Metallothionein in bladder cancer: correlation of overexpression with poor outcome after chemotherapy

We examined metallothionein (MT) expression in bladder cancer and its relationship to clinicopathologic factors, survival data, and outcome of chemotherapy. In 97 patients who underwent radical cystectomy for bladder cancer, 34 of whom received cisplatin-based chemotherapy, MT expression was evaluated immunohistochemically. Results were correlated with histopathologic data, survival rates, and outcome of chemotherapy. MT overexpresison was present in 33 patients (34.0%): strong in 7 (7.2%) and focal in 26 (26.8%). Overexpression was an independent prognostic factor and was significantly associated with poor survival. Patients undergoing chemotherapy showed worse survival if their tumours were MT-positive than if they were MT-negative. MT overexpression predicts unfavorable survival in bladder cancer patients. In those treated with cisplatin chemotherapy, survival is significantly poorer if tumours express MT. Our results show that MT overexpression may mediate resistance to alkylating agents. Therefore, further studies are warranted to define those patients who need a more aggressive therapy.     

Evidence that Treatment with Risedronate in Women with Postmenopausal Osteoporosis Affects Bone Mineralization and Bone Volume

Risedronate is used in osteoporosis treatment. Postmenopausal women enrolled in the Vertebral Efficacy with Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for 3 years. Subjects received calcium and vitamin D supplementation if deficient at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline and at 3 years. Quantitative back-scattered electron imaging (qBEI) was performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13) before and after treatment, and the mineral volume fraction in the trabecular bone was calculated. Combining dual-energy X-ray absorptiometric values with the mineral volume fraction for the same patients allowed us to calculate the relative change in trabecular bone volume with treatment. This showed that the effect on BMD was likely to be due partly to changes in matrix mineralization and partly due to changes in bone volume. After treatment, trabecular bone volume in the lumbar spine tended to increase in the risedronate group (+2.4%, nonsignificant) but there was a significant decrease (−3.7%, P < 0.05) in the placebo group. Calcium supplementation with adequate levels of vitamin D led to an ∼3.3% increase in mineral content in the bone material independently of risedronate treatment. This increase was larger in patients with lower matrix mineralization at baseline and likely resulted from correction of calcium/vitamin D deficiency as well as from reduced bone remodeling. Combining BMD and bone mineralization density distribution data show that in postmenopausal osteoporosis 3-year treatment with risedronate preserves or may increase trabecular bone volume, unlike placebo. This analysis also allows, for the first time, separation of the contributions of bone volume and matrix mineralization to the increase in BMD.     

The relationship between the expression of E-cadherin and tumor recurrence and progression in high-grade stage T1 bladder urothelial carcinoma

Objective To evaluate the relationship between the expression of E-cadherin (E-CD) and tumor recurrence and progression in patients with high-grade stage T1 urothelial carcinoma of bladder. Methods Fifty-two patients who had primary high-grade stage T1 urothelial carcinoma were enrolled to the study. The pathologic specimens of patients were evaluated and staged as T1a and T1b according to muscularis mucosae involvement by the tumor. The immunohistochemical demonstration of E-CD was accomplished by using immunoperoxidase method and all the specimens were examined under light microscope for E-CD level. Results The mean age of the patients was 64.0 ± 7.7 (range 36–81) years. The mean follow-up period was 56.4 ± 19.4 (range 14–84) months. Among 52 patients, 27 (52%) of them were stage T1b and 25 (48%) were T1a tumors. The recurrence rates for T1a and T1b groups were 52% (n = 13) and 92.6% (n = 25), respectively (P < 0.05). The expression of E-CD was homogenous in 52% of pT1a and 14.8% of T1b tumors (P < 0.05). In T1a group with recurrence, homogeneous E-CD staining ratio was 30.7% (n = 4/13), but it was 75% (n = 9/12) in T1a patients without recurrence (P < 0.05). In T1b group with recurrence, the homogenous expression of E-CD was 12% (n = 3/25) and the expression of E-CD was heterogenous in 88% (n = 22/25) of them (P < 0.05). In T1a group, progression of the disease was detected in 28% (n = 7/25) of the patients, but disease progression was seen in 55.5% (n = 15/27) of T1b group patients (P < 0.05). In T1a group with progression, heterogeneous E-CD staining ratio was 85.7% (n = 6/7), but it was 80% (n = 12/15) in T1b patients with progression. The effects of tumor number, tumor size and carcinoma in situ presence on recurrence were evaluated within each group. It was determined that parameters such as tumor number and tumor size had no significant effect on recurrence of the groups. The mean survival rates were statistically different between the groups. On multivariate analysis only E-cadherin expression (P = 0.012, odds ratio 6.291, 95% confidence interval for odds ratio 1.303–4.72) and tumor stage (P = 0.003, odds ratio 11.58, 95% confidence interval for odds ratio 2.446–8.542) remained independently significant as predictors of recurrence. Conclusion E-CD expression was decreased in pathologic specimens of bladder tumor patients with muscularis mucosae involvement and this condition correlated well with tumor recurrence.     

An Innovative Option for Venous Reconstruction After Pancreaticoduodenectomy: the Left Renal Vein

Introduction Pancreatic ductal adenocarcinoma has a high mortality rate with limited treatment options. One option is pancreaticoduodenectomy, although complete resection may require venous resection. Pancreaticoduodenectomy with venous resection and reconstruction is becoming a more common practice with many choices for venous reconstruction. We describe the technique of using the left renal vein as a conduit for venous reconstruction during pancreaticoduodenectomy. Methods The technique for use of the left renal vein as an interposition graft for venous reconstruction during pancreaticoduodenectomy is described as well as outcomes for nine patients that have undergone the procedure. Results Nine patients, seven men, with a mean age of 57 years, have undergone the operation. There were eight interposition grafts and one patch graft. Mean operating time was 7.8 hours, and mean tumor size was 3.4 cm. Eight patients had node-positive disease, and six had involvement of the vein. Mean hospital stay was 14 days and perioperative morbidity included a superficial wound infection, delayed gastric emptying, ascites, and gastrointestinal bleeding in one patient each. Creatinine ranged from 0.8–1.1 mg/dl preoperatively and from 0.7–1.3 mg/dl at discharge. Mean follow-up was 6.8 months with normal creatinine values noted through the follow-up period. Two patients had died during follow-up from recurrent disease at 8.3 and 18.2 months after the operation. Conclusions The left renal vein provides an additional choice for an autologous graft during pancreaticoduodenectomy with venous resection. The ease of harvesting the graft and maintenance of renal function distinguish its use.     

Association of Hypoalbuminemia on the First Postoperative Day and Complications Following Esophagectomy

Objective Changes in serum albumin may reflect systemic immunoinflammation and hypermetabolism in response to insults such as trauma and sepsis. Esophagectomy is associated with a major metabolic stress, and the aim of this study was to determine if the absolute albumin level on the first postoperative day was of value in predicting in-hospital complications. Methods A retrospective study of 200 patients undergoing esophagectomy for malignant disease at St. James Hospital between 1999 and 2005 was performed. Patients who had pre and postoperative (days 1, 3, and 7) serum albumin levels measured were included in the study. Patients were subdivided into three postoperative albumin categories <20 g/l, 20–25 g/l, >25 g/l. Logistic regression analysis was performed to calculate the odds of morbidity and mortality according to the day 1 albumin level. Results Patients with an albumin of less than 20 g/l on the first postoperative day were twice as likely to develop postoperative complications than those with an albumin of greater than 20 g/l (54 vs 28% respectively, p < 0.011). Correspondingly, these patients also had a significantly higher rate of Adult Respiratory Distress Syndrome (22 vs 5%, p < 0.001), respiratory failure (27 vs 8%, p < 0.01) and in-hospital mortality (27 vs 6% (p < 0.001). On multivariate logistic regression analysis, day 1 albumin level was independently related to postoperative complications (odds ratios, 0.89: 95%; confidence intervals, 0.83–0.96; p < 0.005). In addition, albumin <20 g/l on the first postoperative day was associated with the need for further surgery and a return to ICU. Conclusion Serum albumin concentration on the first postoperative day is a better predictor of surgical outcome than many other preoperative risk factors. It is a low cost test that may be used as a prognostic tool to detect the risk of adverse surgical outcomes.     

Diagnosis and Management of Internal Hernias after Laparoscopic Gastric Bypass

BACKGROUND: Internal hernia is a known complication of laparoscopic Roux-en-Y gastric bypass (LRYGBP). However, no consensus exists regarding optimal diagnostic modality and management. We reviewed the literature and our own experience, and present an algorithm for the diagnosis and management of internal hernia after LRYGBP. METHODS: A retrospective review of 290 retrocolic LRYGBPs was performed to identify those who developed postoperative small bowel obstruction due to internal hernia. Demographics, clinical symptoms, radiologic characteristics, and operative outcomes were analyzed to determine clinical and radiological diagnostic accuracy. RESULTS: Over a 43-month period, 11 out of 290 (3.79%) post-LRYGBP patients with symptoms suggestive of a small bowel obstruction underwent operative exploration. The most common clinical symptoms included intermittent abdominal pain, and/or nausea/vomiting. All patients were initially explored laparoscopically. Etiology of obstructions included internal hernias--6 [at the transverse mesocolon (n = 1), Petersen's space (n = 2), and at the jejunojejunostomy (n = 3)], adhesions (n = 4) and a negative laparoscopy (n = 1). The mean time for development of internal hernias was 13.7 months. Mean loss of BMI units at time of re-operation was 17 kg/m2. Of the 6 patients with internal hernia, 2 (30%) had normal preoperative radiological work-up. On review of the preoperative films by the surgeon, signs of internal herniation were seen in all the patients. Management included initial laparoscopic exploration, lysis of adhesions, reduction of internal hernia and closure of mesenteric defects in all the patients. There were 2 conversions to laparotomy. CONCLUSION: Small bowel obstruction in the post-LRYGBP patient is difficult to diagnose, especially when due to an internal hernia. Most patients present with intermittent abdominal pain and/or nausea. The most frequently used radiologic study is CT scan, which is most accurate when reviewed by the bariatric surgeon preoperatively.     

CT Scan Diagnosis of Bleeding Peptic Ulcer after Gastric Bypass

Investigation of the bypassed stomach in patients with suspected peptic ulcer disease presents a major challenge to bariatric surgeons. Various methods have been suggested for visualization of the duodenum and bypassed stomach. These include endoscopy via percutaneous gastrostomy access, retrograde endoscopy and virtual gastroscopy using CT scan. We present a case of peptic ulcer bleeding diagnosed with the help of conventional CT scan. To the best of our knowledge, this is the second such case reported in the literature and the first in the bariatric population.     

Pancreatic Redo Procedures: To do or Not To Do—This is the Question

Background  Pancreatic redo procedures belong to the most difficult abdominal operations because of altered anatomy, significant adhesions, and the potential of recurrent disease. We report on our experience with 15 redo procedures among a series of 350 consecutive pancreatic operations. Patient and Methods  From January 1, 2004 to May 31, 2006 a total of 350 patients underwent pancreatic surgery in our department. There were 15 patients identified who had pancreatic redo surgery for benign (14) or malignant (1) disease. Perioperative parameters and outcome of 15 patients undergoing redo surgery after pancreatic resections were evaluated. Results  Operative procedures included revision and redo of the pancreaticojejunostomy after resection of the pancreatic margin (6), completion pancreatectomy (3), conversion from duodenum-preserving pancreatic head resection to pylorus-preserving pancreaticoduodenectomy (3), classic pancreaticoduodenectomy after nonresective pancreatic surgery (1), redo of left-sided pancreatectomy (1), and classic pancreaticoduodenectomy after left-sided pancreatectomy (1). Histology revealed chronic pancreatitis in 14 and a mucinous adenocarcinoma of the pancreas in 1 patient. Median operative time was 335 min (235–615 min) and median intraoperative blood loss was 600 ml (300–2,800 ml). Median postoperative ICU stay was 20 h (4–113 h) and median postoperative hospital stay was 15 days (7–30 days). There was no perioperative mortality and morbidity was 33%. Conclusion  Pancreatic redo surgery can be performed with low morbidity and mortality. Redo surgery has a defined spectrum of indications, but to achieve good results surgery may be performed at high-volume centers.     

Thoracic ossification of ligamentum flavum caused by skeletal fluorosis

Thoracic ossification of ligamentum flavum (OLF) caused by skeletal fluorosis is rare. Only six patients had been reported in the English literature. This study reports findings from the first clinical series of this disease. This was a retrospective study of patients with thoracic OLF due to skeletal fluorosis who underwent surgical management at the authors' hospital between 1993 and 2003. Diagnosis of skeletal fluorosis was made based on the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis was present. Neurological status was evaluated preoperatively, at the third day postoperatively, and at the end point of follow-up using the Japanese Orthopaedic Association (JOA) scoring system of motor function of the lower extremities. A total of 23 cases were enrolled, 16 (69.6%) males and 7 (30.4%) females, age ranging from 42 to 72 years (mean 54.8 years). All patients came from a high-fluoride area, and 22 (95.7%) had dental fluorosis. Medical imaging showed OLF together with ossification of many ligaments and interosseous membranes, including interosseous membranes of the forearm (18/23 patients 78.3%), leg (14/23 patients 60.9%), and ribs (11/23 patients 47.8%). OLF was classified into five types based on MRI findings: localized (4/23 patients 17.4%), continued (12/23 patients 52.2%), skip (3/23 patients 13.0%), combining with anterior pressure (2/23 patients 8.7%), and combining with cervical and/or lumbar stenosis (2/23 patients, 8.7%). Urinalysis showed a markedly high urinary fluoride level in 14 of 23 patients (60.9%). Patients were followed up for an average duration of 4 years, 5 months. Paired t-test showed that the JOA score was slightly but nonsignificantly increased relative to preoperative measurement 3 days after surgery (P = 0.0829) and significantly increased at the end of follow-up (P = 0.0001). In conclusion, Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. Comparing with other OLF series, a larger number of spinal segments were involved. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptom, imaging study findings, and urinalysis. En bloc laminectomy decompression was an effective method.     

Incorporation of Nissen fundoplication in a rat model of duodenoesophageal reflux

BACKGROUND: Few in vivo models of esophageal reflux and fundoplication suitable for the study of the pathogenesis of Barrett's esophagus and esophageal cancer exist. We describe a modification of a rat model of duodenoesophageal reflux that incorporates Nissen fundoplication and uses it to study the role of fundoplication in ameliorating esophageal reflux. METHODS: A previously described rat model of duodenoesophageal reflux was modified to include Nissen fundoplication. Reflux threshold (RT), defined as the gastric pressure required to cause gastroesophageal reflux during transgastric instillation of saline, was measured in 12 Sprague-Dawley rats at baseline, after cardiomyotomy with esophagogastroduodenal anastomosis (EGDA), after subsequent Nissen fundoplication, and, finally, after takedown of Nissen fundoplication (NF). RESULTS: Cardiomyotomy with EGDA induced no significant change in RT compared with baseline (mean RT +/- SD: 4.0 +/- 1.9 mmHg and 6.0 +/- 2.5 mmHg, respectively, p = 0.741). Nissen fundoplication led to a 14-fold increase in RT (56.4 +/- 18.2 mmHg) compared with cardiomyotomy. RT pressure reverted to baseline levels after NF takedown (4.7 +/- 2.9 mmHg, p < 0.001). Antegrade esophageal flow was demonstrated without an increase in distal esophageal pressure after NF. CONCLUSIONS: Nissen fundoplication creates a one-way antireflux mechanism that eliminates gastroesophageal reflux in this rat model. This modification of an in vivo model of duodenoesophageal reflux represents a unique opportunity to investigate the effect of NF on cardiomyotomy-induced reflux and distal esophageal exposure to duodenogastric refluxate, and could be useful in the study of the role of NF in preventing progression to BE and ECA.