Optimal Assessment of Frailty Predicts Postoperative Complications in Older Patients with Colorectal Cancer Surgery.

OBJECTIVES: The increasingly elderly worldwide population has affected the incidence of colorectal cancer. Establishment of reliable assessment of frailty and proposals for multi-disciplinary interventions are urgently required in oncology practices. Kihon Checklist (KCL) was published by the Japanese Ministry of Health, Labor and Welfare originally to identify individuals ≥ 65 years old at probable risk for requiring care or social support. We investigate the validity of KCL for frailty assessment to predict postoperative complication in older patients with colorectal cancer. METHODS: Consecutive colorectal cancer patients aged ≥ 65 (n = 500) were prospectively examined between May 2017 and December 2018. Preoperative frailty assessment was conducted by the G8 questionnaire and KCL. The main outcome measures were correlation between frailty, other clinical variables, and postoperative complications within 30 days after elective surgery. RESULTS: Of the 500 patients, 278 (55.6%) and 164 (32.8%) patients were classified as 'frail' by G8 and KCL, respectively. Overall complications counted among 97 patients (19.4%), and they were significantly associated with KCL ≥ 8-frail (46/164, p = 0.001), as opposed to G8 ≤ 14-frail (56/278, p = 0.531). Multivariate analysis showed that KCL ≥ 8 (hazard ratio 1.88, 95% confidence interval 1.16-3.04, p = 0.011) was an independent risk factor for these complications. CONCLUSIONS: KCL assessment can identify frail older patients likely to suffer from postoperative complications after colorectal cancer surgery. Preoperative screening of frailty, particularly by KCL, would help older patients prevent their worse outcomes in colorectal cancer. TRIAL REGISTRATION: UMIN000026689.

The effects of rikkunshito on body weight loss after esophagectomy.

BACKGROUND: After esophagectomy, esophageal cancer patients suffer from malnutrition, anorexia, and dysfunction of digestion and absorption. Rikkunshito, a traditional Japanese herbal medicine, reportedly attenuates gastrointestinal symptoms and appetite loss after gastrointestinal surgery. We evaluated the clinical effect of rikkunshito and its relationship with ghrelin in esophageal cancer patients after esophagectomy. METHODS: This prospective nonrandomized study included 40 patients with esophageal cancer who underwent esophagectomy at Wakayama Medical University Hospital. They were assigned to either the control group (n = 20, April 2011-January 2012) or the rikkunshito group (n = 20, January 2012-August 2012). Patients in the rikkunshito group received 2.5 g of rikkunshito before every meal for 48 wk beginning 4 wk after surgery. During the 48-week treatment, we assessed body weight loss, nutritional parameters, and quality of life (Functional Assessment of Cancer Therapy-Esophageal scale). The primary end point was the rate of body weight loss in two groups after the 48-week treatments. RESULTS: The rate of body weight loss was significantly less in the rikkunshito group than in the control group (P = 0.016). The acyl ghrelin level after the 48-week treatments was significantly higher in the rikkunshito group (131.7% ± 74.5%) than in the control group (75.6% ± 47.5%, P = 0.039). For the Functional Assessment of Cancer Therapy-Esophageal symptom scale, satisfaction of food consumption in the rikkunshito group was significantly better than in the control group at 52 wk postoperatively (P = 0.031). CONCLUSIONS: For esophageal cancer patients after esophagectomy, rikkunshito is useful for improving body weight loss in connection with an increase in plasma acyl ghrelin levels.

Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: in comparison to bone marrow-derived DCs.

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a (51) Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

Is preoperative colonoscopy necessary for patients undergoing gastric cancer surgery?

PURPOSE: The aim of this study was to evaluate the necessity of preoperative colonoscopy (CS) in gastric cancer (GC) patients and to assess the outcomes of different treatments in patients with synchronous GC and colorectal neoplasms (CRN). We also determined the risk factors influencing the comorbidity of colorectal cancer (CRC) in patients with GC. METHODS: This retrospective study included 1891 consecutive GC patients who underwent CS before surgery from January 1, 1999, through June 30, 2012. RESULTS: There was a high prevalence of concurrent CRN (28.4 %) and CRC (3.2 %) in our patients with GC. Sixty-one patients with GC had synchronous CRC. Twenty-three of the 61 tumors were perioperatively treated by endoscopic resection. The other 38 tumors were treated by simultaneous surgery for the GC and CRC. Surgical complications were not found in either the endoscopic or surgical resection group. The multivariate logistic regression analysis indicated that the prevalence of synchronous CRC in patients with GC was significantly associated with the incidence of multiple GCs [P < 0.0001; odds ratio (OR) 15.3], having anemia (P = 0.002; OR 3.0), and having a smoking history (P = 0.021; OR 1.9). CONCLUSIONS: We recommend preoperative CS screening for GC patients. In particular, preoperative CS screening is indispensable for patients with multiple GCs. In addition, simultaneous treatments for patients with synchronous GC and CRN are safe and feasible procedures.

Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial.

BACKGROUND: The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. RESULTS: Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. CONCLUSIONS: Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

Endoscopic submucosal dissection for gastric tumors in various types of remnant stomach.

BACKGROUND AND STUDY AIMS: The aim of this study was to examine the clinical outcomes of endoscopic submucosal dissection (ESD) for gastric tumors in various types of remnant stomach. PATIENTS AND METHODS: Between January 2002 and March 2013, ESD was performed for 750 gastric tumors. Of these lesions, 49 were in a remnant stomach, and were included in the study. RESULTS: The en bloc resection rate was 100 %. The curative resection rate was 82 %. The rate of perforation was high in patients with gastric conduits (28.6 %). Perforation was significantly more common in patients with lesions located on the suture line (4.9 % vs. 50.0 %; P = 0.0043). CONCLUSION: ESD for gastric tumors in the remnant stomach can be considered feasible and safe in clinical practice. However, the procedure is technically more difficult in patients with a gastric conduit, due to the increased risk of perforation at the suture line.

Atrial fibrillation after esophageal cancer surgery: an analysis of 207 consecutive patients.

PURPOSE: The aim of this study was to identify perioperative risk factors that are associated with postoperative atrial fibrillation (AF) and the outcomes of different pharmacological interventions in esophageal cancer patients who underwent transthoracic esophagectomy. METHODS: This study included 207 patients who underwent a transthoracic esophagectomy for esophageal cancer resection by a single surgeon from January 1, 2004, through December 31, 2010. RESULTS: Postoperative AF occurred in 19 patients (9.2 %), all of whom received antiarrhythmic drug therapy at the early stage. Antiarrhythmic treatment was effective in 12 cases (63.2 %). In this study, landiolol hydrochloride, an ultrashort-acting ß1-selective ß-blocker, was the first-line therapy for postoperative AF. A multivariate logistic regression analysis showed that postoperative AF was significantly associated with the use of an ileo-colon for reconstruction after esophagectomy (P = 0.0023, odds ratios [OR] = 13.6) and with the presence of tachycardia with a heart rate of >100 bpm on postoperative day (POD) 1 (P = 0.0004, OR = 18.4). CONCLUSIONS: Postoperative AF is associated with the use of a colon conduit for reconstruction after esophagectomy and with tachycardia with a heart rate >100 bpm on POD 1. Identifying patients at high risk for postoperative AF will allow for more direct application of pharmacological methods of prophylaxis.

Clinical benefits of thoracoscopic esophagectomy in the prone position for esophageal cancer.

PURPOSES: The clinical benefits of thoracoscopic radical esophagectomy in the prone position compared to conventional open esophagectomy have not been fully documented. METHODS: Forty-six patients with esophageal cancer who underwent MIE in the prone position (MIE-P group) were enrolled, and 46 case-matched controls that underwent open esophagectomy (OE group) were identified using propensity score methods to achieve a valid comparison of outcomes between MIE and open esophagectomy. RESULTS: The duration of systemic inflammatory response syndrome was shorter in the MIE-P group than in OE group (P = 0.005). The time to first walking was earlier in the MIE-P group (P < 0.001). Although the vital capacity ratio (%VC) declined after the operation in both groups, the change ratio of the %VC was 85.3% in the MIE-P group and 69.6% in the OE group (P < 0.001). No mortality occurred in either group. The postoperative morbidity rate was lower in the MIE-P group (13%) than in the OE group (30.4%) (P = 0.020). Two patients (4.3%) in the OE group and one patient in the MIE-P group (2.2%) had pneumonia. CONCLUSIONS: MIE in the prone position was associated with less impairment of the pulmonary function, earlier recovery of activity and lower subsequent morbidity compared to open esophagectomy. Further investigation of the long-term outcomes is, therefore, needed.

New prognostic score for the survival of patients with esophageal squamous cell carcinoma.

PURPOSE: Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS. METHODS: One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP. RESULTS: Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000-9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021-7.112, p = 0.0449). CONCLUSIONS: The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.

An armed oncolytic herpes simplex virus expressing thrombospondin-1 has an enhanced in vivo antitumor effect against human gastric cancer.

Advanced gastric cancer is a common disease, but the conventional treatments are unsatisfactory because of the high recurrence rate. One of the promising new therapies is oncolytic virotherapy, using oncolytic herpes simplex viruses (HSVs). Thrombospondin-1 (TSP-1) suppresses tumor progression via multiple mechanisms including antiangiogenesis. Our approach to enhance the effects of oncolytic HSVs is to generate an armed oncolytic HSV that combines the direct viral oncolysis with TSP-1-mediated function for gastric cancer treatment. Using the bacterial artificial chromosome (BAC) system, a 3rd generation oncolytic HSV (T-TSP-1) expressing human TSP-1 was constructed for human gastric cancer treatment. The enhanced efficacy of T-TSP-1 was determined in both human gastric cancer cell lines in vitro and subcutaneous tumor xenografts of human gastric cancer cells in vivo. In addition, we examined the apoptotic effect of T-TSP-1 in vitro, and the antiangiogenic effect of T-TSP-1 in vivo compared with a non-armed 3rd generation oncolytic HSV, T-01. No apparent apoptotic induction by T-TSP-1 was observed for human gastric cancer cell lines TMK-1 cells but for MKN1 cells in vitro. Arming the viruses with TSP-1 slightly inhibited their replication in some gastric cancer cell lines, but the viral cytotoxicity was not attenuated. In addition, T-TSP-1 exhibited enhanced therapeutic efficacy and inhibition of angiogenesis compared with T-01 in vivo. In this study, we established a novel armed oncolytic HSV, T-TSP-1, which enhanced the antitumor efficacy by providing a combination of direct viral oncolysis with antiangiogenesis. Arming oncolytic HSVs may be a useful therapeutic strategy for gastric cancer therapy.

[Cancer vaccine therapy using genetically modified induced pluripotent stem cell-derived dendritic cells expressing the TAA gene].

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) poses a serious problem in DC-based immunotherapy. Therefore, we used induced pluripotent stem (iPS) cell-derived DCs (iPSDCs) instead. If the therapeutic efficacy of iPSDCs was equivalent to that of bone marrow-derived DCs( BMDCs), then the above-mentioned problems may be solved. In this study, we generated iPSDCs from iPS cells and compared their capacity to mature and migrate to the regional lymph nodes with that of BMDCs. We adenovirally transduced the hgp100 gene, which codes for a natural tumor antigen, into the DCs and immunized the mice with these genetically modified DCs. The cytotoxic activity of CD8( +) cytotoxic T lymphocytes( CTLs) was assayed using a 51Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results demonstrated that iPSDCs equaled BMDCs in terms of their maturation and migration capacity. Furthermore, hgp100-specific CTLs were generated in mice that were immunized with the genetically modified iPSDCs. These CTLs exhibited a high level of cytotoxicity against B16 cells, which is similar to that exhibited by CTLs generated in BMDCs immunized mice. Moreover, vaccination with genetically modified iPSDCs elicited a high level of therapeutic efficacy equaling that of vaccination with BMDCs. This study clarified experimentally that genetically modified iPSDCs are equivalent to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

Elective colorectal cancer surgery in nonagenarians and postoperative outcomes.

OBJECTIVES: The population of very elderly patients is increasing, and nonagenarians have significantly higher mortality rates and poorer rates of survival than younger patients. Meanwhile, recent studies have shown colorectal cancer surgery in nonagenarian patients to be feasible regarding postoperative outcomes. This retrospective study aims to evaluate the postoperative outcomes of nonagenarians in the latest clinical settings. METHODS: Consecutive nonagenarian patients who underwent elective colorectal cancer surgery between 2018 and 2020 retrospectively enrolled (Trial registration number: UMIN000046296 on December 7th, 2021). Clinicopathological data and short-term postoperative outcomes were collected for statistical analysis. RESULTS: This study included 81 nonagenarian patients (31 males, 50 females). Postoperative complications occurred in 21 patients (25.9%), and 3 patients died within 90 days (3.7%). Multivariate analysis revealed prognostic nutritional index was a significant predictor of postoperative complications (OR 2.99, 95% CI 0.78-9.10, P = 0.048), and performance status ≥ 3 could be an independent risk factor of 90-day mortality (HR 32.30, 95% CI 3.20-326.10, P = 0.032). CONCLUSIONS: Short-term outcomes after surgical treatment for nonagenarian patients with colorectal cancer were acceptable. Low prognostic nutritional index was closely related to postoperative complications and poor performance status could also lead to 90-day mortality. In aging populations, risk stratification to prevent poorer postoperative outcomes in nonagenarian patients is needed.

The evaluation of surgical treatment for gastric cancer patients with noncurative resection.

PURPOSE: This study aims to analyze the results of treatment in a series of 233 gastric cancer patients who underwent a noncurative resection. METHODS: We performed a retrospective study of patients with noncurative treatment for advanced gastric cancer who were divided into three treatment groups: total gastrectomy (TG, n=150), distal gastrectomy (DG, n=44), and nonresection (NR, bypass procedure or chemotherapy only, n=39). RESULTS: In multivariate analysis, surgical treatment (TG) and an absence of chemotherapy were significant independent prognostic factors for a poor survival. In the late period, the overall survival rate was significantly lower in the TG group than in the DG group (p=0.005) and was marginally lower than in the NR group (p=0.054). The resection group had a poorer compliance for chemotherapy than the NR group, and the TG group had a poorer compliance than the DG group (p<0.01). The morbidity rate was higher in the TG group than in the DG group (p<0.05). CONCLUSIONS: TG is considered to be inappropriate for the treatment of noncurative gastric cancer because of the poor prognosis, high morbidity rates, and poor compliance for chemotherapy associated with the procedure. However, noncurative DG was acceptable and postoperative chemotherapy should be used in selected patients.

The impact of abdominal shape index of patients on laparoscopy-assisted distal gastrectomy for early gastric cancer.

PURPOSE: The aim of this study was to explore the effects of the abdominal shape index on gastric cancer patients' short-term surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) in both genders. METHODS: This retrospective study included 231 consecutive patients with early gastric cancer who underwent LADG with Billroth I anastomosis between 1998 and 2009. The abdominal shape index of patients was calculated using preoperative abdominal computed tomography scans and the Fat Scan software program. RESULTS: In male patients, the duration of surgery was longer in patients with a body mass index ≥25 kg/m(2) (P = 0.016), with the anterior to posterior diameter ≥200 mm (P < 0.0001), with the transverse diameter (TD) ≥300 mm (P = 0.030), with the waist ≥85 cm (P = 0.039), and with the visceral fat area (VFA) ≥100 cm(2) (P = 0.029). The intraoperative blood loss was higher in the large TD group (P = 0.049), in the high waist group (P = 0.006), and in the large VFA group (P = 0.007). In female patients, the correlations between these surgical outcomes and this abdominal shape index were not found. No significant relationships between each body shape index and the number of lymph nodes retrieved were found in either gender. Postoperative complications were not associated with the fat volume and abdominal shape index. CONCLUSIONS: Accumulation of fat did not affect short-term surgical outcomes except for the duration of surgery and intraoperative blood loss in male patients.

Optimal period for the prophylactic administration of neutrophil elastase inhibitor for patients with esophageal cancer undergoing esophagectomy.

BACKGROUND: The present study was designed to determine the optimal period for the prophylactic administration of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing transthoracic esophagectomy. Sivelestat is reported to be effective in patients who undergo esophagectomy by providing an increased oxygenation ability and suppressing the serum inflammatory cytokines in the postoperative period. However, the optimal period for the prophylactic administration of Sivelestat remains to be elucidated. METHODS: The 30 patients who underwent esophagectomy for thoracic esophageal cancer were enrolled in one of two groups. The initial 15 patients were assigned to group A and received intravenous infusion of Sivelestat sodium hydrate until postoperative day (POD) 2, and the subsequent 15 patients were assigned to group B and received Sivelestat until POD 5. Historical controls without Sivelestat administration were used. The postoperative courses and serum inflammatory cytokines were evaluated. RESULTS: Sivelestat improved oxygenation in the postoperative period; however, there were no differences between the two groups in terms of duration of mechanical ventilation, intensive care unit stay, systemic inflammatory response syndrome, and postoperative change of oxygenation. In addition, there were no differences in the postoperative changes in the serum interleukin (IL)-6 and high mobility group box chromosomal protein 1. Although the serum IL-8 on POD 3 was lower in group B than in group A, the neutrophil elastase showed no difference between these groups. None of the patients in either group suffered respiratory complications. CONCLUSIONS: The two-day administration of Sivelestat initiated immediately after intrathoracic manipulation was found to be sufficient for prophylactic use to prevent pulmonary complications by suppressing hypercytokinemia after esophagectomy.

[Peptide vaccine therapy with TLR-9 agonist for patients with esophageal squamous cell carcinoma].

Patients with advanced carcinoma are thought to have an impaired immune surveillance system. Therefore, the potent helper action is required for the induction of an antitumor immune response in such patients. We evaluated the efficacy of CpG-ODN, which is TLR-9 agonist, as cancer vaccine adjuvant through in vitro experiments. We also conducted a phase I clinical trial for patients with advanced esophageal squamous cell carcinoma (ESCC) using peptide vaccine in combination with CpG-B. In vitro experiments showed that CpG-ODN caused various immune-modifications, suggesting an efficacy of CpG-ODN as peptide vaccine adjuvant. Moreover, the immune monitoring data in phase I clinical trial suggested that CpG-B augmented the generation of antigen-specific T cell responses and innate immunity. These data indicated that the vaccination with cancer-testis antigen derived peptide in combination with CpG-B may be useful as a new immunotherapy for patients with advanced ESCC.

Laparoscopic anterior resection with or without transanal tube for rectal cancer patients - A multicenter randomized controlled trial.

BACKGROUND: In rectal cancer surgery, insertion of transanal tube has been shown to have efficacy to prevent anastomotic leakage. This randomized controlled study aims to clarify the incidence of anastomotic leakage with or without transanal tube in patients with rectal cancer. METHODS: Patients who underwent elective low anterior resection were randomly allocated to either have transanal tube insertion or not for five days after surgery. We examined the incidence of anastomotic leakage, postoperative 30-day morbidity and mortality. RESULTS: 157 patients were randomized to the transanal tube group or the no-transanal tube group. Symptomatic anastomotic leakage occurred in six patients (7.6%) of the former group and eight patients (10.3%) in the latter group, without significant difference (p = 0.559). There was also no significant difference in morbidity between groups (p = 0.633) and no mortality was detected. CONCLUSIONS: Transanal tube insertion had no significant benefit towards prevention of anastomotic leakage in rectal cancer surgery.

Asymptomatic patent processus vaginalis is a risk for developing external inguinal hernia in adults: A prospective cohort study.

BACKGROUND: Inguinal hernia repair is common for children and adults across the world, but the mechanism behind hernia onset still requires elucidation. This prospective study aims to determine whether patent processus vaginalis (PPV) is a factor in the development of external inguinal hernias. METHOD: We enrolled 1008 patients who underwent laparoscopic surgery and in whom the inguinal region was observed. If processus vaginalis existed, we measured the diameter and length. Patients were followed for three years after surgery to investigate the incidence of external inguinal hernias. RESULT: No significant differences were found between age groups. Furthermore, no difference could be recognized in length or opening diameter of the PPVs between age groups. Three-year follow up was possible for 765 of 1008 patients enrolled in this study (76%), eight of whom, all male, developed external inguinal hernia during this period. Multivariate analysis for onset of inguinal hernia onset in male patients showed that PPV and length of the right PPV were independent risk factors for development of external inguinal hernia. CONCLUSION: The patency rate, length, and diameter of the processus vaginalis do not differ according to age. The patency of the processus vaginalis in male patients is an independent risk factor for development of external inguinal hernia in adults.

Intraoperative maneuvers may affect the development of early postoperative small bowel obstruction after laparoscopic colorectal cancer surgery: Multicenter prospective cohort study.

BACKGROUND: Early postoperative small bowel obstruction (EPSBO) is one of the most common complications after colorectal cancer (CRC) surgery, and clarification of its causes is desired. Several reports have demonstrated the risks of EPSBO, but few have focused on laparoscopic surgery for CRC and intraoperative maneuvers. We therefore prospectively examined the risk factors for EPSBO after laparoscopic CRC resection. METHODS: We prospectively enrolled 706 patients with CRC that underwent laparoscopic CRC resection in our hospital and affiliated hospitals. We analyzed several factors concerning EPSBO including intraoperative procedures. RESULTS: EPSBO developed in 43 of the 706 cases (6.1%). Univariate analysis showed that risk factors for EPSBO were male sex, increased operative time, repositioning of the small intestine before wound closure and anastomotic leakage. Risk factors for EPSBO according to multivariate analysis were increased operative time (odds ratio (OR) 2.41; P = 0.032), repositioning of the small intestine before wound closure (OR 3.58; P = 0.005) and anastomotic leakage (OR 3.91; P = 0.006). CONCLUSION: To reduce EPSBO after laparoscopic CRC surgery, the operation should be finished as soon as possible without performing optional maneuvers. To avoid development to EPSBO, particular care is required in cases where the risk of anastomotic leakage is predicted to be high.

Combination of p53 codon 72 polymorphism and inactive p53 mutation predicts chemosensitivity to 5-fluorouracil in colorectal cancer.

There are increasing reports showing the clinical significance of the p53 polymorphism status in terms of the response to chemotherapy. We investigated whether p53 polymorphism and mutation were associated with in vitro sensitivity to 5-fluorouracil (5-FU) in patients with colorectal cancer. Chemosensitivity to 5-FU was evaluated by the collagen gel droplet embedded culture drug sensitivity test. 5-FU sensitivity of tumor cells without inactive p53 mutation in the arginine/arginine (Arg/Arg) variant was significantly higher than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.022), whereas the 5-FU sensitivity of tumor cells with inactive p53 mutation in the Arg/Arg variant was significantly lower than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.002). In the Arg/Arg variant, apoptotic cells induced by 5-FU treatment in patients without inactive p53 mutation were more markedly increased than those in patients with inactive p53 mutation (p = 0.037). Bax and Bcl-2 protein expressions in tumor tissue treated with 5-FU were associated with both 5-FU sensitivity and the apoptotic cell count. Our data show that the Arg/Arg genotype without inactive p53 mutation could be predictive of a more favorable response and the Arg/Arg genotype with inactive p53 mutation a less favorable response to chemotherapy using 5-FU in CRC. The combination of the p53 codon 72 polymorphism and p53 mutation status is a potential predictive marker of sensitivity to 5-FU in CRC.