-mammography, (99m)Tc-sestamibi scintimammography provided high specificity and PPV. Furthermore, (99m)Tc-sestamibi scintimammography detected 33% of patients with axillary lymph node metastases. Therefore, (99m)Tc-sestamibi scintimammography could be of incremental value in the surgical work-up of these patients.

Effect of mechanical bowel preparation with polyethyleneglycol on bacterial contamination and wound infection in patients undergoing elective open colon surgery.

Mechanical bowel preparation is common practice in elective colon surgery. In order to verify the effect of mechanical bowel preparation on the colonic flora, this study followed 185 patients undergoing elective open colon surgery, 90 of whom were assigned randomly to receive mechanical bowel preparation with polyethyleneglycol. Swabs of the anastomosis and the subcutis were taken during surgery. Further swabs were taken of any subsequent wound infections. Mechanical bowel preparation did not reduce contamination of the peritoneal cavity or the subcutis during surgery, and there appeared to be more sterile subcutaneous swabs in the control group.

Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil.

Experimental studies indicate that anastomotic healing in the intestine is compromised by the immediate postoperative administration of 5-fluorouracil and levamisole. Since fibroblast functions are crucial to healing, we investigated the effects of (combinations of) both drugs on proliferation and collagen synthesis of rat skin fibroblasts in vitro. Proliferation was measured in actively dividing cells by cellular [3H]thymidine uptake and collagen synthesis in non-dividing cells by [3H]proline incorporation into collagenase-digestible protein. 5-Fluorouracil strongly and significantly (P < 0.05) reduced DNA synthesis and collagen synthesis at concentrations of 1 microM or more. The latter effect was not specific for collagen since total protein production was affected similarly. Both effects depended on the duration of exposure to the drugs. Levamisole also inhibited fibroblast proliferation dose-dependently, but less effectively than 5-fluorouracil: 50% inhibition was observed at approximately 0.1 mM. Collagen synthesis was unaffected by levamisole. If levamisole was added together with a low (0.1 microM) concentration of 5-fluorouracil, which in itself did not decrease thymidine incorporation, levamisole's antiproliferative effects became apparent at concentrations as low as 1 microM. A similar effect, but at a much higher concentration (1 mM) was noted on fibroblast collagen synthesis. These results indicate that levamisole potentiates 5-fluorouracil effects in fibroblast cultures and that direct effects of these drugs, alone or in combination, on fibroblast proliferation and collagen synthesis may be responsible for their negative influence on wound repair.

Retinol may promote fluorouracil-suppressed healing of experimental intestinal anastomoses.

OBJECTIVES: To examine the effects of perioperative administration of fluorouracil on healing variables of internal anastomoses and to explore ways to promote repair under these conditions. DESIGN: Seven-day, prospective randomized experimental trial. SETTING: Animal research laboratory. ANIMALS: Male young-adult Wistar rats after resection and anastomosis of both ileum and colon. INTERVENTIONS: Random assignment to groups receiving placebo, daily fluorouracil (20 mg/kg per day, intraperitoneally), daily fluorouracil plus retinol palmitate (5000 IU/kg per day, orally), daily fluorouracil plus interleukin-2 (2 x 10(6) IU/kg per day, subcutaneously), or daily fluorouracil plus granulocyte macrophage colony-stimulating factor on the first 4 days after operation (20 micrograms/kg per day, intraperitoneally. MAIN OUTCOME MEASURES: Anastomotic bursting pressure, breaking strength, hydroxyproline content, and ex vivo collagen synthetic capacity. RESULTS: Administration of fluorouracil decreased anastomotic breaking strength by more than 40% and caused a shift in bursting site from outside to within the suture line. It also lowered anastomotic hydroxyproline content. The capacity for collagen synthesis, which was greatly enhanced in 4-day-old anastomoses from the control group, was significantly (P < .05) and specifically reduced. Concomitant administration of retinol resulted in restoration of strength and hydroxyproline content, particularly in the ileum. Interleukin-2 and granulocyte macrophage colony-stimulating factor did not improve fluorouracil-suppressed repair: both wound strength and collagen content were similar in the fluorouracil, fluorouracil/interleukin-2, and fluorouracil/granulocyte macrophage colony-stimulating factor groups. CONCLUSION: Intraperitoneal administration of fluorouracil, delivered from the day of operation onward, severely reduces anastomotic strength at the end of the first postoperative week. This negative effect may be prevented by oral administration of retinol.

[Radionuclide-guided minimally invasive rib biopsy for metastases]. / Radionuclidegeleide minimaal invasieve biopsie van voor metastase verdachte ribafwijkingen.

OBJECTIVE: To determine the feasibility of radionuclide-guided surgical rib biopsy in patients in whom a local metastasis is suspected. DESIGN: Descriptive. METHOD: In eight patients (three men and five women) with a known primary carcinoma, radionuclide-guided surgical rib biopsy was performed because a local metastasis was suspected. The skin was marked on the basis of a technetium-99m-(99mTc)-medronate scintigram. During surgery, a gamma probe was used to look for the hot spot in the rib in the vicinity of the skin marking; this hot spot was then minimally excised and submitted for pathological examination. RESULTS: In all patients, the radionuclide-guided rib biopsy resulted in an unequivocal histopathologic diagnosis: tumour metastasis (n = 2), necrosis (n = 1), old fracture (n = 5). CONCLUSION: Radionuclide-guided surgical bone biopsy has been shown to be a specific, simple, minimally invasive technique for obtaining a representative histological specimen with little stress on the patient. This technique can be used in every hospital that is equipped to carry out the sentinal node procedure in case of breast cancer or melanoma.

[Femoral neck fractures in bicyclists due to clipless pedals]. / Collum femoris-fractuur bij fietsers door 'clipless' pedalen.

Femoral neck fractures in healthy young adults caused by a relatively low-energy trauma are uncommon. The cases are presented of four cyclists, men of 37, 42 (n = 2) and 43 years old, with a femoral neck fracture, in which so called clipless pedals played an important part. The shoes of the cyclist are affixed to these pedals, and the patients had been unable to remove their feet quickly when they fell. They were treated by osteosynthesis using screws, but one of them developed intra-articular infection which eventually necessitated implantation of a total hip prosthesis.

99mTc Nanocoll: a radiopharmaceutical for sentinel node localisation in breast cancer--in vitro and in vivo results.

This study evaluated labelling efficiency and radiochemical purity of (99m)Tc colloid albumin to identify an optimal labelling protocol for sentinel node detection. Results indicate that a 72 h eluate is not recommended for high specific labelling of (99m)Tc colloid albumin. Ex vivo, significantly higher count rates were reached using a 2h eluate in vacuum or nitrogen. Labelling 26 MBq/microg (99m)Tc colloid albumin with a 2 h eluate under nitrogen is recommended because of the ease of labelling.

Early post-operative 5-fluorouracil does not affect the healing of experimental intestinal anastomoses.

5-Fluorouracil (5-FU) remains the mainstay for systemic treatment of colorectal cancer. In view of the increasing interest in peri-operative administration of antineoplastic agents, we have investigated the effects of early postoperative 5-FU on the healing of intestinal anastomoses in the rat. Animals underwent resection and anastomosis of both ileum and colon and 5-FU (20 mg/kg body weight) was given, either intravenously or intraperitoneally, on the day of surgery and the two subsequent days. Healing was assessed three and seven days after operation. Administration of 5-FU led to a reduced white blood cell count. However, anastomotic strength was not significantly reduced at either time point and anastomotic hydroxyproline content was not significantly affected. We suggest that limited use of 5-FU during or immediately after operation does not necessarily affect early anastomotic healing in the intestine.

Carpometacarpal dislocation: report of three cases.

The case reports of three patients with carpometacarpal dislocations are described. The diagnosis of this condition may be difficult and is often missed. Swelling, dislocation and a palpable lump are the main clinical findings. X-ray findings, the key to the diagnosis, are loss of parallelism, interruption of the so-called M-line and overlapping of articular surfaces. Additional X-rays in different planes are to be recommended if carpometacarpal dislocation is suspected.

Carpal tunnel sonography by the rheumatologist versus nerve conduction study by the neurologist.

OBJECTIVE: To determine the value of sonography (SG) performed by the rheumatologist to diagnose carpal tunnel syndrome (CTS). METHODS: Sixty-three patients with clinical signs of CTS according to the neurologist, based on patient history and clinical examination, were studied. In the 6 weeks prior to surgery, SG was performed by a rheumatologist and nerve conduction study (NCS) was assessed. Improvement of initial complaints of 90% or more 3 months after surgery was considered to be the post-hoc gold standard for the diagnosis of CTS. RESULTS: After surgery, 47 patients (75%) experienced > or = 90% relief of complaints. Mean cross sectional area of the median nerve for patients with CTS was 11.3 mm2 compared to 6.1 mm2 in the control group. The sensitivity to detect CTS was 0.70 for SG and 0.98 for NCS, and specificity was 0.63 for SG and 0.19 for NCS. Positive predictive value was 0.85 for SG and 0.78 for NCS; negative predictive value was 0.42 for SG and 0.75 for NCS. Accuracy was 0.68 for SG and 0.78 for NCS. CONCLUSION: CTS can be identified by SG less sensitively but more specifically than by NCS.

Post-operative levamisole may compromise early healing of experimental intestinal anastomoses.

There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess it potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P < 0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing.

The effects of 5-fluorouracil and interferon-alpha on early healing of experimental intestinal anastomoses.

The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anastomotic breaking strength was reduced significantly in ileum (P = 0.0221) and colon (P = 0.0054) of the 5-FU/interferon-alpha group and in colon of the interferon-alpha group (P = 0.0221). Collagen synthetic capacity was strongly suppressed by 5-FU but not by interferon-alpha. However, no differences in anastomotic hydroxyproline content were observed between groups at both days 3 and 7. Thus, post-operative use of interferon-alpha, in particular in combination with 5-FU, may be detrimental to anastomotic repair in the intestine.

Unilateral vascular reconstruction for iliac obstructive disease.

PURPOSE: Controversy exists regarding the extent of vascular reconstructive surgery in the presence of unilateral symptomatic iliac obstructive disease. This study reviews the results of unilateral iliac reconstruction, with special emphasis on the need for consecutive contralateral intervention. METHODS: The outcomes of 184 unilateral and 350 aortobilateral reconstructions for obstructive disease performed during the same period were retrospectively analyzed. Treatment allocation was based on hemodynamic parameters. Unilateral reconstruction was performed by a way of a retroperitoneal approach through a pararectal incision and bilateral reconstruction by way of a transperitoneal approach through a midline abdominal incision. RESULTS: Symptom relief, improvement of noninvasively measured parameters, and graft patency were similar after unilateral and bilateral reconstruction. Both groups had a 10-year primary patency rate greater than 80%. There were no differences in morbidity rate, although respiratory complications occurred more often after bilateral reconstruction. Mortality rates were 1.6% after unilateral reconstruction and 4.9% after bilateral reconstruction. Secondary contralateral reconstruction was performed in only 6% of the patients who underwent an initial unilateral operation. CONCLUSIONS: The unilateral vascular reconstruction for iliac obstructive disease is a well-tolerated procedure with an excellent long-term outcome. It is a valuable alternative to conventional aortobilateral reconstruction in carefully selected patients. Prophylactic reconstruction of an asymptomatic iliac stenosis without signs of significant hemodynamic impairment is most often not indicated.

Effect of increased (99m)Tc/(99)Tc ratios on count rates in sentinel node procedures: a randomised study.

The aim of this study was to evaluate the count rates of sentinel lymph nodes (SLNs) in patients with breast cancer in the operating theatre, using (99m)Tc-Nanocoll with different ratios of technetium-99m to technetium-99. After written informed consent had been obtained, we tested different ratios of (99m)Tc/(99)Tc-Nanocoll in a double-blinded randomised study performed in 161 patients. Twenty-five MBq/ microg (99m)Tc-colloid albumin was prepared in vacuum. In 87 patients (group A) a 2-h elution was used and in 74 patients (group B) a 24-h elution was used. Patients were subcategorised into subgroups 1 and 3, in which an SLN procedure for breast carcinoma was performed simultaneously with lumpectomy, and subgroups 2 and 4, in which an SLN procedure was performed 2-3 weeks after prior excision biopsy. All patients were injected along the lateral border of the areola (two injections: 50 MBq/0.3 ml intradermally and 50 MBq/2 ml intraparenchymally). Ex vivo measurement of count rates was performed with a gamma probe. Comparing groups A and B in respect of registered counts per second (cps) of excised SLNs, a significant difference was found ( P<0.004). When comparisons were made between subgroups 1 and 2 (2-h elution) and between subgroups 3 and 4 (24-h elution) in respect of registered cps of excised SLNs, no significant difference was found (subgroup 1 vs 2, P=0.825; subgroup 3 vs 4, P=0.915). Use of a 2-h elution in vacuum yielded a significantly higher count rate of maximum specific activity of (99m)Tc-colloid albumin in SLNs than was achieved using a 24-h elution in vacuum. SLN procedures performed 2-3 weeks after prior excision biopsy proved reliable as compared to SLN procedures performed simultaneously with lumpectomy.

Further optimisation of 99mTc-Nanocoll sentinel node localisation in carcinoma of the breast by improved labelling.

The sentinel node (SLN) procedure has gained widespread acceptance for the axillary staging of patients who present with carcinoma of the breast. A first series of 21 patients were imaged 2 and 4 h after the injection of technetium-99m colloidal albumin. Preoperatively, axillary foci were located scintigraphically and with a hand-held gamma probe that was also used to detect the radiolabelled nodes 22 h later in the operating theatre. In a high percentage of our first series it was difficult to localise the sentinel node owing to a low count rate ex vivo. The aim of this study was to facilitate the detection of sentinel nodes by improving the count rate by the use of higher specific concentrations of 99mTc-colloidal albumin, with increased radiochemical labelling efficiency and stability. In vitro tests were performed to establish the radiochemical labelling efficiency and stability of different concentrations of 99-mTc-colloidal albumin. Concentrations of 2.5, 10, 20, 25, 30, 37 and 50 MBq 99mTc/microg colloidal albumin (Nanocoll) were prepared under nitrogen and in vacuum. The quality of the solutions was assessed by testing the radiochemical labelling efficiency and stability after 0.5, 2, 5, 8 and 24 h. The particle size of colloidal albumin was tested by dynamic light scattering at 30.2 degrees, 62.6 degrees and 90.0 degrees angles. Following the results of the in vitro studies, higher concentrations of 99mTc-colloidal albumin were used in vivo in a further series of 98 patients. For labelling under nitrogen, a maximum acceptable concentration of 10 MBq/microg was found, which complies with the specifications of the manufacturer. By preparing the labelling in vacuum vials, a 2.5 times greater radiochemical labelling efficiency over the entire period was achieved, and a significant improvement (P<0.002) in the in vivo series was found. It is concluded that although the rate of successful visualisation of the SLN was high in all studies, a better count rate (nine times higher) was achieved with the highest concentration of 99mTc-colloidal albumin, which facilitated the detection of the SLN by the gamma probe during surgery.