Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide produced by tissue-specific alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is widely distributed in the central and peripheral neuronal systems and exhibits numerous biological activities in mammals. We examined in the present study whether or not endogenous CGRP released from neuronal systems facilitates neovascularization indispensable to wound healing. In CGRP knockout mice (CGRP−/−), wound-induced angiogenesis and wound closure were significantly suppressed compared with those in wild-type mice. The suppressed healing in CGRP−/− was accompanied by reduction in expressions of vascular endothelial growth factor (VEGF) in the wound granulation tissues. A CGRP antagonist, CGRP8-37 when infused with mini-osmotic pumps subcutaneously blocked the wound healing processes and reduced the expressions of CD31 and VEGF expression in the wound granulation tissues. Wound healing process was significantly delayed in neuropeptide-depleted mice pretreated with capsaicin, compared with vehicle-treated mice. These results indicate that CGRP derived from neuronal systems may facilitate wound healing and angiogenesis. Targeting of CGRP may be promising in controlling angiogenesis related to pathophysiological conditions.

3723 Background: Unlike long-term survival of colorectal cancer the time distribution of recurrences is not well known and no clear role of serum tumour markers to detect them has been defined. Methods: 173 operated colorectal cancer patients, prolongly followed-up with serial instrumental examinations and serum CEA,TPA,CA19.9,CA72.4 tumour markers, were retrospectively evaluated; 78 (46%) had relapsed, while the 95 others, all followed up longer than 48 months, did not. At the time of primary surgery 28 (36%) of the 78 relapsed patients, were metastatic (M1) and in the 50 (64%) remaining the mod. Duke’s stage was: B1 (2) (2.5%), B2 (21) (27%) and C2 (27) (35%). As to the 95 disease-free patients, 3 (3%) were metastatic, and in the 92 remaining the mod. Duke’s stage was: A (14), B1 (18), B2 (34), C1 (6) C2 (20); their mean follow up was 87 + 12 (74–99 range), 127 + 50 (48–210 range), 120 + 47 (49–222 range), 126 + 50 (48–236 range), 118 + 79 (51–237 range) and 124 + 57 months (52–200 range) respectively. Sensitivity of combined serum CEA, TPA, CA19.9 and CA72.4 was evaluated in 64 (82%) relapsed patients. Results: In 49 (98%) of the 50 post-operatively recurred patients, recurrence occurred within 46 months and the median time was: 38 (30–46 range), 16 (3–39 range) and 15 (2–41 range) months for B1, B2 and C2 stages respectively. In the last 1 (2%) patient, with C2 stage, recurrence occurred 105 months after primary surgery. So recurrences were 20 (40%), 18 (36%), 8 (16%) 3 (6%) and 1 (2%) during the first, second, third, fourth year after primary surgery and thereafter respectively. Sensitivity of CEA-TPA, CEA-TPA-CA19.9 and CEA-TPA-CA19.9-CA72.4 panels was 86%, 87.5% and 93% respectively and the mean lead time of the 3 panels from tumour marker increase to the first pathological instrumental sign ranged from 3.6 to 3.9 months (0–18 range). Conclusions: These data suggest: a) 4 years after primary surgery is a principal end-point for colorectal cancer recurrences; b) serum CEA-TPA-CA19.9-CA72.4 and alternately serum CEA-TPA are sensitive tumour marker panels to post-operatively early detect colorectal cancer recurrences. No significant financial relationships to disclose.

Article Tools Breast Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/jco.2004.22.90140.753 Journal of Clinical Oncology - published online before print July 15, 2004 PMID: 28014168 Intensive post-operative follow-up of breast cancer patients with tumour markers: Accuracy of serum MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels for early detection of relapse A. NicolinixA. NicoliniSearch for articles by this author , G. TartarellixG. TartarelliSearch for articles by this author , P. FerrarixP. FerrariSearch for articles by this author , A. CarpixA. CarpiSearch for articles by this author , M. ContexM. ConteSearch for articles by this author , C. SpinellixC. SpinelliSearch for articles by this author , L. AnselmixL. AnselmiSearch for articles by this author , R. SpisnixR. SpisniSearch for articles by this author , P. MiccolixP. MiccoliSearch for articles by this author Show More University of Pisa, Department of Internal Medicine, Pisa, Italy; University of Pisa, Department of Reproduction, Pisa, Italy; University of Pisa, Department of Surgery, Pisa, Italy https://doi.org/10.1200/jco.2004.22.90140.753 Abstract Abstract 753 Background: In breast cancer serum CEA-TPA-CA15.3 tumour marker panel is a cheap tool with high accuracy for the "early" detection of relapse (A Nicolini, Br J Cancer 1997); serum MCA and CA15.3 are also reported among the most useful serum tumour markers. However the most suitable cut-off of MCA has not yet been defined. The aims were to compare the MCA-CA15.3 with the CEA-TPA-CA15.3 tumour marker panel and to assess the effect of two different MCA cut-off values on this comparison. Methods: From May 2000 to February 2003, 264 breast cancer patients every 6 or 4 months, according to whether they were at low or high risk of relapse, were monitored with serial serum MCA, CEA, CA15.3, and TPA levels besides history and routine lab examinations. Cut-off value was 4.3 ng/mL (CEA), 32 U/mL (Ca15.3), 95 U/L (TPA), 11 and 16 U/mL (MCA). Tumour marker increase was dynamically evaluated according to a previously described method (A Nicolini, Br J Cancer 2000) Bone scintigraphy, liver echography and chest x-ray were carried out at the beginning of the study then at about 18 month interval. When a relapse was suspected by tumour markers, they were performed immediately. Results: So far 18 (7%) of the 264 patients relapsed. Accuracy of MCA-CA15.3 and CEA-TPA-CA15.3 was 46% and 69% respectively for MCA cut-off 11 U/mL and it was 77% and 71% for MCA cut-off 16 U/mL. For MCA cut-off 16 U/mL sensitivity, specificity and lead time were 58%, 78.5%, 7.4 months (mean; 0–22 range) for MCA-CA15.3 and 74%, 71%, 4.1 months (mean; 0–16 range) for CEA-TPA-CA15.3. Conclusions: 16 U/mL is MCA cut-off value more suitable than 11 U/mL. With MCA cut-off value of 16 U/mL, CEA-TPA-CA15.3 has similar accuracy but much higher sensitivity than MCA-CA15.3. No significant financial relationships to disclose. American Society of Clinical Oncology

Objectives. - Randomised trials on breast cancer showed no significant benefit from post-operative follow-up with clinical and/or conventional radiological means. We hypothesised that carcinoembryonic antigen (CEA), tissue polipeptyde antigen (TRA), breast cancer associated antigen 115 D8/DF3 (CA15.3) tumour marker panel is sensitive enough for significantly anticipating salvage treatment and prolonging survival of relapsing breast cancer patients.Methods. - From October 1981 to May 1999, 68 (62%) of 109 patients with distant metastases were recruited. Thirty-six (53%) received salvage treatment at the time of significant increase in one or more components of CEA-TPA-CA15.3 tumour marker panel and negative instrumental examinations ("tumour marker guided" treatment) and 32 (47%) were treated only after radiological confirmation of metastases (conventional treatment). The prognostic factors of the two groups did not show any statistically significant difference.Results. - The time from one or more tumour marker increase to clear clinical and/or radiological signs of distant metastases (lead time) was significantly prolonged in the 36 patients with "tumour marker guided" treatment (17.3 +/- 13.1 vs. 2.9 +/- 2.9 months, P < 0.001, Wdcoxon test) as well as the survival curves from salvage therapy and from mastectomy (the proportion of survivors was: at 36 months from salvage therapy 28% vs. 9%, P = 0.0094; at 84 months from mastectomy 42% vs, 19%, P = 0.0017). The multivariate Cox analysis showed that time from mastectomy to tumour marker increase and "turnour marker guided" salvage treatment were the only significantly different variables (P = 0.00001 and 0.005, respectively).Conclusion. -These data point out that -tumour marker guided" salvage treatment significantly prolongs disease-free and overall survivals of relapsing responsive patients. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

The external branch of the superior laryngeal nerve (ESLN) innervates the cricothyroid muscle, which regulates the tension of the vocals cords. Damage to the ESLN causes changes of the voice like hoarseness, weakness, decreased range of pitch or volume, and fatigue after extensive use. This complication will diminish the preservation of the recurrent laryngeal nerve during the same operation and can be a disaster, especially for singers and professional speakers. Visualization of the ESLN, which always should be achieved, is not routinely obtained during thyroidectomy, because of the small diameter of this branch (0.2 mm), its very variable course, and the anatomic position (the space between the medial surface of the upper pole of the thyroid and the cricothyroid muscle, which is covered by the strap muscles). In about 10% to 15% of cases, the nerve runs within the cricothyroid muscle in its entire course, so it cannot be seen by direct inspection using any technique, but luckily, in this case it is not at risk. To preserve the ESLN, most surgeons tend to avoid rather than expose the nerve, suggesting selective ligation of the upper pedicle vessels. In fact, the ESLN usually crosses the superior thyroid artery more than 1 cm above the upper edge of the superior thyroid pole (type 1) and successively runs on the surface of the cricothyroid muscle. But this “blind” step will jeopardize the nerve variants type 2a and type 2b (20% to 35%) crossing the upper pedicle less than 1 cm, respectively, above and below the upper edge of the superior thyroid pole. In minimally invasive video-assisted thyroidectomy, a procedure introduced by Miccoli and colleagues in No competing interests declared.

BACKGROUND:Minimally invasive video-assisted thyroidectomy (MIVAT) has been practiced in our department since 1998. It has some advantages over conventional surgery in terms of postoperative pain and cosmetic result. The aim of this study was to evaluate the use of the Harmonic scalpel (HS) on the performance of this procedure.METHODS:Between October 1998 and January 2001, 116 patients underwent MIVAT. The HS was used for the last 26 operations. We compared this group of patients (HS-G) with a control group (C-G) of 26 patients who had undergone MIVAT before the introduction of the HS. The following parameters were considered: age, gender, preoperative diagnosis, size of the lesion, type of operation (lobectomy or total thyroidectomy), operative time, complication rate, and postoperative hospital stay.RESULTS:The two groups were well matched for age, gender, preoperative diagnosis, lesion size, and type of operation. The mean operative time was significantly reduced in the HS-G for both lobectomy (37.3 +/- 8.4 vs 49.4 +/- 18.0 min) and total thyroidectomy (53.8 +/- 16.3 vs 90.6 +/- 22.1 min). No differences were found for postoperative stay. One patient in the C-G experienced a transient recurrent nerve palsy. There were no other complications.CONCLUSIONS:This study showed that the utilization of the HS for MIVAT is safe and associated with a shorter operative time. A reduction of the rates for such complications such as hypoparathyroidism and recurrent nerve injuries was not possible to demonstrate in the present study. Much larger series are needed for further evaluation of this instrument.

BACKGROUND AND PURPOSE:During the last 3 years, a minimally invasive video-assisted approach for parathyroidectomy and thyroidectomy has been developed. Because of the good exposure of the cervical spine during these procedures, the authors decided to perform an anatomic-radiologic study in order to evaluate which cervical vertebrae could be reached by this minimally invasive approach.PATIENTS AND METHODS:Three consenting patients, two undergoing minimally invasive parathyroidectomy and one a conventional operation for C4-C5 disc herniation, were selected for this study. The procedure was carried out through a single 1.5-cm central skin incision above the sternal notch. After opening of the cervical linea alba, dissection was performed under endoscopic vision, without using any CO2 insufflation or trocar. After exposure of the prevertebral fascia, an operative tube was introduced through the cervical incision in order to maintain the operative space without using conventional retractors.RESULTS:Through this operative tube, it was possible to introduce both a 5-mm (or 3-mm) endoscope and the surgical instruments. In our patients, we inserted a 1-mm metal probe to exactly localize during fluoroscopy the vertebrae reached by the dissection (C2-C7).CONCLUSIONS:This study shows the feasibility of an anterior minimally invasive approach to the cervical spine. Although the exact indications have to be verified, a video-assisted approach could add some advantages to the well-known benefits coming from the anterior approaches to the cervical spine, especially in terms of cosmetic results and postoperative course and recovery.

The aim of this retrospective study was to assess the value of a serum tumour marker panel in selecting from among the patients with equivocal chest X-ray (CXR) or liver echography (LE) those with thoracic or liver metastases respectively. Between January 1984 and December 1999, 467 (341 non-relapsed and 126 metastatic) breast cancer patients were followed-up postoperatively. Among the 126 metastatic patients 36 showed thoracic (19 patients) or liver (17 patients) metastases, alone or in conjunction with other organs as the first evidence of distant spread. We focused on this series of 377 patients including 341 non-relapsed plus 36 with liver or thoracic metastases. The patients were followed-up after mastectomy with serial determinations of a panel of CEA-TPA-CA15.3 tumour markers, bone scintigraphy, CXR and LE. Up to December 1999, equivocal CXR occurred in 23 (6.1%) patients of whom 11 (47.8%) developed thoracic metastases; 14 (3.7%) patients showed an equivocal LE of whom 5 developed liver metastases. In the 37 patients with equivocal CXR or equivocal LE prolonged clinical and imaging follow-up over 41 ± 36 months (mean ± SD, range 3–163) was used to ascertain the presence or absence of thoracic or liver metastases. In the 23 patients with equivocal CXR the negative and positive predictive values of the tumour marker panel to predict thoracic metastases were 92% and 100% respectively. In the 14 patients with equivocal LE the negative and positive predictive values of the tumour marker panel for prediction of liver metastases were 90% and 100% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value for selecting those patients at high risk of developing clinically evident pulmonary or liver metastases from amongst those subjects with equivocal CXR or equivocal LE. © 2000 Cancer Research Campaign http://www.bjcancer.com

Background: Endoscopic thyroidectomy has not yet met the favor of most endocrine surgeons. We evaluated the technical feasibility of a video-assisted approach to thyroid surgery. Patients and methods: The study group comprised 22 females and 5 males, all with a single thyroid nodule. The nodule was “hot” in 4 patients, microfollicular in 17 and with Hürthle cell cytology in 6. A 15-mm skin incision was made above the sternal notch. The mid-line was opened and a 12-mm trocar inserted into the thyro-tracheal groove. It was inflated with CO2 for 3 min. The trocar was then removed and the procedure performed using external retractors and needlescopic instruments. The upper pedicle was dissected. Identification of recurrent nerve and parathyroid glands was facilitated by endoscopic magnification. The upper gland portion was then retracted out of the operative cavity; inferior veins were ligated and the lobe entirely extracted and dissected. Frozen section was obtained for “cold” nodules. Results: Video-assisted hemithyroidectomy was accomplished in 24 patients; 1 underwent video-assisted total thyroidectomy (positive frozen section). Cervicotomy was required once to achieve hemostasis and once to perform total thyroidectomy (positive frozen section). Mean operative time was 82 min (range 60–120 min). No complications were registered. The cosmetic result was excellent. Conclusions: Video-assisted thyroid surgery is feasible and may improve cosmetic outcome; total thyroidectomy can be accomplished through the same access point.

The authors analyzed the preliminary results of a personal technique of minimally invasive video-assisted thyroidectomy (MIVAT).From July 1998 to February 2000, 58 patients were selected for MIVAT. Eligibility criteria were: nodule size less than or equal to 3 cm, no previous neck surgery or irradiation, no history of thyroiditis. A 15-mm skin incision is made above the sternal notch. Dissection of the gland is performed under endoscopic vision, without any CO2 insufflation. We performed 47 lobectomies and 11 total thyroidectomies. Mean operative time was 82 minutes for lobectomy and 121 minutes for total thyroidectomy. The conversion rate was 3.4%. One transient postoperative hypocalcemia occurred. Cosmetic result was excellent.MIVAT is a feasible and safe procedure. Despite the indications are still limited, the preliminary results are encouraging.

BACKGROUND:Since February 1997, a technique of minimally invasive video-assisted parathyroidectomy (MIVAP) was developed at our institution for the treatment of sporadic primary hyperparathyroidism (sPHPT). In this study we analyzed the entire series of patients who underwent MIVAP during the last 3 years. STUDY DESIGN:One hundred thirty-seven patients with sPHPT were selected for MIVAP. Selection criteria were: diagnosis of single adenoma based on preoperative localization studies (ultrasonography, sestamibi scintigraphy, or both), and no previous neck surgery or concomitant large multinodular goiter. The procedure, already described, is performed by a gasless video-assisted technique through a single 1.5-cm central skin incision above the sternal notch. Quick, intraoperative parathyroid hormone assay was used in 134 cases (97.8%) to confirm the complete removal of all hyperfunctioning parathyroid tissue. RESULTS:Mean operative time was 54.3 +/- 22.6 minutes. The conversion rate was 8.8%. One laryngeal nerve palsy was registered (0.7%), as was one case of persistent hyperparathyroidism. In six patients (4.4%) a transient symptomatic postoperative hypocalcemia was observed. Two thyroid lobectomies were associated using the same minimally invasive access. At a mean followup of 15.4 +/- 10.6 months, all but two patients were normocalcemic. The cosmetic result was considered excellent by most of the patients (92.8%). CONCLUSIONS:Although not all patients with sPHPT are eligible for MIVAP, this approach can now be proposed in a bigger proportion (67% of patients). As already demonstrated in a previous study, also in a large series of patients, after greater experience has been achieved, the results and the operative time are the same as in traditional surgery, with better cosmetic result and a less painful course.