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.

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.

High expression of LGR6 is a poor prognostic factor in esophageal carcinoma.

BACKGROUND: Leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) promotes carcinogenesis and progression in some cancer types. However, there are few reports of LGR6 expression in esophageal squamous cell carcinoma (ESCC). LGR6 expression and clinicopathological features in ESCC were investigated by RNAscope, a highly sensitive RNA in situ hybridization method. METHODS: Appropriate tumors were selected from 41 cases of ESCC from which tissue microarrays were generated, and LGR6 expression was identified by RNAscope. RESULTS: Thirty-seven patients had LGR6 expression. High LGR6 expression was observed in 17 cases and low LGR6 expression in 24 cases. LGR6 expression was significantly higher in high histological grade ESCC than in low histological grade ESCC (P = 0.0023). ESCC patients who received neoadjuvant chemotherapy had significantly higher LGR6 expression than those without neoadjuvant chemotherapy (P = 0.0109). Furthermore, high LGR6 expression showed a poorer prognosis than low LGR6 expression (log-rank test, P = 0.0365). CONCLUSIONS: LGR6 may be a prognostic factor and a potential new therapeutic target in ESCC.

Osteopontin expression in the invasive front stroma of colorectal adenocarcinoma is associated with tumor budding and prognosis.

BACKGROUND: Tumor budding (TB) is an important prognostic factor in colorectal carcinoma (CRC). Osteopontin (OPN) functions in various processes such as immune response, migration and invasion, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis. However, the involvement of OPN and CD44v6, which is a receptor for OPN, in TB has not been clarified. Therefore, we examined the relationship of OPN with TB in CRC and compared the clinicopathological features. METHODS: We investigated the expression of OPN and CD44v6 in 83 cases of CRC by immunostaining and analyzed the clinicopathological features. RESULTS: OPN expression was observed mostly in the cytoplasm of stromal cells such as macrophages and fibroblasts, and rarely in cancer cells. There was a significant correlation between OPN positivity and the degree of differentiation at the invasive front and TB grade. CD44v6 was positive in cancer cells in 72 cases (86.7 %) and negative in 11 cases (13.3 %). A statistically significant effect on overall survival (OS) was identified between the OPN-positive group [median OS: 1586 (range, 30-2749) days] and the OPN-negative group [median OS: 1901 (range, 8-2665) days] (log-rank test, p = 0.011). CONCLUSIONS: OPN analysis in CRC stromal cells may have prognostic implications.

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.

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.

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.

LGR5 expression is associated with prognosis in poorly differentiated gastric adenocarcinoma.

BACKGROUND: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is an important cancer stem cell marker in gastric cancer. However, no detailed studies are available on LGR5 expression in poorly differentiated gastric adenocarcinoma (PD-AC). Therefore, we investigated the relationship between LGR5 expression and clinicopathological data in PD-AC. METHODS: LGR5 mRNA expression levels were quantified in 41 PD-AC specimens using a highly sensitive RNAscope in situ hybridization technique. Epstein-Barr virus (EBV) infection was also detected by EBV in situ hybridization. RESULTS: LGR5 expression levels were measured in 38 of 41 PD-AC cases, and 17 cases were identified as LGR5 high. The frequency of EBV positivity tended to be higher in the LGR5-low group than in the LGR5-high group (P = 0.0764). Furthermore, the frequency of vascular invasion tended to be higher in the LGR5-high group than in the LGR5-low group (P = 0.0764). The overall survival of PD-AC patients in the LGR5-high group was significantly lower than in the LGR5-low group (log-rank test, P = 0.0108). The Cox proportional hazard regression model revealed that the LGR5-low group (HR = 0.29; 95% CI: 0.11-0.74; P = 0.01) showed independently better OS for PD-AC. CONCLUSIONS: Quantifying the levels of LGR5 expression may facilitate defining prognosis in Japanese patients with PD-AC. Further study of LGR5 in this context is warranted.

Low­dose trametinib and Bcl­xL antagonist have a specific antitumor effect in KRAS­mutated colorectal cancer cells.

KRAS­mutant colorectal cancer (CRC) is a highly malignant cancer with a poor prognosis, however specific therapies targeting KRAS mutations do not yet exist. Anti­epidermal growth factor receptor (EGFR) agents, including cetuximab and panitumumab, are effective for the treatment of certain patients with CRC. However, these anti­EGFR treatments have no effect on KRAS­mutant CRC. Therefore, new therapeutic strategies targeting KRAS­mutant CRC are urgently needed. To clarify the direct effect of KRAS gene mutations, the present study transduced mutant forms of the KRAS gene (G12D, G12V and G13D) into CACO­2 cells. A drug­screening system (Mix Culture assay) was then applied, revealing that the cells were most sensitive to the MEK inhibitor trametinib among tested drugs, Cetuximab, Panitumumab, Regorafenib, Vemurafenib, BEZ­235 and Palbociclib. Trametinib suppressed phosphorylated ERK (p­ERK) expression and inhibited the proliferation of KRAS­mutant CACO­2 cells. However, low­dose treatment with trametinib also increased the expression of the anti­apoptotic protein Bcl­xL in a dose­dependent manner, leading to drug resistance. To overcome the resistance of KRAS­mutant CRC to apoptosis, the combination of trametinib and the Bcl­xL antagonist ABT263 was assessed by in vitro and in vivo experiments. Compared with the effects of low­dose trametinib monotherapy, combination treatment with ABT263 had a synergistic effect on apoptosis in mutant KRAS transductants in vitro. Furthermore, in vivo combination therapy using low­dose trametinib and ABT263 against a KRAS­mutant (G12V) xenograft synergistically suppressed growth, with an increase in apoptosis compared with the effects of trametinib monotherapy. These data suggest that a low dose of trametinib (10 nM), rather than the usual dose of 100 nM, in combination with ABT263 can overcome the resistance to apoptosis induced by Bcl­xL expression, which occurs concurrently with p­ERK suppression in KRAS­mutant cells. This strategy may represent a promising new approach for treating KRAS­mutant CRC.

Treatment of Rectal Cancer-Induced Disseminated Carcinomatosis of the Bone Marrow with FOLFOX plus Cetuximab and Panitumumab.

Disseminated carcinomatosis of the bone marrow (DCBM) in colorectal cancer is an extremely rare complication with a poor prognosis. Here, we report a case of DCBM due to rectal cancer successfully treated with a combination of FOLFOX and an anti-epidermal growth factor receptor (EGFR) agent. The patient was a 38-year-old man diagnosed with rectal cancer with multiple bone and para-aortic lymph node metastases complicated by disseminated intravascular coagulation (DIC). He first recovered from DIC following cotreatment with FOLOX plus cetuximab; subsequently, the second attack was successfully treated with FOLFOX plus panitumumab. His initial condition was extremely poor, but he survived with two FOLFOX plus anti-EGFR regimens and died 333 days after introduction of chemotherapy.

High incidence of other primary malignancies in patients with synchronous multiple gastric cancers "a multi-center retrospective cohort study".

This study evaluated the relationship between synchronous multiple gastric cancer and other primary malignancies. During 2002-2013, 1094 consecutive surgically treated gastric cancer patients were enrolled. Preoperatively, we performed total colonoscopy and whole-body computed tomography. When malignancies in other organs were suspected, detailed organ-specific examinations were performed. Synchronous multiple gastric cancer occurred in 102 patients (9.3%)which was frequently observed in patients with preoperative other primary malignancies (p < 0.001). Preoperative other primary malignancy was an independent risk factor for synchronous multiple gastric cancer (p = 0.001; hazard ratio: 2.145, 95% confidence interval: 1.354-3.399) and an independent prognostic factor of overall survival in patients undergoing gastrectomy with curative intent (p = 0.021; hazard ratio: 1.481, 95% confidence interval: 1.060-2.070). Thus, patients with preoperative other primary malignancies have a high risk of synchronous multiple gastric cancer. Careful preoperative examination is recommended to improve survival.

Three Cases of Pseudo-Meigs' Syndrome Secondary to Ovarian Metastases from Colorectal Cancer.

Pseudo-Meigs' syndrome is used to describe cases of ascites and/or pleural effusion associated with ovarian neoplasms other than benign tumors, which improve after removal of the ovarian lesion. We present three cases of pseudo-Meigs' syndrome secondary to ovarian metastasis from colorectal cancer. In case 1, the patient has severe dyspnea and hypoxia due to massive right pleural effusion; therefore preoperative thoracic drainage was needed. In case 2, the patient needed paracentesis every two or three days to improve abdominal distension. After two courses of 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6), her ascites could be controlled by diuretics without aspiration and her general condition improved. Then she underwent operation. In case 3, the patient developed a massive pleural effusion and ascites coincident with a rapid enlargement of ovarian tumor after resection and adjuvant chemotherapy for rectal cancer. In all cases, pleural effusions and/or ascites resolved and general conditions and daily activities of the patients improved after oophorectomy. They are all currently in good health without recurrence of pleural effusion or ascites. In patients with suspected pseudo-Meigs' syndrome secondary to ovarian metastasis of colorectal cancer, operation including oophorectomy may reduce pleural effusions and/or ascites and improve the general condition.

[Two Cases of Fournier's Gangrene That Occurred during Chemotherapy for Rectal Cancer].

Two cases of Fournier's gangrene occurred during chemotherapy for advanced rectal cancer. Patients were treated using surgical debridement and antibiotic therapy. Case 1: A 66-year-old man had advanced rectal cancer with para-aortic and inguinal lymph node metastases. He received a sigmoid colostomy and chemotherapy(capecitabine, oxaliplatin, bevacizumab). Due to progression of the rectal mass, we performed radiotherapy(30 Gy)and chemotherapy(irinotecan, S-1, bevacizumab). After 14 days, he was hospitalized with a diagnosis of Fournier's gangrene with anal pain and fever. Case 2: A 63-year-old man had mucinous rectal carcinoma with sacrum invasion. He received a sigmoid colostomy and chemotherapy. Sixteen days after regorafenib therapy, as a fifth-line of chemotherapy, he was hospitalized with a diagnosis of Fournier's gangrene with hip pain, swollen perineum, and fever. There have been no reports of Fournier's gangrene occurring during chemotherapy for rectal cancer. We report 2 cases with a review of literature.