Incisional hernias post cytoreductive surgery/peritonectomy and hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis.

PURPOSE: Cytoreductive surgery (CRS) is often combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal tumour deposits. Considering CRS, the evidence relating the large incisions, local chemotherapy and abdominal wall trauma to incisional hernias (IH) has not been synthesized. This systematic review and meta-analysis was conducted to examine the proportion of IH present in patients post CRS and the effect HIPEC had on these rates. METHODS: PubMed, EMBASE, and Cochrane Central Registry of Trials were searched up to June 2023 to examine studies relating IH and CRS plus or minus HIPEC. The most up to date PRISMA guidelines were followed. Pertinent clinical information was synthesized in tabular form. A meta-analysis reporting the pooled proportions of IH post CRS plus or minus HIPEC, the odds of IH in HIPEC versus non-HIPEC CRS and the difference in follow-up time between groups was conducted. RESULTS: Nine studies comprising 1416 patients were included. The pooled proportion of IH post CRS was 12% (95% confidence interval (CI) 8-16%) in HIPEC and 7% (95% CI 4-10%) in non-HIPEC patients and 11% (95% CI 7-14%) overall. Previously reported rates of IH in midline laparotomy range from 10 to 30%. The odds of IH in the HIPEC was 1.9 times higher compared to non-HIPEC cohorts however this was not statistically significant (odds ratio (OR) 1.9, 95% 0.7-5.2; p = 0.21). There was no significant difference in average follow-up times between HIPEC and non-HIPEC cohorts. CONCLUSIONS: IH post CRS plus or minus HIPEC were in the expected range for midline laparotomies. IH in patients receiving HIPEC may occur at a greater proportion than in non-HIPEC patients, however, there were too few studies in our meta-analysis to determine this with statistical significance.

[A Qualitative Proteome-Wide Lysine Succinylation Profiling of Tea Revealed its Involvement in Primary Metabolism].

Lysine succinylation of proteins has potential impacts on protein structure and function, which occurs on post-translation level. However, the information about the succinylation of proteins in tea plants is limited. In the present study, the significant signal of succinylation in tea plants was found by western blot. Subsequently, we performed a qualitative analysis to globally identify the lysine succinylation of proteins using high accuracy nano LC-MS/MS combined with affinity purification. As a result, a total of 142 lysine succinylation sites were identified on 86 proteins in tea leaves. The identified succinylated proteins were involved in various biological processes and a large proportion of the succinylation sites were presented on proteins in the primary metabolism, including glyoxylate and dicarboxylate metabolism, TCA cycle and glycine, serine and threonine metabolism. Moreover, 10 new succinylation sites were detected on histones in tea leaves. The results suggest that succinylated proteins in tea plants might play critical regulatory roles in biological processes, especially in the primary metabolism. This study not only comprehensively analyzed the lysine succinylome in tea plants, but also provided valuable information for further investigating the functions of lysine succinylation in tea plants.

Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial.

BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up. PATIENTS AND METHODS: Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. RESULTS: Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. CONCLUSIONS: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. TRIAL NUMBERS: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).

Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature.

In the UK, the standard of care for esophageal cancer has generally combined surgery with neoadjuvant chemotherapy, with definitive chemoradiotherapy (dCRT) being reserved for certain subgroups. Chemoradiotherapy followed by surgery (trimodality therapy) has not been widely adopted. The outcomes of patients undergoing dCRT or trimodality therapy at our cancer center between 2004 and 2012 were restrospectively analyzed. Trimodality therapy was offered to selected patients of good performance status (World Health Organisation performance status 0/1), with squamous cell carcinoma or bulky adenocarcinoma. dCRT was offered to patients of good PS but with comorbidities, upper third tumors or at patient's request. Patients received four cycles of chemotherapy with a platinum agent (mostly cisplatin) and a fluoropyrimidine (mostly 5-fluorouracil) over a total of 11 weeks. Cycles 3 and 4 were given concurrently with radiotherapy: 50 Gy in 25 fractions for dCRT and 45 Gy in 25 fractions in the trimodality group. Surgery occurred 8-10 weeks following the completion of chemoradiotherapy. The cut-off length for maximum gross tumor volume length was 10 cm. One hundred two patients were included (47 received dCRT, and 55 received trimodality treatment). The majority of tumors were stage III (80.4%), and two-thirds were located in the distal esophagus (64.7%). Median follow-up was 44 months. The 2-year overall survival (OS) was 57.3% (median OS 39.7 months) for the dCRT group and 77.8% (median not reached) for the trimodality group. The 5-year OS rates were 38% and 58%, respectively. Postoperative mortality rate was low at 1.8%, and the pathological complete response rate was 23.6%. In conclusion, trimodality treatment for patients with esophageal and junctional gastroesophageal tumors offers high rates of 2-year survival, and the potential for long-term cure. dCRT is an established alternative for patients that are not fit or suitable for surgery.

Optimal treatment of early-stage ovarian cancer.

BACKGROUND: There is no clear consensus regarding systemic treatment of early-stage ovarian cancer (OC). Clinical trials are challenging because of the relatively low incidence and good prognosis. Initial results of the International Collaborative Ovarian Neoplasm (ICON)1 trial demonstrated benefit in both overall survival (OS) and recurrence-free survival (RFS) with adjuvant chemotherapy. We report results of 10-year follow-up to establish whether benefits are maintained longer term and discuss how this and other available evidence from randomised trials can be used to guide treatment options regarding the need for, and choice of, adjuvant chemotherapy regimen. PATIENTS AND METHODS: ICON1 recruited women with OC following primary surgery in whom there was uncertainty as to whether adjuvant chemotherapy was indicated. Patients were randomly assigned to adjuvant or no adjuvant chemotherapy. Platinum-based chemotherapy was recommended and 87% received single-agent carboplatin. Analyses of long-term treatment benefits and interaction with risk groups were carried out. A high-risk group of women was defined with stage 1B/1C grade 2/3, any stage 1 grade 3 or clear-cell histology. RESULTS: With a median follow-up of 10 years, the estimated hazard ratio (HR) for RFS was 0.69 [95% confidence interval (CI) 0.51-0.94, P = 0.02] and OS 0.71 (95% CI 0.52-0.98, P = 0.04) in favour of chemotherapy. In absolute terms, there was a 10% (60%-70%) improvement in RFS and a 9% (64%-73%) improvement in OS; the benefit of chemotherapy might be greater in high-risk disease (18% improvement in OS). Uncertainty remains about the optimal chemotherapy regimen. The only randomised trial data available are from a subset of 120 stage 1 patients in ICON3 where the treatment difference, comparing carboplatin with carboplatin/paclitaxel was estimated with relatively wide CIs [progression-free survival HR = 0.71 (95% CI 0.39-1.32) and OS HR = 0.98 (95% CI 0.49-1.93)]. CONCLUSIONS: Extended follow-up from ICON1 confirms that adjuvant chemotherapy should be offered to women with early-stage OC, particularly those with high-risk disease. CLINICAL TRIAL NUMBERS: ISRCTN11916376 for ICON1 and ISRCTN57157825 for ICON3.

Short pulse gastric electrical stimulation for cisplatin-induced emesis in dogs.

BACKGROUND: In a previous study, we investigated the ameliorating effect of gastric electrical stimulation (GES) with a single set of parameters on emesis and behaviors suggestive of nausea induced by cisplatin in dogs. The aim of this study was to investigate the effects of GES with different parameters on cisplatin-induced emesis in dogs. METHODS: Seven dogs implanted with gastric serosal electrodes were studied in six randomized sessions: one control session with cisplatin (2 mg kg(-1)) and five sessions with cisplatin plus GES of different parameters: GES-A: 14 Hz, 5 mA, 0.3 ms, 0.1 s on and 5 s off; GES-B: increased frequency and on-time; GES-C: increased frequency; GES-D: increased frequency and pulse width; and GES-E: increased frequency and amplitude. Gastric slow waves and emetic responses were recorded in each session. KEY RESULTS: (i) Cisplatin induced emetic responses and gastric dysrhythmia. The peak time of the emetic response was during the fourth hour after cisplatin. (ii) GES with appropriate parameters reduced cisplatin-induced emesis. The number of vomiting times during the 6 h after cisplatin was 7.0 ± 1.4 in the control, 4.7 ± 1.2 with GES-A (P = 0.179), 4.2 ± 1.2 with GES-B (P = 0.109), 7.0 ± 0.8 with GES-C (P = 0.928), 2.1 ± 0.3 with GES-D (P = 0.005) and 4.7 ± 1.5 with GES-E (P = 0.129). However, none of the GES parameters could improve gastric dysrhythmia. CONCLUSIONS & INFERENCES: Gastric electrical stimulation with appropriate parameters reduces cisplatin-induced emetic responses and behaviors suggestive of nausea in dogs. Among the tested parameters, GES with increased pulse width seems to produce better relief of cisplatin-induced emesis.

A novel, non-substrate-based series of glycine type 1 transporter inhibitors derived from high-throughput screening.

The synthesis and structure-activity relationships (SAR) of a series of indane and tetralin inhibitors of the type 1 glycine transporter, derived from a high-throughput screening (HTS) hit, are described. Key modifications that reduced the 5HT1B receptor affinity of the HTS hit and the P450 2D6 inhibition of subsequent analogues are delineated. While these modifications led to potent and selective GlyT1 inhibitors, HERG affinity and human microsomal clearance remain an issue for this series of compounds.

Reproduction and cytogenetic characterization of interspecific hybrids derived from crosses between Brassica carinata and B. rapa.

The tri-genomic hybrid (ABC, 2n=27) between Brassica carinata (BBCC, 2n=34) and B. rapa (AA, 2n=20) is a unique material for studying genome relationships among Brassica species and a valuable bridge for transferring desirable characteristics from one species to the other within the genus Brassica. The crossability between B. carinata and B. rapa was varied with the cultivar of B. rapa. Hybrid pollen mother cells (PMCs), confirmed by morphological observation and molecular marker assay, could be grouped into 20 classes on the basis of chromosome pairing configurations. More than 30% of the PMCs had nine or more bivalents. Genomic in situ hybridization confirmed that two of the bivalents most likely belonged to the B genome. Nearly one-half of the PMCs had trivalents (0-2) and quadrivalents (0-2), which revealed partial homology among the A, B, and C genomes and suggested that there is a good possibility to transfer genes by means of recombination among the three genomes. The advantages of using the tri-genomic hybrids as bridge material for breeding new types of B. napus are discussed.

Nasal nitric oxide is not altered by topical anesthesia.

This prospective study was undertaken to determine whether topical nasal anesthetic agents affect nasal nitric oxide (NO) output in healthy adults. Seven volunteers (aged: 29-56 (40.6 +/- 10.7) years, six male), were recruited. A topical anesthetic (4% lidocaine or 0.5% tetracaine) was sprayed into the subject's right nostril while the left nostril served as a control. Unilateral nasal NO and nasal volume were measured before administration of the anesthetic and at 15 and 30 minutes after the administration. The mean (+/- SD) unilateral nasal NO output was 307 +/- 45.9 nL/minute from the right nostril (exposure side) before the topical application of lidocaine. At 30 minutes after topical application (n = 6), it was 295.5 +/- 41.5 in the right nostril and 297.5 +/- 39.8 in the left (control side). In the tetracaine group (n = 7), the mean (+/- SD) unilateral nasal NO output was 302 +/- 53.3 before the administration and 307 +/- 39.7 at 30 minutes after the administration in the right nostril. The mean NO output in the left nostril at 30 minutes after the administration was 297.7 +/- 40.75. In neither group was there any significant difference in nasal NO output between either the pre- and postlocal anesthetic application on the exposure side (Group 1, P = 0.76; group 2, P = 0.41) or the two nostrils after topical anesthesia application (group 1, P = 0.83; group 2, P = 0.62). Topical anesthesia with either lidocaine or tetracaine does not alter nasal NO output. NO measurement should not be affected in circumstances that require topical anesthesia of the nasal cavity.

[Analysis of paracetamol, caffeine and chlorphenamine maleate in suxiaoshangfeng capsules by capillary gas chromatography].

A simple and rapid method for simultaneous determination of paracetamol, caffeine and chlorphenamine maleate in Suxiaoshangfeng capsule by capillary gas chromatography with n-hexadecane as internal standard has been reported. In the capsule, the three components can be separated on a 5% Ph-Me-Silicone column (2.65 microns x 0.53 mm x 10 m), with programmed column temperature from 180 degrees C to 230 degrees C at 8 degrees C/min, hold 6 min and then 230 degrees C to 260 degrees C at 10 degrees C/min, hold 10 min. Both the injector and FID detetor temperatures were 280 degrees C. N2 flow rate was 3.5 mL/min and H2 35 mL/min. The injection volume was 1 uL with splitting ratio of 1/25. These components were identified by their retention times and quantitatively determined by their peak areas. The calibration curves were, r = 0.9996 for paracetamol, r = 0.9984 for caffeine and r = 0.9996 for chlorphenamine maleate. The linear ranges were 4.0-20 g/L, 0.15-0.75 g/L and 0.080-0.40 g/L, respectively. The average recoveries were 99.62% (RSD = 0.40%, n = 5), 96.46%. (RSD = 1.32%, n = 5) and 98.55% (RSD = 0.65%, n = 5), respectively.

EPR studies of singlet oxygen (1O2) and free radicals (O2.-, .OH, HB.-) generated during photosensitization of hypocrellin B.

Hypocrellin B(HB), a peryloquinone derivative, is one of the main photosensitive agents, hypocrellin. This pigment, in combination with phototherapy, has been used in human medicine to cure various skin diseases. The photochemistry (Type I and II) of HB has been studied using spin-trapping and spin-counteraction techniques. The results show that the active oxygen (1O2, O2.-, .OH) mechanism of HB photosensitization can be converted into nonoxygen free radical (HB.-) mechanism completely when oxygen is exhausted in the experimental system. Under anaerobic conditions, HB only undergoes Type I reaction, generating nonoxygen free radical (HB.-).