A Randomized Clinical Trial Evaluating rh-FGF-2/ß-TCP in Periodontal Defects.

Biological mediators have been used to enhance periodontal regeneration. The aim of this prospective randomized controlled study was to evaluate the safety and effectiveness of 3 doses of fibroblast growth factor 2 (FGF-2) when combined with a ß-tricalcium phosphate (ß-TCP) scaffold carrier placed in vertical infrabony periodontal defects in adult patients. In this double-blinded, dose-verification, externally monitored clinical study, 88 patients who required surgical intervention to treat a qualifying infrabony periodontal defect were randomized to 1 of 4 treatment groups-ß-TCP alone (control) and 0.1% recombinant human FGF-2 (rh-FGF-2), 0.3% rh-FGF-2, and 0.4% rh-FGF-2 with ß-TCP-following scaling and root planing of the tooth prior to a surgical appointment. Flap surgery was performed with EDTA conditioning of the root prior to device implantation. There were no statistically significant differences in patient demographics and baseline characteristics among the 4 treatment groups. When a composite outcome of gain in clinical attachment of 1.5 mm was used with a linear bone growth of 2.5 mm, a dose response pattern detected a plateau in the 0.3% and 0.4% rh-FGF-2/ß-TCP groups with significant improvements over control and 0.1% rh-FGF-2/ß-TCP groups. The success rate at 6 mo was 71% in the 2 higher-concentration groups, as compared with 45% in the control and lowest treatment groups. Percentage bone fill in the 2 higher-concentration groups was 75% and 71%, compared with 63% and 61% in the control and lowest treatment group. No increases in specific antibody to rh-FGF-2 were detected, and no serious adverse events related to the products were reported. The results from this multicenter trial demonstrated that the treatment of infrabony vertical periodontal defects can be enhanced with the addition of rh-FGF-2/ß-TCP (ClinicalTrials.gov NCT01728844).

Gemcitabine as palliative treatment in patients with unresectable pancreatic cancer previously treated with placement of a covered metal stent. A randomized controlled trial.

PURPOSE: To evaluate the efficacy of gemcitabine as palliative treatment in patients with advanced pancreatic cancer (PC) previously treated with placement of a covered metal biliary stent, taking into account survival and quality of life (QoL). PATIENTS AND METHODS: Forty-nine patients with unresectable PC and obstructive jaundice, previously treated with the placement of a covered metal biliary endoprosthesis, were randomized to receive gemcitabine (group A: 9 males, 7 females) or to be followed without any anticancer intervention (group B: 18 males, 15 females). Gemcitabine was administered weekly as intravenous (i.v.) 30 min infusion of 1000 mg/m2 for 3 consecutive weeks followed by 1-week rest (28-day cycle). QoL was evaluated with the QLQ-C30 questionnaire. RESULTS: 229 gemcitabine doses were administered (median doses per patient 14.3, range 7-22). No statistically significant differences were observed regarding survival (group A: median 21 weeks, range 13-33; group B: median 22 weeks, range 13-29; p=0.809). According to the average QLQ-C30 score, group B patients showed statistically significant higher values (p=0.0001). Leukopenia, neutropenia, thrombocytopenia and anemia were the most common side effects in group A (81.25, 68.75, 62.50 and 31.25%, respectively). CONCLUSION: Gemcitabine didn't show to improve survival and QoL in patients with advanced PC previously treated with a covered metallic biliary endoprosthesis due to obstructive jaundice.

Reconstruction of the chest wall.

Chest wall reconstructions can be a complex and challenging procedure and may require a multidisciplinary approach. The most common indications for chest wall reconstruction are repair of defects due to tumor resection, infection, radiation necrosis, congenital deformities or trauma. The repair of complex chest wall defects presents a challenging problem for the reconstructive surgeon. Although the majority of such defects can be repaired with the use of local and regional musculocutaneous flaps, more complicated cases require increasingly sophisticated reconstructive techniques. As defects increase in size, microsurgical techniques are necessary to augment blood flow to pedicled flaps or to provide free flap coverage from distant sites. A better understanding of the respiratory mechanics and local anatomy is crucial in managing these complex defects.

Melanoma of the head and neck: a review.

Melanoma of the head and neck and its treatment are complex issues. The behavior of head and neck melanoma is aggressive, and it has an overall poorer prognosis than that of other skin sites. Current understanding of the behavior of head and neck melanoma is reviewed and treatment strategies are presented. Controversies in treatment include the role of lymphoscintigraphy with sentinel node biopsy, nodal dissection, margin size, role of radiation therapy, and reconstruction. The therapeutic goal is to treat melanoma aggressively while minimizing the effects of treatment on patient's quality of life. Due to its biological behavior, head and neck melanoma should be treated in an aggressive manner when morbidity is not significantly increased. Patient's specific treatment is imperative.

Dermatofibrosarcoma protuberans: clinicopathological aspects of an unusual cutaneous tumor.

Dermatofibrosarcoma protuberans is a rare cutaneous tumor with particular characteristics and a high frequency of recurrence after inadequate primary treatment. Its histopathological diagnosis might be difficult. Dermatofibrosarcoma protuberans can be safely distinguished from other similar neoplasms of mesenchymal origin based on the immunohistochemical expression of CD34 antigen and the genetic presence of specific chromosomal translocations. Although rarely metastatic, it is followed by a significantly high rate of locoregional failure due to an indolent subcuticular tissue spread. Aggressive surgical management is the therapeutic approach of choice. A wide resection with microscopically disease-free margins is always recommended. Mohs' micrographic surgery together with advanced reconstructive techniques provides satisfactory results even for tumors involving the face or distal extremities.

Merkel cell carcinoma: clinicopathological aspects of an unusual neoplasm.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous cancer that predominately affects elderly Caucasians with fair skin and has a propensity for local recurrence and regional lymph node metastases. It can occur on the face, the trunk, the genitalia, and the perianal region. The median age of the patients is 69 years, but it may occur earlier and more frequently in immunosuppressed patients. MCC usually arises in the dermis and extends into the subcutis. It may be difficult to accurately diagnose MCC by light microscopy alone and ancillary techniques, including electron microscopy and immunohistochemistry, may be necessary for a definitive diagnosis. The management of MCC is dependent on the stage of the disease and is hampered by its rarity and lack of randomized trials. Nonetheless, for localized disease most guidelines include wide local excision of the primary tumor either alone or followed by radiation therapy. Sentinel lymph node biopsy can be helpful in staging and prognosis, but its benefit in survival remains to be seen. Systemic chemotherapy may be considered as an adjuvant following surgery or to treat locoregional or distant disease. The prognosis of MCC is variable. In patients with localized disease the course is indolent and is well-controlled with local excision alone. On the other hand, many tumors are aggressive and have a tendency for locoregional recurrence and distant metastases. Such patients have a grim prognosis, with a median survival of 9 months. Successful outcome most often is seen in patients with early diagnosis and complete excision.

Malignant hidradenoma: a report of two cases and review of the literature.

INTRODUCTION: Malignant tumors of the sweat glands are very rare. Clear cell hidradenoma is a lesion with histopathological features resembling those of eccrine poroma and eccrine spiradenoma. The biological behavior of the tumor is aggressive, with local recurrences reported in more than 50% of the surgically-treated cases. MATERIALS AND METHODS: Two patients are presented, the first with tumor in the right axillary region, the second with a recurrent tumor of the abdominal wall. The first patient underwent wide excision with clear margins and axillary lymph node dissection and the second patient underwent wide excision of the primary lesion and bilateral inguinal node dissection due to palpable nodes. RESULTS: The patients had uneventful postoperative courses. No additional treatment was administered. However, sixteen months after surgery, patient 2 developed extensive and massive recurrence involving almost the whole abdominal wall. Although he had received several chemotherapeutic agents, the disease had a relentless course and the patient succumbed two and a half years following surgery. CONCLUSION: Malignant tumors of the sweat glands are very rare neoplasms with no discrete clinical characteristics. It is necessary to suspect any lesion which shows evidence of enlargement and to verify its status by histological evaluation. Additional resection is generally required, with at least 2-cm clear margins, since surgery is the only effective treatment.

Mucocele of the appendiceal stump due to benign mucinous cystadenoma.

Mucocele of the appendix is a rare lesion, characterized by distension of the lumen due to accumulation of mucus material. Correct preoperative diagnosis is seldom achieved. If left untreated, the mucocele may rupture producing a potentially fatal peritoneal spread. The type of surgical treatment is related to the dimensions and histology of the mucocele. In this paper, the case of a 49-year-old woman, with a previous appendectomy, suffering from a painful mass in the right lower quadrant of the abdomen, is reported. Imaging showed a large, cystic structure at the base of the cecum. Surgery revealed a 8x5.5 cm calcified tumor, which was excided together with the appendiceal remnant. Pathological diagnosis was that of a mucocele arising from the appendiceal stump due to the development of a benign mucinous cystadenoma.

Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer.

BACKGROUND AND AIMS: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (5x5 Gy) not only reduces the risk of local recurrence but also improves overall survival rate. An increase in postoperative mortality and morbidity has also been observed, however. We therefore evaluated early postoperative complications in patients treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma. PATIENTS/METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on CT scan and, in several cases, on endorectal ultrasonography. They were 55 men and 30 women, with a median age of 68 years. They were retrospectively divided into two groups: Group A, which included 40 patients undergoing preoperative radiotherapy (25 Gy in five fractions) followed by surgery within 1 week, and Group B, which included 45 patients with rectal cancer receiving surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of the disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. RESULTS/FINDINGS: No postoperative deaths were recorded in either group. Low anterior resection with total mesorectal excision was performed in all group A patients, whereas eight patients in group B underwent abdominoperineal resection (P<0.05). Diverting stoma was performed in seven patients of group A and it was closed 3-6 months later on every occasion. Postoperative morbidity was not statistically significant between the two groups (40 vs 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection, and delayed ileus was similar. The percentage of major anastomotic leak was also equivalent (5 vs 6.6%). INTERPRETATION/CONCLUSION: Short-term preoperative radiotherapy does not increase the rate of postoperative complications and is a safe therapeutic adjunct for the treatment of locally advanced rectal cancer.

Unusual metastatic spread of follicular thyroid carcinoma: report of a case.

Concurrent skull and liver metastases from follicular thyroid carcinoma is a very rare event. We herein present the case of a 72-year-old woman who initially presented with a swelling in the right supraorbital region that proved to be metastasis from a well-differentiated follicular thyroid carcinoma of clear-cell type. The metastatic workup disclosed a huge liver metastasis and an additional metastasis in the left iliac fossa. The treatment of this patient included a total thyroidectomy, an excision of the skull lesion, and the administration of radioiodine therapy, as well as thyroid-stimulating hormone (TSH) suppression therapy. However, the course of her disease was relentless. Although well-differentiated thyroid carcinoma tends to show an excellent course, the presence of metastatic disease leads to a very dismal prognosis.

Short-term preoperative radiotherapy in locally advanced rectal cancer does not increase postoperative complications and improves the rate of sphincter-preserving surgery.

PURPOSE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (RT) (5x5 Gy) not only reduces the risk for local recurrence, but also improves the overall survival rate. However, an increase in postoperative mortality and morbidity has also been observed. We, therefore, evaluated the early postoperative complications in patients treated with neoadjuvant RT for locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on computed tomography (CT) scan and, in several cases, with endorectal ultrasonography. There were 55 men and 30 women, with a median age of 68 years. Patients were retrospectively divided into two groups: group A, which included 40 patients receiving preoperative RT (25 Gy in 5 fractions), followed by surgery within one week, and group B, which included 45 patients with rectal cancer undergoing surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. RESULTS: No postoperative deaths were recorded in either group. In group A, complete pathologic response was observed in 6 (15%) patients and microscopic residual cancer was found in 8 (20%). Low anterior resection (LAR) with total mesorectal excision (TME) was performed in all group A patients, whereas 8 patients in group B underwent abdominoperineal resection (APR) (p < 0.05). Diverting stoma was performed in 7 patients of group A; this was closed 3-6 months later in all cases. Postoperative morbidity was not statistically significant between the two groups (40% versus 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection and delayed ileus was similar. The percentage of major anastomotic leak was also similar in both groups (5 versus 6.6%). CONCLUSION: Short-term preoperative RT in locally advanced rectal cancer does not increase postoperative complications and improves the rate of sphincter-preserving surgery.

Ovarian fibrothecoma associated with Meigs' syndrome and elevated serum CA 125.

Meigs' syndrome consists of a benign ovarian tumor accompanied by ascites and hydrothorax. Elevated serum CA 125 in postmenopausal women with a solid adnexal mass, ascites and pleural effusion is highly suggestive of a malignant ovarian tumor. We report on an unusual case of a benign fibrothecoma of the ovary associated with Meigs' syndrome and elevated CA 125 level in an 62-year-old white female. Although rarely, a benign ovarian tumor should be considered in the differential diagnosis of an adnexal mass associated with Meigs' syndrome and elevated serum CA 125 levels.

Is gastroscopy still a valid diagnostic tool in detecting gastric MALT lymphomas? A dilemma beyond the eye. Mucosa-associated lymphoid tissue.

BACKGROUND: Primary gastric lymphomas are distinct entities with an indolent clinical course and biologic behavior. They account for 2-8% of all gastric malignancies. We conducted this study to evaluate the role of gastroscopy as the principal diagnostic method in detecting gastric MALT lymphomas. METHODS: Sixty-three consecutive patients with gastric MALT lymphomas, who were evaluated and treated at our institution between January 1978 and December 1997, are retrospectively reviewed. There were 36 males and 27 females, with a mean age of 53 years (range 20-80 years). All patients underwent the standard diagnostic evaluation, including gastroscopy and biopsy. Patients were staged according to revised Musshof modification of the Ann Arbor classification system, whereas histological evaluation was made according to the Isaacson classification system for gastric MALT lymphomas. RESULTS: According to endoscopic findings, the antrum harbored the neoplasm in 31 patients (49%), the body in 38% (24 patients), and the fundus in 4% (3 patients), whereas in 5 patients (8%) the neoplasm occupied the entire stomach. The macroscopic appearance was not in most cases pathognomonic of the disease. Three macroscopic patterns were recognized at endoscopy: (a) the ulcerative in 51% (32 patients), (b) the polypoid in 33% (21 patients) and (c) the diffuse infiltrative in 16% (10 patients). The neoplasm was characterized as a benign disease in 24 patients (38%), with malignancy being suspected in 62% (39 patients). Endoscopy displayed a sensitivity of 61% in detecting malignancy; however, the sensitivity dropped to 27% when endoscopic diagnosis of non-Hodgkin's lymphoma was hypothesized. CONCLUSIONS: Although the impact of gastroscopy as a diagnostic tool in the patients of our study was of limited value, due to the nonspecific gross pattern of gastric MALT lymphomas, it should be maintained in the diagnostic intervention of the upper GI tract pathologies.

Unusual spread of liposarcoma.

BACKGROUND: The aim of our study was to investigate the unusual pattern of metastatic spread of liposarcoma. MATERIALS AND METHODS: We retrospectively studied thirty-two patients with liposarcoma (in seventeen located in the retroperitoneum and in fifteen in the extremities) who were managed at our institution over a ten-year period. Six patients with extremity liposarcoma developed local recurrence and or distal metastases and in three the site of the distal spread was other than the lungs. In only one patient with retroperitoneal liposarcoma we observed extra-pulmonary spread. The histologic type of all four cases with unusual spread was myxoid, with small areas of round cell differentiation in two cases. RESULTS: The survival of the patients after the initial recurrence was relatively prolonged (6, 1.5, 8 and 3 years with the last patient alive and well). CONCLUSION: Physicians should maintain a low threshold for initiating evaluation of relatively minor symptoms in patients with liposarcoma, as these symptoms may reflect the first manifestation of an extrapulmonary metastasis. Such an approach should result in earlier detection and hopefully improve survival for patients with liposarcoma.

Treatment-related acute gastric bleeding managed successfully with surgical devascularization.

BACKGROUND AND OBJECTIVES: Patients with gastric lymphoma treated by chemotherapy or radiation therapy are at high risk of developing complications, most commonly perforation or bleeding. In any case of upper gastrointestinal tract bleeding during conservative treatment for gastric lymphoma, thorough investigation is required to exclude other causes of hemorrhage which could be managed appropriately. When the source of bleeding is the tumor, the only effective measure is resection of the stomach, a very dangerous operation in these poor-risk patients. METHODS: We treated 3 consecutive patients with life-threatening gastric bleeding from lymphoma treated by chemotherapy. RESULTS: We successfully controlled the hemorrhage by surgical devascularization. CONCLUSION: Devascularization of the involved part of the stomach is safe and effective.

Administration of tamoxifen in the perioperative period to patients with breast carcinoma prolongs axillary fluid drainage.

Compelling evidence points to an estrogen receptor independent mechanism of action of tamoxifen in the extracellular matrix, in addition to its action via the estrogen receptors. We retrospectively studied 380 patients who underwent curative resection for primary breast cancer in our institution from January 1994 to December 1998, of which 227 received tamoxifen in the perioperative period and the remaining 153 never received tamoxifen or delayed the initiation of treatment for at least two weeks following the operation. The administration of tamoxifen in the perioperative period resulted in the prolongation of axillary drainage (mean 10.07 SD 4.18 days vs mean 8.33 SD 2.85 days), which was statistically significant for patients younger than 70 years. There was no difference in the duration of fluid drainage in relation to the number of positive nodes, except in cases of more than 9 nodes involved by the tumor. We assumed that tamoxifen causes a delay in would healing through the secretion of active transforming growth factor beta(TGF-beta), which is the principle negative growth modulator and which can be secreted from epithelial and stromal elements, independently of hormonal receptor status.

Colorectal cancer trends by anatomic sides, age and staging. A twenty-year study of 1412 Greek cases.

The purpose of this study was to investigate whether Greek patients, suffering from colorectal adenocarcinoma, showed the same changes in the side distribution, as has been observed in the patients of many western countries. We retrospectively analysed 1412 consecutive cases of colorectal adenocarcinoma admitted to our institute over in a twenty-year period. The side distribution, the staging and the grade were evaluated in correlation with the age. We found that the number of patients with colorectal adenocarcinoma has steadily increased. The right-sided colonic carcinomas remained stable over the years in the total number of cases, however, for the elderly patients (age > 65 years), there was trend of gradual but steady increase in the incidence. We did not observe any evidence of earlier diagnosis in recent years. We conclude that a delayed but similar trend in the incidence and distribution of colorectal adenocarcinoma is present in Greek patients. The maintenance of the traditional dietary habits could change the pattern.

Epirubicin plus tamoxifen versus tamoxifen alone in node-positive postmenopausal patients with breast cancer: A randomized trial of the International Collaborative Cancer Group.

PURPOSE: To assess whether the addition of epirubicin (EPI) therapy to prolonged treatment with tamoxifen (TAM) improves relapse-free and overall survival in postmenopausal women with node-positive primary breast cancer. PATIENTS AND METHODS: Six hundred four patients entered onto a randomized clinical trial were allocated to receive TAM 20 mg/d for 4 years or TAM 20 mg/d for 4 years plus EPI 50 mg/m(2) intravenously on days 1 and 8 every 4 weeks for six cycles. Analysis was performed according to allocated treatment, with all randomized patients included (intention to treat), irrespective of eligibility status. RESULTS: After a median follow-up period of 5.7 years, an improvement in relapse-free survival (RFS) was observed for the TAM and EPI-treated patients, compared with those who received TAM alone. The unadjusted hazard ratio was 0.72 (95% confidence interval, 0.54 to 0.96), with a corresponding reduction in the odds of recurrence of 27.9% (SD, 12. 3), which was statistically significant (P =.023). Adjustment for prognostic and/or predictive factors did not materially affect the hazard ratio. No difference was observed in terms of overall survival (reduction in odds of death, 11.9% [SD, 16.3]; P =.46). Combined chemohormonal treatment was associated with a higher incidence of acute side effects but without a clear increase in long-term cardiotoxicity. Twelve nonbreast second malignancies, including five hematologic malignancies (two of which were cases of acute myelogenous leukemia), were observed. CONCLUSION: The data show that combined chemohormonal treatment reduces the risk of relapse in postmenopausal patients with node-positive breast cancer. No evidence was found, however, for an improvement in overall survival. The size of benefit observed for both outcomes was consistent with that reported in the Early Breast Cancer Trialists' Collaborative Group overview. The trial presented here, however, provides the first report of an improvement in RFS associated with the provision of a single cytotoxic drug in addition to prolonged TAM.

Competent gastrostomy for patients with head and neck cancer.

This study was performed to evaluate the efficiency and patient satisfaction with a modified Janeway gastrostomy for patients with head and neck cancer and cancer of the upper GI tract and involved 24 consecutive patients with serious malnutrition caused by advanced cancer of these sites. All underwent surgery during which a tube was constructed from the anterior gastric wall with the aid of GIA-75 automatic stapler. The operation was performed under local anaesthesia, with a senior anaesthesiologist, who sedated the patients, in attendance. The operation was successful in all cases. No postoperative mortality could be attributed to the operation. The complications were minor. The patient's close relatives were able to feed them intermittently with home-made formula made according to the instructions of our dietician. No late complications were recorded. Overall, the patients were satisfied with his technique for managing their feeding problem. The modified Janeway gastrostomy is an easy and safe operative procedure; it is an effective way of managing patients with malnutrition as a result of cancer of the head and neck or of the upper GI tract.