Isolated aberrant right cysticohepatic duct injury during laparoscopic cholecystectomy: Evaluation and treatment challenges of a severe postoperative complication associated with an extremely rare anatomical variant.

A typical bile duct branching patterns represent one of the major causes of bile duct injury (BDI) during laparoscopic cholecystectomy (LC). The most common classified variations of bile duct branching, involve the right posterior sectoral duct (RPSD) and its joining with the right anterior or left hepatic duct. Variant bile duct anatomy can rarely be extremely complex and unclassified. This report describes an extremely rare case of an isolated injury to an aberrant right hepatic duct formed by the joining of ducts from segments V, VII, and VIII draining into the cystic duct (cysticohepatic duct) during LC, associated with an inferior RPSD opening to left hepatic duct. Detailed evaluation of both endoscopic and magnetic cholangiograms established the diagnosis. Bile duct injury was subsequently managed surgically by a demanding Roux-en-Y hepaticojejunostomy. This extremely rare case aims to serve as a useful reminder of the consistent inconsistency of biliary anatomy, alerting surgeons to beware of variant bile duct branching patterns during open or LC that constitute a dreadful pitfall for severe and life-threatening bile duct injuries.

Is Post-ERCP Pancreatitis a Genetically Predisposed Complication?

Background/Objectives. Pancreatitis remains the most common complication of ERCP. History of post-ERCP pancreatitis is an independent risk factor for a new episode, suggesting a genetic background. The N34S mutation in serine protease inhibitor Kazal type 1 (SPINK 1) gene may downregulate the threshold for the development of pancreatitis. The aim of the present study is to evaluate the presence of this mutation among patients with post-ERCP pancreatitis. Methods. During a period of four years, thirty patients with post-ERCP pancreatitis entered the study. Patients and procedural data were collected, focusing on risk factors for pancreatitis. Blood samples were taken for genetic testing for the presence of N34S mutation in SPINK 1 gene. After DNA extraction, we used an allele-specific polymerase chain reaction as an initial screening method for the N34S mutation, and in order to confirm the results and to determine the hetero- and homozygosity genotype status, we used a restriction fragment length polymorphism (RFLP) method. Results. None of the thirty patients was found to carry the N34S mutation, with both of the applied methods. Patients had an average of two of the known risk factors. Conclusion. SPINK1 N34S mutation does not seem to play a role in post-ERCP pancreatitis, but larger studies needed to confirm our results.

Tumor-primed natural killer cells from patients with multiple myeloma lyse autologous, NK-resistant, bone marrow-derived malignant plasma cells.

Natural killer (NK) cells are cytotoxic lymphocytes able to kill tumor cells and virus-infected cells. Human-resting NK cells can be activated by co-culture with NK-resistant CTV-1a cells. These tumor-activated cells (TaNKs) are cytotoxic to a range of NK-resistant tumor cells in vitro. This potential, however, has not been explored in multiple myeloma (MM). In this study, we demonstrate that TaNK cells from 21 MM patients lyse a variety of myeloma targets, including primary isolates of autologous and allogeneic CD138+ myeloma cells whilst sparing CD138-ve bone marrow cells. Myeloma patients' TaNK-induced lysis of the U266 cell line was significantly higher compared to normal controls (median-specific lysis 79.1% vs. 69.5%) (P = 0.003). In addition, TaNKs induced substantial lysis of autologous and allogeneic CD138+ myeloma cells (median-specific lysis 52.5% and 37.4%, respectively). The percentage of specific lysis did not correlate with important disease characteristics (ISS, age, and high-risk molecular abnormalities) or with the disease status and antimyeloma treatment, including novel agents and dexamethasone. In conclusion, tumor-primed NK cells are able to induce substantial lysis of myeloma targets including autologous and allogeneic CD138+ myeloma plasma cells and could be an additional therapeutic approach in MM, particularly in the era of novel agents.

Double probe pH-monitoring findings in patients with benign lesions of the true vocal folds: comparison with typical GERD and the effect of smoking.

We conducted a pH-monitoring study to determine the prevalence of pathologic gastroesophageal reflux (GER+) and laryngopharyngeal reflux (LPR+) in patients with resected benign true vocal fold lesions (TVFLs) and positive reflux finding score (RFS). We compared our findings with those of patients with typical GER disease (GERD) symptoms and normal laryngoscopy. In the group of patients with TVFLs, we compared the pH-monitoring findings of smokers with those of non-smokers. Seventy-two [females 32, mean (SD) age 49.3 (13.1) years] patients with resected TVFLs (polyps: 32, nodules: 20, Reinke's edema: 12, granulomas: 4, leukoplakia: 4) and 24 [females 14, mean (SD) age 42.2 (13.4) years] patients with typical GERD symptoms, who served as controls for the hypopharyngeal measurements, underwent 24-h double probe, hypopharyngeal and distal esophageal, ambulatory pH monitoring. Thirty-eight (52.8%) patients with TVFLs had GER+ and 52 (72.2%) had LPR+. More laryngopharyngeal reflux episodes (LPREs) were detected in patients with TVFLs compared to those with GERD (P < 0.001). With respect to the specific TVFLs, 12 (37.5%) patients with polyps had GER+ and 24 (75%) had LPR+, 6 (30%) patients with nodules had GER+ and 12 (60%) had LPR+, 6 (50%) patients with Reinke's edema had GER+ and 8 (66.7%) had LPR+ and all the patients with granuloma or leucoplakia had both GER+ and LPR+. Twenty (55.6%) of the 36 smokers and 32 (88.9%) of the 36 non-smokers with TVFLs had LPR+ (P = 0.003), while GER+ was recorded in 16 (44.4%) smokers and 22 (61.1%) non-smokers (P = 0.238). Smokers had significantly less LPREs (P < 0.001). In conclusion, 24-h double probe pH monitoring may detect GER+ and/or LPR+ in a substantial proportion of patients with resected TVFLs and positive RFS. Our study suggests that LPR+ is more prevalent in patients with TVFLs compared with typical GERD patients and that non-smokers with TVFLs are more likely to have LPR+ than smokers with TVFLs.

ERCP in acute biliary pancreatitis.

The role of urgent endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis is for many years a subject for disagreement among physicians. Although the evidence seemed to be in favor of performing ERCP, endoscopists usually hesitate to conform to the guidelines. ERCP is an invasive procedure, with complications which can affect patients' outcome. Recent evidence suggests that we should probably modify our policy, recruiting less invasive procedures, like magnetic resonance cholangiopancreatography and endoscopic ultrasound, before conducting ERCP in patients with acute biliary pancreatitis. In this editorial the different aspects regarding the role of ERCP in acute biliary pancreatitis are discussed.

Conservative management for an esophageal perforation in a patient presented with delayed diagnosis: a case report.

BACKGROUND: Esophageal perforation is a serious condition with a high mortality rate. Successful therapy depends on the size of the rupture; the time elapsed between rupture and diagnosis, and the underlying health of the patient. Common causes of esophageal perforation include medical instrumentation, foreign-body ingestion, and trauma. CASE REPORT: A case of esophageal perforation due to fish bone ingestion in a 67-year-old male is described here, with a review of the pertinent literature. The patient presented with chest pain, fever and right-sided pleural effusion. Initial evaluation was nondiagnostic. The water-soluble contrast swallow test showed no evidence of leakage. Computed tomography scan demonstrated a pneumomediastinum, and right-sided hydropneumothorax. CONCLUSION: The patient was successfully treated using conservative measures.

Conservative management for an esophageal perforation in a patient presented with delayed diagnosis: a case report review of the literature.

Esophageal perforation is a serious condition with a high mortality rate. Successful therapy depends on the size of the rupture; the time elapsed between rupture and diagnosis, and the underlying health of the patient. Common causes of esophageal perforation include medical instrumentation, foreign-body ingestion, and trauma. A case of esophageal perforation due to fish bone ingestion in a 67-year-old male is described here, with a review of the pertinent literature. The patient presented with chest pain, fever and right-sided pleural effusion. Initial evaluation was nondiagnostic. The water-soluble contrast swallow test showed no evidence of leakage. Computed tomography scan demonstrated a pneumomediastinum, and right-sided hydropneumothorax. The patient was successfully treated using conservative measures.

Randomized study of the effect of pentoxifylline or octreotide on serum levels of TNF-alpha and IL-6 after endoscopic retrograde cholangiopancreatography.

OBJECTIVES: To study the effect of pentoxifylline and octreotide administration on serum levels of TNF-alpha and IL-6, in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), whether they developed pancreatitis or not. METHODS: Out of 590 patients undergoing ERCP, 30 who developed pancreatitis and 25 who did not (controls) were enrolled. Pentoxifylline was given to 23 patients (15 with and eight without pancreatitis) and octreotide to 19 patients (nine with and 10 without pancreatitis, respectively). Thirteen patients did not receive any preventive medication (six with and seven without pancreatitis, respectively). Blood samples were collected at baseline, 6 and 24 h after ERCP. RESULTS: IL-6 increased significantly in patients with pancreatitis at the 6 h (4.2 pg/ml SD: 5.8) and at the 24 h (6.6 pg/ml SD: 9.8) compared with patients without pancreatitis at the 6 h (2.1 pg/ml SD: 3.6) and 24 h (1.9 pg/ml SD: 2.5) (P < 0.01). No significant difference in the values of TNF-alpha and IL-6 obtained among the three study groups in patients with or without pancreatitis was observed. TNF-alpha levels at the 24 h were lower than baseline in patients with pancreatitis who received octreotide (P = 0.04). CONCLUSION: IL-6 increased in the first 24 h of post-ERCP pancreatitis. Pentoxifylline and octreotide cannot prevent IL-6 elevation but octreotide reduces TNF-alpha levels, which may have an impact on the severity of post-ERCP pancreatitis.

Erythropoiesis-stimulating agents are associated with reduced survival in patients with multiple myeloma.

The impact of erythropoiesis-stimulating agent (ESA) on cancer patients' survival has recently become a matter of extensive discussion. Studies in solid tumors demonstrated that ESA adversely affects survival. This issue has not been sufficiently studied in patients with multiple myeloma. In this study, which included 323 multiple myeloma patients followed in our Institution between 1988 and 2007, we demonstrated by using a proportional hazards model including multiple covariates (age, LDH, Hb, platelets, serum creatinine, ISS score, beta2 microglobulin, and ESA administration) that ESA administration is associated with reduced survival (hazards ratio: 1.88, 95% CI: 1.28-2.77). Anemia, which is considered a predictor for survival, platelets, serum creatinine, ISS score, and LDH, were not significant, whereas, age and beta2 microglobulin confirmed their predicting value in the multivariate analysis. With a median follow-up of 31 months (range 1-238), the median survival of patients in the ESA group was 31 months (95% CI: 25-37), whereas in the group without ESA administration it was 67 months (95% CI: 55-79) (P < 0.001). The median progression-free survival for patients in the ESA group was 14 months (95% CI: 12-16), and for the group without ESA it was 30 months (95% CI: 24-36) (P < 0.001). These results indicate that ESA may have a detrimental impact on MM patients' outcomes and, thus, in this context, they should be used with rigorous criteria.

A randomized controlled trial of pentoxifylline for the prevention of post-ERCP pancreatitis.

BACKGROUND: Pentoxifylline can ameliorate pancreatitis in animal models because of its anti-tumor necrosis factor properties. OBJECTIVE: Our purpose was to study the safety and efficacy of pentoxifylline in the prevention of post-ERCP pancreatitis. DESIGN: Patients due to undergo ERCP for various indications were randomized to receive pentoxifylline 400 mg orally 3 times, beginning the day before ERCP (2 and 10 pm) until the night after the procedure (6 am and 2 and 10 pm) or to receive no preventive medication. Serum amylase values were determined before and 6 and 24 hours after ERCP. Diagnosis and grading of the severity of complications was performed according to consensus criteria. PATIENTS: One hundred fifty-eight patients received pentoxifylline (group A) and 162 had no medication (group B). The groups were similar in distributions of sex, biliary sphincterotomy, pancreatography, pancreatic duct cannulations, stone extraction, stent placement, and presence of periampullary diverticulum. Group A patients were younger (mean age 63 vs 68 years, P<.05) and biliary colic was a more frequent indication (30 vs 12, P<.05). RESULTS: Nine (5.6%) patients in group A and 5 (3%) in group B had pancreatitis (2 and 1 severe, respectively; P=.28). Serum amylase values were similar in baseline and 6- and 24-hour samples. Two (1.2%) patients in group A and 7 (4.3%) in group B had hemorrhage. LIMITATIONS: This was not a double-blind trial. CONCLUSIONS: In this study pentoxifylline did not protect against post-ERCP pancreatitis or hyperamylasemia.

The value of serum amylase and elastase measurements in the prediction of post-ERCP acute pancreatitis.

BACKGROUND/AIMS: Acute pancreatitis is the most serious complication of endoscopic retrograde cholangiopancreatography (ERCP) but is not very common. A test that could predict the occurrence of pancreatitis would help to decide whether to discharge a patient after ERCP or not. The aim of this prospective study was to compare the value of serum amylase and elastase in the prediction of post-ERCP pancreatitis and its severity. METHODOLOGY: Ninety-seven patients underwent ERCP. Serum samples were taken before, two and six hours after ERCP for amylase and elastase measurement. Fifty-four patients (group A) were treated with continuous intravenous infusion of octreotide, beginning 6 hours before ERCP and terminating 24 hours after. Forty-three patients (group B) received no preventive treatment. RESULTS: In group A, 9 patients (16.6%) developed pancreatitis, 8 of them (14.8%) mild and 1 (1.8%) severe. Two patients in group B developed mild pancreatitis (p = 0.1). In all patients the predictive accuracy in the second hour for amylase >3N, >5N and elastase >N was 79%, 87% and 86% respectively. The likelihood ratio of positivity (LRP) was 3.6, 6.5 and 6.1. In the sixth hour the respective values were 76%, 86%, 85% and 4, 7.3 and 6.4. In group A, the respective values in the second hour were 85%, 91%, 94% and 5, 25.2, infinity, and in the sixth hour 85%, 94%, 98% and 5.7, 11.5, infinity. CONCLUSIONS: Serum amylase (with cutoff value >5N) and elastase (>N), 6 hours after ERCP, were the most accurate tests for the prediction of post-ERCP pancreatitis, especially in patients receiving octreotide. The measurement of serum elastase could supplement that of serum amylase in the prediction of more cases of post-ERCP pancreatitis.

Hypochromic erythrocytes (%): a reliable marker for recognizing iron-restricted erythropoiesis and predicting response to erythropoietin in anemic patients with myeloma and lymphoma.

The aim of the study was to evaluate the role of hypochromic erythrocytes (HYPO%) compared to "traditional" and novel markers of iron status and erythropoiesis in recognizing iron-restricted erythropoiesis (IRE) and predicting response to erythropoietin (rHuEPO) in anemic patients with myeloma and lymphoma. Forty-one newly diagnosed patients who received epoetin-beta at a subcutaneous weekly dose of 30,000 IU for 6 weeks were studied. Response to rHuEPO was observed in 27 patients (65.8%). Twelve non-responders received, additionally, 200 mg of IV iron sucrose, weekly, for 4 weeks. Evaluation of markers was performed at baseline and on weeks 1, 2 and 6 for all patients and also on weeks 7-10 for non-responders to rHuEPO. Baseline HYPO%, at a cut-off value of <5%, and an increment in reticulocyte absolute number (RETICS-AB) >or= 50,000/microl and reticulocyte hematocrit (RETICS-Hct) >or= 50%, between baseline and week 2, were independent predictive factors for response to rHuEPO. We found that these markers had superior predictive value for response to rHuEPO than four widely used predictive models. Furthermore, a baseline HYPO% count of above 5% proved superior over serum ferritin < 100 ng/ml and transferrin saturation < 20% in recognizing IRE. In conclusion, baseline HYPO% either alone or in combination with RETICS-AB or RETICS-Hct after 2 weeks of rHuEPO treatment could be reliably used in predicting response to rHuEPO. Additionally, HYPO% has proved a reliable marker for recognizing IRE before rHuEPO treatment and, thus, could be used for identifying patients who will benefit from IV iron supplementation.

Reliability of selective surveillance colonoscopy in the early diagnosis of colonic ischemia after successful ruptured abdominal aortic aneurysm repair.

PURPOSE: To evaluate the reliability of selective surveillance colonoscopy based on 6 specific perioperative risk factors in the early diagnosis of colonic ischemia (CI) after successful ruptured abdominal aortic aneurysm (rAAA) repair. PATIENTS AND METHODS: From 1999 to 2005, 62 consecutive patients underwent rAAA repair. In 59 of them, routine aggressive surveillance colonoscopy was offered every 12 hours within the first 48 hours, and CI was graded consistently. Patients with stage I or stage II CI were treated conservatively and were followed up with repeat colonoscopy, whereas patients with stage III CI underwent immediate laparotomy and colectomy. In parallel, 6 specific perioperative risk factors (PRFs) were retrospectively analyzed. RESULTS: Overall mortality was 33.9%. Nineteen patients (32.2%) developed CI and 12 (63.2%) of them survived. Thirteen (22%) had grade III CI and among these 6 survived. In patients with CI the mortality rate was 36.2%. Patients with less than 3 PRFs had no CI whereas all instances of CI could be diagnosed if colonoscopy was offered selectively in patients with more than 3 PRFs. The positive predictive value of CI increased with the number of PRFs. Patients with 5 or 6 PRFs were about 101 times more likely to develop CI compared with patients with 0 to 4 PRFs (P<.001). CONCLUSION: Our study showed that CI is a frequent complication after successful rAAA repair and could reliably be early diagnosed if surveillance colonoscopy was offered selectively in patients with more than three PRFs.

Evaluation of hypochromic erythrocytes in combination with sTfR-F index for predicting response to r-HuEPO in anemic patients with multiple myeloma.

The purpose of this study was to evaluate the sTfR-F index and hypochromic erythrocytes (HYPO%) as potential predictors of response to recombinant human erythropoietin (r-HuEPO) of anemic patients with multiple myeloma (MM) before treatment, as well as early in the course of treatment. Twenty-six newly diagnosed anemic MM patients received r-HuEPO 30,000 IU/wk sc, for six weeks. The sTfR-F index and HYPO% were determined at baseline and at weeks 2 and 6. Patients were classified in 1 of 4 categories of a diagnostic plot, according to erythropoietic state (ES I-IV), defined by the combination of sTfR-F index and HYPO%. Sixteen of 20 patients in ES I and II before treatment responded to r-HuEPO, whereas none of the 6 patients in ES III and IV responded (P < .001). At week 2, 44% of patients who responded and 60% of the nonresponders were in functional iron deficiency (FID) and the proportion increased to 69% and 80%, respectively, by week 6. Seven of the patients who did not respond received in addition 200 mg iron sucrose IV weekly, for the next 4 weeks, and 6 of them responded. These results suggest that combination of sTfR-F index and HYPO% in a diagnostic plot can be used as a predictive model to recognize patients who will benefit from r-HuEPO and identify FID requiring iron supplementation, before treatment and early in the course of treatment, contributing thus to optimization of r-HuEPO therapy.