Predictive significance of preoperative serum VEGF-C and VEGF-D, independently and combined with Ca19-9, for the presence of malignancy and lymph node metastasis in patients with gastric cancer.

BACKGROUND: Cumulative evidence demonstrate that lymphangiogenic vascular endothelial growth factors (VEGF)-C and -D are over-expressed and associated to lymph node metastasis (LNM) in gastric cancer. The aim of this study is to investigate whether preoperative serum levels of VEGF-C and VEGF-D could be useful tumor markers in patients with operable gastric adenocarcinoma. METHODS: We prospectively examined serum samples from 40 patients and 40 non-cancer controls using enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was implemented. VEGF-C and VEGF-D were studied independently and in combination with Ca19-9. RESULTS: In gastric cancer patients, preoperative VEGF-C was significantly lower as compared to controls and to postoperative VEGF-C (P < 0.001); preoperative VEGF-D was significantly higher as compared to controls and to postoperative VEGF-D (P < 0.001). ROC curve analysis identified a VEGF-C/VEGF-D cut-off value of < 2.7 for the presence of gastric cancer, with 83% sensitivity and 75% specificity (P < 0.001). Backward stepwise selection modeling including sex, age, VEGF-D and Ca19-9, predicted the presence of LNM with 86% sensitivity and 82% specificity (P < 0.001). CONCLUSION: Circulating levels of VEGF-C and VEGF-D could play a role as biomarkers for serological detection and staging in gastric cancer.

Swordfish bill injury involving abdomen and vertebral column: case report and review.

BACKGROUND: Penetrating injuries of the abdomen and spinal canal that involve organic material of animal origin are extremely rare and derive from domestic and wild animal attacks or fish attacks. CASE PRESENTATION: In this case report we present the unique, as far as the literature is concerned, unprovoked woman's injury to the abdomen by a swordfish. There are only four cases of swordfish attacks on humans in the literature - one resulted to thoracic trauma, two to head trauma and one to knee trauma, one of which was fatal - none of which were unprovoked. Three victims were professional or amateur fishermen whereas in the last reported case the victim was a bather as in our case. Our case is the only case where organic debris of animal's origin remained in the spinal canal after penetrating trauma. CONCLUSIONS: Although much has been written about the management of penetrating abdominal and spinal cord trauma, controversy remains about the optimal management. Moreover, there is little experience in the management of patients with such spinal injuries, due to the fact that such cases are extremely rare. In this report we focus on the patient's treatment with regard to abdominal and spinal trauma and present a review of the literature.

Prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis.

BACKGROUND: Most patients with pancreatic adenocarcinoma are diagnosed with locally advanced (unresectable) or metastatic disease. The aim of this study was to investigate possible prognostic factors of survival in such patients. PATIENTS AND METHODS: Two hundred and fifteen patients were studied retrospectively. Twenty-four potential prognostic variables (demographics, clinical parameters, biochemical markers, treatment modality) were examined. RESULTS: Mean survival was 29.0 weeks. 21.9% survived more than 36 weeks. On multivariate analysis, 10 factors had an independent effect on survival: tumour localisation, metastasis, performance status, jaundice, weight loss, C reactive protein, CEA, CA 19-9, palliative surgery and chemotherapy. Patients managed only with palliative care had a hazard ratio of 8.94 versus those offered a combination of palliative surgery and chemotherapy. CONCLUSION: Many factors could be used as predictors of survival in patients with advanced or metastatic pancreatic cancer. Chemotherapy and palliative surgery are associated with increased survival, and should be offered to all eligible patients.

Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?

Metastasis is the principal cause of cancer mortality, with the lymphatic system being the first route of tumor dissemination. The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF) family, whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation, lymphatic system disorders and malignant tumor metastasis. They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell, resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis). Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Experimental and clinicopathological studies have linked the VEGF-C, VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors. The majority of these data are derived from surgical specimens and malignant cell series, rendering their clinical application questionable, due to subjectivity factors and post-treatment quantification. In an effort to overcome these drawbacks, an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric, esophageal and colorectal cancer. Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.

Sequential administration of 5-fluorouracil (5FU)/leucovorin (LV) followed by irinotecan (CPT-11) at relapse versus CPT-11 followed by 5-FU/LV in advanced colorectal carcinoma. A phase III randomized study.

PURPOSE: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). PATIENTS AND METHODS: Chemotherapy-naïve patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m(2) LV and 425 mg/m(2) 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m(2)), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. RESULTS: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. CONCLUSIONS: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse.

Open and laparoscopic approach in incisional hernia repair with ePTFE prosthesis.

BACKGROUND: The aim of this retrospective study was to analyze the results of incisional hernia laparoscopic and open surgery, focusing on the morbidity and postoperative implications. MATERIALS AND METHODS: A group of 106 (42 men, 64 women) patients suffering from incisional hernias were treated with either a laparoscopic (30) or an open (76) placement of a prosthetic mesh between January 1997 and December 2004. The age and gender of the patients, the size and type of the mesh, operation note, the length of postoperative hospital stay, and morbidity were recorded. RESULTS: An expanded polytetrafluoroethylene (ePTFE) mesh was used in 103 patients, whereas a polypropylene mesh was used in 3 patients. In the open technique, 3 patients with the ePTFE prosthetic material developed a mesh infection and required a mesh removal, which was easily performed under local anesthesia. Moreover, 2 patients from the same group developed a hernia recurrence. As for the laparoscopic approach, the only complication observed was one hernia recurrence. Finally, it should be mentioned that 1 patient with a polypropylene mesh developed a colocutaneous fistula. CONCLUSIONS: The benefits of the laparoscopic mesh technique, compared to the open technique, include a shorter hospital stay, less postoperative pain, and possibly, a reduction in wound and mesh complications. Regarding the recurrence rate, the two techniques show similar results.

Laparoscopic surgery for adrenal tumors. A retrospective analysis.

OBJECTIVE: Laparoscopic adrenalectomy has rapidly replaced open adrenalectomy as the procedure of choice for benign adrenal tumors. The aim of this study was to evaluate the short- and long-term results of 100 consecutive laparoscopic and open adrenalectomies performed during a period of 8.5 years in our Surgical Unit. DESIGN: A retrospective analysis of patients operated on for adrenal tumors was conducted. From May 1997 to August 2005, one hundred adrenalectomies were performed on 95 patients. Five patients underwent either synchronous or metachronous bilateral adrenalectomy. There were 38 men and 57 women, aged 16 to 80 years. The size of tumors in our series ranged from 3.2 to 27 cm. The largest laparoscopically excised tumor was a ganglioneuroma with a diameter of 13 cm. RESULTS: In 73 patients laparoscopic procedure was completed successfully. In 8 cases the laparoscopic procedure was converted to open. Fourteen patients were treated with open approach. One patient with pheochromocytoma succumbed following pulmonary embolus. In one patient with morbid obesity, Cushing's syndrome, and bilateral adrenal macronodular hyperplasia, the left laparoscopic adrenalectomy was complicated by a low output pancreatic fistula, conservatively treated. All other patients had an uneventful course. Operative time for laparoscopic adrenalectomies ranged from 65 to 180 minutes. The average postoperative hospital stay for laparoscopic adrenalectomy ranged from 1 to 2 days (1.5 days), versus 5 to 20 days for patients who underwent open or converted procedure. CONCLUSIONS: Laparoscopic adrenalectomy should be the treatment of choice for all benign adrenal tumors. Laparoscopic resection of large adrenal tumors necessitates experience in open surgery and advanced laparoscopic surgery.

Esophageal Doppler (ODM II) improves intraoperative hemodynamic monitoring during laparoscopic surgery.

Minimally invasive laparoscopic surgery has been expanded to the elderly and high-risk surgical patients with underlying cardiac and pulmonary disease. However, possible cardiovascular changes during CO2 pneumoperitoneum necessitate close intraoperative monitoring. In this prospective study, 55 patients (mean age 62.52 years, range 26-82) undergoing laparoscopic surgery were included. Patients were categorized into 3 groups of low (group A: 12 patients, mean age 55.5 years), moderate (group B: 22 patients, mean age 59.5 years), and high (group C: 21 patients, mean age 69.71 years) surgical risk according to ASA physical status classification. Similar anesthetic agents and anesthetic techniques were used in the above cases. An esophageal Doppler (ODM II, Abbott Laboratories) was used to measure aortic blood flow velocity and thereby estimating stroke volume (SVe) and cardiac output (COe) throughout anesthesia, in addition to traditional monitoring. After abdominal insufflation (peak intra-abdominal pressure: 13-15 mm Hg) COe values decreased from the initial value after induction of anesthesia by 22%, 20%, and 18% for groups A, B, and C, respectively (P < 0.05). The above values further deteriorated (25%, 28%, and 30% for groups A, B, and C, respectively) in the anti-Trendelenburg positioning of the patient. The peak aortic blood flow velocity (PV) followed the changes, thus indicating that heart muscle contractility is affected during the procedure. Stabilization of the above values was achieved after 20 minutes of CO(2) pneumoperitoneum and improvement was noted only after deflation of the abdomen. Heart rate and blood pressure essentially remained unchanged throughout the procedure, although the final values were increased compared with initial. Insufflation of the abdomen with CO(2) produces measurable effects on the cardiovascular system that require reappraisal of hemodynamic monitoring during anesthesia. ODM II offers a reliable, relatively noninvasive, cost-effective tool for intraoperative monitoring of the hemodynamic changes with a potential for future application for improvement of intraoperative hemodynamic status of patients.

Preoperative imaging and localization of small sized insulinoma with EUS-guided fine needle tattoing: a case report.

We report a case of an insulinoma that was not identified on either Computerized Tomography (CT) scan and Magnetic Resonance Imaging (MRI). Endoscopic ultrasonography (EUS) revealed a small insulinoma located at the body of the pancreas, which was histologically confirmed. The patient underwent a laparotomy but no tumour was identified either on palpation or with intra-operative ultrasound (IOUS). Subsequently, a further EUS was performed and after the tumour was identified was injected with blue dye. The patient then underwent a second exploratory laparotomy and a tumour at the posterior aspect of the pancreas close to the left side of the portal vein was identified and was successfully excised. Histology confirmed the presence of an endocrine tumour staining for chromogranin A and insulin. The patient had an uneventful postoperative recovery and has developed no further episodes of hypoglycemia 3 years after surgery.

ACTH-Producing Cholangiocarcinoma Associated with Cushing's Syndrome.

A 61-year~old woman was admitted to the hospital with clinical manifestations of Cushing's syndrome. The ACTH level was 1340 pglmL, the urinary free cortisol level > 900 pg/mL, and the serum K+ levels 21 meqlL. The brain/pituitary MRI and thoracic CT scan were normal. Gastroscopy, colonoscopy, and small bowel follow through were normal. Abdominal CT and MRI showed normal adrenals, but dilated gallbladder with numerous gallstones, as well as peripancreatic and hepatoduodenal lymphadenopathy. A large meta-static deposit and three smaller lesions were also seen in the liver. Because of the poor respiratory function tests and the severe hypokalaemia, laparoscopy under local anaesthesia was performed. Following the procedure the patient became gradually jaundiced and thus underwent exploratory laparotomy. Locally advanced cholangiocarcinoma was found, infiltrating the liver hilum, with multiple small bilateral liver metastatic deposits. Acute cholecystitis with pericholecystic abscess was also found. Cholecystostomy as well as gallbladder, liver and hilar node biopsies were performed. Histopathology showed liver adenocarcinoma of bile duct origin, while immunocytochemistry revealed scattered, chromogranin A positive cells, some of them strongly immunoreactive for ACTH. Small clusters of chromogranin A positive cells were also found to be immunoreactive for CRH, but not for ACTH.

Etoposide added to weekly leucovorin (LV)/5-fluorouracil (5-FU) in LV/5-FU pre-treated patients with advanced colorectal cancer.

BACKGROUND: We evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV + 5-FU. MATERIAL/METHODS: Etoposide was administered at 3 different dose levels (DL), in 3 groups of patients (total=60): DL-I - etoposide 80 mg/m2, 45 min i.v. infusion, DL-II - etoposide 120 mg/m2, and DL-III - etoposide 180 mg/m2. In all three levels etoposide was followed by LV 100 mg/m2 i.v., 1-hour infusion, and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered until disease progression or unacceptable toxicity. RESULTS: No patients responded at DL-I, while 2 patients at DL-II and 3 at DL-III had a partial response (PR) (P<0.1). Two patients had stable disease (SD) at DL-I, 8 at DL-II, and 9 at DL-III (P<0.01). More patients progressed at DL-I (n=19) compared to DL-II (n=10) and DL-III (n=8) (p<0.0007). The time to progression was 17, 15, and 14 weeks, respectively, for DL-I, -II, and -III (P=0.9). Median survival was 30, 30, and 32.5 weeks, respectively, for DL-I, -II, and -III (P= 0.27). Toxicity was mainly neutropenia, diarrhea and mucositis at all DLs, significantly more intense in DL-III. No difference was noticed in responses between DL-II and DL-III, but toxicity in DL-III was more severe. CONCLUSIONS: The combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC.

Weekly gemcitabine for the treatment of biliary tract and gallbladder cancer.

OBJECTIVES: To evaluate the efficacy and safety of weekly administration of gemcitabine treatment in chemotherapy-naïve patients with advanced biliary tract and gallbladder cancer. PATIENTS AND METHODS: Gemcitabine at a dose of 800 mg/m2 was administered weekly as a 30-min infusion to patients with previously operated, histologically confirmed, metastatic, or unresectable locally advanced cholangiocarcinoma. Treatment was continued until unacceptable toxicity or disease progression. RESULTS: A total of 30 patients (median age 66 years; range 54-72 years) were included in the study. A median of 14 (range, 4-33) weekly doses was administered. Out of 30 patients evaluable for response, nine partial responses were observed (30.0%), while a further 11 patients demonstrated stable disease (36.7%). The median time to disease progression was 7 months (range, 5-34). Overall response rate was superior in patients with cancer of the gallbladder (ORR = 35.7%) compared with those patients with biliary duct cancer (ORR = 27.3%). This correlated to a significantly longer time to progression of 6.4 months (95% confidence interval (CI), 5.6-7.1 months) versus 3.6 months (95% CI, 2.9-4.3 months; p = 0.03) and a significantly better overall survival of 17.1 months (95% CI, 15.8-18.5 months) versus 11.4 months (95% CI, 10.2-12.6 months, p = 0.021). Toxicities were generally mild with only one case of grade 3 neutropenia. There were no cases of febrile neutropenia and no treatment-related deaths. CONCLUSIONS: Weekly administration of gemcitabine provides a safe, well-tolerated, and effective treatment for chemotherapy naïve patients with advanced cholangiocarcinoma, particularly with a gallbladder origin.