Laparoscopic repair of perforated peptic ulcer: single-center results

Background

Perforated peptic ulcer (PPU), the most common indication for emergency gastric surgery, is associated with high morbidity and mortality rates. Outcomes might be improved by performing this procedure laparoscopically, but no consensus exists on whether the benefits of laparoscopic repair (LR) of PPU outweigh the disadvantages.

Methods

From January 2002 to December 2012, 111 patients underwent surgery for perforated ulcer. A “laparoscopy-first” policy was attempted and then applied for 56 patients. The exclusion criteria for LR ruled out patients who had shock at admission, severe cardiorespiratory comorbidities, or a history of supramesocolic surgery. The aim of this study was a retrospective analysis of the 56 patients treated laparoscopically.

Results

The patient distribution was 30 men and 26 women, who had a mean age of 59 years (range 19–95 years). The mean ulcer size was 10 mm, and the Mannheim peritonitis index (MPI) was 21. LR was performed for 39 (69.6 %) of the 56 patients and included peritoneal lavage, suturing of the perforation, and omental patching. Conversion to laparotomy was necessary in 17 cases (30.4 %). The “conversion group” showed significant differences in ulcer size (larger ulcers: 1.9 vs 0.7 mm; p < 0.01), ulcer-site topography (higher incidence of posterior ulcers: 5 vs 0; p < 0.01), and MPI score (higher score: 24 vs 20; p < 0.05). The LR group had a mean operating time of 86 min (range 50–125 min), an in-hospital morbidity rate of 7.6 %, a mortality rate of 2.5 %, and a mean hospital stay of 6.7 days (range 5–12 days). None of these patients required reintervention.

Conclusions

The results showed that LR for PPU is feasible with acceptable mortality and morbidity rates. Skill in laparoscopic abdominal emergencies is required. Perforations 1.5 cm or larger, posterior duodenal ulcers, and an MPI higher than 25 should be considered the main risk factors for conversion.     

Mapping protein signal pathway interaction in sarcoma bone metastasis: linkage between rank, metalloproteinases turnover and growth factor signaling pathways

We applied reverse phase protein microarrays technology to map signal pathway interactions in a discovery set of 34 soft tissue sarcoma (STS) bone metastases compared to healthy bone. Proteins associated with matrix remodeling (MMP), adhesion (FAK Y576/577, Syndecan-1), and growth/survival (IGF1R Y1135/1136, PI3K, EGFR) were elevated in metastasis compared to normal bone. Linkage between Syndecan-1, FAK Y576/577, Shc Y317, and EGFR, IGF Y1135/1136, PI3K/AKT was a prominent feature of STS bone metastasis. Elevated linkage between RANKL and 4EBP1 T37/46, EGFR, IGF1R Y1135/1136, Src Y41, Shc Y317, PI3Kp110γ was associated with short survival. Finally, we tested the hypothesis that signal pathway proteins augmented in the STS bone metastasis may provide clues to understand the subset of primary STS that metastasize. The most representative molecules identified in the discovery set were validated on an independent series of 82 primary STS by immunohistochemistry applied to a tissue microarray. The goal was to correlate the molecular profile in the primary tumors with a higher likelihood of metastasis. Elevation of activated kinase substrate endpoints IRS1 S612, 4EBP1 T37/46, FAK Y576/577 and loss of Fibronectin, were associated with a higher likelihood of metastases. These data indicate that the linkage between matrix remodeling, adhesion, and growth signaling may drive STS metastasis and can be the basis for prognostic and therapeutic strategies.     

Role of mandibular displacement and airway size in improving breathing after rapid maxillary expansion

Background

Oral breathing and maxillary deficiency are often associated with steep mandibular plane angle, and retrognathic mandible compared with the faces of healthy controls. Some studies suggested that after rapid maxillary expansion, improvement in nasal breathing and repositioning of mandible with transitory increasing of facial height and, in some cases, spontaneous forward repositioning might occur. The abovementioned mandibular effects could contribute to enlarge oropharynx volume with repositioning of tongue and soft palate with an improvement of upper airway volume after treatment. The aim of this study was to investigate by cone beam computed tomography the role of oropharyngeal volume and mandibular position changes after rapid maxillary expansion in patients showing improved breathing pattern confirmed by polysomnography exam.

Methods

The final sample of this retrospective study comprised 14 Caucasian patients (mean age 7.6 years) who undergone rapid maxillary expansion with Haas-type expander banded on second deciduous upper molars. Cone beam computed tomography scans and polysomnography exams were collected before placing the appliance (T0) and after 12 months (T1). Mandibular landmarks localization and airway semiautomatic segmentation on cone beam computed tomography scans allowed airway volume computing and measurements.

Results

No significant differences were found between oropharyngeal airway changes and mandibular displacement after rapid maxillary expansion in growing patients.

Conclusions

The suggested improvement in upper airway and breathing after rapid maxillary expansion should be further related to different compartments of airway such as rhinopharynx and nasal cavity.     

Stage-related differences of mitotic and apoptotic indices,and bcl-2 protein expression in diffusely growing non-Hodgkin's lymphomas

The present study examined whether growth characteristics of diffusely growing non-Hodgkin's lymphomas (NHL) may differ as a function of stage. Among 105 NHL of various types and sub-types (REAL [Revised European-American Lymphoma] classification), localized (Ann Arbor pathologic stages I + II) lymphomas exhibited clearly higher indices for mitotic activity, apoptosis and cell turnover, as well as a significantly lower percentage of cells containing immunohistochemically detectable bcl-2 protein, than disseminated (stages III + IV) NHL. A similar pattern emerged when high-grade (Kiel classification) lymphomas only were evaluated. Low-grade NHL showed analogous, but less marked, stage-dependent characteristics, with the exception of median percentages of bcl-2⁺ cells, which remained comparable in all stages. Our findings are consistent with the notion that dissemination of diffusely growing NHL is usually associated with reduced cell turnover and, in high-grade lymphomas, with the generation of longer-lived cells. © 1996 Wiley-Liss, Inc.     

Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas

To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P < 0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second-hit mutation. Genes Chromosom Cancer 15:18–25 (1996). © 1996 Wiley-Liss, Inc.     

Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

BackgroundMonoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.MethodsThis observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO).ResultsWe enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01).ConclusionMigraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.