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Recurrence-free survival and 5-year survival rates are still commonly used as prognostic indicators for gastrointestinal cancer. We believe that there is a need to find an appropriate index to evaluate changes in health status over time in postoperative patients. We evaluated changes in "frailty" after esophageal cancer surgery using the Kihon Checklist (KCL) developed by the Japanese Ministry of Health, Labour and Welfare, and examined risk factors for worsening health status after surgery. Twenty-four patients (21 thoracoscopic sub-total esophagectomy, 1 mediastinoscopic sub-total esophagectomy, and 2 total laryngopharyngoesophagectomy) who underwent esophageal cancer surgery in our department from December 2019 to April 2021 were included. Patients were asked to write down their KCL before surgery and one year after surgery at an outpatient clinic, and changes over time were checked. We compared the background factors in the "maintain" group (M group) and the "worsened" group (W group), and investigated the risk factors for pre-frail and frail states one year after the surgery. 8 patients worsened from robust to pre-frail to frail and pre-frail to frail, and 16 patients maintained their condition, with 33% of them worsening. Age (M/W: 70/72, p=0.296), male (M/W: 0.88/1.0, p=0.536), BMI (M/W: 22.4/19.6, p=0.142), pStage≥3 (M/W: 0.38/0.38, p=1.0), preoperative chemotherapy (M/W: 0.69/0.63, p=1.0), operative time (M/W: 566/610 minutes, p=0.327), blood loss (M/W: 103/151 ml, p=0.342), postoperative pneumonia (M/W: 0.25/0.25, p=1.0), and cancer recurrence (M/W: 0.19/0.50, p=0.167). The preoperative blood samples were Alb (M/W: 4.3/3.8 g/dl, p=0.046), Hb (M/W: 14.2/12.8 g/dl, p=0.015) and Cre (M/W: 0.85/0.79 mg/dl, p=0.713). At 1 year after esophageal cancer surgery, health worsened and 33% of patients were in a pre-frail or frail state. Risk factors for worsening health were low Alb and low Hb, which were not related to stage or actual age. Further study is needed to clarify risk factors for frailty.

Situs inversus totalis is defined as a complete mirror-image transposition of the thoracic and abdominal viscera. Cancer surgery in patients with situs inversus totalis can be more difficult than in patients without situs inversus totalis; however, robotic surgery using the da Vinci Surgical System allows for intuitive operation with its multi-articular function and stereopsis effect. In addition, prevention of shaking and the motion scale allows for efficient surgical procedures. We evaluated a 64-year-old man who had gastric cancer, and situs inversus totalis and a blood-vessel variation. To facilitate intuitive handling of the robot in this patient with organs reversed from the norm, we arranged the instruments and ports in such a way that the Maryland bipolar forceps could be used with the surgeon’s right hand. We performed a successful robotic distal gastrectomy with lymph node dissection. The operative time was 286 min, and the blood loss was 44 mL. There were no intra- or post-operative complications. The patient was discharged on postoperative day 7 and has had no evidence of a recurrence for 18 months. We conclude that robotic surgery is an efficient tool for operating on patients with gastric cancer, and situs inversus totalis and vessel variations.

Various innovative robotic systems have been developed to improve surgery precision. The Senhance Surgical System (SSS) is a digital laparoscopic system offering eye tracking and haptic feedback. Several reports have described application of the SSS to general surgeries, including cholecystectomy and colectomy. However, use of the SSS for gastric tumor has not been reported. We experienced a case of laparoscopic local gastrectomy (LLG) for gastrointestinal stromal tumor (GIST) with the SSS. A 74-year-old man diagnosed with GIST underwent LLG with the SSS. Operation, docking, and console times were 117, 11, and 59 minutes, respectively. No perioperative complications were encountered. This study is the first to report LLG for GIST with the SSS. LLG with the SSS was safe and feasible. The SSS can use reusable forceps and contribute to reducing medical costs. The development of instruments is also progressing, and various kinds of surgery are likely to be indicated.

In esophageal cancer surgery, the significance of preserving the azygos arch during thoracoscopic esophagectomy remains unknown. To determine the significance, we examined the difference in postoperative courses between patients who underwent an azygos arch-preserving technique and patients whose azygos arch had been dissected. We retrospectively analyzed 119 patients with esophageal cancer who underwent thoracoscopic esophagectomy from January 2017 to December 2019. Statistical tests, including univariate or multivariate analyses and propensity score-matched analysis, were performed focusing on changes in fluid balance caused by the preservation of the azygos arch. The azygos arch was preserved in 65 patients and dissected in 54 patients. Urine output on postoperative day 2 was higher, and the IN-OUT balance on postoperative day 2 or accumulated IN-OUT balance up to postoperative day 2 tended to be lower in the azygos arch-preserving group than in the dissected group. The azygos arch-preserving technique did not affect the number of dissected mediastinal lymph nodes. The azygos arch-preserving technique during thoracoscopic esophagectomy facilitated postoperative refilling and avoided postoperative fluid excess. This technique might be a novel minimally invasive option for an otherwise highly invasive esophageal cancer surgery.

Esophageal gastrointestinal stromal tumors (E-GIST) are very rare tumors, and there is no consensus regarding the optimal surgical approach for E-GISTs. Here, we report a case of a large E-GIST that was resected via video-assisted thoracoscopic surgery (VATS) and hand-assisted laparoscopic surgery (HALS). When examining for comorbidities of myasthenia gravis using computed tomography, a 7-cm-sized tumor was detected in the lower esophagus of a 68-year-old woman. Further examination revealed the tumor to be an E-GIST with high malignant potential, and thus, esophagectomy was performed. The hybrid procedure for VATS and HALS techniques was safe and minimally invasive for this E-GIST that required esophagectomy. Thus, esophagectomy with VATS and HALS is thought to be a reasonable surgical option for resecting large E-GISTs, for which enucleation is not recommended.

Additional surgery is recommended for patients with noncurative resection after endoscopic submucosal dissection (ESD) for early gastric cancer. Additional resection requires the excision of an area larger than that of the resected mucosa in ESD, which is larger than the lesion, with convergence of the gastric mucosa due to scarring. Thus, the selection of the surgical procedure for lesion removal in specific areas can be affected by ESD. This study therefore aimed to evaluate the impact of ESD on the selection of additional gastrectomy in patients with early gastric cancer in the boundary area between the upper third and middle third of the stomach (UM boundary region). Between January 2013 and June 2018, laparoscopic gastrectomy was performed in 89 patients with cT1N0M0 gastric cancer located only in the UM boundary region. The patients’ backgrounds and surgical and pathological results were retrospectively investigated. The predictive factors for performing laparoscopic distal gastrectomy (LDG) were evaluated by multivariate analysis. Among 89 patients, 23 patients underwent ESD before surgery. LDG was significantly less often performed in the ESD-surgery group than in the surgery-only group (34.8% vs. 72.7%; p = 0.003). Preoperative ESD was an independent negative predictor of LDG (odds ratio = 0.266; p = 0.025). Preoperative ESD has an impact on the selection of the type of additional gastrectomy, including reducing the conduct of LDG for early gastric cancer in the UM boundary region.

BackgroundThe treatment for nonampullary duodenal adenoma remains to have no consensus and established methods. Although endoscopic treatment is minimally invasive, it was reported to cause delayed perforation in more than 20% of cases. MethodsFor adenomas in the duodenum, we have performed ESD-aid surgery, which is a procedure to prophylactically suture the seromuscular structure of the duodenum after ESD. In this procedure, we did not perform Kocher mobilization prior to ESD to facilitate endoscopic resection and full-thickness resection to prevent spread of the tumor and infection to the abdominal cavity. The duodenal wall was reinforced in planes using a suture clip. ResultsOf the 13 cases of duodenal adenoma that underwent ESD-aid surgery at our hospital between April 2018 and December 2020, 1 developed postoperative bleeding, but there was no late perforation. ConclusionsFor duodenal adenomas, ESD-aid surgery was considered a safe and minimally invasive treatment.Trial registrationThis research was approved by the institutional review board of Nagoya City University Hospital, Approval Number: 60-19-0021, Approval Date: 4 June 2019.

Boerhaave syndrome (BS) is frequently reported in cases of esophageal perforation; however, there are relatively few studies on non–Boerhaave syndrome (nBS). This study clarifies the appropriate diagnosis and treatment for patients with nBS among those with esophageal ruptures. Twelve patients with esophageal ruptures who underwent surgery at our department over 14 years were classified into 2 groups: 4 in the nBS group and 8 in the BS group. Patient characteristics, surgical methods, surgical outcomes, and complications were compared between the groups. The chief complaints varied between the groups. The nBS group had significantly higher preoperative C-reactive protein ( P = .007) and required 5 days (median) from onset to surgery. Moreover, the perforation diameter was significantly smaller in the nBS group than in the BS group ( P = .013). Suturing of the perforation site was performed during the initial surgery in 8 BS group patients (100%) and 1 nBS group patient (25%; P = .018). Only drainage was performed during the initial surgery for 3 nBS group patients (75%). The complications did not significantly differ between the groups ( P = 1.000), and no deaths were reported. The chief complaints of patients with nBS are diverse, and esophageal perforation should be cited as a differential diagnosis even in the absence of vomiting or chest pain symptoms. In the initial surgery for patients with nBS, the perforation site does not necessarily need to be closed. It is treatable by second-stage surgery or by natural closing.

Advancements in thoracoscopic surgery have provided us with a deeper anatomical understanding of recurrent laryngeal nerve paralysis (RLNP), which is likely to occur after lymph node dissection. Taking a novel approach to researching the diagnosis of RLNP, we evaluated movement of the vocal cords and arytenoid cartilages using ultrasonography in patients who underwent thoracoscopic esophagectomy. RLNP occurred in six of the 24 patient cohort. The rate of hoarseness and difficulty in discharging sputum was significantly higher in the paralyzed group than in the non-paralyzed group. The diagnostic accuracy of RLNP by ultrasonography had a sensitivity of 83.3% (5/6), a specificity of 88.8% (16/18), a false positive rate of 5.6% (1/18), and a false negative rate of 0% (0/6). Although it is not completely accurate, our findings indicate that ultrasonography is quite effective for diagnosing RLNP, more so in combination with clinical symptoms. Ultrasonography may also be effective for identifying patients who are amenable to laryngoscopy for diagnosing RLNP, or for evaluating the recovery status of nerve paralysis.

We report the case of a patient with esophageal cancer accompanied by esophago-bronchial fistula and pneumonia, who experienced improved quality of life following multimodal therapy that included esophageal bypass surgery. A 56-year-old man was diagnosed with advanced esophageal cancer with an esophago-bronchial fistula on computed tomography scan. He underwent esophageal bypass surgery followed by definitive chemoradiotherapy. He started eating 12 days after the surgery and was discharged home after the completion of chemoradiotherapy. On follow-up, the primary lesion was found to be significantly decreased in size and the esophago-bronchial fistula was closed. Although the patient ultimately died owing to distant metastases, he enjoyed a prolonged period of survival following surgery. Multimodal therapy including esophageal bypass surgery is an useful strategy for treating patients with critical conditions such as esophago-bronchial fistula induced by esophageal cancer.

The effect of the cyclooxygenase-2 (COX-2) inhibitor etodolac on the mechanical allodynia induced by paclitaxel was investigated in mice and compared with the effects of the nonselective COX inhibitors indomethacin and diclofenac, the selective COX-2 inhibitor celecoxib, the calcium channel α(2)δ subunit inhibitor pregabalin, the sodium channel blocker mexiletine, and the serotonin-norepinephrine reuptake inhibitor duloxetine. The decrease in the paw-withdrawal threshold induced by paclitaxel was reversed by oral administration of etodolac at 10 mg/kg but was not affected by indomethacin, diclofenac, or celecoxib. The antiallodynic effect of etodolac gradually increased during repeated administration, and after 2 weeks the paw-withdrawal threshold at the preadministration point was significantly increased. Pregabalin, duloxetine, and mexiletine also showed an antiallodynic effect in this model. Whereas pregabalin had a preadministration effect similar to that of etodolac during repeated administration, mexiletine or duloxetine had no such effect. There was almost no difference in the distribution of etodolac and diclofenac in nervous tissue, indicating that COX inhibition is unlikely to be involved in the antiallodynic effect of etodolac. Etodolac did not show a neuroprotective effect against morphological transformations such as the axonal degeneration induced by paclitaxel. Instead, etodolac probably acts at the level of functional changes accompanying paclitaxel treatment, such as alterations in the activation state of components of the pain transmission pathway. Our findings suggest that etodolac attenuates paclitaxel-induced peripheral neuropathy by a COX-independent pathway and that it might be useful for the treatment of paclitaxel-induced peripheral neuropathy.

Background and Purpose: The excitability of nociceptors is modulated by the transient receptor potential cation channel, ankyrin subfamily, member 1 (TRPA1). We have previously reported that etodolac, a nonsteroidal anti-inflammatory drug, attenuates mechanical allodynia in a mouse model of neuropathic pain by a mechanism that is independent of cyclooxygenase inhibition. Here, we investigate the role of TRPA1 in the mechanism of the antinociceptive action of etodolac in vitro and in vivo. Experimental Approach: Ca2+ influx was measured in HEK-293 cells expressing mouse TRPA1 and in mouse dorsal root ganglion (DRG) neurons. The effect of etodolac on the nociceptive behavior induced in mice by the TRPA1 agonist allyl isothiocyanate (AITC) was also measured. Results: Etodolac induced Ca2+ influx in HEK-293 cells expressing mouse TRPA1 and in mouse DRG neurons. The Ca2+ influx induced by etodolac was inhibited by pretreatment with the TRPA1-specific antagonist HC-030031. In contrast, etodolac did not induce Ca2+ influx in cells expressing TRPV1, TRPV2 or TRPM8. In addition, pretreatment with etodolac inhibited the Ca2+ influx induced by AITC. Conclusion and Implication: Etodolac showed a selective TRPA1 agonist action, providing evidence that etodolac desensitizes nociceptors by the selective activation of TRPA1. Etodolac may be clinically useful in the treatment of neuropathic pain.

The anti-inflammatory agent etodolac is used worldwide and it has a good gastrointestinal safety profile. Etodolac consists of two enantiomers, S- and R-etodolac. Here, we investigated the beneficial activities of racemic etodolac and its enantiomers. First, we compared S- and R-etodolac in terms of their inhibition of cyclooxygenase (COX) activity in vitro and their suppression of paw swelling in adjuvant-induced arthritic rats. The COX-2 inhibitory and anti-inflammatory effects of etodolac were found to be due to the S-enantiomer. We previously reported that etodolac attenuates allodynia in a mouse model of neuropathic pain by a COX-2-independent mechanism [N. Inoue et al., J. Pharmacol. Sci., 109, 600-605 (2009)]. In the present study, we showed that the anti-allodynic effects of etodolac in mice were also due to the S-enantiomer. In addition, we investigated the ulcerogenic activity of racemic etodolac and its enantiomers. At high doses, racemic etodolac showed a lower gastric lesion index in rats than the equivalent dose of S-etodolac. In contrast, R-etodolac showed no ulcerogenic activity and even showed protection against HCl/ethanol-induced gastric damage in rats. In conclusion, S-etodolac exhibited anti-inflammatory effects mediated by COX-2 inhibition and anti-allodynic effects that were independent of COX-2 inhibition, while R-etodolac showed gastroprotective effects that may contribute to the low gastrointestinal toxicity of racemic etodolac. Our results show that each enantiomer plays a different role in the efficacy and gastrointestinal safety of etodolac.

Cyclooxygenase (COX) contributes to neuropathic pain after peripheral nerve injury, yet COX inhibitors are generally ineffective against mechanical allodynia and hyperalgesia in neuropathic pain patients and animal models. In the present study, we investigated the effects of etodolac, a selective COX-2 inhibitor, on mechanical allodynia in mice after partial sciatic nerve ligation (PSNL) compared to indomethacin (a nonselective COX inhibitor) or celecoxib (a selective COX-2 inhibitor). PSNL decreased the paw-withdrawal threshold (PWT) as assessed by the von Frey hair test, and etodolac, but not indomethacin or celecoxib, administered daily for two weeks, partially or wholly reversed the decrease. The efficacy of etodolac gradually increased throughout the administration period, and the higher dosages restored preligation PWT values by day 21. The positive control pregabalin also partially or wholly reversed the decrease in PWT, but in contrast to etodolac, it showed no increase in efficacy throughout the administration period. In normal mice, etodolac did not affect the PWT, whereas pregabalin increased it. These findings suggest that the mechanisms of inhibition of mechanical allodynia by etodolac and pregabalin are different and demonstrate that in contrast to other COX inhibitors, etodolac is effective against mechanical allodynia in a mouse neuropathic pain model. Keywords:: etodolac, neuropathic pain, cyclooxygenase (COX)-2, partial sciatic nerve ligation, mechanical allodynia

To clarify neuronal networks controlling swallowing water, inhibitory neurotransmitters were searched on the glossopharyngeal–vagal motor complex (GVC) of the medulla oblongata (MO), which is proposed as a motor nucleus controlling swallowing. Spontaneous firing (20–30 Hz) in the GVC was inhibited by adrenaline (AD), noradrenaline (NA) and dopamine (DA). The inhibitory effects of these catecholamines (CAs) were dose-dependent, and the effects of AD and NA were completely blocked by phenoxybenzamine or yohimbine, indicating that at least these two CAs act on the same receptor, presumably on α2-adrenoceptor. Even after blocking the α2-adrenoceptor with yohimbine, the inhibitory effect of DA still remained, indicating separate action of DA from AD or NA. Although DA receptor type was not determined in the present study, these results suggest existence of CA receptors in the GVC neurons. Almost 70% GVC neurons were inhibited by CAs. The CA-sensitive neurons were specifically restricted in the middle part of the GVC area. There were many tyrosine hydroxylase (TH)-immunoreactive somata and fibers in the eel MO. Among these TH-immunoreactive nuclei, the area postrema (AP) and the commissural nucleus of Cajal (NCC) appeared to project to the GVC morphologically. Significance of the catecholaminergic inhibition in the GVC activity is discussed in relation to controlling swallowing water. J. Exp. Zool. 305A, 2006. © 2006 Wiley-Liss, Inc.