We describe a case of repair of the antegrade anastomosis between the “ileal segment” and amputated ureter for recurrent rectal cancer, in which some postoperative complications occurred but ...eventually resolved. If the length of the ureter is inadequate for end-to-end anastomosis, an ileal segment can be used as a conduit. This surgical technique is not difficult because an ileal conduit is typically created during total pelvic exenteration of rectal cancers. Therefore, anastomosing the ureter to an “ileal segment” is easy and feasible. Hence, we consider that knowledge of this technique would be beneficial for surgical oncologists who perform colorectal surgeries.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The reported incidence of rectovaginal fistula is very low. Although some case reports have described surgical procedures, no systematic approach to the treatment of rectovaginal fistula according to ...diagnostic image and colonoscopy findings has been proposed. We present a comprehensive surgical strategy for rectovaginal fistula after colorectal anastomosis according to diagnostic image and colonoscopy findings.
This retrospective study included 11 patients who developed rectovaginal fistula after colorectal anastomosis. Rectovaginal fistula was classified into 4 types according to contrast enema images and colonoscopy findings, i.e., "Alone type", "Dead space type", "Anastomotic stricture type", and "Dead space and Anastomotic stricture type". The surgical strategies were "Diversion (Stoma)", "Percutaneous drainage", "Anastomotic stricture type", "Endoscopic balloon dilation", "Curettage of foreign bodies", "Simple full-thickness closure", "Split-thickness closure", "Pedicled flaps packing", and "Reanastomosis". The surgical strategy appropriate for each rectovaginal fistula type was investigated.
Among "Alone type" cases, 5 (71.4%) healed with "only Diversion (Stoma)". "Alone type" cases (n=11) and all other cases (n=4) healed with "only Diversion (Stoma)" (n=5) or any other method (n=6) (p=0.022).
For treatment of rectovaginal fistula after colorectal anastomosis, less invasive treatment approaches should be attempted first.
Small cell lung cancer (SCLC) is a highly malignant form of cancer, which originates from primitive neuroendocrine cells in the lung. SCLC cells express several autocrine ...neurotransmitters/neuropeptides and their respective receptors. Expression of these neuronal markers is frequently regulated by RE1-silencing transcription factor (REST). In SCLC cells, an SCLC-specific isoform of REST (sREST) is highly expressed, whereas REST expression is undetectable, suggesting that the expression of sREST correlates with the pathogenesis of SCLC. Expression of sREST, which is derived through alternative splicing of REST, is abnormally regulated in SCLC cells, but the mechanism is unknown. Most recently, nSR100 (SRRM4) was described as an activator of REST alternative splicing. We now show that nSR100 is highly expressed in SCLC cells correlating with high sREST and low REST expression. Adhesion to the extracellular matrix (ECM) is thought to enhance tumorigenicity and confer resistance to apoptosis. Interestingly, nSR100 expression is enhanced in cells grown with ECM. Overexpression of REST caused repression of sREST and nSR100, the latter containing RE1 element controlled by REST. Culturing the SCLC cell line NCI-N417 cells with ECM also upregulated RE1-containing gene, the voltage-gated calcium channel subunit. Inhibition of the PI3K/Akt/mTOR pathway by LY294002 induced nSR100 expression, whereas the specific MEK/ERK inhibitor U0126 inhibited nSR100 expression. Repressing nSR100 by siRNA effectively repressed sREST, and conversely increased REST in NCI-N417 cells. Taken together, this report clarifies the ECM-dependent signaling pathway that impacts nSR100 expression and its regulation of alternative splicing in SCLC.
The splicing factor nSR100 may be novel SCLC-specific biomarker, as well as a therapeutic target.
The frequency of resection for the recurrence of colorectal cancer has not been investigated in previous studies. Likewise, the related postoperative complications and the limit for indicating ...surgical resection has not been reported. Herein, we reported the complications of a highly frequent surgical approach for rectal cancer recurrence, i.e., exceeding three reoperations, based on our clinical experience. We included 15 cases exceeding two operations for the local recurrence of colorectal cancer from 2014 to 2019. We examined the postoperative complications classified as Clavien?Dindo IIIb. The positive rates of the complications were 0 (0.0%), 0 (0.0%), 2 (13.3%), 3 (37.5%), and 0 (0.0%) for the primary, 1st recurrent, 2nd recurrent, 3rd recurrent, and 4th recurrent operation group (p=0.027), respectively. It is important to exercise caution in handling cases exceeding two reoperations (exceeding three reoperations including the primary operation). J. Med. Invest. 70 : 369-376, August, 2023
The present study aimed to investigate the clinical relevance of lateral pelvic lymph node dissection (LPLND) in low rectal cancer without preoperative treatment, with a focus on the presence of LPLN ...enlargement in preoperative imaging.
Consecutive patients with cT3 to T4 low rectal cancer who underwent mesorectal excision and LPLND without preoperative treatment between 2007 and 2018 at a single dedicated cancer center were included. LPLN short-axis diameter (SAD) measured using preoperative multi-detector row computed tomography (MDCT) was evaluated retrospectively.
A total of 195 consecutive patients were analyzed. Overall, 101 (51.8%) and 94 (48.2%) patients had visible and no visible LPLNs in preoperative imaging, including 56 (28.7%), 28 (14.4%), and 17 (8.7%) patients had SADs of <5 mm, 5-7 mm, and ≥7 mm, respectively. Incidence of pathologically confirmed LPLN metastasis were 18.1%, 21.4%, 28.6%, and 52.9%, respectively. Overall, thirteen (6.7%) patients developed local recurrence (LR), including one patient who developed lateral recurrence, yielding a 5-year cumulative risk for LR of 7.4%. Five-year RFS and OS for all patients were 69.7% and 85.7%, respectively. No differences were observed in the cumulative risk for LR and OS between any pairs of groups.
No significant difference was observed in the cumulative risk for LR and OS regardless of LPLN SAD, implying the good impact of LPLND on the prevention of lateral recurrence, as well as the difficulty of predicting LPLN metastasis using only LPLN SAD in preoperative imaging.
Nivolumab and pembrolizumab are promising therapies for gastric adenocarcinoma. The 22C3 and 28-8 pharmDx immunohistochemistry assays for programmed death ligand-1 scoring criteria have been ...developed. This study compared the programmed death ligand-1 staining patterns of gastric adenocarcinoma evaluated by the 22C3 and 28-8 pharmDx assays.
Tissue microarray analysis was performed for 226 patients with gastric adenocarcinoma who underwent curative surgery. Interobserver concordance between the 22C3 and 28-8 pharmDx assays was assessed to compare the dichotomized expression values. Programmed death ligand-1 positivity was assessed by combined positive score and tumor proportion score. Immunohistochemistry for deficient mismatch repair proteins and Epstein-Barr virus-encoded RNA
hybridization was examined.
Programmed death ligand-1 positivity with a combined positive score ≥5 was detected in 63 patients (28%) by the 22C3 pharmDx assay, and in 45 patients (20%) by the 28-8 pharmDx assay. A pairwise comparison of the 22C3 and 28-8 pharmDx assays showed 87% of pairs were concordant and 11% higher expressions for the 22C3 pharmDx assay, with strong concordance (kappa score =0.881 with a combined positive score cutoff of 5). The programmed death ligand-1 positivity rate (range, 3-5%) of the tumor proportion score was markedly lower than that of the combined positive score in the two assays. Programmed death ligand-1 positivity of the combined positive score in these two assays was associated with mismatch repair proteins and Epstein-Barr virus status. There was no significant difference in the overall survival between programmed death ligand-1, mismatch repair proteins, and Epstein-Barr virus status.
The study findings suggest the potential interchangeability of the 22C3 and 28-8 pharmDx assays to determine programmed death ligand-1 expression levels in gastric adenocarcinoma patients.
Purpose
Peritoneal dissemination is the key to the prognosis of gastric cancer (GC) and can be detected early with peritoneal lavage cytology. No studies have examined preoperative prognostic factors ...in GC patients who have positive cytology but no other non-curative factors.
Methods
We conducted a retrospective analysis using a multicenter database of 3575 patients who underwent gastrectomy between 2010 and 2014. Patients with positive peritoneal lavage cytology as a sole non-curative factor were retrieved, and correlations between parameters and the prognosis were compared.
Results
A total of 66 patients were identified as eligible. In the receiver operating characteristic (ROC) curve analysis, the neutrophil-to-platelet ratio (NPR) had the greatest area under the curve value and was selected. We divided the NPR into two groups based on the optimal cutoff value of the NPR (2.000), as determined by the ROC curve analysis. A high preoperative NPR was the only prognostic factor. The NPR-high group had shorter overall survival than the NPR-low group (hazard ratio 1.85, 95% confidence interval 1.05–3.28,
P
= 0.032).
Conclusion
Our analysis indicated that the preoperative NPR serves as a prognostic factor in GC patients with positive peritoneal lavage cytology in the absence of other non-curative factors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Previously we demonstrated that phosphorylation of NR2B subunits of the
N-methyl-
d-aspartate (NMDA) glutamate receptor at Tyr1472 is increased in a neuropathic-pain model and that this ...phosphorylation is required for the maintenance of neuropathic pain by L5-spinal nerve transection. We obtained these results by using a selective NR2B antagonist and mice deficient in Fyn, which is an Src-family tyrosine protein kinase. However, how Tyr1472 phosphorylation of NR2B is involved in the maintenance of neuropathic pain was unclear. Here, we demonstrated that neuropathic pain was markedly attenuated in the spared nerve injury model of mice with a knock-in mutation of the Tyr1472 site to phenylalanine of NR2B (Y1472F-KI). While phosphorylation of Ca
2+/calmodulin-dependent protein kinase II (CaMKII) at its Thr286 and that of the GluR1 subunit of the AMPA receptor at its Ser831 was enhanced in the spinal dorsal horn after spared nerve injury in wild-type mice, such phosphorylation was markedly impaired in Y1472F-KI mice. Inhibition of CaMKII by intrathecal injection of KN93, an inhibitor of CaMKII, reduced mechanical allodynia and phosphorylation of CaMKII at its Thr286 and that of GluR1 at its Ser831 in the spinal cord 7 days after spared nerve injury. These results demonstrate that the phosphorylation of CaMKII and GluR1 occurs downstream of the Tyr1472 phosphorylation of NR2B subunits in the spinal cord and give the first suggestion that activation of CaMKII and GluR1-AMPA receptors may be involved in mechanical allodynia caused by peripheral nerve injury.
► The mice with a mutation of the Tyr1472 to Phe of NR2B (Y1472F-KI) were analyzed. ► We applied a neuropathic-pain model, spared nerve injury (SNI) to Y1472F-KI mice. ► Phosphorylation cascade of Y1472-NR2B, T286-CaMKII and S831-GluR1 occurs by SNI. ► Allodynia by SNI is reduced in Y1472F-KI mice and by i.t. KN93, CaMKII inhibitor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
The insulin‐like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer ...risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non‐cancer control subjects were enrolled in this case–control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per‐allele model after adjusting for other risk factors (OR: 1.14 95% CI: 1.00–1.30 and OR: 1.18 95% CI: 1.02‐1.36, respectively). We also observed a positive and dose‐dependent association between the number of risk alleles and stomach cancer risk (P‐trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted. (Cancer Sci 2011; 102: 2231–2235)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Itch and pain are intimately related and may share similar peripheral and central mechanisms and pathways. However, it has been believed that synaptic glutamate release from a group of peripheral ...nociceptors is required to sense pain and suppress itch. Although we previously demonstrated that phosphorylation of GluN2B subunits of the NMDA receptor at Tyr1472 is important for central sensitization in a neuropathic pain model of mice with a knock‐in mutation of the Tyr1472 site to phenylalanine of GluN2B (Y1472F‐KI), the role of NMDA receptors in itch transmission remains unknown. Here, we demonstrated that the scratching behaviors elicited by various pruritogens applied to the cheek and c‐fos expression in the region innervated by the trigeminal nerve were markedly attenuated in the Y1472F‐KI mice. The c‐fos immunoreactivity was co‐localized with the receptor of gastrin‐releasing peptide (GRP). Scratching behaviors evoked by chloroquine were inhibited by the NMDA receptor antagonists D‐AP5 and CP101,606 and by the Src kinase inhibitor PP2. Direct activation of the trigeminal region by intracisternal administration of NMDA and GRP induced robust scratching behaviors, both of which were reduced by the GRP receptor antagonist RC‐3095. Taken together, the data obtained in this present study are the first to demonstrate that phosphorylation of GluN2B subunit at Tyr1472 is important for trigeminal transmission of itch and suggest that the NMDA receptor activation occurs upstream of the GRP‐GRP receptor pathway.
In this study, we showed that the phosphorylation of GluN2B subunits of the NMDA receptor at its Tyr1472 is important for trigeminal transmission of itch. NMDA receptor activation occurs upstream of the gastrin‐releasing peptide (GRP)‐GRP receptor pathway.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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