Intraneural fibrosis within ilioinguinal nerve in inguinal hernia patients with preoperative pain: it's the sign of irreversible nerve injury, isn't it?

PURPOSE: Preoperative pain is known as one of the most powerful risk factors for chronic postoperative inguinal pain (CPIP), while its pathogenesis has not been fully elucidated. The aim of the present study was to evaluate patients with preoperative pain from the pathological perspective and discuss the potential pathogenesis of CPIP in those patients. METHODS: This was a single-institutional retrospective study. The study population was inguinal hernia patients with preoperative pain who underwent open anterior hernia repair for primary inguinal hernia with pragmatic ilioinguinal neurectomy during surgery between March 2021 and March 2023. The primary and secondary outcomes were proportion of collagen deposition and mucus accumulation within ilioinguinal nerve in those patients, respectively, which were evaluated histologically using Image J software. RESULTS: Forty patients were evaluated. Median value of proportion of intraneural collagen deposition was 38.3% (27.7-95.9). These values were positively correlated with the duration of pain (r2=0.468, P<0.001). Median value of proportion of mucus accumulation in ilioinguinal nerve was 50.1% (0-82.0). These values had no correlation with any clinicopathological variables. CONCLUSIONS: In the present study population, all patients with preoperative pain had intraneural fibrosis within ilioinguinal nerve, and its degree had a positive correlation with the pain duration.

Laparoscopic resection of an intra-abdominal esophageal duplication cyst in the ileum: a case report.

BACKGROUND: Esophageal duplication cyst (EDC) is a type of gastrointestinal duplication cyst that involves congenital malformations of the gastrointestinal tract. EDCs are frequently found in the mediastinum and thoracoabdominal region, but rarely occur in the abdominal cavity. However, intra-abdominal EDCs are frequently found in the upper abdomen near the abdominal esophagus. Here, we report, for the first time, a case of intra-abdominal EDC that occurred in the ileum. CASE PRESENTATION: A 14-year-old female patient presented to our hospital with complaints of epigastric pain and vomiting. Abdominal computed tomography (CT) revealed a cystic tumor in the pelvis, suspected of ovarian origin. She was admitted to our gynecology department and underwent emergency surgery. The laparoscopic examination revealed that both ovaries were intact and that a primary tumor had developed from the ileal mesentery. Since the patient's condition was not urgent at the time of the gynecological surgery, the procedure was completed by only performing exploratory laparotomy; the patient was admitted to our department after the surgery. Pelvic magnetic resonance imaging performed on the next day revealed a cystic mass measuring 90 × 65 mm with a smooth margin and homogeneous signal intensity, arising posterior to the uterus. The mass was suspected as an intestinal duplication cyst. On another day, after the examinations were completed, we resected the portion of the small intestine containing the tumor by laparoscopy. The patient had a successful postoperative course and was discharged on the 5th postoperative day. Histological examination showed that the cyst was lined by stratified squamous epithelium, contained esophageal glands, and had a two-layer muscularis propria. Therefore, a diagnosis of intra-abdominal EDC was performed. CONCLUSIONS: An intra-abdominal EDC cyst is relatively rare; this is the first case reported at the distal ileum.

Colon inflammatory index as a useful prognostic marker after R0 resection in patients with colorectal cancer liver metastasis.

BACKGROUND: Although R0 resection for colorectal cancer liver metastasis (CRLM) is a promising treatment with improved prognosis, the recurrence rate is still high. No prognostic markers have been reported after resection of CRLM. In this study, we investigated the association between inflammation-based score and prognosis after R0 resection in patients with CRLM. METHODS: We retrospectively investigated 90 patients who underwent R0 resection for CRLM between 2008 and 2018. We calculated colon inflammatory index (CII) (CII0, low risk; CII1, intermediate risk; and CII2, high risk), modified Glasgow prognostic score, prognostic nutritional index, and CRP-to-albumin ratio; and retrospectively assessed the relationship between these scores, the clinicopathological features, and prognosis. RESULTS: The median follow-up period was 44 months (range, 2-101 months). Five-year relapse-free survival (RFS) (CII2; 12.5%, CII1; 14.5%, CII0; 42.9%) and 5-year overall survival (OS) (CII2; 32.4%, CII1; 25.4%, CII0; 57.7%) were significantly lower in the high CII groups (CII1-2) compared with the low CII group (CII0) (p = 0.021 and p = 0.006, respectively). CEA level was significantly higher in the high CII group than the low CII group (12.4 vs 7.3, p = 0.004). Multivariate analysis showed CII score as an independent predictor of RFS (hazard ratio 2.128, 95%CI 1.147-3.430, p = 0.015) and OS (hazard ratio 2.639, 95%CI 1.331-5.323, p = 0.005). CONCLUSION: CII shows promise as a prognostic marker after R0 liver resection in patients with CRLM.

Efficacy of risk-stratified indicators for adjuvant chemotherapy with fluorouracil and oxaliplatin after hepatectomy for colorectal cancer liver metastasis.

BACKGROUND: The recurrence rate after hepatectomy for colorectal cancer liver metastasis (CRLM) is high, and there is no consensus regarding the effect of adjuvant chemotherapy (AC) using oxaliplatin (doublet AC) in these patients. METHODS: The present study included 91 patients who underwent hepatectomy for complete resection at our hospitals between 2008 and 2018. Based on whether or not they had undergone doublet AC, patients were divided into AC (n = 35) and non-AC (n = 56) groups. The recurrent risk was evaluated by the Memorial Sloan Kettering Cancer Center clinical risk score (MSKCC-CRS). RESULTS: The number of females and median age were higher in the AC group (51.4% vs 25.0%, p = 0.010 and 67 vs 61 years, p = 0.012, respectively). The median follow-up period was 45 months (range, 6-101 months). Doublet AC was an independent prognostic factor for 5-year relapse-free survival (hazard ratio, 0.225; 95%CI, 0.097-0.522; p < 0.001) and for 5-year overall survival (hazard ratio, 0.165; 95%CI, 0.057-0.476; p < 0.001) in multivariate analysis. In patients with a high risk of recurrence (MSKCC-CRS 3-5), 5-year relapse-free survival and 5-year overall survival was higher in the doublet AC group than in the non-AC group (p < 0.01). In low-risk patients (MSKCC-CRS 0-2), 5-year relapse-free survival and 5-year overall survival were similar between the groups. CONCLUSIONS: Doublet AC could have a positive effect on prognosis after curative resection of CRLM, especially in high-risk patients. The selection of patients and AC regimen should take into consideration the risk of recurrence.

Successful use of bio plugs for delayed bronchial closure after pneumonectomy in experimental settings.

OBJECTIVES: Cell therapies, such as stem cell suspension injection, are used to treat bronchopleural fistula. Although it is safe and effective, injected cells cannot remain within the bronchioles of the fistula due to cell leakage into the thoracic cavity. Here, we inserted a 'bio plug' into the fistula, produced using cells and a bio-3D printer, to examine the effectiveness of bio plugs for the closure of bronchopleural fistulas, the optimal cell source and the closure mechanism. METHODS: Bio plugs were made with mesenchymal stem (stromal) cells derived from bone marrow (MSCBM), fibroblasts and rat lung micro-vessel endothelial cells using a bio-3D printer with different cell mixing ratios. Six groups, according to the presence or absence and the type of bio plugs, were compared. The plugs were inserted into the bronchi of F344 rats. The obstruction ratio and histological and immunohistochemical findings were evaluated. RESULTS: MSCBM+ rat lung micro-vessel endothelial cell group exhibited a higher obstruction ratio among all groups excluding the MSCBM group (P = 0.039). This group had fibrosis and CD31-positive cells and fewer CD68-positive cells than MSCBM and MSCBM+ fibroblast groups. CONCLUSIONS: Bio plugs with mixed cells, including stem cells, contribute to bronchial closure in the current experimental setting. Endothelial cells effectively maintain the structure in this model. Although bronchial closure for bronchopleural fistula could not be described as clinical conditions were not reproduced, we collected essential data on bronchial closure; however, further experiments are warranted.

Usefulness of structured-cadaveric training for trans-anal pelvic exenteration.

PURPOSE: Structured training using cadaveric simulation is useful for trans-anal surgery; however, no studies have examined the effectiveness of cadaveric training for advanced trans-anal surgery including pelvic exenteration (PE). METHODS: Twelve colorectal surgeons attended a total of 10 cadaveric simulation training courses between 2016 and 2021 and completed a questionnaire at the end of the program. We divided 14 consecutive patients who underwent trans-anal PE between 2015 and 2021 into two groups: pre-training group and post-training group, and compared the clinico-pathological features between the groups. RESULTS: The median length of clinical experience of the surgeons was 12 years. There was high score agreement among the surgeons that the course was useful for recognition of anatomical and layer structure, training for trans-anal total mesorectal excision and trans-anal PE, and reducing complications specific to the trans-anal approach. Compared with the pre-training group, patients in the post-training group had a higher rate of two-team surgery (77.8% vs 0%, P = .021), and shorter time to specimen removal (273 vs 423 min, P = .045). CONCLUSIONS: Structured-cadaveric training has potential use as a technical step-up in advanced trans-anal surgery that might contribute to better short-term outcomes in the clinical setting.

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability.

Pembrolizumab is a novel immune-checkpoint inhibitor used for treatment of microsatellite instability-high (MSI-H) colorectal cancer. Several studies have reported clinical complete response (CR) after treatment with pembrolizumab, but none has confirmed pathological CR. Here we provide the first description of pathological CR with R0 resection after immune-checkpoint therapy. A 45-year-old man presented at our hospital with abdominal distention and highly elevated tumor markers. Contrast-enhanced abdominal CT showed a 110 × 75 mm bulky mass with markedly swollen lymph nodes and an isolated peritoneal metastasis in the pelvic space. Biopsy revealed poorly differentiated adenocarcinoma. We diagnosed ascending colon cancer cT4aN2bM1c Stage IVc. A biopsy specimen obtained during systemic chemotherapy (FOLFOXIRI) was confirmed pathologically as MSI-H, after which the treatment was changed to pembrolizumab. The tumor markers rapidly decreased to within normal ranges after three courses of treatment. After twenty courses, CT revealed shrinkage of the main tumor, lymph node metastases, and the peritoneal metastasis, and we performed extended right hemi-colectomy with dissection of the peritoneal metastasis. No residual tumor cells were found histologically. The patient achieved pathological CR and the postoperative course was uneventful. An accurate diagnosis and appropriate follow up are crucial for obtaining sufficient therapeutic effect of pembrolizumab.

Complete closure of a colo-duodenal fistula in a patient with advanced ascending colon cancer after pembrolizumab combined with radiation therapy: a case report.

BACKGROUND: A colo-duodenal fistula is a very rare complication of colon cancer that presents with not only severe clinical symptoms, but a poor prognosis due to locally advanced cancer. A novel immune checkpoint inhibitor for colon cancer patients provides a high objective response rate. Recently, radiation therapy combined with immune checkpoint inhibitor therapy has been reported to have a synergistic antitumor effect. A case of complete closure of a colo-duodenal fistula in a patient with locally advanced colon cancer after combined pembrolizumab and radiation therapy is reported. CASE PRESENTATION: A 66-year-old man presented with abdominal distention. Abdominal contrast-enhanced computed tomography (CT) showed a 80-mm bulky mass in the right upper quadrant. The tumor created a fistula to the second portion of the duodenum. Upper gastrointestinal endoscopy showed a colo-duodenal fistula. Gastro-jejunal bypass and ileostomy were performed to prevent bowel obstruction, followed by systemic chemotherapy. MSI-high was diagnosed on examination of the biopsy specimen. Treatment was then changed to immunotherapy using pembrolizumab; after six courses, the tumor markers were decreased to within normal ranges, but the main tumor increased. Radiation therapy was then given for local control of the main tumor, after which CT showed that all of the tumor, including the main tumor, lymph node metastases, and the colo-duodenal fistula, had gradually shrunk. Follow-up upper gastrointestinal endoscopy showed that the colo-duodenal fistula had closed completely. PET-CT showed no abnormal uptake in all tumors, and clinical complete response was diagnosed. Now, 21 months after diagnosis, the tumor is well controlled without evidence of regrowth. CONCLUSIONS: Pembrolizumab combined with radiation therapy has a potentially dramatic therapeutic effect for advanced colon cancer.

Colorectal cancer in Crohn's disease: a series of 6 cases.

BACKGROUND: Colorectal cancer (CRC) is the most malignant complication in patients with Crohn's disease (CD). We report 6 cases of CD-related CRC treated surgically at our hospital. CASE PRESENTATION: From 2010 to 2016, six CD patients were diagnosed with CRC. All patients were diagnosed with CD at < 25 years old, and the interval from onset of CD to diagnosis of CRC was > 10 years (range, 15-42 years) in all patients. The histological type of cancer was mucinous carcinoma in two cases, well-differentiated tubular adenocarcinoma in two cases, and moderately differentiated tubular adenocarcinoma in two cases. CRC was detected by screening colonoscopy in three cases (50%), and from clinical symptoms in the remaining three cases (50%). Two cases underwent colonoscopy within 2 months after symptom onset, detecting CRC in the relatively early stage. However, one case was diagnosed with advanced-stage CRC by endoscopy 1 year after symptom onset, and experienced poor prognosis. CONCLUSIONS: Regular surveillance colonoscopy is needed to detect early-stage CRC in CD patients. Clear surveillance methods need to be established based on evidence.

Epidermoid cyst of the cecum resected by single-incision laparoscopic colectomy: a case report.

BACKGROUND: Epidermoid cyst arising from the cecum is extremely rare. Single-incision laparoscopic surgery is the latest innovation in minimally invasive surgery, and shortens incisions, improves cosmesis, and reduces postoperative pain. We report here the first description of a patient with epidermoid cyst of the cecum treated by ileocecal resection by single-incision laparoscopic surgery. CASE PRESENTATION: A 20-year-old woman presented to our hospital with abdominal pain in the right lower quadrant. Abdominal contrast-enhanced computed tomography showed a 56 × 35-mm cystic mass in the ileocecal area. Magnetic resonance imaging revealed a 56 × 43-mm, T1-hypointense, T2-hyperintense mass attached to the cecum. Gastrointestinal tumor or duplication cyst was suspected, and ileocecal resection was performed using single-incision laparoscopic surgery. Intraoperative examination showed the tumor as a round, whitish mass arising from the cecum. Operation time was 162 min, and intraoperative blood loss was 10 ml. Macroscopic examination showed a 56 × 45-mm elastic-hard, whitish, round mass arising from the cecal wall. Microscopic examination revealed the cyst wall lined by keratinized stratified squamous epithelium. No malignant findings were identified. The final diagnosis was epidermoid cyst of the cecum. The postoperative course was uneventful and she was discharged on postoperative day 5. CONCLUSIONS: A rare case of cecal epidermoid cyst is reported. Single-incision laparoscopic colectomy using an organ retractor represents a promising option for treating cecal epidermoid cyst.

A new method using a vessel-sealing system provides coagulation effects to various types of bleeding with less thermal damage.

BACKGROUND: Hemostasis is very important for a safe surgery, particularly in endoscopic surgery. Accordingly, in the last decade, vessel-sealing systems became popular as hemostatic devices. However, their use is limited due to thermal damage to organs, such as intestines and nerves. We developed a new method for safe coagulation using a vessel-sealing system, termed flat coagulation (FC). This study aimed to evaluate the efficacy of this new FC method compared to conventional coagulation methods. METHODS: We evaluated the thermal damage caused by various energy devices, such as the vessel-sealing system (FC method using LigaSure™), ultrasonic scissors (Sonicision™), and monopolar electrosurgery (cut/coagulation/spray/soft coagulation (SC) mode), on porcine organs, including the small intestine and liver. Furthermore, we compared the hemostasis time between the FC method and conventional methods in the superficial bleeding model using porcine mesentery. RESULTS: FC caused less thermal damage than monopolar electrosurgery's SC mode in the porcine liver and small intestine (liver: mean depth of thermal damage, 1.91 ± 0.35 vs 3.37 ± 0.28 mm; p = 0.0015). In the superficial bleeding model, the hemostasis time of FC was significantly shorter than that of electrosurgery's SC mode (mean, 19.54 ± 22.51 s vs 44.99 ± 21.18 s; p = 0.0046). CONCLUSION: This study showed that the FC method caused less thermal damage to porcine small intestine and liver than conventional methods. This FC method could provide easier and faster coagulation of superficial bleeds compared to that achieved by electrosurgery's SC mode. Therefore, this study motivates for the use of this new method to achieve hemostasis with various types of bleeds involving internal organs during endoscopic surgeries.

Impact of obesity on short-term outcomes of laparoscopic colorectal surgery for Japanese patients with colorectal cancer: A multicenter study.

INTRODUCTION: The impact of obesity on short-term outcomes after laparoscopic colorectal surgery (LAC) in Asian patients is unclear. The purpose of the present multicenter study was to evaluate the safety and feasibility of LAC in obese Japanese patients. METHODS: We retrospectively reviewed 1705 patients who underwent LAC between April 2016 and February 2019. Patients were classified according to body mass index (BMI): non-obese (BMI < 25 kg/m2 , n = 1335), obese I (BMI 25-29.9 kg/m2 , n = 313), and obese II (BMI ≥30 kg/m2 , n = 57). Clinical characteristics and surgical outcomes were compared among the three groups. RESULTS: The proportion of patients with comorbidities (non-obese, 58.1%; obese I, 69.6%; obese II, 75.4%; P < .001) and median operation time (non-obese, 224 minutes; obese I, 235 minutes; obese II, 258 minutes; P = .004) increased significantly as BMI increased. The conversion rate was similar among the groups (P = .715). Infectious complications were significantly high in obese II patients (non-obese, 10.4%; obese I, 8.3%; obese II, 28.1%; P < .001). Multivariate analysis revealed that in obese II patients, BMI was an independent predictive factor of infectious postoperative complications (odds ratio 2.648; 95% confidence interval, 1.421-4.934; P = .002). CONCLUSION: LAC has an increased risk of postoperative infectious complications in obese II patients, despite improvements in surgical technique. Management of obese II colorectal cancer patients requires meticulous perioperative management.

Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection.

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson's disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD.

A case report of adult rectal duplication cyst resected by synchronous trans-abdominal and trans-anal total mesorectal excision.

INTRODUCTION: Rectal duplication cyst is extremely rare. Most of the cases diagnosed before two years old. Adult onset rectal duplication cyst usually contains malignant formation. Then complete tumor resection is needed for the disease to prevent malignant change. PRESENTATION OF CASE: A 52-year-old man was referred to our hospital due to bloody stool. Colonoscopy showed 20-mm of sub-mucosal tumor at low rectum. Biopsy revealed no specific findings. Abdominal computed tomography showed that a 20-mm low density mass at posterior of lower rectum. As the existence of malignant lesion was unassailable, we planned two team, trans abdominal and trans-anal, laparoscopic low anterior resection. Perioperative course was good. Macroscopically, rectum had a submucosal cystic mass fulfilled mucinous content. Histologically, cyst wall was covered with heterotopic ciliated epithelium and composed of smooth muscle. DISCUSSION: Trans-anal total mesorectal excision (ta-TME) was introduced as beneficial approach for rectal malignancies. CONCLUSION: Complete resection was possible by TME was necessary for patients with adult rectal duplication cyst, and synchronous trans-abdominal and trans-anal approach is a promising option.

Correction: Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

[This corrects the article DOI: 10.1371/journal.pone.0211339.].

Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.

Replacement of Rat Tracheas by Layered, Trachea-Like, Scaffold-Free Structures of Human Cells Using a Bio-3D Printing System.

Current scaffold-based tissue engineering approaches are subject to several limitations, such as design inflexibility, poor cytocompatibility, toxicity, and post-transplant degradation. Thus, scaffold-free tissue-engineered structures can be a promising solution to overcome the issues associated with classical scaffold-based materials in clinical transplantation. The present study seeks to optimize the culture conditions and cell combinations used to generate scaffold-free structures using a Bio-3D printing system. Human cartilage cells, human fibroblasts, human umbilical vein endothelial cells, and human mesenchymal stem cells from bone marrow are aggregated into spheroids and placed into a Bio-3D printing system with dedicated needles positioned according to 3D configuration data, to develop scaffold-free trachea-like tubes. Culturing the Bio-3D-printed structures with proper flow of specific medium in a bioreactor facilitates the rearrangement and self-organization of cells, improving physical strength and tissue function. The Bio-3D-printed tissue forms small-diameter trachea-like tubes that are implanted into rats with the support of catheters. It is confirmed that the tubes are viable in vivo and that the tracheal epithelium and capillaries proliferate. This tissue-engineered, scaffold-free, tubular structure can represent a significant step toward clinical application of bioengineered organs.