Assessment of tumor budding in colorectal carcinoma: Correlation with β-catenin nuclear expression

BackgroundTumor budding (TB) is showing increasing promise as a colorectal cancer (CRC) prognosticator that is independent of TNM staging. β-Catenin is a component of the Wingless/Wnt signaling pathway that is bound to membrane-associated E-cadherin and is essential for its correct position and function.MethodsThis study was designed to detect TB in 44 resected primary CRC cases and also to compare β-catenin expression in the tumor budding sites (TBS) and in the tumor center. Tumor budding was assessed in both H&;E and pankeratin immunostained sections. Agreement between TB scoring using pancytokeratin and H&;E was tested. Also, typing of the tumor margin and determination of degree of cytoplasmic pseudo-fragmentation was done. Tumor budding, cytoplasmic pseudofragments and β-catenin expression were related to known CRC prognosticators.ResultsTen tumors (22.7%) showed low grade (LG) budding and 34 tumors (77.3%) showed high grade (HG) budding. The 34 HG budding tumors were further subdivided into moderate and severe (n = 13, n = 21, respectively) budding cancers. Twenty nine tumors (65.9%) showed LG cytoplasmic pseudofragments and 15 tumors (34.1%) showed HG pseudofragments. Scoring of TB on H&;E and pankeratin stained sections revealed moderate agreement (Kappa = .558; p = <.000).A significant relation between TB and cytoplasmic pseudofragments was observed (p = .009). Both TB and cytoplasmic pseudofragments did not significantly associate with clinicopathologic parameters. Immunoreactivity of nuclear and cytoplasmic β-catenin was significantly higher at TBS compared to tumor center (p = .005, p = .000, respectively). In opposition, membranous β-catenin expression was significantly higher in the tumor center than in TBS (p = .001). Although, nuclear β-catenin accumulation at TBS was noted, yet, it did not relate significantly with both TB and cytoplasmic pseudofragments around TBS (p = .649; p = .675, respectively). Also, nuclear β-catenin immunoreactivity did not relate significantly with the various clinicopathological variables.ConclusionPankeratin immunostaining facilitates typing of CRC invasive margin, and determination of the degree of TB and cytoplasmic pseudo-fragmentation. β-Catenin expression differs significantly between tumor center and TBS in CRC. Cut-offs for TB assessment should be unified and further studies are recommended to allow a better understanding of this process before establishing TB as a prognostic factor beyond the TNM staging in CRC.     

Feasibility and Oncological Outcomes of Limited Duodenal Resection in Patients with Primary Nonmetastatic Duodenal GIST

Introduction

Duodenal gastrointestinal stromal tumors (GISTs) are rare but still represent approximately 30?% of primary duodenal tumors. This study aimed to audit the feasibility and oncological outcomes of limited duodenal resection in patients with primary nonmetastatic duodenal GIST.

Methods

Twelve patients who underwent surgery at our institution since 2002 were prospectively followed up. The duodenal GISTs were located in the first (n?=?3), second (n?=?1), third (n?=?3), and fourth of duodenum (n?=?1). Involving both D1/D2 (n?=?2), D2/D3 (n?=?1), and D3/D4 (n?=?1). The primary endpoint for this analysis was disease-free survival.

Results

The commonest presentation was melena and anemia (83?%). All the patients underwent limited resection; six wedge resections with primary closures and six segmental resections with end-to-end anastomosis. The median tumor size was 8?cm (range, 5?C16?cm). According to Fletcher scale, two GISTs were low risk, while 10 patients were intermediate and high risk. The latter received adjuvant therapy. All the patients had a complete resection with no postoperative mortality. One patient had three liver metastases 4?months after limited resection and had partial hepatectomy. After median follow-up of 45 (15?C78)?months, all patients are alive and disease free.

Conclusion(s)

When technically feasible, limited resection should be considered a reliable and curative option for duodenal GIST achieving satisfactory disease-free survival. The technical feasibility is guided by the tumor size, possible adjacent organ involvement, and its exact anatomical location.     

Antimycotic Activity of Some Alkaloidal Salts: Antimykotische Aktivität von einigen Alkaloiden

Summary: Caffeine citrate, quinine hydrochloride and quinine sulphate among 12 alkaloidal salts were highly effective against yeasts Rhodotorula species, Torulopsis sacchari, Torulopsis annulata and Candida albicans, moulds (Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Penicillium, Cladosporium, Rhizopus, Mucor and Geotrichum candidum) and dermatophytes (Trichophyton mentagrophytes and Microsporum canis). The antimycotic activity of caffeine citrate (in vitro) was more potent against moulds than yeasts and dermatophytes as its minimal inhibitory concentrations were 3–4, 5–8, and 5–8 mg/ml media respectively. Whereas, quinine hydrochloride and quinine sulphate were more effective against yeasts than moulds and dermatophytes and their minimal inhibitory concentrations were 5, 10 and 10 mg/ml media, respectively. Quinine hydrochloride and quinine sulphate were nearly equipotent. Morphological examinations of yeasts and moulds showed that caffeine citrate produced partial or complete inhibition of vesicles, sporulation, swelling and vaculation of hyphae particularly in Penicillium, Cladosporium, Rhizopus and Mucor. Moreover, it caused abnormal budding and elongation of various yeast strains. Quinine hydrochloride and quinine sulphate produced no morphological changes in the tested fungi. Therapeutic application of 5% solution and ointments of caffeine citrate, quinine hydrochloride and quinine sulphate were more potent in curing experimental ringworm infection in guinea pigs than clotrimazol ointment. Zusammenfassung: Coffeinzitrat, Chininhydrochlorid und Chininsulfat waren unter 12 alkaloiden Salzen hochwirksam gegen Hefen (Rhodoturula sp., Torulopsis sacchari, Torulopsis annulata und Candida albicans), Schimmelpilze (Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Penicillium, Cladosporium, Rhizopus mucor und Geotrichum candidum). Die antimyzetische Aktivität von Coffeinzitrat (in vitro) war stärker ausgeprägt gegen Schimmelpilze als gegen Hefen und Dermatophyten, da die minimalen Hemmkonzentrationen 3–4, 5–8 und 5–8 mg/ml betrugen. Dagegen waren Chininhydrochlorid und Chininsulfat wirksamer gegen Hefen als gegen Schimmelpilze und Dermatophyten mit minimalen Hemmkonzentrationen von 5,10 und 10 mg/ml. Diese beiden Verbindungen waren fast gleich stark wirksam. Morphologisch zeigten Hefen und Schimmelpilze unter Coffeinzitrat Hemmung der Ausbildung von Vesikeln und Sporulation sowie Schwellung und Vakuolisierung der Hyphen, besonders bei Penicillium, Cladosporium, Rhizopus und Mucor. Außerdem verursachte es abnorme Sprossung und eine Elongation der Zellen bei zahlreichen Hefestämmen. Chininhydrochlorid und Chininsulfat verursachten keine morphologischen Veränderungen in den getesteten Pilzen. Die therapeutischen Anwendung von einer 5%igen Lösung oder 5%igen Salbe von Coffeinzitrat, Chininhydrochlorid und Chininsulfat waren bei der Behandlung der experimentellen Dermatophytose des Meerschweinchens wirksamer als Clotrimazol-Salbe.     

Pharmacokinetic and tissue distribution of doxycycline in broiler chickens pretreated with either: Diclazuril or halofuginone

Following IV injection of doxycycline in a dose of 20 mg kg⁻¹ b.wt., its serum concentration was best fitted in two-compartment open model in chickens fed either on control or on anticoccidials-containing rations. Diclazuril and halofuginone resulted in a significant short distribution half-life (t_½α) (7.17 ± 0.39 and 11.88 ± 1.05 min, respectively) and increased total body clearance (Cl_tot) 0.37 ± 0.024 and 0.295 ± 0.034 L/kg/h, respectively. Following oral dosing the tested drug absorbed with t_½ab of 41.38 ± 1.6, 17.48 ± 0.86 and 41.83 ± 1.8 min, respectively and their C_max values (3.18 ± 0.18, 5.425 ± 0.48 and 0.986 ± 0.037 μg/ml) were attained at 2.07 ± 0.097, 1.403 ± 0.074 and 2.55 ± 0.106 h. For doxycycline alone and in presence of diclazuril and halofuginone, respectively. Systemic bioavailability was 22.64 ± 3.46, 86.74 ± 9.23 and 22.38 ± 3.09%, respectively. Following IM injection t_½ab were 9.096 ± 1.34 for doxycycline alone, 16.24 ± 2.21 and 15.6 ± 1.7 min in the presence of diclazuril and halofuginone, respectively. C_max was 3.10 ± 0.28, 4.63 ± 0.57 and 0.55 ± 0.07 μg/ml reached at 0.8 ± 0.083, 1.13 ± 0.126 and 1.21 ± 0.105 h. For the antibiotic alone, and in presence of either diclazuril and halofuginone, respectively. Systemic bioavailability was 22.41 ± 3.86, 88.97 ± 12.9 and 12.31 ± 0.99% in chickens fed on anticoccidial-free, diclazuril- and halofuginone-containing rations, respectively. Both the tested anticoccidials induced higher doxycycline tissue residues in all tested tissue samples.     

Intraoperative Ablation for Small HCC not Amenable for Percutaneous Radiofrequency Ablation in Child A Cirrhotic Patients

Background

Radiofrequency ablation (RFA) was initially started by radiologists as a percutaneous treatment, but surgeons started to use RFA by surgical approach for patients with tumors at locations difficult for the percutaneous procedure. The aim was to evaluate the results of intraoperative RFA for small hepatocellular carcinomas (HCCs) (<3 cm) in locations difficult for a percutaneous approach.

Methods

Two hundred forty-seven patients with small solitary HCC (<3 cm) were treated; 196 via percutaneous RFA while 51 patients presented at sites not amenable for percutaneous route. Twenty-seven out of 51 patients underwent surgical resection, while 24/51 patients underwent intraoperative RFA.

Results

The location and depth of the tumor from the liver capsule was the only significant factors in the choice of the surgeon between resection and RFA. RFA was successful in all tumors (complete ablation rate of 100 %). In the surgery group, all patients achieved R0 resection. Complication rate was comparable (p?=?1.0). After a median follow-up of 37 months (range, 10–45 months), no tumors showed neither local progression nor local recurrence and no significant difference was observed between two groups as regards early recurrence and number of de novo lesions (p?=?0.49). One-year and 3-year survival rates were 93 % and 81 %, respectively, in the resection group comparable to the corresponding rates of 92 % and 74 % in the RFA group (p?=?0.9).

Conclusion

For small HCC in locations difficult for a percutaneous approach, intraoperative RFA can be an alternative option for deep-seated tumors necessitating more than one segmentectomy achieving similar tumor control, and overall and disease-free survival.