Targeting KRAS-mutant pancreatic cancer through simultaneous inhibition of KRAS, MEK, and JAK2.

The Kirsten rat sarcoma (KRAS) oncogene was considered "undruggable" until the development of sotorasib, a KRASG12C selective inhibitor that shows favorable effects against lung cancers. MRTX1133, a novel KRASG12D inhibitor, has shown promising results in basic research, although its effects against pancreatic cancer are limited when used alone. Therefore, there is an urgent need to identify effective drugs that can be used in combination with KRAS inhibitors. In this study, we found that administration of the KRAS inhibitors sotorasib or MRTX1133 upregulated STAT3 phosphorylation and reactivated ERK through a feedback reaction. The addition of the MEK inhibitor trametinib and the JAK2 inhibitor fedratinib successfully reversed this effect and resulted in significant growth inhibition in vitro and in vivo. Analyses of sotorasib- and MRTX1133-resistant cells showed that trametinib plus fedratinib reversed the resistance to sotorasib or MRTX1133. These findings suggest that the JAK2-mediated pathway and reactivation of the MAPK pathway may play key roles in resistance to KRAS inhibitors in pancreatic cancers. Accordingly, simultaneous inhibition of KRAS, MEK, and JAK2 could be an innovative therapeutic strategy against KRAS-mutant pancreatic cancer.

Short-term outcomes of laparoscopic and robotic distal gastrectomy for gastric cancer: Real-world evidence from a large-scale inpatient database in Japan.

BACKGROUND AND OBJECTIVES: Robotic distal gastrectomy (RDG) has been widely performed throughout Japan since it became insured in 2018. This study aimed to evaluate the short-term outcomes of RDG and laparoscopic distal gastrectomy (LDG) for gastric cancer using real-world data. METHODS: A total of 4161 patients who underwent LDG (n = 3173) or RDG (n = 988) for gastric cancer between April 2018 and October 2022 were identified through the Japanese Diagnosis Procedure Combination Database, which covers 42 national university hospitals. The primary outcome was postoperative in-hospital mortality rate. The secondary outcomes were postoperative complication rates, time to diet resumption, and postoperative length of stay (LOS). RESULTS: In-hospital mortality and postoperative complication rates in the RDG group were comparable with those in the LDG group (0.1% vs. 0.0%, p = 1.000, and 8.7% vs. 8.2%, p = 0.693, respectively). RDG was associated with a longer duration of anesthesia (325 vs. 262 min, p < 0.001), similar time to diet resumption (3 vs. 3 days, p < 0.001), and shorter postoperative LOS (10 vs. 11 days, p < 0.001) compared with LDG. CONCLUSIONS: RDG was performed safely and provided shorter postoperative LOS, since it became covered by insurance in Japan.

Impact of Oophorectomy on Survival and Improving Nutritional Status in Ovarian Metastasis from Colorectal Adenocarcinoma.

INTRODUCTION: Ovarian metastasis of colorectal cancer is known to have a poor prognosis. This study aimed to elucidate the characteristics of patients who underwent oophorectomy for ovarian metastasis from colorectal cancer. METHODS: This retrospective study included 16 patients who underwent oophorectomy for colorectal cancer metastasis to the ovary from January 2004 to December 2017. Improvement in patient's symptoms and pre- and postoperative changes in various nutritional and inflammatory indicators were assessed. Survival analysis and identification of prognostic factors were conducted with a median follow-up of 40.7 (5-109) months. RESULTS: Of 16 patients, 12 had (75%) synchronous and 4 (25%) had metachronous metastasis. Fourteen patients were symptomatic but symptoms resolved postoperatively. Thirteen patients (81.3%) had ascites and 5 (31.3%) had pleural effusion on preoperative computed tomography that disappeared after surgery in all cases. The median value of prognostic nutritional factor was significantly increased postoperatively (36.0 [preoperatively] vs. 47.5, p < 0.0001). The median (interquartile range) values for lymphocyte-C-reactive protein ratio were 715.2 (110-2,607) preoperatively and 6,095.2 (1,612.3-14,431.8) postoperatively (p = 0.0214). The median survival of the entire cohort was 60.4 months. The 3-year survival rates for R0 + R1 and R2 cases were 83% and 24% (p = 0.018), respectively. Univariate analysis showed that R2 resection and low postoperative lymphocyte-C-reactive protein ratio were associated with poor prognosis. CONCLUSIONS: Oophorectomy for ovarian metastasis from colorectal cancers was safely performed. It improved the patients' symptoms and nutritional status and may result in improved prognosis.

Cetuximab Enhances the Efficacy of MRTX1133, a Novel KRASG12D Inhibitor, in Colorectal Cancer Treatment.

BACKGROUND/AIM: Kirsten Rat Sarcoma viral oncogene homolog (KRAS) has remained undruggable for decades. KRAS has predominantly been used to evaluate the applicability of anti-Epidermal Growth Factor Receptor (EGFR) antibody drugs. However, various KRAS inhibitors have recently emerged. Unfortunately, KRAS inhibitors have not been effective against colorectal cancer. Therefore, this study aimed to determine the effects of MRTX1133, a novel KRASG12D inhibitor, in combination with an anti-EGFR antibody, cetuximab, on signal transduction and cell proliferation. MATERIALS AND METHODS: The KRASG12D-mutated LS513 and KRAS wild-type CACO-2 human colon cancer cell lines were utilized. The KRASG12D mutation was stably transduced into the CACO-2 cells using a retrovirus. We evaluated the effects of the drugs using the CCK-8 assay and assessed the activity of proteins related to the MAPK pathway using western blotting. RESULTS: We demonstrated that the administration of MRTX1133, a novel KRASG12D inhibitor, to KRASG12D-mutated colorectal cancer cells led to feedback activation of the ERK pathway via EGFR activation, inducing drug resistance. Intriguingly, when MRTX1133 was used in combination with cetuximab, KRASG12D-mutant colorectal cancer growth was effectively inhibited, both in vitro and in vivo. CONCLUSION: The combination of MRTX1133 and cetuximab serves as a potential and promising therapeutic approach for colorectal cancer with KRASG12D mutation. KRASG12D is a frequent genetic mutation not only in colorectal cancer, but also in pancreatic and lung cancer, and the results of this study open new avenues for potential treatment of many cancer patients.

Transmesenteric approach for laparoscopic endoscopic cooperative surgery for a duodenal adenoma located in the third portion of the duodenum.

We report our experience in a patient with adenoma located in the horizontal part of the duodenum, which was effectively treated with the transmesenteric laparoscopic endoscopic cooperative surgery (LECS) approach. This approach, which entails incising the mesentery of the colon, simplified laparoscopic access to the horizontal part of the duodenum, which was minimally mobilized. Thus, the bulb and descending part of the duodenum were fixed to the retroperitoneum, facilitating stable handling of the endoscope and enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. This approach enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. The advantages of this method include a secure field of view, lower probability of damage to large vessels, and minimizing the defect to the intestine caused by the incision.

Comparison of Short-term Outcomes Between Esophageal Bypass Surgery and Self-expanding Stent Insertion in Esophageal Cancer: A Propensity Score-matched Analysis Using a Large-scale Inpatient Database.

BACKGROUND: Advanced esophageal cancer is occasionally accompanied by difficulty swallowing owing to esophageal stenosis or tracheoesophageal fistula formation. Esophageal bypass surgery and stent insertion are considered feasible palliative management options. The aim of this study was to evaluate the short-term outcomes of these palliative treatments. MATERIALS AND METHODS: Patient data were obtained from a large-scale inpatient database of 42 National University Hospitals in Japan. Patients with advanced esophageal cancer who underwent esophageal bypass surgery or stent insertion between April 2016 and March 2021 were included in this study. One-to-one propensity score matching of patients who underwent bypass surgery or stent insertion was performed. The primary outcomes were time to diet resumption and length of hospital stay after surgery. The secondary outcome was the incidence of postoperative complications. RESULTS: In 43 propensity score-matched pairs, the incidence of postoperative respiratory complications was significantly higher in the bypass group than in the stent group (32.6% vs. 9.3%, P = 0.008). Postoperative length of hospital stay was longer in the bypass group than in the stent group (24 vs. 10 d, P < 0.001). Logistic regression analysis revealed that stent insertion was associated with a decreased risk of respiratory complications (odds ratio 0.077, P < 0.007). Among patients who underwent the interventions (bypass surgery or stent insertion) and subsequently underwent anticancer therapy (chemotherapy/radiotherapy) during hospitalization, the interval between the intervention and anticancer therapy was longer in the bypass group than in the stent group (25 vs. 7 d, P = 0.003). CONCLUSIONS: Esophageal stent insertion provides better short-term outcomes than bypass surgery in patients with advanced unresectable esophageal cancer.

MEK inhibitor and anti-EGFR antibody overcome sotorasib resistance signals and enhance its antitumor effect in colorectal cancer cells.

The Kirsten rat sarcoma (KRAS) oncogene was "undruggable" until sotorasib, a KRASG12C selective inhibitor, was developed with promising efficacy. However, inhibition of mutant KRAS in colorectal cancer cells (CRC) is ineffective due to feedback activation of MEK/ERK downstream of KRAS. In this study, we screened for combination therapies of simultaneous inhibition to overcome sotorasib resistance using our previously developed Mix Culture Assay. We evaluated whether there was an additive effect of sotorasib administered alone and in combination with two or three drugs: trametinib, a MEK inhibitor, and cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody. The MAPK pathway was reactivated in KRASG12C-mutated cell lines treated with sotorasib alone. Treatment with KRAS and MEK inhibitors suppressed the reactivation of the MAPK pathway, but upregulated EGFR expression. However, the addition of cetuximab to this combination suppressed EGFR reactivation. This three-drug combination therapy resulted in significant growth inhibition in vitro and in vivo. Our data suggest that reactive feedback may play a key role in the resistance signal in CRC. Simultaneously inhibiting KRAS, MEK, and EGFR is a potentially promising strategy for patients with KRASG12C-mutated CRC.

Goblet cell adenocarcinoma of the appendix: A case report of three cases.

INTRODUCTION AND IMPORTANCE: Appendiceal goblet cell adenocarcinoma is in 0.3-0.9 % of appendectomy specimens. There is still controversy regarding whether surgery with dissection or additional resection is necessary for goblet cell adenocarcinoma and whether adjuvant chemotherapy is practical. We present three cases of goblet cell adenocarcinomas. CASE PRESENTATION: Case 1: A 30-year-old woman was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells and tumour infiltration into the subserosa. The patient underwent laparoscopic ileocecal resection, and the main lymph nodes at the root of the feeding vessels were removed. Case 2: A 50-year-old man was diagnosed with appendicitis and underwent appendicectomy. Histopathological evaluation revealed a malignant neoplasm with goblet-like cells; malignant cells were found at the surgical resection margins. The patient underwent laparoscopic ileocolic resection. Case 3: A 60-year-old man undergoing treatment for malignant melanoma. He was diagnosed with appendicitis associated with an appendiceal tumour, and emergency laparoscopic caecal resection was performed and diagnosed as goblet cell adenocarcinoma. We decided to prioritize treatment for malignant melanoma, and the patient is under follow-up for goblet cell adenocarcinoma and no metastasis was detected. CLINICAL DISCUSSION: We performed additional resection in two case of goblet cell adenocarcinoma. Diagnosing appendiceal goblet cell adenocarcinoma is difficult, and the prognosis of patients with positive lymph nodes is poor. Surgical treatment should be considered for the advanced stages of this disease. CONCLUSION: Goblet cell adenocarcinoma, diagnosed after appendectomy, additional resection including lymph node dissection may provide a long-term prognosis.

Importance of intraoperative indocyanine green imaging in the management of non-occlusive mesenteric ischemia: a case report.

BACKGROUND: Non-obstructive intestinal ischemia (NOMI) is caused by intestinal vascular spasm and has a poor prognosis if not diagnosed and treated early. Indocyanine green (ICG) fluorescence imaging has been reported to be useful for the intraoperative assessment of the extent of intestinal resection required for NOMI. Few reports have described massive intestinal bleeding after conservative management of NOMI. We report a case of NOMI with massive postoperative bleeding from the site of an ICG contrast defect found before the initial surgery. CASE PRESENTATION: A 47-year-old woman with hemodialysis-dependent chronic kidney disease presented complaining of severe abdominal pain. A computed tomography scan showed portal gas and dilation of the small intestine, leading to a diagnosis of NOMI and subsequent emergency surgery. At the time of initial surgery, the contrast effect of ICG was slightly reduced, showing a granular distribution in the ascending colon to cecum (fine grain pattern) and significantly reduced in parts of the terminal ileum except around blood vessels (perivascular pattern). However, there was no obvious gross necrosis of the serosal surface, and the intestinal tract was not resected. The acute postoperative course was uneventful; however, the patient went into shock on the 24th postoperative day due to massive, small intestinal bleeding, and emergency surgery was performed. The bleeding originated from the section of the ileum that had complete loss of ICG contrast effect before the initial surgery. A right hemicolectomy with the terminal ileum resection was performed, and an ileo-transverse anastomosis was performed. The second post-operative course was uneventful. CONCLUSIONS: We report a case of delayed hemorrhage of the ileum shown to have poor blood flow on ICG imaging at the initial surgery. Intraoperative ICG fluorescence imaging is useful in assessing the degree of intestinal ischemia for NOMI. When patients with NOMI are followed up without surgery, complications such as bleeding should be noted.

Gastric glomus tumor resection using laparoscopic endoscopic cooperative surgery: A case report.

Gastric glomus tumors are rare submucosal mesenchymal neoplasms that are difficult to diagnose preoperatively. We present a case of a 60-year-old woman who was diagnosed with a gastric glomus tumor using endoscopic ultrasonography-guided fine-needle aspiration biopsy. The tumor was successfully resected with laparoscopic endoscopic cooperative surgery (LECS). LECS could be an effective method for the resection of gastric glomus tumors.

RhoA G17E/Vav1 Signaling Induces Cancer Invasion via Matrix Metalloproteinase-9 in Gastric Cancer.

BACKGROUND: RAS homolog family member A (RhoA), a member of the Rho family of small GTPases, and Vav1, a guanine nucleotide exchange factor for Rho family GTPases, have been reported to activate pathways related to the actin cytoskeleton and regulation of cell shape, attachment, and motility. The interaction between these molecules in lymphoma is involved in malignant signaling, but its function in epithelial malignancy is unknown. Here, we investigated the malignant signal of mutant RhoA in gastric cancer and demonstrated the potential of RhoA G17E/Vav1 as a therapeutic target for diffuse gastric cancer. METHODS: The RhoA mutants R5W, G17E, and Y42C were retrovirally transduced into the gastric cancer cell line MKN74. The stably transduced cells were used for morphology, proliferation, and migration/invasion assays in vitro. MKN74 cells stably transduced with ectopic wild-type RhoA and mutant RhoA (G17E) were used in a peritoneal xenograft assay. RESULTS: The RhoA mutations G17E and Y42C induced morphological changes in MKN74. G17E induced Vav1 expression at the mRNA and protein levels and promoted the migration and invasion of MKN74. An RNA interference assay of Vav1 revealed that RhoA G17E enhanced cancer cell invasion via Vav1. Furthermore, immunoprecipitation revealed that Vav1 and RhoA G17E specifically bind and function together through matrix metalloproteinase -9. In a peritoneal xenograft model of nude mice, RhoA G17E promoted peritoneal dissemination, whereas Vav1 knockdown suppressed it. CONCLUSION: Overall, our findings indicate that RhoA G17E is associated with Vav1 and promoted cancer invasion via matrix metalloproteinase -9 in gastric cancer cells. Thus, RhoA G17E/Vav1 signaling in diffuse gastric cancer may be a useful therapeutic target.

Intraoperative visualization of morphological patterns of the thoracic duct by subcutaneous inguinal injection of indocyanine green in esophagectomy for esophageal cancer.

To prevent chylothorax after esophageal cancer surgery, it is important to recognize morphological patterns of the thoracic duct intraoperatively. The present study aimed to evaluate the safety and usefulness of near-infrared (NIR) fluorescence imaging with subcutaneous inguinal injection of indocyanine green (SII-ICG) to detect the thoracic duct during thoracoscopic esophagectomy for esophageal cancer. Patients (n = 16) who underwent thoracoscopic esophagectomy in the prone position with SII-ICG at Shinshu University Hospital between June 2020 and January 2022 were enrolled in the present study and retrospectively reviewed. Immediately prior to thoracoscopic esophagectomy, we injected 0.2-0.5 mg/kg ICG into the subcutaneous tissue in the bilateral inguinal region. The identification rate of the thoracic duct was 93.8% (n = 15), and the success rate of fluorescence using SII-ICG was 87.5% (n = 14). The visible thoracic ducts had four patterns: a typical pattern in 50% (n = 8), duplication pattern in 18.8% (n = 3), branching pattern in 12.5% (n = 2), and plexiform pattern in 12.5% (n = 2). In all cases, ICG fluorescence did not disappear and was visible during the thoracic surgery. No SII-ICG-related complications were observed. Intraoperative NIR fluorescence imaging of the thoracic duct using SII-ICG is a simple and safe method with very high detection sensitivity. This method can be a powerful tool for avoiding thoracic duct injuries during esophageal cancer surgery.

Risk factors for umbilical incisional hernia after laparoscopic colorectal surgery.

BACKGROUND: Laparoscopic colorectal surgery (LCRS) requires a small laparotomy at the umbilicus. The wound is small and inconspicuous, but if the patient develops an umbilical incisional hernia (UIH), the wound is visible and the patient suffers from symptoms of discomfort. However, the incidence of UIH after LCRS and its risk factors are not well understood. The purpose of this study was to investigate the risk factors for UIH after LCRS for colorectal cancer. METHODS: This was a single-centre retrospective study of 135 patients with colorectal cancer, conducted at our hospital from April 2013 to March 2019. The diagnosis of UIH was based on computed tomography and physical examination findings. Preoperative patient data such as enlargement of the umbilical orifice (EUO), subcutaneous fat thickness (SFT) and intraperitoneal thickness (IPT) were collected and analysed using univariate and multivariate analyses for the presence of risk factors for UIH. RESULTS: A total of 135 patients who underwent LCRS were analysed. The incidence of UIH was 20.7%. Univariate analysis revealed significantly high body mass index (BMI) ≥ 25 (P = 0.032), EUO (P < 0.001), SFT ≥18 mm (P = 0.011), and IPT ≥61 mm (P < 0.01) in the UIH group. Multivariate analysis revealed significant differences in EUO (P < 0.001), SFT ≥18 mm (P = 0.046) and IPT ≥61 mm (P = 0.022). CONCLUSION: EUO was the most important risk factor for UIH, followed by IPT and SFT. These findings are predictive indicators of the development of UIH after LCRS and can be assessed objectively and easily with preoperative computed tomography.

Impact of seasonal and meteorological factors on the incidence of adhesive small bowel obstruction: A large-scale study using a national inpatient database.

Aim: Whether seasonal and meteorological factors affect the incidence of adhesive small bowel obstruction (ASBO) remains unclear. This study aimed to clarify the impacts of seasonal and meteorological factors on the occurrence of ASBO. Methods: Clinical data of patients with ASBO were acquired from 42 national university hospitals in Japan, using a national inpatient database, between April 2012 and March 2020. Meteorological data were obtained from the Japan Meteorological Agency. The number of monthly admissions of patients with ASBO was compared between each of the 12 months. Daily weather variables were investigated to clarify their association with ASBO patient admissions on a total of 119 802 days (Formula for calculation: study period [2922 days] ×41 cities). Results: Overall, 4985 patients with ASBO were admitted. The number of admissions in June was smaller than that in October, November, and December (39 vs 63.5, P = .002, 39 vs 65, P = .004, and 39 vs 59.5, P = .002, respectively). Logistic regression analysis revealed that January, October, November, and December were associated with increased risk of admission compared to June (odds ratio [OR], 1.264; P = .001; OR, 1.454; P < .001; OR, 1.408; P < .001; OR, 1.330; P < .001), respectively. Regarding the weather variables, higher barometric pressure and lower humidity were associated with increased risk of admission (OR, 1.011; P < .001 and OR, 0.995; P < .001), respectively. Conclusion: The incidence of ASBO is susceptible to barometric pressure and humidity and varies monthly. These results can contribute to the prevention, early detection, and immediate and appropriate management of ASBO.

Association of Daily Variance in Air Temperature With Postoperative Adhesive Small Bowel Obstruction.

INTRODUCTION: The influence of air temperature on adhesive small bowel obstruction (ASBO) is unknown. This study aimed to investigate the relationship between air temperature and postoperative ASBO. METHODS: Overall, 312 patients with postoperative ASBO were included. They were categorized into two groups: the surgery group (n = 83) comprising patients who needed surgery, and the non-surgery group (n = 229) comprising patients who responded to conservative treatment. The associations between patients' characteristics and weather variables on days of symptom onset with the need for surgical management were investigated. Weather variables included the daily mean barometric pressure, daily mean air temperature, day-to-day differences, daily variances, and diurnal variation in the air temperature. Day-to-day differences in weather variables were calculated as the daily mean variables on the day of symptom onset minus those on the previous day. The daily variances in weather variables were defined as the absolute value of day-to-day differences. RESULTS: Compared to the non-surgery group, the surgery group had older patients (75 vs. 70 years, p = 0.009), a higher proportion of female patients (44.6% vs. 32.3%, p = 0.046), increased incidence of closed-loop sign (50.6% vs. 0.9%, p < 0.001), a lower proportion of feces sign (18.1% vs. 31.3%, p = 0.024), and a prolonged hospital stay (11 vs. 22 days, p < 0.001). The number distribution of patients in the surgery group in day-to-day differences in air temperature was different from that of the non-surgery group; the former has several peaks whereas the latter has almost one peak. Daily variance in mean air temperature on the day of symptom onset was higher in the surgery group than in the non-surgery group (2.3 vs. 1.3℃, p < 0.001). Multiple logistic regression analysis revealed that increased daily variance in air temperature on the onset day was associated with the need for surgical management (odds ratio 1.254, p = 0.002) and closed-loop obstruction (odds ratio 1.235, p = 0.017). Regarding seasonal variations, the risk of the need for surgery and closed-loop obstruction in each ASBO patient was the highest in spring, followed by that in summer, autumn, and winter. Consistently, the daily variance in mean air temperature in spring was higher than that in summer, autumn, and winter (p < 0.0001, p < 0.0001, and p = 0.0047, respectively). The risk of the need for surgery and closed-loop obstruction in each ASBO patient was the highest in spring, followed by that in summer, autumn, and winter. Consistently, daily variance in mean air temperature was higher in spring than that in summer, autumn, and winter (p < 0.0001, p < 0.0001, and p = 0.0047, respectively). CONCLUSION: Increased daily variance in mean air temperature on the day of onset is associated with the need for surgical management and closed-loop obstruction. Spring is characterized by the highest daily variance in mean air temperature among the four seasons, and is associated with high proportions of the need for surgery and closed-loop obstruction. These results can be clinically useful in terms of hospital resource reallocation and staffing, and can help clarify the pathogenesis of ASBO.

Comparison of Clinical Outcomes and Safety Between Open and Laparoscopic Surgery for Adhesive Small Bowel Obstruction: A Propensity-Matched Analysis of a National Inpatient Database.

Background: The effectiveness of laparoscopic surgery for adhesive small bowel obstruction (ASBO) remains unclear. We aimed to compare the outcomes and safety of open and laparoscopic surgeries for ASBO. Methods: In this retrospective study, we analyzed an inpatient database of 42 national university hospitals in Japan. Patients who underwent surgery for the first episode of ASBO between April 2013 and March 2018 were identified. Using the propensity score method, patients who underwent laparoscopic surgery were matched one-to-one with those who underwent open surgery. We investigated postoperative clinical outcomes, including morbidity, mortality, length of hospital stay (LOS), and recurrence. Results: Overall, 306 and 96 patients underwent open and laparoscopic surgery, respectively (96 propensity score-matched pairs). The incidence rates of postoperative morbidity, mortality, and recurrence were comparable between the two groups. Cox regression analysis revealed a hazard ratio (HR) of 1.020 (P = .959) for readmission due to ASBO in the laparoscopic surgery group relative to the open surgery group. Postoperative hospital stay was longer for open surgery than for laparoscopic surgery (13.0 days versus 10.0 days, P < .001). Cox regression analysis revealed that laparoscopic surgery was associated with earlier postoperative discharge compared with open surgery (HR 1.641, P = .002). Conclusions: The postoperative LOS was shorter with laparoscopic surgery than with open surgery for ASBO, but there were no differences between the procedures in other clinical outcomes. Laparoscopic surgery is suitable to treat patients with ASBO.

Association of Serum Creatinine Level with Prognosis of Laparotomy for Acute Mesenteric Ischemia after Cardiovascular Surgery.

Introduction: Acute mesenteric ischemia is a life-threatening complication after cardiovascular surgery with a mortality rate of 52.9-81.3%. However, few studies have evaluated the predictors of clinical outcome after treatment for acute mesenteric ischemia following cardiovascular surgery. Therefore, this study aimed to elucidate prognostic factors in patients who underwent laparotomy for acute mesenteric ischemia after cardiovascular surgery. Methods: We retrospectively analyzed 29 patients (20 men and 9 women; median age, 71.0 years) who underwent laparotomy for acute mesenteric ischemia after cardiovascular surgery between January 2010 and August 2020. These patients were classified into the survivor group (comprising patients who were discharged or referred to another hospital, n = 16) and the nonsurvivor group (comprising those who experienced in-hospital mortality, n = 13). We compared clinical parameters between the groups to identify the predictors of outcomes. Results: More patients in the nonsurvivor group underwent emergency cardiovascular surgery (62.5% vs. 100%, p = 0.017) and received hemodialysis (12.5% vs. 61.5%, p = 0.008) at the onset of acute mesenteric ischemia than those in the survivor group. The prelaparotomy serum creatinine level was higher in the nonsurvivor group than in the survivor group (1.27 vs. 2.33 mg/dL, p = 0.004). Logistic regression analysis revealed an association between preoperative serum creatinine level and in-hospital mortality (odds ratio 5.047, p = 0.046), and Cox regression analysis demonstrated a relationship between serum creatinine level and in-hospital mortality (hazard ratio 1.610, p = 0.009). The area under the curve (receiver operating characteristic analysis) for the serum creatinine level was 0.813. Furthermore, the optimal cutoff value of the serum creatinine level was 1.59 mg/dL with a sensitivity and specificity of 0.846 and 0.687, respectively, in predicting in-hospital mortality. Conclusions: The elevated serum creatinine level was associated with a poor clinical outcome after surgery for acute mesenteric ischemia following cardiovascular surgery.

Laparoscopic left-sided mesocolic leaf flap repair for pelvic reconstruction after sacral tissue necrosis. A case report.

Radical surgical procedures for malignant diseases of the pelvis result in a large pelvic defect that requires soft tissue reconstruction. The mesentery can be used for pelvic floor reconstruction when debridement with intestinal resection is required. A 75-year-old woman was diagnosed with sacral necrosis, infection and sepsis after carbon ion radiotherapy for sacral chordoma. She underwent sacral debridement three times, which resulted in a large pelvic defect of 14 × 13 cm. Surgery was performed to completely resect the necrotic tissue. We performed extended debridement of sacrum and adjacent tissue around the rectum and anus. Since it was impossible to preserve the anus, laparoscopic left hemicolectomy, abdominosacral resection, and left-sided mesocolic leaf repair for the pelvic defect, and reconstructed the pelvis and buttocks using a gluteal thigh flap were performed. Indocyanine green fluorescent (ICG) imaging was used to detect the margin of the pelvic floor and necrotic tissue and the blood flow of the left-sided mesocolic leaf flap. Left-sided mesocolic leaf reconstruction is useful for large pelvic defects. ICG imaging enabled the detection of the resection margins and the blood flow of the mesocolic leaf.

Mesh Migration into the Neobladder and Ileum with Complicated Fistula Formation following Incisional Hernia Repair.

BACKGROUND: Tension-free repair using mesh has become the standard treatment for abdominal wall incisional hernias. However, its postoperative complications reportedly include mesh infection, adhesions, and fistula formation in other organs. Here, we report an extremely rare case of mesh migration into the neobladder and ileum with entero-neobladder and neobladder-cutaneous fistulas. Case Presentation. An 80-year-old male who had undergone radical cystectomy 5 years ago and abdominal wall incisional hernia repair 3 years ago presented with fever and abdominal pain. Computed tomography (CT) scan revealed mesh migration into the neobladder and ileum. He was treated conservatively with antibiotics for a month but did not show improvement; hence, he was transferred to our hospital. He was diagnosed with mesh migration into the neobladder and ileum with complicated fistula formation. He underwent mesh removal, partial neobladder resection, and partial small bowel resection. He developed superficial incisional surgical site infection, which improved with drainage and antibiotics, and he was discharged 40 days after the surgery. CONCLUSIONS: We reported a rare case of mesh migration into the neobladder and ileum with fistula formation. Successful conservative treatment cannot be expected for this condition because mesh migration into the intestinal tract causes infection and fistula formation. Hernia repair requires careful placement of the mesh such that it does not come into contact with the intestinal tract. Early surgical intervention is important if migration into the intestinal tract is observed.

A case of appendiceal ganglioneuroma in neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant inherited disease associated with multiple skin neurofibromas or other neurogenic tumors, such as nodular plexiform neurinoma or cerebrospinal tumor. Gastrointestinal stromal tumors are often complicated in patients with neurofibromatosis type 1, although involvement of the appendix is rare, and there have been few reports of appendiceal ganglioneuroma. CASE PRESENTATION: The patient was a 29-year-old man diagnosed with neurofibromatosis type 1 based on physical findings and his family history. During the follow-up of neurofibromatosis, computed tomography was performed to detect neurological tumors, such as neurofibromas in the brain, spinal cord, and gastrointestinal tract. Computed tomography showed a markedly thickened appendix wall, and an appendiceal tumor was suspected. Laparoscopic appendectomy was performed, and a 50 × 35 mm appendiceal submucosal tumor was resected with a negative resection margin. At histopathological examination, the tumor was diagnosed as ganglioneuroma; it showed short spindle-shaped cells and ganglion cells diffusely infiltrated into the proper muscle layer and fibrous tissue that grew around nerve cells. The patient was discharged on the 5th postoperative day without postoperative complications and was doing well at 13 months following the operation. CONCLUSIONS: Gastrointestinal stromal tumor and neurofibroma are the most common gastrointestinal tumors associated with neurofibromatosis type 1, but ganglioneuroma of the appendix is rare. Appendiceal neurogenic tumors should be considered in patients with neurofibromatosis type 1, and surgical resection is necessary because of the risk of malignancy.