An adult right inguinal hernia and cryptorchidism treated simultaneously with laparoscopic transabdominal preperitoneal repair and laparoscopic orchiectomy: a case report.

Pediatric health checkups have been mandatory for all citizens since 1966 based on the Maternal and Child Health Law in Japan, and cryptorchidism or undescended testis in adult males are rare. We report a case of an adult right inguinal hernia and cryptorchidism treated simultaneously with laparoscopic transabdominal preperitoneal repair and laparoscopic orchiectomy. A 35-year-old man came to our department with a chief complaint of bulging in the right inguinal region for several months. He was diagnosed with a right inguinal hernia and was scheduled for transabdominal preperitoneal repair. During intraoperative intraperitoneal observation, a white 30-mm mass was found in the hernia orifice. A diagnosis of right cryptorchidism was made, and transabdominal preperitoneal repair and laparoscopic orchiectomy were performed. Laparoscopic simultaneous surgery could be safely performed in an adult patient with a hernia complicated by a cryptorchidism. It can be recommended as a surgical option in such cases.

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.

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.

Hereditary diffuse gastric cancer in a Japanese family with CDH1 mutation three case reports.

BACKGROUND: Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1-3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan. METHOD: In this study we report the clinical courses of three cases with HDGC from a single Japanese family. RESULTS: The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy. CONCLUSION: It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries.

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.

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.

Impact of DNA double-strand breaks on pancreaticobiliary maljunction carcinogenesis.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a condition characterized by chronic inflammation due to refluxed pancreatic juice into the biliary tract that is associated with an elevated risk of biliary tract cancer. DNA double-strand breaks (DSBs) are considered the most serious form of DNA damage. DSBs are provoked by inflammatory cell damage and are recognized as an important oncogenic event in several cancers. This study used γ-H2AX, an established marker of DSB formation, to evaluate the impact of DNA damage on carcinogenesis in PBM. METHODS: We investigated γ-H2AX expression immunohistochemically in gallbladder epithelium samples obtained from 71 PBM cases and 19 control cases. RESULTS: Fourteen PBM cases with gallbladder adenocarcinoma were evaluated at non-neoplastic regions. A wide range of nuclear γ-H2AX staining was detected in all PBM and control specimens. γ-H2AX expression was significantly higher in PBM cases versus controls (median γ-H2AX-positive proportion: 14.4 % vs. 4.4 %, p = 0.001). Among the PBM cases, γ-H2AX expression was significantly higher in patients with carcinoma than in those without (median γ-H2AX-positive proportion: 21.4 % vs. 11.0 %, p = 0.031). CONCLUSIONS: DSBs occurred significantly more abundantly in the PBM gallbladder mucosa, especially in the context of cancer, indicating an involvement in PBM-related carcinogenesis.

Sex differences in non-strangulated postoperative adhesive small bowel obstruction: a retrospective cohort study.

BACKGROUND: Adhesive small bowel obstruction (ASBO) is one of the major causes of postoperative morbidity. Non-surgical management is generally applied to non-strangulated ASBO. Several factors have been reported to affect the response to non-surgical management in patients with ASBO. However, the association between sex differences and non-strangulated ASBO remains unclear. This study aimed to elucidate the effect of sex differences in non-strangulated postoperative ASBO. METHODS: We divided 139 patients with a first episode of non-strangulated postoperative ASBO into two groups: male group (n = 83) and female group (n = 56). Clinical features and prognosis were compared between the two groups. RESULTS: Female patients had lower proportions of oesophageal/gastric malignancies (P = 0.044) and colorectal malignancies (P = 0.030) and a higher proportion of uterine/ovarian malignancies (P < 0.001) than male patients did. More female patients required surgical management than male patients (P = 0.003) did. Hospital length of stay (LOS) was longer (P = 0.046) in the female group than in the male group. Multiple logistic regression analysis showed that the female sex was associated with an increased risk of the need for surgical management (odds ratio 5.318, P = 0.006). Cox proportional hazards regression analysis revealed that the female sex was positively associated with increased LOS (hazard ratio 0.687, P = 0.045). CONCLUSION: Female sex was associated with failure of non-surgical management and increased LOS in patients with non-strangulated postoperative ASBO.

Lymphocyte-to-Monocyte Ratio Is a Predictive Biomarker of Response to Treatment with Nivolumab for Gastric Cancer.

INTRODUCTION: Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. METHODS: In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. RESULTS: Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022). CONCLUSIONS: Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.

Drug sensitivity profile of minor KRAS mutations in colorectal cancer using mix culture assay: The effect of AMG-510, a novel KRAS G12C selective inhibitor, on colon cancer cells is markedly enhanced by the combined inhibition of MEK and BCL-XL.

Colorectal cancer with a Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) gene mutation is considered to be resistant to anti-EGFR agents. G12D is the most common KRAS mutation in colorectal cancer, followed by G12V and G13D. According to clinical and basic research data, patients with colorectal cancer exhibiting G12D and G12V KRAS mutations are resistant to anti-EGFR agents; however, this is not true of G13D and other minor mutations, which are still not well understood. The current study focused on minor KRAS mutations (G12A, G12C, G12S, Q61H and A146T) and evaluated whether these were resistant to anti-EGFR antibodies using a mix culture assay. The results demonstrated that all KRAS mutations, including minor mutations, were resistant to two anti-EGFR agents: Cetuximab and panitumumab. The combined effect of MEK and BCL-XL inhibition on colorectal cancer cells with KRAS minor mutations were subsequently evaluated. The combined effect of MEK and BCL-XL inhibitors was confirmed in all KRAS minor mutations. The sensitivity of AMG510, a novel KRAS G12C selective inhibitor, was also assessed. The mix culture assay revealed that AMG510 selectively exerted an antitumor effect on colon cancer cells with a G12C KRAS mutation. The combination of MEK and BCL-XL inhibition markedly enhanced the effect of AMG510 in colon cancer cells. The current study suggested that AMG510 may have potential clinical use in combination with MEK and BCL-XL inhibitors in the treatment of patients with colorectal cancer exhibiting the G12C KRAS mutation.

A case of sigmoidectomy for sigmoid colon cancer with severe pulmonary arterial hypertension associated with mixed tissue connected disease: A case report.

INTRODUCTION: Patients with mixed connective tissue disease (MCTD) have higher rates of pulmonary arterial hypertension (PAH) than the general population. PAH is a risk for perioperative respiratory and heart failure, and marked edema of colonic stoma after sigmoidectomy. We report a case of sigmoidectomy for sigmoid colon cancer in a patient with PAH associated with MCTD for whom perioperative treatment was planned to control pulmonary arterial pressure (PAP), and a surgical strategy to avoid complications attributable to PAH and MCTD was employed. CASE PRESENTATION: A 52-year-old woman with sigmoid cancer and severe PAH associated with MCTD underwent surgery. We controlled PAH by using intravenous epoprostenol. We selected open surgery without laparoscopy and Hartmann's operation. After surgery, severe perioperative complications were not detected, and the patient discharged from hospital 17 days after the operation. DISCUSSION: During surgery under general anesthesia, the mortality rate of PAH is high because of heart and respiratory failure. We planned to switch the PAH treatment from an oral agent to intravenous epoprostenol only in the preoperative period, and selected open surgery. We ligated the inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) below the branch of LCA to avoid marked edema of stoma. Consequently, we could avoid severe intraoperative and postoperative complications. CONCLUSIONS: Controlling PAP using epoprostenol, open surgery, stoma and the ligation level for the IMA and IMV preventing are important to avoid perioperative complications of sigmoid colon cancer complicated by severe PAH.

Inverse correlation between PD-L1 expression and LGR5 expression in tumor budding of stage II/III colorectal cancer.

We investigated the expression of LGR5, the most robust and reliable known cancer stem cell (CSC) marker of colorectal cancer, and PD-L1 in tumor budding (TB), as well as clinicopathological features. Tissue microarrays (TMAs) were generated from TB samples from 32 stage II/III colorectal adenocarcinoma patients, and LGR5 expression in TMAs was evaluated by RNAscope, an extremely sensitive RNA in situ hybridization technique. LGR5 expression was significantly lower in the PD-L1-positive group than in the PD-L1-negative group (P = 0.0256). In the PD-L1-positive group, the tumor-infiltrating lymphocytes (TILs) score tended to be higher while the TNM stage was lower compared with the PD-L1 negative group (P = 0.0822 and P = 0.0765, respectively). There was no significant difference in Overall Survival between the PD-L1-positive and PD-L1-negative groups (log-rank test, P = 0.8218). This study showed that PD-L1-positive patients are a unique population with low LGR5 expression, and that LGR5-positive cells may be a promising therapeutic target in PD-L1-negative patients.