In vitro analysis of exfoliated tumor cells in intraluminal lavage samples after colorectal endoscopic submucosal dissection.

PURPOSE: Colorectal endoscopic submucosal dissection (ESD) produces exfoliated tumor cells that occasionally cause local recurrence. However, the biological characteristics of these tumor cells have not been clarified. The aim of this study was to clarify the genetic background and viability of exfoliated tumor cells in colorectal ESDs, as well as possible method for their elimination. METHODS: Post-ESD intraluminal lavage samples from 19 patients who underwent colorectal ESDs were collected. In four patients with adenocarcinoma, gene mutations in the primary tumors and exfoliated cells in lavage samples were analyzed using a next-generation sequencer (NGS). In 15 patients with adenoma or adenocarcinoma, the viability of exfoliated cells and the cell-killing effect of povidone-iodine on exfoliated cells were evaluated. RESULTS: The analysis using a NGS demonstrated that tumors targeted for ESD had already acquired mutations in many genes involved in cell proliferation, angiogenesis, and invasions. Furthermore, gene mutations between the exfoliated tumor cells and tumors resected by ESDs showed a 92 to 100% concordance. The median viable cell counts and the median viability of exfoliated cells in intraluminal lavage samples after ESDs were 4.9 × 105 cells/mL and 24%, respectively. The viability of the exfoliated cells did not decrease even 12 h after ESD. However, contact with 2.0% povidone-iodine solution reduced both viable cell counts and viability, significantly. CONCLUSION: A large number of tumor cells exfoliated during colorectal ESDs had acquired survival-favorable gene mutations and could survive for some time. Therefore, a lavage using a solution of 2.0% povidone-iodine may be effective against such cells. TRIAL REGISTRATION: The prospective study registered 1317, and the retrospective study registered 2729. The prospective study approved on June 20, 2016, and the retrospective study approved on October 6, 2020.

Effect of preoperative asymptomatic renal dysfunction on the clinical course after colectomy for colon cancer.

PURPOSE: To evaluate the effect of mild renal dysfunction on the clinical course after colectomy in patients with colon cancer. METHODS: The subjects of this retrospective study were 263 patients who underwent surgical resection for colon cancer at our hospital between 2011 and 2015. Renal function was assessed based on preoperative estimated glomerular filtration rate (eGFR) values. Patients were divided into groups based on their eGFR value of 55 ml/min/1.73 m2. The Mann-Whitney U test, chi-square or Fisher exact test, and log-rank test were used in the data analysis. RESULTS: There were 59 patients (22.4%) in the low eGFR group and 204 patients in the normal eGFR group. There were differences between the groups in age, comorbidities, and the levels of hemoglobin, albumin, and serum creatinine. The overall postoperative complication rate, frequency of severe complications, and length of stay were significantly higher in the low eGFR group than in the normal eGFR group. Multivariate analysis revealed that low eGFR was the only independent risk factor for severe complications (Clavien-Dindo classification III/IV). There were no differences in survival between the groups. CONCLUSION: Preoperative asymptomatic renal dysfunction may be correlated with the development of postoperative complications and a possible significant risk factor for severe complications after colon cancer surgery.

The middle rectal artery detected by contrast-enhanced magnetic resonance imaging predicts lateral lymph node metastasis in lower rectal cancer.

PURPOSE: Lateral lymph node (LLN) metastasis is one of the leading causes of local recurrence in patients with lower rectal cancer. Unfortunately, no diagnostic biomarkers are currently available that can predict LLN metastasis preoperatively. Accordingly, we investigated the relationship between the middle rectal artery (MRA) identified by contrast-enhanced magnetic resonance imaging (ceMRI) and LLN metastases. METHODS: Data from 102 patients with lower rectal cancer who underwent surgery, and were evaluated by preoperative ceMRI, between 2008 and 2016 were reviewed retrospectively. Two expert radiologists evaluated the MRA findings. The diagnostic performance of MRA for LLN metastasis was evaluated by a multivariate analysis with conventional clinicopathological factors. RESULTS: The MRA was detected in 67 patients (65.7%), including 32 (31.4%) with bilateral MRA and 35 (34.3%) with unilateral MRA. The tumor size, presence of the MRA, and clinical LLN status were significantly correlated with LLN metastasis. A multivariate analysis demonstrated that the presence of MRA (P = 0.045) and clinical LLN status (P = 0.001) were independent predictive factors for LLN metastasis. Furthermore, the sensitivity and negative predictive value of MRA for LLN metastasis were 95% and 97.1%, respectively. CONCLUSION: We successfully demonstrated that MRAs could be clearly detected by ceMRI, and the presence of MRA robustly predicted LLN metastasis in patients with lower rectal cancer, highlighting its clinical significance in the selection of more appropriate treatment strategies. TRIAL REGISTRATION: Trial registration number: retrospectively registered 2126 Trial registration date of registration: August 23, 2019.

A combination of subcuticular sutures and subcutaneous closed-suction drainage reduces the risk of incisional surgical site infection in loop ileostomy closure.

PURPOSE: The purpose of this study was to evaluate the effectiveness of a wound closure method using a combination of subcuticular sutures and subcutaneous closed-suction drainage (SS closure) for preventing incisional surgical site infection (SSI) in loop ileostomy closure. METHODS: A total of 178 consecutive patients who underwent loop ileostomy closure at Nara Medical University Hospital between 2004 and 2018 were retrospectively assessed. The patients were divided into 2 groups: the conventional skin closure (CC) group from 2004 to 2009 (75 patients) and the SS closure (SS) group from 2010 to 2018 (103 patients). The incidence of incisional SSI was compared between the two groups, and the factors associated with incisional SSI were examined by univariate and multivariate analyses. RESULTS: Incisional SSI occurred in 7 cases (9.3%) in the CC group but was significantly reduced to only 1 case (0.9%) in the SS group (p = 0.034). In the univariate analysis, the hemoglobin levels, serum creatinine levels, and SS closure were associated with incisional SSI. SS closure was the only independent preventive factor for incisional SSI according to the multivariate analysis (hazard ratio = 0.24, p = 0.011). CONCLUSION: The combination of subcuticular sutures and subcutaneous closed-suction drainage may be a promising way of preventing incisional SSI in loop ileostomy closure.

Influence of motor instruction words on body movements in step-over motions.

[Purpose] To quantitatively analyze the characteristics of movements evoked by certain motor instruction words on the basis of measurements of ankle elevation and related body movements in step-over motion tasks. [Participants and Methods] Sixty-one healthy adult participants were presented with motor instructions and asked to step over an obstacle in accordance with the instructions. The motor instructions were as follows: "Raise your XX (body part) up YY (expression)" in four combinations using "thigh" and "knee" for body part and "high" and "firmly" for expression. Using Kinect to analyze movements, ankle elevation, trunk-anteversion angle, hip-flexion angle, and knee-flexion angle were measured and statistically processed. [Results] With respect to body part, there was no significant difference in the mean and standard deviation (individual variation) values for ankle elevation. With respect to expression, hip joint and knee joint were bent significantly more for "high" than for "firmly", and although the mean value for ankle elevation was high, ankle elevation standard deviation (individual variation) values were significantly lower for "firmly" than for "high". [Conclusion] Explicit motor instruction words such as "high" may be effective in improving performance, while ambiguous motor instruction words like "firmly" may be effective in stabilizing movements.

Visualization of Lymph/Blood Flow in Laparoscopic Colorectal Cancer Surgery by ICG Fluorescence Imaging (Lap-IGFI).

PURPOSE: In laparoscopic colorectal cancer (Lap-CRC) surgery, determination of a suitable mesentery division line and the appropriate degree of lymphadenectomy by tracing the blood supply is critical. We performed visualization of the lymph and blood flow by laparoscopic indocyanine green (ICG) fluorescence imaging (Lap-IGFI). METHODS: ICG is injected into the submucosa near the tumor via colonoscopy, and the lymph flow is observed. Intestinal blood flow is evaluated by administering ICG intravenously. RESULTS: For lymph flow, visualization of the main lymph node basin helped to determine the surgical division line for cases in which the blood flow was not completely visualized. Lap-IGFI changed the surgical plan of the lymphadenectomy in 23.5 %. In our experience, the metastatic rate of ICG-positive nodes was 10.0 %, and the metastatic rate of ICG-negative nodes was 5.3 %. Furthermore, there were no metastatic nodes that were ICG negative more than 5 cm from the tumor. For blood flow, the blood flow distribution of the intestinal wall from the last branch of the vasa recta of the anastomotic site was clearly visualized and proved useful in choosing the extent of intestinal resection. Lap-IGFI changed the surgical plan of the extensive intestinal resection in 16.7 %. CONCLUSIONS: Lap-IGFI can noninvasively provide detailed lymph and blood flow information and is a useful device to aid in the accurate identification of individual patients' lymph drainage. This helps dictate adequate lymphadenectomy and the extent of intestinal resection in Lap-CRC surgery.

Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD. METHODS: Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital. RESULTS: No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml. CONCLUSION: Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.

[Long-Term Survival of a Patient with Sigmoid Colon Cancer with Multiple Visceral Metastases].

A 66-year-old woman underwent total pelvic exenteration for a pelvic tumor. The pathological diagnosis was sigmoid colon cancer T4b(in the small intestine, uterus, and vagina), N0, M0, Stage II . The patient was treated with XELOX for 6 months as adjuvant chemotherapy and was then treated with IRIS for another 6 months. Brain metastasis developed in the left occipital lobe after 12 months, and she underwent craniotomy and enucleation of the tumor. Liver metastasis and peritoneal dissemination metastasis developed 16 months after her initial diagnosis. The patient underwent re-craniotomy and radiotherapy for recurrence of the brain metastasis 18 months after diagnosis and started taking TAS-102 3 months later. She began treatment with CPT-11 plus panitumumab 24 months after diagnosis, and the dose was increased 9 months later(ie, 35 months after the initial diagnosis). The patient remains alive 42 months after surgery.

[A Resected Case of Cecal Cancer with Simultaneous Liver, Spleen, and Ovarian Metastasis and Peritoneal Dissemination].

We herein report the case of a patient with a cecal cancer with simultaneous liver, spleen, and ovarian metastases as well as peritoneal dissemination who achieved a long-term survival. The patient was a 67-year-old female. Ileocecal resection with partial hepatectomy, splenectomy, simple total hysterectomy, bilateral salpingo-oophorectomy, and resection of the peritoneal dissemination were performed. The final diagnosis was Stage IV (T4a, N1, M1b[H1, P3, OTH]). Adjuvant chemotherapy was administered, but abdominal computed tomography(CT)revealed a metachronous liver metastasis 41 months later. We performed partial hepatectomy, and the patient continued adjuvant chemotherapy. The patient is currently alive and disease-free 30 months after the last operation, 72 months after the initial surgery.

[Long-Term Survival in a Case of Sigmoid Colon Cancer with Multiple Liver Metastases Treated with Repeated Hepatectomies].

A 75-year-old man was diagnosed with sigmoid colon cancer with multiple liver metastases at our hospital in May 2010. He underwent mFOLFOX6 and panitumumab chemotherapy for 6 months. He then underwent sigmoidectomy, lymphadenectomy D3, partial resection of 2 parts of S6, and cholecystectomy in January 2011. However, he underwent partial resection of the liver an additional 4 times in the 5 years followingthe primary operation. Despite multiple liver metastases, he is alive 5 years after the primary operation, havingsurvived 5 hepatectomies for multiple resectable liver metastases.

Erythropoietin attenuates intestinal inflammation and promotes tissue regeneration.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) is increasing. Since patients usually need long-term treatment and suffer from reduced quality of life, there is a need to develop new therapeutic strategy. The aim of this study was to investigate the therapeutic potential of erythropoietin (EPO) for the treatment of IBD. METHODS: Murine colitis was induced by 3.0% Dextran Sulfate Sodium (DSS). Recombinant human EPO (rhEPO) was given to evaluate the anti-inflammatory and regenerative effects on intestinal inflammation. The effect of rhEPO on human colon epithelial cells was also evaluated. Immunohistochemical analysis of EPO receptor was performed in human IBD tissues. RESULTS: While about 62% of control mice with severe colitis induced by 5-day DSS died, 85% of mice treated with rhEPO survived. Histological analysis confirmed that EPO treatment reduced the colonic inflammation. Furthermore, EPO treatment significantly downregulated the local expressions of IFN-γ, TNF-α and E-selectin in the colon, suggesting that the effect was associated with inhibiting local immune activation. In a 4-day DSS-induced colitis model, rhEPO significantly improved the recovery of body weight loss compared to controls. Furthermore, proliferating cell nuclear antigen expression was significantly upregulated in the colon tissue from mice treated with rhEPO compared to controls. In addition, rhEPO increased the growth of cultured human colon epithelial cells in a dose-dependent manner. Furthermore, EPO-receptor expression was confirmed in human IBD colon tissues. CONCLUSION: Three major functions of EPO, hematopoiesis, anti-inflammation and regeneration, may produce significant effects on intestinal inflammation, therefore suggesting that rhEPO might be useful for IBD.

Laparoscopic surgery after endoscopic resection for rectal cancer and neuroendocrine tumors.

BACKGROUND: Endoscopic resection (ER) of tumors causes inflammation, edema, fibrosis, and adhesions in the surrounding tissue. However, little is known about the effect of ER on subsequent laparoscopic surgery for rectal tumors. The objective of this retrospective study was to analyze the effect of ER on subsequent laparoscopic surgery for rectal tumors. METHODS: Twenty-eight patients underwent laparoscopic surgery for rectal adenocarcinoma with submucosal invasion or a rectal neuroendocrine tumor at our hospital between January 2005 and December 2012. A group of 14 patients who underwent laparoscopic surgery with previous ER was compared to a group of 14 patients who underwent laparoscopic surgery without previous ER. RESULTS: Though most fibrosis involved the submucosa after polypectomy and endoscopic mucosal resection, fibrosis after endoscopic submucosal dissection involved the muscularis propria in two patients, and the subserosa in one patient. There were no statistically significant differences in clinical outcomes between the groups. CONCLUSION: Laparoscopic surgery after ER for rectal tumors is safe and feasible. Laparoscopic surgery is the reasonable first-choice for radical treatment of rectal tumors after ER.

[A case of idiopathic portal vein obstruction identified by severe bleeding after a routine hemorrhoid operation].

We report our experiences of a case of repeated bleeding after hemorrhoid ligation. A 53-year-old man underwent hemorrhoid ligation for internal hemorrhoids at another hospital. Postoperatively, he developed severe and repeated bleeding. Scanning revealed extrahepatic portal venous obstruction. The severe bleeding persisted after transfer to our institution, where we re-sutured the ligature and performed superior rectal artery embolism, leading to arrest of bleeding. The rectal varix arose due to portal hypertension, which resulted in the diagnosis of idiopathic extrahepatic portal vein obstruction.

Exfoliated Tumor Cells in Intraluminal Lavage Samples after Colorectal Endoscopic Submucosal Dissection: A Pilot Study.

Endoscopic submucosal dissection involves dissecting manipulation performed with tumors in an exposed condition for a long period of time. Thus, there is a risk for implantation of tumor cells. The objectives of this study were to examine exfoliated tumor cells after colorectal endoscopic submucosal dissection and to elucidate the effectiveness of intraluminal lavage to remove these cells. The subjects were 8 patients who had undergone colorectal endoscopic submucosal dissection at our hospital between September and December 2012. A retrospective study was conducted on the cytological findings of intraluminal lavage samples in these patients. Seven of the 8 patients (88%) had exfoliated tumor cells in the lavage samples at the beginning of lavage. Only 3 patients (3 8%) had exfoliated tumor cells after lavage with 300 ml of water. A large number of tumor cells were thought to have exfoliated into the intestinal lumen after endoscopic submucosal dissection. Sufficient intraluminal lavage after colorectal endoscopic submucosal dissection is necessary to remove exfoliated tumor cells.

Prophylactic laparoscopic lateral pelvic lymph node dissection for lower rectal cancer: remarking on the vesicohypogastric fascia.

OBJECTIVE: To introduce the prophylactic laparoscopic lateral pelvic lymph node dissection performing by remarking the vesicohypogastric fascia following total mesorectal excision for patients with advanced lower rectal cancer without radiological evidence of lymph node involvement. SURGICAL METHOD: We set 5 ports for conventional laparoscopic rectal surgery. During the prophylactic laparoscopic lateral pelvic lymph node dissection, we retrieved the lymph nodes from the internal iliac area and obturator area. We recognized the pelvic nerve plexus, vesicohypogastric fascia (including internal iliac vessels), and parietal fascia (psoas muscle fascia, pubic bone and internal obturator muscle fascia) as the dissection borders from internal to external. Of note, the vesicohypogastric fascia can be recognized under magnified clear vision, and can be preserved by precise dissection, resulting in reduced hemorrhage from the internal iliac vessels and complications such as urinary dysfunction. CONCLUSION: Prophylactic laparoscopic lateral pelvic lymph node dissection after remarking on the vesicohypogastric fascia may contribute to a less invasive surgery compared with conventional laparoscopic lateral pelvic lymph node dissection.

[Four resections of metachronous liver metastases and lateral lymph node metastases of a rectal carcinoid tumor - a case report].

The authors present a case of rectal carcinoid tumor with lateral lymph node metastases and liver metastases that was successfully treated by 4 resections. A 70-year-old man was diagnosed with a rectal carcinoid tumor (20 mm in diameter) with submucosal (SM) invasion. Radical resection was performed at 25 months, 38 months, and 57 months, when abdominal computed tomography (CT) revealed metachronous liver metastases of the rectal carcinoid tumor. At 50 months, metachronous lateral lymph node metastases were also revealed. Three hepatectomies and a laparoscopic lateral lymph node dissection were performed. The patient is currently free of disease at 25 months after the last intervention.

Mucinous adenocarcinoma associated with a chronic perianal fistula - a review of cases from a single institution.

PURPOSE: The purpose of this study was to evaluate the clinicopathological features of mucinous adenocarcinoma associated with perianal fistulas (MAF), to assess the importance of preoperative MRI analysis, and to determine the optimal surgery. METHODS: We performed a retrospective analysis of the data from seven patients with MAF treated at our hospital between 2000 and 2013, and herein discuss the importance of preoperative magnetic resonance imaging (MRI) and of radical surgery. RESULTS: The male to female ratio was 5:2, and the mean age of the patients was 63 years old (28-70). The median duration of chronic fistulation was 16 years (5-40). The tumor extension was classified as II+III+IV in five patients and as II+III in 2 patients according to the Sumikoshi classification, as determned by pelvic MRI. The performed surgeries were 3 abdominoperineal resections with sacral resection and 4 pelvic exenterations with sacral resection. Two local recurrences developed in patients with R1 resection, and 1 distant metastasis occurred in 1 patient with R0 resection. CONCLUSION: For patients with MAF, a curative surgical resection is the only definitive treatment that can be expected to provide a good prognosis. The application of the Sumikoshi classification using MRI may provide a precise assessment of the extension of MAF, which can allow the appropriate surgery to be selected for the patients with MAF.

Clinical outcomes of pelvic exenteration for locally advanced primary or recurrent non-colorectal pelvic malignancies.

OBJECTIVE: The aim of this study was to evaluate the outcomes of patients who underwent extensive pelvic surgery for locally advanced primary or recurrent non-colorectal pelvic malignancies. PATIENTS AND METHODS: We performed a retrospective review of the medical records of 19 patients with non-colorectal pelvic malignancies who underwent extensive surgery at our institution between January 2005 and May 2013. Overall survival and progression-free survival were estimated using the Kaplan-Meier method and compared using the logrank test. RESULTS: With regard to tumor histology, 6 patients (31.6%) had gynecological tumors, 8( 42.1%) had urological tumors, 2( 10.5%) had sarcomas, and 3( 15.8%) had other malignancies. Total pelvic exenteration was performed in 13 patients (68.4%), and other procedures were performed in 6 patients( 31.6%). For all patients, the median operation time and blood loss were 699 min and 2,930 mL, respectively. Complete tumor resection( R0) was achieved in 13 patients( 68.4%), and 16 patients had complications( 84.2%). The median overall survival was 18.5 months for patients who underwent R0 resection, compared with 7.3 months for those who underwent R1/R2 surgery (p=0.113), and the median progression-free survival was 7.3 months for cases of R0 resection, compared with 2.0 months for cases of R1/R2 surgery (p=0.035). CONCLUSION: Our findings indicate that extensive pelvic surgery may be an optimal treatment for some patients with locally advanced primary or recurrent non-colorectal pelvic malignancies. Careful patient selection according to oncological, anatomical, and patient-related factors may improve the outcomes of patients undergoing this extensive, aggressive pelvic surgical procedure.

The "sliding door" technique for closure of abdominal wall defects after rectus abdominis musculocutaneous flap transposition.

Radical surgery is often necessary in patients with local recurrence of rectal cancer or in those with carcinoma associated with an anal fistula. The surgery may include extended excision of the perineal area and can create a large dead space in the pelvis and a large skin defect, often necessitating reconstruction of the pelvic floor using rectus abdominis musculocutaneous (RAM) flap transposition. Wound dehiscence and incisional hernia are common complications of RAM flap transposition. We report herein our encounter with 3 patients in whom we used a "sliding door" technique for reconstruction of the abdominal wall after the creation of a RAM flap. One patient underwent abdominoperineal resection with sacrectomy and RAM flap transposition; he experienced a postoperative surgical site infection and wound dehiscence, which we urgently repaired by reconstructing the abdominal wall using the sliding door technique. Two other patients underwent posterior pelvic exenteration with sacrectomy and RAM flap transposition. These patients underwent simultaneous abdominal wall reconstruction using the sliding door technique. No patient experienced postoperative pelvic sepsis, wound dehiscence, or incisional hernia. The sliding door technique might be useful for preventing wound dehiscence and incisional hernia in patients undergoing RAM flap transposition.