Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia.

A child, 2 years with the 'hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38°C, thrombocythaemia of > 700 × 109 /l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 2·0 array in blood on three occasions 3-5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

[Operative therapy of hepatocellular carcinoma]. / Operative Therapie des hepatozellulären Karzinoms.

BACKGROUND: Curative surgical strategies for hepatocellular carcinoma are liver resection and transplantation. METHODS: This overview is based on a selective literature search on therapeutic strategies for hepatocellular carcinoma. The new German S3 guidelines are outlined in detail but guidelines from other societies were also taken into consideration. RESULTS: The question of resectability is of utmost importance and should not only be evaluated in an interdisciplinary tumor board but also in an experienced liver center. Primary resectable hepatocellular carcinoma in patients without portal hypertension should be resected. Most patients without cirrhosis qualify for resection. In patients with Child grade A cirrhosis but without severe portal hypertension and a stable health status, a liver resection should be considered. At resection intraoperative ultrasound is standard. Intrahepatic tumor recurrences also can be re-resected or thermally ablated. New techniques for extended liver resections or minimally invasive liver resections are commonly used and have to be studied further. CONCLUSION: In addition to liver resection, liver transplantation now represents a standard therapy for hepatocellular carcinoma in cirrhosis. Observing the Milan selection criteria 5-year survival rates of 70-90 % can be achieved; however, increasing organ shortage leads to longer waiting times and thus higher risk of tumor progression. Therefore, patients on the waiting list should have follow-up imaging and bridging with surgical resection, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) by interventional radiology. Living donor liver transplantation should be considered in all these patients with expected longer waiting times.

[Surgical treatment of liver metastases]. / Chirurgische Therapie von Lebermetastasen.

The treatment of liver metastases has become more and more complex in recent years. More individualized therapeutic concepts have become feasible by the increase in different treatment options (surgical, interventional and oncological). In the field of surgery the definition of resectability could be broadened. More extensive liver resections are being performed, which are partly carried out as staged resections after neoadjuvant chemotherapy in combination with portal vein embolization (PVE), radio frequency ablation (RFA) or other procedures in order to increase complete resection rates and patient survival. Consequently the overall 5 year survival rate of patients with resected colorectal liver metastases has doubled from 30% to nearly 60% in the past decade. Due to the complexity of the different treatment approaches an interdisciplinary assessment of the individual patient in experienced centers is necessary.

Preferential migration of CD62L cells into the appendix in mice with experimental chronic colitis.

BACKGROUND: Clinical and experimental studies suggest that appendectomy can protect against development of ulcerative colitis and Crohn's disease. However, how T cells in the appendix affect the development of colitis has not been clarified. AIM: To investigate the in vivo migration and activation of colitis-inducing CD62L+ cells during development of chronic colitis. METHODS: CD62L+CD4+ cells were fluorescently labeled and transferred to severe combined immunodeficient (SCID) mice to induce colitis. In vivo migration of T cells into the mucosa of the appendix and colon was quantified by in vivo microscopy after 7 weeks. In a second experiment, unlabeled CD62L+CD4+ cells were transferred, reisolated after 7 weeks, and adhesion molecule (integrin alpha4beta7) and costimulatory molecule (CD154) expression was analyzed. RESULTS: Six to eight weeks after CD62L+CD4+ cell transfer, SCID mice developed chronic colitis. In vivo microscopic analysis demonstrated a preferential migration of fluorescence-labeled CD62L+CD4+ cells into the mucosa of the appendix versus the colon. Re-isolation of lamina propria cells from mice with colitis confirmed that CD62L+CD4+ cell migration was significantly enhanced in the appendix, compared to the colon (3.5-fold). Furthermore, a higher proportion of CD62L+CD4+ cells re-isolated from the appendix expressed integrin alpha4beta7 and CD154 than from the colon. CONCLUSION: This study demonstrates the preferential migration of CD62L+CD4+ cells into the appendix as compared to the colon. This migration pattern correlated with upregulation of integrin alpha4beta7 and CD154 (CD40 ligand) on T cells. Our results suggest an important role of the appendix in the pathogenesis of colitis.

Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group.

OBJECTIVE: To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections. DESIGN: Prospective, nonblind, randomized trial. SETTING: Multicenter trial conducted at 22 centers. PATIENTS: Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy. INTERVENTIONS: One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin. MEASUREMENTS AND MAIN RESULTS: The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment. CONCLUSIONS: Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.

A new therapeutic option for the treatment of pneumonia.

Patients with bacterial pneumonia often are treated empirically with parenteral broad-spectrum antimicrobials intended to cover potential gram-negative and gram-positive pathogens. However, beta-lactamase-mediated resistance has developed to many of these antimicrobials, particularly third-generation cephalosporins, and has led to the development of fourth-generation agents that are relatively beta-lactamase stable. The purpose of these studies was to compare the efficacy and safety of the fourth-generation agent, cefepime, with that of the third-generation agent, ceftazidime, in the treatment of hospitalized patients with moderate-to-severe bacterial pneumonia. A total of 336 (97 evaluable) patients were enrolled in an open-label study, and 99 (23 evaluable) patients were enrolled in a blinded study of patients with lower respiratory tract infections (LRTI) including pneumonia. Patients were randomized to receive either cefepime 1 g every 12 hours or ceftazidime 1 g every 8 hours given as an intravenous infusion over 30 minutes. Efficacy analysis included the evaluable patients while the safety analysis included all patients. The results in the open-label study were as follows: In patients with pneumonia, clinical response was satisfactory in 58 (85%) of 68 patients in the cefepime group and 21 (72%) of 29 patients in the ceftazidime group. Bacteriologic eradication occurred for 75 (93%) of 81 pathogens and 30 (94%) of 32 pathogens isolated from the 68 cefepime-treated patients and 29 ceftazidime-treated patients, respectively. The results in the blinded study were as follows: In patients with pneumonia, clinical response was satisfactory in 12 (80%) of 15 cefepime patients and in 7 (88%) of 8 ceftazidime patients, and the bacteriologic eradication rates were 85% (17/20 pathogens) and 73% (8/11 pathogens) isolated from the 15 cefepime-treated patients and the eight ceftazidime-treated patients, respectively. Among the most frequent adverse events in both groups were nausea, diarrhea, vomiting, and abdominal pain. Similar adverse events were noted in the 99 patients in the blinded study. These studies indicate that the efficacy and safety of cefepime administered at 1 g twice daily is comparable to that of ceftazidime administered at 1 g three times daily for treatment of hospitalized patients with pneumonia caused by susceptible pathogens.

Intravenous fleroxacin versus ceftazidime in the treatment of acute nonpneumococcal lower respiratory tract infections.

Fleroxacin, administered intravenously at a dosage of 400 mg once a day, was compared with ceftazidime, 0.5-2 g three times daily or 1-2 g twice daily, administered for 4-21 days, for treatment of nonpneumococcal lower respiratory tract infections. A total of 319 patients were enrolled and randomized to receive treatment with fleroxacin or ceftazidime in a 2:1 ratio. Of those enrolled, 68 fleroxacin- and 49 ceftazidime-treated patients were included in the efficacy analysis. The most common diagnoses were pneumonia or pneumonitis (47% of the fleroxacin group and 57% of the ceftazidime group) and exacerbation of chronic bronchitis (38% and 33%, respectively). In the fleroxacin group, 59 (88%) of 67 patients were bacteriologic cures, and in the ceftazidime group, 40 (90%) of 49 were bacteriologic cures. It could be concluded with 95% confidence that the bacteriologic outcomes, by infection, for the two groups were equivalent (fleroxacin, 88%; ceftazidime, 90%). The rates of clinical cure were 59 (88%) of 67 for the fleroxacin group and 40 (82%) of 49 in the ceftazidime group, but since the 95% confidence limit around the between-group difference was greater than the stipulated +/- 15%, it could not be concluded that the outcomes were equivalent. The percentage of patients who experienced adverse clinical or laboratory events was similar in the two treatment groups (12% and 13%). The bacteriologic outcomes, by infection, were equivalent for the two treatment groups. Protocol requirements permitting a determination of equivalence of the outcomes for clinical cure were not met, although the rates were similar.

Necrotizing fasciitis of the total abdominal wall after sterilization by partial salpingectomy. Case report and review of literature.

A case of necrotizing fasciitis with full-thickness loss of the entire abdominal wall is reported after an uncomplicated sterilization by bilateral partial salpingectomy through a minilaparotomy incision in a healthy young patient. Salvage was accomplished by early wide surgical debridement and multiple reconstructive procedures.

PIP: The medical literature includes reports of necrotizing fascitis after Bartholin abscesses, vaginal delivery, cesarean section, abdominal hysterectomy, sterilization by bilateral total salpingectomy, and diagnostic laparoscopy. This paper presents the 1st documented report of necrotizing fascitis after sterilization by bilateral partial salpingectomy. The patient, a healthy 41-year-old, presented with severe abdominal pain, nausea, and vomiting 1 day after undergoing bilateral partial resection and ligation of the fallopian tubes through a suprapubic minilaparotomy incision (Pomeroy procedure). Disseminated intravascular coagulopathy developed soon after admission. Surgery, performed once the patient has been stabilized through corticosteroids and broad-spectrum antibiotics, revealed extensive necrotizing fascitis involving the entire abdominal wall. There was no perforation of the bowel or uterus. Escherichia coli was cultured from the patient's abdominal wall, urine, and blood. The patient was treated successfully with piperacillin, gentamicin, and clindamycin. 15 days later, multiple reconstructive procedures were initiated to close the abdominal defect. This patient's good recovery was due to the speed of the diagnosis and wide surgical debridement of all devitalized tissue. Since she showed no evidence of salpingitis at the time of the sterilization procedure, the source of bacterial inoculum in this case was most likely the patient's skin.