Ability of minimally invasive surgery to decrease incisional surgical site infection occurrence in patients with colorectal cancer and other gastroenterological malignancies.

Background: Surgical site infection (SSI) is one of the most important complications of surgery for gastroenterological malignancies because it leads to a prolonged postoperative hospital stay and increased inpatient costs. Furthermore, SSI can delay the initiation of postoperative treatments, including adjuvant chemotherapy, negatively affecting patient prognosis. Identifying the risk factors for SSI is important to improving intra- and postoperative wound management for at-risk patients. Methods: Patients with gastroenterological malignancies who underwent surgery at our institution were retrospectively reviewed and categorized according to the presence or absence of incisional SSI. Clinicopathological characteristics such as age, sex, body mass index, malignancy location, postoperative blood examination results, operation time, and blood loss volume were compared between groups. The same analysis was repeated of only patients with colorectal malignancies. Results: A total of 528 patients (330 men, 198 women; mean age, 68 ± 11 years at surgery) were enrolled. The number of patients with diseases of the esophagus, stomach, small intestine, colon and rectum, liver, gallbladder, and pancreas were 25, 150, seven, 255, 51, five, and 35, respectively. Open surgery was performed in 303 patients vs. laparoscopic surgery in 225 patients. An incisional SSI occurred in 46 patients (8.7%). Multivariate logistic regression analysis showed that postoperative hyperglycemia (serum glucose level ≥140 mg/dl within 24 h after surgery), colorectal malignancy, and open surgery were independent risk factors for incisional SSI. In a subgroup analysis of patients with colorectal malignancy, incisional SSI occurred in 27 (11%) patients. Open surgery was significantly correlated with the occurrence of incisional SSI (P = 0.024). Conclusions: Postoperative hyperglycemia and open surgery were significant risk factors for SSI in patients with gastroenterological malignancies. Minimally invasive surgery could reduce the occurrence of incisional SSI.

Clinical impact of lymphocyte/C-reactive protein ratio on postoperative outcomes in patients with rectal cancer who underwent curative resection.

Cancer-related systemic inflammation influences postoperative outcomes in cancer patients. Although the relationship between inflammation-related markers and postoperative outcomes have been investigated in many studies, their clinical significance remains to be elucidated in rectal cancer patients. We focused on the lymphocyte count/C-reactive protein ratio (LCR) and its usefulness in predicting short- and long-term outcomes after rectal cancer surgery. Patients with rectal cancer who underwent curative resection at our institution between 2010 and 2018 were enrolled in this study. We comprehensively compared the effectiveness of 11 inflammation-related markers, including LCR and other clinicopathological characteristics, in predicting postoperative complications and survival. Receiver operating characteristic curve analysis indicated that LCR had the highest area under the curve value for predicting the occurrence of postoperative complications. In the multivariate analysis, male sex (odds ratio [OR]: 2.21, 95% confidence interval [CI] 1.07-4.57, P = 0.031), low tumor location (OR: 2.44, 95% CI 1.23-4.88, P = 0.011), and low LCR (OR: 3.51, 95% CI 1.63-7.58, P = 0.001) were significantly and independently associated with the occurrence of postoperative complications. In addition, multivariate analysis using Cox's proportional hazard regression model for the prediction of survival showed that low LCR (≤ 12,600) was significantly associated with both poor overall survival (hazard ratio [HR]: 2.07, 95% CI 1.03-4.15, P = 0.041) and recurrence-free survival (HR: 2.21, 95% CI 1.22-4.01, P = 0.009). LCR is a useful marker for predicting both short- and long-term postoperative outcomes in rectal cancer patients who underwent curative surgery.

Strangulated small bowel obstruction caused by isolated obturator nerve and pelvic vessels after pelvic lymphadenectomy in gynecologic surgery: two case reports.

BACKGROUND: Although small bowel obstruction (SBO) is a major complication occurring after abdominal surgery, few reports have described strangulated SBO after pelvic lymphadenectomy (PL). This report describes two cases of strangulated SBO caused by a skeletonized obturator nerve and pelvic vessels after laparoscopic PL during gynecologic surgery. CASE PRESENTATION: Case 1: A 57-year-old woman with endometrial cancer underwent a laparoscopic semi-radical total hysterectomy with PL. Nine months after the operation, she visited our emergency room complaining about subacute pain spreading in the right groin, right buttock, and dorsal part of the right thigh. She had no abdominal pain. Although her symptoms were not typical, computed tomography (CT) revealed strangulated SBO in the right pelvis. Laparoscopic surgery revealed that the small bowel was ischemic. Then we converted to open surgery. We transected the right obturator nerve and umbilical artery, which constructed an internal hernia orifice in the right pelvis, followed by resection of the ischemic small bowel. Fortunately, during 6-month follow-up, she showed only slight difficulty in walking as a postoperative complication. Case 2: A 62-year-old woman with cervical cancer underwent laparoscopic radical hysterectomy with PL. Six months after the operation, she visited our hospital emergently because of sudden onset of abdominal pain and vomiting. CT showed strangulated SBO. Urgent laparoscopic surgery exhibited the incarcerated small bowel at the right pelvis. Consequently, we converted to open surgery. The terminal ileum was detained into the space constructed by the right umbilical artery. We cut the umbilical artery and performed ileocecal resection. After the surgery, she was discharged with no complication or sequela. CONCLUSION: When examining a patient after PL who complains of severe pain or symptoms, one should consider the possibility of PL-related SBO, even if the pain is apparently atypical for SBO.

Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair.

The maintenance of human skeletal stem cells (hSSCs) and their progeny in bone defects is a major challenge. Here, we report on a transplantable bandage containing a three-dimensional Wnt-induced osteogenic tissue model (WIOTM). This bandage facilitates the long-term viability of hSSCs (8 weeks) and their progeny, and enables bone repair in an in vivo mouse model of critical-sized calvarial defects. The newly forming bone is structurally comparable to mature cortical bone and consists of human and murine cells. Furthermore, we show that the mechanism of WIOTM formation is governed by Wnt-mediated asymmetric cell division of hSSCs. Covalently immobilizing Wnts onto synthetic materials can polarize single dividing hSSCs, orient the spindle and simultaneously generate a Wnt-proximal hSSC and a differentiation-prone Wnt-distal cell. Our results provide insight into the regulation of human osteogenesis and represent a promising approach to deliver human osteogenic constructs that can survive in vivo and contribute to bone repair.

Robot-assisted low anterior resection after aluminum potassium sulfate and tannic acid sclerosing therapy for internal hemorrhoids.

BACKGROUND: Internal hemorrhoids are the most common anal diseases. Aluminum potassium sulfate and tannic acid (ALTA) injection is a new sclerosing therapy for the treatment of internal hemorrhoids. Although ALTA injection has been widely used, there are no previous reports of rectal cancer patients who underwent robot-assisted low anterior resection (Rob-LAR) after ALTA injection to treat internal hemorrhoids. CASE PRESENTATION: A 70-year-old man with rectal cancer was presented to our hospital. He had an ALTA injection 2 months before presentation at a clinic due to hematochezia with internal hemorrhoids. The rectal tumor was located 7 cm above the anal verge, and Rob-LAR with the da Vinci Xi system was performed. The patient had sclerosis on the stump of the anal side, which made it difficult to transect the rectum with linear staplers. This required multiple repeats of compression through the SmartClamp feedback. After anastomosis with the double-stapling technique, we constructed a diverting ileostomy. CONCLUSION: Although ALTA injection is a promising strategy for internal hemorrhoids, rectal cancer should be excluded before the sclerosing therapy.

Simultaneous robotic surgery with low anterior resection and prostatectomy/hysterectomy.

Cooperation with multiple departments is essential for the treatment of patients with rectal cancer and other pelvic cancers. In our department, we experienced two cases of rectal cancer that underwent robotic low anterior resection (LAR) and simultaneous resection of other pelvic organs (case 1 with prostatectomy and case 2 with hysterectomy) using the da Vinci Xi system. Here, we show the precise procedures of these two robotic surgeries. Under general anesthesia and lithotomy position, five da Vinci ports were symmetrically placed along the umbilical horizontal line with a 7 cm interval, and a 5 mm AirSeal Access Port was added in the right or left upper quadrant. Patients were placed with 22-degree Trendelenburg and 8-degree tilt to the right. The operators used the center port on the umbilicus as a camera port and chose the docking arms with either two-left-one-right or one-left-two-right setting depending on their preference. This port setting was quite useful for the operators from multiple departments to change the docking arms, even if their preference may be different. Moreover, assistants could use the remaining two ports to provide a well-expanded and safer surgical field. "With a familiar view" and "with a wide view" are our two concepts to safely perform extended pelvic surgeries. We have employed this symmetrical horizontal port site position as a general setting for usual rectal surgeries.

Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis.

Aging-associated alterations of cellular functions have been implicated in various disorders including cancers. Due to difficulties in identifying aging cells in living tissues, most studies have focused on aging-associated changes in whole tissues or certain cell pools. Thus, it remains unclear what kinds of alterations accumulate in each cell during aging. While analyzing several mouse lines expressing fluorescent proteins (FPs), we found that expression of FPs is gradually silenced in the intestinal epithelium during aging in units of single crypt composed of clonal stem cell progeny. The cells with low FP expression retained the wild-type Apc allele and the tissues composed of them did not exhibit any histological abnormality. Notably, the silencing of FPs was also observed in intestinal adenomas and the surrounding normal mucosae of Apc-mutant mice, and mediated by DNA methylation of the upstream promoter. Our genome-wide analysis then showed that the silencing of FPs reflects specific gene expression alterations during aging, and that these alterations occur in not only mouse adenomas but also human sporadic and hereditary (familial adenomatous polyposis) adenomas. Importantly, pharmacological inhibition of DNA methylation, which suppresses adenoma development in Apc-mutant mice, reverted the aging-associated silencing of FPs and gene expression alterations. These results identify aging-associated gene expression signatures that are heterogeneously induced by DNA methylation and precede intestinal tumorigenesis triggered by Apc inactivation, and suggest that pharmacological inhibition of the signature genes could be a novel strategy for the prevention and treatment of intestinal tumors.

Short- and mid-term outcomes after early surgical training in laparoscopic colorectal cancer surgery: trainees' performance has no negative impact.

BACKGROUND: This study aimed to evaluate the safety and quality of laparoscopic colorectal cancer surgery undertaken by trainees. PATIENTS AND METHODS: From a prospectively maintained database, we identified 456 consecutive patients who underwent laparoscopic resection for colorectal cancer between 2006 and 2010. Short-term operative outcomes, relapse-free survival (RFS), and overall survival (OS) were compared between operations undertaken by the experts (E group) and trainees (T group). Multivariate analyses were performed for RFS and OS in stage II/III disease. RESULTS: Trainees performed 313 surgeries (68.6%) and completed the procedure by themselves in 297 cases (94.9%). Short-term outcomes, including operative time, blood loss, conversion, complication, mortality, and retrieval of less than 12 lymph nodes, were comparable between the E group and the T group. After a median follow-up period of 35 months, RFS and OS were similar between the two groups, with the exception of OS for stage II (3-year OS for E group versus T group, 96.9% versus 87.0%; P=.029); however, this difference disappeared after multivariate analyses. Multivariate analyses showed that positive resection margin and higher log carcinoembryonic antigen (CEA) levels were associated with lower RFS. Furthermore, increasing age, positive resection margin, higher log CEA levels, intraoperative surgeon exchange, rectal cancer, postoperative complications, absence of postoperative chemotherapy, and shorter operative time were associated with poor OS. CONCLUSIONS: Laparoscopic operations undertaken by trainees did not negatively affect short-term outcomes and were not associated with impaired mid-term oncologic outcomes. Our findings support early initiation of training in laparoscopic surgery for colorectal cancer treatment.

In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines.

Many chemical mediators regulate neutrophil recruitment to inflammatory sites. Although the actions of each chemical mediator have been demonstrated with neutrophils in vitro, how such chemical mediators act cooperatively or counteractively in vivo remains largely unknown. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance energy transfer, we time-lapse-imaged the activities of extracellular signal-regulated kinase (ERK) and protein kinase A (PKA) in neutrophils in inflamed intestinal tissue. ERK activity in neutrophils rapidly increased during spreading on the endothelial cells and showed positive correlation with the migration velocity on endothelial cells or in interstitial tissue. Meanwhile, in the neutrophils migrating in the interstitial tissue, high PKA activity correlated negatively with migration velocity. In contradiction to previous in vitro studies that showed ERK activation by prostaglandin E2 (PGE2) engagement with prostaglandin receptor EP4, intravenous administration of EP4 agonist activated PKA, inhibited ERK, and suppressed migration of neutrophils. The opposite results were obtained using nonsteroidal antiinflammatory drugs (NSAIDs). Therefore, NSAID-induced enteritis may be caused at least partially by the inhibition of EP4 receptor signaling of neutrophils. Our results demonstrate that ERK positively regulates the neutrophil recruitment cascade by promoting adhesion and migration steps.

Laparoscopic resection for sigmoid and rectosigmoid colon cancer performed by trainees: impact on short-term outcomes and selection of suitable patients.

PURPOSE: This study aimed (1) to evaluate the impact of clinical factors, particularly operation by trainees, on the short-term outcomes of laparoscopic resection for sigmoid and rectosigmoid cancer, and (2) to determine patients suitable for operation by trainees. METHODS: From a prospectively maintained single-institution database, we identified 133 patients who underwent laparoscopic resection for sigmoid or rectosigmoid cancer between 2007 and 2010. Gender, age, body mass index (BMI), previous abdominal surgery, tumor location, tumor size, tumor stage, extent of lymph node dissection, and primary surgeon were evaluated using univariate and multivariate analyses to determine the predictive significance of these variables on surgical outcomes including operative time, blood loss, complication, postoperative stay, and retrieved lymph nodes. RESULTS: Multivariate analysis showed that location of the tumor in the rectosigmoid (p < 0.001), higher BMI (p < 0.001), operation by trainees (p < 0.001), male gender (p = 0.002), and greater tumor depth (p = 0.011) were independently predictive of longer operative time. Larger tumor size (p = 0.025) and higher BMI (p = 0.040) were independently predictive of greater blood loss. Larger tumor size was also related to longer postoperative stay (p = 0.001) and a greater number of retrieved lymph nodes (p = 0.001). CONCLUSIONS: This study identified operation by trainees as an independent risk factor for longer operative time but with no negative impact on any of the other outcomes. Female patients with a low BMI, sigmoid cancer, shallow tumor depth, and/or small tumor are suitable for operation by trainees.

[Oral capecitabine as postoperative adjuvant chemotherapy in stage III colon cancer patients].

Capecitabine(Xeloda®)has been a global standard drug for the treatment of colon cancer since large randomized controlled trials demonstrated its efficacy and safety in treating patients suffering from the disease. Few studies have been conducted to assess the effects of oral capecitabine treatment on Japanese patients. Therefore, we conducted this study to evaluate oral capecitabine as postoperative adjuvant chemotherapy in 50 patients who underwent surgery for stage III colon cancer at our department. Patients received an 8 courses treatment with capecitabine during the study, and the incidence of adverse events, treatment completion rate, and treatment compliance were assessed. Adverse events were reported in a total of 46 patients(92%). The most common adverse event was hand foot syndrome(HFS), reported in 39 patients(78%), whereas bone-marrow toxicity and diarrhea were reported in as few as 2(4%)and 3(6%)patients, respectively. Both these events were mild in severity, and no patients required hospitalization, nor were they associated with treatment-related deaths. The median treatment duration was 8 courses ranging from 3 to 8 courses, and the 8 courses treatment completion rate was 96%. The relative dose intensity, which was used as a treatment compliance index, is expressed as the actual dose taken by the patient divided by the dose planned at baseline. The median and mean of the relative dose intensity were 100%(ranging from 37% to 100%)and 93%, respectively. The results of this study showed that the safety profile of oral capecitabine therapy was generally favorable, with a lower incidence and lesser severity of life-threatening bone-marrow toxicity and diarrhea, although the treatment is still associated with frequent HFS. This is the great advantage of capecitabine when it is used as postoperative adjuvant chemotherapy for gastrointestinal cancer. Indeed, a satisfactory treatment completion rate was achieved in this study while maintaining a sufficient dose and treating HFS, by reducing the dose, interrupting treatment, or providing appropriate corrective measures.

VEGF hypersecretion as a plausible mechanism for pseudo-meigs' syndrome in advanced colorectal cancer.

We present a case of pseudo-meigs' syndrome caused by a metastatic ovarian tumor of rectal cancer origin, and examine the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of refractory fluid retention. A 42-year-old woman with advanced rectal cancer underwent a laparoscopic anterior resection of the rectum. During systemic chemotherapy treatment, she complained of severe abdominal distension 16 months following the operation. We failed to improve massive ascites by diuretics and repeated abdominocenteses. Without any definite evidence of carcinomatous peritonitis, we chose to extirpate an enlarged ovarian tumor on the presumptive diagnosis of pseudo-meigs' syndrome. Ascites disappeared promptly after resecting the ovarian tumors and the subject resumed systemic chemotherapy. Preoperative high levels of serum VEGF were normalized promptly after the operation. Levels of VEGF expression in metastatic ovarian tumors were as weak as in the primary tumor upon immunohistochemical staining. In contrast, increased VEGF expression was evident in epithelial cells of oviducts. For patients with massive and refractory ascites, we need to keep in mind the disease entity of pseudo-meigs' syndrome, since surgical intervention possibly improves conditions. Furthermore, the hypersecretion of VEGF from oviducts may play a role in the pathogenesis of clinical manifestations of pseudo-meigs' syndrome.