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.

Factors associated with treatment outcome, and long-term prognosis of patients with ulcerative colitis undergoing selective depletion of myeloid lineage leucocytes: a prospective multicenter study.

BACKGROUND: Patients with ulcerative colitis (UC) have elevated/activated myeloid lineage leucocytes and may respond favorably to adsorptive granulocyte/monocyte apheresis (GMA). However, there are patients who respond well to GMA, and patients who do not benefit. Therefore, predictive factors of GMA efficacy need to be defined. METHODS: In a prospective multicenter setting, 200 UC patients at 32 institutes received one GMA session per week over 10 weeks. Patients who achieved remission were followed for 12 months. The Clinical Activity Index (CAI) ≤3 meant remission, and response meant CAI decreased by ≥3. Quality of life was evaluated by the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: After final GMA, remission, response and no response rates were 67.0%, 15.0% and 18%, respectively. The remission group had a significant decrease in myeloid leucocytes and platelets. Corticosteroid dose decreased (P < 0.001); 49 of 97 patients on corticosteroids became steroid-free. Baseline CAI was lower in the remission group versus non-remission (P < 0.01), whereas IBDQ was higher in the remission group versus non-remission (P < 0.05). After 12 months, 52 of 134 patients had maintained remission. Disease duration was longer in the relapsed group versus maintained remission group (P = 0.041). Male gender, first UC episode and corticosteroid responder were significant factors for maintaining remission, whereas corticosteroid dependent UC was associating with relapse. DISCUSSION: Selective myeloid leucocyte depletion was effective for remission induction and improving patients' quality of life. Baseline demographics such as disease activity level, duration and corticosteroid dependency appear to predict response to GMA. Additionally, patients with a first UC episode who were drug naive responded well to GMA and achieved a favorable long-term disease course by avoiding pharmacologics from an early stage of their inflammatory bowel disease. These findings should help to end unnecessary use of medical resources by targeting GMA to patients who may respond well.

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.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

BACKGROUND AND AIMS: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. METHODS: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. RESULTS: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. CONCLUSIONS: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

Comparison of effects of a selective 5-HT reuptake inhibitor versus a 5-HT4 receptor agonist on in vivo neurogenesis at the rectal anastomosis in rats.

It was recently reported that activation of enteric neural 5-HT(4) receptors (SR4) promotes reconstruction of enteric neural circuit injury in distal gut of guinea pigs and that this reconstruction involves neural stem cells. We aimed to explore a novel approach using a selective serotonin reuptake inhibitor (SSRI), which increases endogenous 5-HT, to repair enteric nerve fiber injury in the rat distal gut. Enteric nerve fiber injury was performed by rectal transection and subsequent end-to-end one-layer anastomosis. The SSRI fluvoxamine maleate (100 µmol/l) was applied locally at the anastomotic site to compare with the 5-HT(4) agonist mosapride citrate (100 µmol/l) (applied for patent) applied locally and orally. Unlike mosapride, fluvoxamine failed to promote the regeneration of the nerve fiber tract across the anastomosis. Furthermore, fluvoxamine did not generate anti-distal-less homeobox 2 (DLX2)- and anti-SR4-positive cells (neural stem cells) and/or anti-neurofilament (NF)-positive cells (neural cells) in newly formed granulation tissue at the anastomosis, whereas these cell types were observed in mosapride-treated preparations. In contrast to its effects in guinea pigs, mosapride generated 5-bromo-2'-deoxyuridine (BrdU)-positive neural cells in ganglia sites 3 mm oral and anal from the anastomosis 2 wk after nerve fiber injury. All actions of mosapride were observed after local and or oral applications. These findings indicate that local SSRI treatment does not induce in vivo nerve fiber tract growth across the anastomosis in the rat distal gut. Mosapride induces nerve fiber tract growth across the anastomosis, mediated through enteric neural stem cells possibly from neural crest-derived stem cells or mesenchymal stem cells in the bone marrow.

Laparoscopic lateral pelvic lymph node dissection for lower rectal cancer: initial clinical experiences with prophylactic dissection.

AIM: To evaluate the technical feasibility of laparoscopic lateral pelvic lymph node dissection (LPLD) following total mesorectal excision (TME) as prophylaxis for patients with advanced lower rectal cancer but no radiologic evidence of lymph node involvement. PATIENTS AND METHODS: TME was performed on 30 patients with cT3N1-2M0 lower rectal cancer. LPLD was performed by laparoscopic surgery in 12 patients (LAP group),and open surgery in 18 patients (Open group). Statistical analysis was used to compare the number of harvested lymph nodes, operative time, operative blood loss, transfusion rate, and volume of transfusion between the groups. RESULTS: No significant difference was observed in the number of harvested lymph nodes. Operative time was significantly longer in the LAP group; however, operative blood loss, transfusion rate, and volume of transfusion were significantly lower in the LAP group. CONCLUSION: Laparoscopic LPLD, when performed by a well-trained laparoscopic team, is safe and feasible in some selected lower rectal cancer patients. This approach has the potential to achieve oncologic lymph node clearance equivalent to open surgical LPLD, and to overcome the cited disadvantages of LPLD, which include greater operative blood loss and urinary dysfunction.

[A case of multiple gastrointestinal stromal tumors of the small intestine associated with von Recklinghausen disease].

A 63-year-old woman was admitted to our hospital because of tarry stool several years previously. At the time, café-au-lait spots and dermal nodules were found on her entire body, and a diagnosis of von Recklinghausen disease was established. Small bowel endoscopy revealed a submucosal tumor in the jejunum. Laparotomy was therefore performed on the suspicion of intestinal GIST. Numerous extramural tumors with a diameter of 3-5mm were observed along the jejunum and ileum, in addition to the primary tumor. Partial resection of the jejunum, including the primary tumor and only one small nodule was performed to prevent short bowel syndrome. Immunopathological studies of the tumors were positive for KIT and CD34 and we diagnosed multiple intestinal GISTs. Imatinib mesylate was not administered, but no growth of the residual tumors have been recognized for 10 months after surgery.