Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

BACKGROUND: despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5 weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. METHODS: eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12 days. The follow-up of patients alive at the time of analysis ranges from 12-120 months (median 48). RESULTS: mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P = 0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P = 0.23). CONCLUSION: postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

Regenerated Nerve Defects with a Nerve Conduit Containing Dental Pulp Stem Cells in Pigs: An Immunohistochemical and Electrophysiological Evaluation.

BACKGROUND: Dental pulp stem cells (DPSCs) present an exciting new tool in the field of peripheral nerve regeneration due to their close embryonic origin. In this study, we examined their potential in pigs, using biodegradable collagen conduits filled with DPSCs. To our knowledge, this is the first time DPCSs are tested for peripheral nerve regeneration in such large animal model. MATERIALS AND METHODS: The second lateral incisor was extracted from every animal's lower jaw and stem cells were isolated and cultured. The collagen nerve conduits containing the DPSCs were subsequently transplanted into the transected fifth and sixth intercostal nerves, while the seventh intercostal nerve was used as a control and no stem cells were added on the respective collagen conduit. RESULTS: A histological examination was performed on the 3rd and 6th postoperative months and showed the gradual development of neural tissue and immunohistochemical expression of neuron-specific enolase. An electrophysiological study was performed on the 6th postoperative month and showed similar potentials between the stem cell infusion region (5 ± 0.04 units) and their proximal stumps (5 ± 0.05 units) and slightly smaller potentials in the respective distal stumps (4 ± 0.045 units). CONCLUSION: The nerves where DPSCs were injected exhibited morphological and functional recovery, in contrast to the control nerves where no recovery was detected; thus, there is a first evidence of the therapeutic potential of DPSCs in peripheral nerve regeneration.

Management of vesicoenteric fistulas arising from perforated Meckel's diverticulum: a report of a case and review of the literature.

Vesicoenteric fistulas are rare, with an incidence of 0.1%-0.2% in the general population, and Meckel's diverticulum is a rare cause, accounting for less than 5% of cases with challenging diagnosis due to atypical symptoms at the admission. This article presents a case of a vesicoenteric fistula formation between Meckel's diverticulum perforated by a foreign body and urinary bladder in a 38-years-old Caucasian male admitted to emergency department due to colicky abdominal pain located in the lower abdomen. An extensive review of the literature was conducted referring all the cases of vesicoenteric fistula incorporating Meckel's diverticulum to elucidate the clinical characteristics, explore the diagnostic yield, and to summarize the therapeutic approach.

Endovascular Retrieval of a Detached and Dislocated Venous Port Catheter in the Right Heart Chamber Using a Triple-Loop Snare Device.

The authors present a case of a successful percutaneous retrieval of a detached port-a-catheter device that had migrated to the right cardiac chambers in a patient with inoperable pancreatic cancer and hepatic metastases. The patient was admitted to the vascular clinic department on an urgent basis due to an accidental detachment of the catheter during removal at another hospital. The catheter had migrated from the initial placement site in the right subclavian vein to the superior vena cava and right heart chambers. Under local anesthesia, the right femoral vein was accessed using the Seldinger technique, and the migrated catheter was retrieved using a triple-snare-loop device for foreign body removal. Chest radiography after the retrieval procedure did not show any foreign bodies in the right heart chambers or superior vena cava. The patient was discharged home the following day.

Evisceration of a Small Bowel Segment Through a Drain Site: Lesson Learnt.

Evisceration is described as the removal of intra-abdominal organs outside the abdominal cavity after partial or complete dehiscence of an operative incision. Multiple organs have been reported in the literature as being eviscerated through a drain site. Zero point five per cent (0.5) to 1.2% of all cases include the small bowel. In most cases, evisceration occurs three to eight hours post-operation. This article reports a case of an eviscerated small bowel segment through a drain site, along with the drain six hours post-operative. To our knowledge, such a complication following open abdominal or laparoscopic surgery has not yet been reported. Due to the imminent risk of strangulation and subsequent necrosis of the eviscerated visceral organ, drain site evisceration requires immediate intervention.

Asymptomatic Spontaneous Migration of the Tip of Port-A-Cath System Into the Right Internal Jugular Vein: A Case Report of an Uncommon Complication.

Venous port catheters are devices that allow access to the central venous system and, in clinical practice, are used for patients who require long-term intravenous therapy. The ideal position of the catheter tip is the distal superior vena cava and can be confirmed by a postoperative chest X-ray. Complications during and after the implantation are not rare, but spontaneous migration of the catheter tip into the internal jugular vein is an uncommon complication. Catheter migration may be accompanied by neck, shoulder, and ear pain. Venous phlebitis and thrombosis, and neurological complications, can become potentially life-threatening. We report a case of a spontaneous catheter tip migration into the right internal jugular vein that was diagnosed in a random chest roentgenography. The patient was taken to the operative room, and the catheter was successfully removed.

Hand compartment syndrome due to extravasation of contrast medium. A technical error. A report of a case and review of the literature.

The extravasation of contrast agents is one of the most common and remarkable complications during a computed tomography (CT) scan. The clinical manifestations are commonly minimal, leading to mild symptoms. However, in rare cases of high-volume extravasation, the complications are extremely threatening. Compartment syndrome of the hand and the forearm leads to critical dysfunction and upper limb necrosis. This article reported an unusual case of hand compartment syndrome following extravasation of iodinated contrast agent from a peripheral venous catheter, during a CT angiography, and its surgical treatment. Moreover, a literature review regarding all published similar surgically treated cases was conducted.

Double appendixes: A rare case report.

Anomalies of the appendix are rare, and one of the rarest is the double appendixes. Most anomalies of the appendix are observed in adults and are discovered incidentally during surgery that does not primarily involve the appendix. It is usually missed, often with life-threatening consequences.

Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine.

PURPOSE: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. METHODS AND MATERIALS: Mice were exposed to 6 Gy of whole body γ-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. RESULTS: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p<0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p<0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p<0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p<0.01), whereas Bnip3 levels increased. CONCLUSIONS: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.

Immunohistochemical study of angiogenesis after local administration of platelet-rich plasma in a patellar tendon defect.

A full thickness defect was made in the central portion of the patellar tendon of 48 New Zealand white rabbits. Platelet-rich plasma (PRP) gel was then applied and filled the tendon defect. The same procedure was performed in the control group, without the application of PRP. Animals were sacrificed after one, two, three, and four weeks. Histological and immunohistochemical analyses using a monoclonal antibody against CD31 were performed. The histological examination showed a superior healing process in the PRP group compared with the control group. Especially in the third week, the tissue formed in the PRP group was more mature and dense with less elastic fibres remaining. Neovascularisation was significantly higher in the PRP group during the first two weeks and significantly lower in the third and fourth weeks (p < 0.0001). Histological examination and study of angiogenesis showed that the application of PRP enhances and accelerates the tendon healing process.

Temporal and spatial expression of TGF-beta1 in an Achilles tendon section model after application of platelet-rich plasma.

BACKGROUND: To investigate the effect of platelet-rich plasma (PRP) on TGF-beta1 expression during tendon healing. METHODS: We used 48 skeletally mature New Zealand White rabbits. 24 rabbits received the PRP, and 24 rabbits served as an untreated control group. Equal numbers of animals were sacrificed at 1st, 2nd, 3rd, and 4th week. The surgical procedure involved a transverse incision to transect the Achilles tendon. A volume of 1ml of PRP was then injected into the tendon mass in the PRP group. Histological and immunohistochemical evaluations with an anti-TGF-beta primary antibody were performed. RESULTS: The pattern of expression of TGF-beta1 in the PRP group was characterized by a significant upregulation during the first 2 weeks and subsequently significant downregulation in the 3rd and 4th week in comparison with the controls. CONCLUSIONS: Our results suggest that PRP may affect the tendon healing process by altering the expression of TGF-beta1.

Comparison of Two Tubularized Incised Plate Urethroplasty Techniques in Hypospadias Reconstructive Surgery.

BACKGROUND: Hypospadias repair is a challenging type of urogenital reconstructive surgery for which different techniques are currently used. The purpose of this study is to determine the outcomes of distal, mid-shaft and proximal hypospadias repair using two new variations of tubularized incised plate (TIP) urethroplasty (TIP-δ and TIP-ελ) and to compare their complication rates with other already known operative techniques made from the same surgical team. METHODS: This study included 269 boys with hypospadias. The preoperative meatal site was distal in 179 patients, mid-shaft in 44 and proximal in 46. The average age at the operation was 17 months. The technique applied in distal hypospadias was Mathieu in 77 patients, Snodgrass in 28 and (TIP)-δ in 74. The technique applied in mid-shaft hypospadias was a tubularized island flap (TIF) in 12 patients, onlay island flap (OIF) in 5 and TIP-ελ in 27. The operative technique for proximal hypospadias was TIF in 15 patients, OIF in 10 and TIP-ελ in 21. TIP-δ and TIP-ελ are two new variants of TIP operation that we have used in our clinic since 2010. Postoperative complications were recorded, and we compared the outcomes obtained by applying the techniques. RESULTS: The use of TIP-δ in the distal hypospadias and long TIP-ελ in the mid-shaft and proximal hypospadias resulted in significantly fewer complications than the other surgical methods across all cases of hypospadias (p<0.05). CONCLUSION: The type of tissue used for neourethral coverage seems to play an important role in the outcome of hypospadias surgery.

The influence of platelet-rich plasma on angiogenesis during the early phase of tendon healing.

BACKGROUND: The poor vascularity of tendons is a major factor in their limited healing capacity. The aim of this study was to assess the effect of Platelet Rich Plasma (PRP) on angiogenesis during tendon healing. MATERIALS AND METHODS: Forty-eight skeletally mature New Zealand White rabbits were used. The Achilles tendon was transected transversely and 0.5 ml of PRP was injected into the tendon mass on each side of the incision on both limbs. The injection in the control group consisted of saline. Six animals from each group (12 tendons each) were sacrificed after 1, 2, 3, and 4 weeks following treatment. Three sections from each Achilles were stained with hematoxylinosin for microscopic examination. Further three sections were immunostained with a monoclonal antibody against CD31 (Daco Co), followed by image analysis to count new vessel numbers and statistical analysis was performed. RESULTS: There was significantly more angiogenesis in the PRP group compared to the control group during the first two weeks of the healing process, i.e., inflammatory and proliferative phase (p < 0.0001). The orientation of collagen fibers in the PRP group was better organized. The number of the newly formed vessels in the PRP group were significantly reduced at 4 weeks compared to the controls (p < 0.0001) suggesting the healing process was shortened. CONCLUSION: PRP seems to enhance neovascularization which may accelerate the healing process and promote scar tissue of better histological quality. CLINICAL RELEVANCE: Although these results need replication and further biomechanical research, PRP may promote tendon healing acceleration.

The effect of platelet-rich plasma gel in the early phase of patellar tendon healing.

INTRODUCTION: The aim of this study is to assess if an application of platelet-rich plasma (PRP) gel would improve the mechanical properties of rabbit's patellar tendon after resecting its central portion. MATERIALS AND METHODS: Forty skeletally mature New Zealand White rabbits were used. Two groups ten rabbits each (PRP and control group) were used to evaluate mechanical properties and histology after 14 days and two groups ten rabbits each (PRP and control groups) were used to evaluate mechanical properties and histology after 28 days. RESULTS: At 14 days, PRP group showed a 72.2% increase in force at failure, a 39.1% increase in ultimate stress, and a 53.1% increase in stiffness, as compared with controls. These changes were statistically significant (P < 0.05). At 28 days, there was no longer any significant difference between PRP and control groups (P > 0.05). DISCUSSION: In our study, the mechanical properties of the regenerated tendon in the PRP group were significantly improved in relation to the control group. It appears that PRP has a strong effect in the early phase of tendon healing. This effect is probably due to the growth factors that are released from the platelets during activation.

Does gender affect laparoscopic cholecystectomy?

The relationship between sex and outcome after laparoscopic surgery for symptomatic cholelithiasis remains unclear. The purpose of this study was to determine the influence of sex on the clinical presentation of patients with symptomatic gallstone disease and the clinical outcomes of laparoscopic cholecystectomy. The rates of conversion to open cholecystectomy, complication rates, operative times, and lengths of hospital stay were compared between the sexes. Compared with female patients, males were significantly older and more likely to have coexisting cardiovascular disease, previous upper abdominal surgery, previous hospitalization for acute cholecystitis and pancreatitis, acute cholecystitis, and suppurative cholecystitis (such as empyema), conversions, and complications. The mortality rate was nil. Analyses revealed an independent effect of sex on the prevalence of complications, even when including all of the major confounding factors in the model. In contrast, the effect of sex on conversion to open cholecystectomy was not significant when controlling for patient age. Operative time and postoperative hospital stay were significantly longer in males than in females. The tendency of male patients to have cholecystitis of greater severity should remind surgeons of the need to inform patients about the higher conversion rate among male patients, to reduce the disappointment of a large laparotomy wound or prolonged recovery period. On the other hand, there may be an increased need for surgeons to strongly advice male patients with symptomatic cholelithiasis to undergo early intervention.

The contribution of acute cholecystitis, obesity, and previous abdominal surgery on the outcome of laparoscopic cholecystectomy.

The aim of this study was to evaluate the impact of acute cholecystitis (AC), obesity, and previous abdominal surgery on laparoscopic cholecystectomy (LC) outcomes. Records of 1940 patients undergoing LC in 1992 and 2004 were reviewed in order to assess the independent and joint effects of the above risk factors on conversion, morbidity, operation time, and hospital stay. In multivariate regression analysis, adjusting for sex and age, AC alone and in combination with obesity or previous abdominal surgery increased the risk of conversion and complications and was associated with prolonged operation time and hospital stay compared with the patients without any of the risk factors (reference group). The independent and joint effects of obesity and previous abdominal surgery were significant only on operation time. On the contrary, previous upper abdominal surgery alone and in combination with AC was associated with 3- and 17-fold relative odds of conversion, respectively. The combined presence of AC, obesity, and previous abdominal surgery yielded an odds ratio for conversion of 7.5 and for complications of 10.7, as well as a longer operation time and hospital stay. The presence of previous upper abdominal surgery with AC and obesity had a substantial effect on conversion, with an odds ratio of 87.1 compared with the reference group. LC is safe in patients with AC, previous abdominal surgery, or obesity. However, the presence of inflammation alone or in combination with obesity and/or previous (especially upper) abdominal surgery is the main factor that influences the adverse outcomes of LC.

Temporal and Spatial Expression of TGF-b1 in the Early Phase of Patellar Tendon Healing after Application of Platelet Rich Plasma.

BACKGROUND: The aim of this study is to find out the spatial and temporal expression of TGF-b1 during the tendon healing, after application of Platelet Rich Plasma (PRP). METHODS: A patellar tendon defect model in rabbits was used for this purpose. 48 skeletally mature New Zealand White rabbits, weighing 3.5 kg, were used for this study. Equal numbers of animals from both groups were sacrificed at 4 different time points (1st, 2nd, 3rd, and 4th week). A full thickness patellar tendon substance in the right limb of each animal was excised from its central portion during the operation. PRP with a gel form was applied and filled the tendon defect in PRP group. No PRP was applied in the tendon defect of controls. Histological sections with hematoxylin-eosin and immunohistochemical sections with an anti-TGF-b1 primary antibody were made for the evaluation of the results. RESULTS: A differentiation of the healing process was observed in the PRP group in comparison with the control group. TGF-b1 expression was detected in various cell populations (inflammatory cells, endothelial cells, macrophages, and tenocytes). Both cytoplasmic and nuclear expressions were present. The larger amounts of immunoexpression were localized in epitenon and in the repair site. PRP group showed stronger and more extensive staining at 1st and 2nd week (P<0.0001), whereas control group showed more extensive staining at the 3(rd) and 4(th) week (P<0.0001). CONCLUSIONS: Our study demonstrates that locally application of PRP result in an alteration of TGF-b1 expression during the healing of a patellar tendon defect.

Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells.

BACKGROUND: Isothiocyanates are constituents of cruciferous vegetables which have been associated with reduced cancer risk partially through their ability to induce apoptosis in malignant cells including melanoma. MATERIALS AND METHODS: We have utilized human malignant melanoma (A375), epidermoid carcinoma (A431) and immortalized keratinocyte (HaCaT) cells exposed to various isothiocyanates, under different experimental conditions. RESULTS: An experimental in vitro model utilizing low isothiocyanate concentrations (0.1-5 µM for 48 h with all treatments being refreshed after 24h) was shown to be (i) most efficient in exerting an anti-cancer effect when compared to higher concentrations (5-100 µM for 24 or 48 h added as a single bolus) and (ii) specific to A375 cells while A431 and HaCaT cells remained unaffected. Such effect involved the activation of several caspases including (iii) initiator caspases 8, 9, 4 (indicating the involvement of intrinsic, extrinsic and endoplasmic reticulum-based pathways) and (iv) effector caspases 3, 7 and 6. CONCLUSION: Utilization of low isothiocyanate concentrations (under the conditions described herein) exerts an anti-cancer effect specific to human malignant melanoma cells thus providing a therapeutic basis for their utilization in management of the disease.

Laparoscopic cholecystectomy in obese patients.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the treatment of choice for gallstones. Obesity was initially considered a contraindication to this approach. The aim of this report is to review our experience with LC, to evaluate the role of BMI in the outcome. METHODS: The records of 1,804 patients who underwent LC for symptomatic cholelithiasis from May 1992 to January 2004 were analyzed retrospectively. Patients were divided into 5 groups according to their BMI: < or =24.9, 25.0-29.9, 30.0-34.9, 35.0-39.9 and > or =40 kg/m2. RESULTS: Of the 1,804 patients [1,379 females (76.4%) and 425 males (23.6%)] who underwent LC, 431(23.9%), 924 (51.2%), 355 (19.7%), 68 (3.8%) and 26 (1.4%) had BMI values of < or =24.9, 25.0-29.9, 30.0-34.9, 35.0-39.9 and > or =40 kg/m2, respectively. Conversion to open cholecystectomy was required in 94 patients (5.2%), and complications occurred in 39 patients (2.2%). There was no correlation between BMI and the conversion rate (P=0.593) and complication rate (P=0.944), while the hospital stay was similar between the groups with successful LC. The only significant difference was the longer operating time in the two obesity groups (P<0.001). CONCLUSIONS: LC is effective and safe in patients with morbid obesity. As it carried low risks of conversion and perioperative complications, we suggest that LC is the select approach for these patients. Moreover, the rapid mobilization and hospital discharge following LC may provide extra benefit to these patients.

The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status?

In this study we describe and discuss the dichotomous effects of docetaxel trastuzumab (Herceptin)/docetaxel therapy on the angiogenic molecular profile in two patients with her-2 + chemo-resistant recurrent breast carcinoma. In the first case, an intensification of angiogenesis occurred following therapy, accompanied by an impressive increase of the cancer cell proliferation index. This tumor did not express HIF1 alpha and shared a HIF-independent VEGF overexpression, which remained unaffected by therapy. An intensified formation of thymidine phosphorylase (TP)-rich stroma, presumably a response to docetaxel, shows a TP-dependent angiogenic response. In the second patient, VEGF and HIF1 alpha were down-regulated in post-treatment biopsies and this was accompanied by a sharp reduction of the vascular density and of the cancer cell proliferation rate. In both cases, c-erbB-2 expression was abrogated by Herceptin. Taking into account that Herceptin down-regulates VEGF through reduction of HIF1 alpha synthesis, this clinical study provides evidence that an anti-angiogenic effect from Herceptin/Docetaxel therapy is expected only in tumors with HIF1 alpha-dependent VEGF overexpression. In contrast, HIF1 alpha-independent VEGF angiogenic activity cannot be abrogated by Herceptin. Docetaxel mediated up-regulation of TP in the tumoral stroma may, on the contrary, result in angiogenesis intersification and rapid tumor relapse. Such an effect should be of clinical importance since Herceptin/Docetaxel-based regimens are currently evaluated for the adjuvant therapy of her-2 + breast cancer patients. Studying the Herceptin-induced phenotypic changes of tumors could lead to the identification of specific molecular profiles that bring about diverging angiogenic responses. Adjustment of the chemotherapy regimen accordingly would prove of clinical importance.