Risk factors for anastomotic leakage after low anterior resection for obese patients with rectal cancer.

PURPOSE: We aimed to analyze the risk factors for anastomotic leakage (AL) after low anterior resection (LAR) in obese patients (body mass index [BMI] ≥ 25 kg/m2) with rectal cancer. METHODS: Data were collected from four hundred two obese patients who underwent LAR for rectal cancer in 51 institutions. RESULTS: Forty-six (11.4%) patients had clinical AL. The median BMI (27 kg/m2) did not differ between the AL and non-AL groups. In the AL group, comorbid respiratory disease was more common (p = 0.025), and the median tumor size was larger (p = 0.002). The incidence of AL was 11.5% in the open surgery subgroup and 11.4% in the laparoscopic surgery subgroup. Among the patients who underwent open surgery, the AL group showed a male predominance (p = 0.04) in the univariate analysis, but it was not statistically significant in the multivariate analysis. Among the patients who underwent laparoscopic surgery, the AL group included a higher proportion of patients with comorbid respiratory disease (p = 0.003) and larger tumors (p = 0.007). CONCLUSION: Comorbid respiratory disease and tumor size were risk factors for AL in obese patients with rectal cancer. Careful perioperative respiratory management and appropriate selection of surgical procedures are required for obese rectal cancer patients with respiratory diseases.

Examination of colorectal cancer cases with metal allergy.

PURPOSE: To report our initiatives and treatment results for patients with colorectal cancer with metal allergy. METHODS: A total of 27 patients (2.6%) with a history of metal contact dermatitis were identified among 1027 patients who underwent curative resection of colorectal cancer from 2014 to 2020. The results of the patch test, perioperative results, and postoperative colonoscopy findings were also investigated. RESULTS: The patch test for metal allergens and staples was performed in 21 patients (77.8%), and 13 of them (61.9%) tested positive for at least one metal allergen. Ni (38.1%), Co (28.6%), and Pd (19.0%) showed higher positive rates than other metals, and 1 patient (4.8%) tested positive for staples. Stapled anastomosis/suturing was performed as planned in 15 of 27 patients. In 10 patients, the anastomosis method was changed from stapled to hand-sewn according to the no-patch test results (60%), positivity for multiple metals (20%), positivity for staples (10%), and surgeon's judgment (10%). No complications and abnormal colonoscopy findings were found to be associated with stapled anastomosis/suturing. CONCLUSION: The patch test is useful for selecting an optimal anastomosis method for patients with suspected metal allergy.

[A Case Report for Peritoneal Recurrences by Laparoscopic Surgery after Colorectal Cancer Resection].

We report a cases report of colorectal cancer who underwent repeated resection for peritoneal recurrences by laparoscopic surgery. In 2013, a 70-year-old woman diagnosed with an ascending colon cancer underwent laparoscopic right hemicolectomy. The pathological diagnosis was tub2, pT4aN1M0, Stage Ⅲb. Postoperative adjuvant chemotherapy(uracil and tegafur/Leucovorin)was administered. PET-CT performed at 25 months after the surgery because of CEA elevation. It revealed a peritoneal recurrence in the pouch of Douglas. The following peritoneal recurrences were removed by laparoscopic Hartmann's procedure. Chemotherapy(5-fluorouracil/levofolinate/oxaliplatin/bevacizumab)was administered 11 courses and after that chemotherapy(5-fluorouracil/levofolinate/bevacizumab)was administered 6 courses. PET-CT performed 37 months after the second surgery revealed a peritoneal recurrence near the right ovary in the pouch of Douglas. The following peritoneal recurrences was removed. Chemotherapy(tegafur/gimeracil/oteracil/bevacizumab)was administered 11 courses. The long-term survival has been continued for 7 years and 7 months after first operation. It was considered that laparoscopic surgery for peritoneal recurrence in colorectal cancer is contributed to one of the surgical procedures in selected patients.

Endocytic trafficking factor VPS45 is essential for spatial regulation of lens fiber differentiation in zebrafish.

In vertebrate lens, lens epithelial cells cover the anterior half of the lens fiber core. Lens epithelial cells proliferate, move posteriorly and start to differentiate into lens fiber cells at the lens equator. Although FGF signaling promotes this equatorial commencement of lens fiber differentiation, the underlying mechanism is not fully understood. Here, we show that lens epithelial cells abnormally enter lens fiber differentiation without passing through the equator in zebrafish vps45 mutants. VPS45 belongs to the Sec1/Munc18-like protein family and promotes endosome trafficking, which differentially modulates signal transduction. Ectopic lens fiber differentiation in vps45 mutants does not depend on FGF, but is mediated through activation of TGFß signaling and inhibition of canonical Wnt signaling. Thus, VPS45 normally suppresses lens fiber differentiation in the anterior region of lens epithelium by modulating TGFß and canonical Wnt signaling pathways. These data indicate a novel role of endosome trafficking to ensure equator-dependent commencement of lens fiber differentiation.

Significance of postoperative adjuvant chemotherapy with an oxaliplatin-based regimen after simultaneous curative resection for colorectal cancer and synchronous colorectal liver metastasis: a propensity score matching analysis.

BACKGROUND: Expansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis. METHODS: The subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (-) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed. RESULTS: Before PS matching, the L-OHP (+) and (-) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1-3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (-) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.40, 95% CI 0.17-0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.42, 95% CI 0.17-1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (-) groups. CONCLUSIONS: PS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.

Metastatic seeding of human colon cancer cell clusters expressing the hybrid epithelial/mesenchymal state.

Emerging evidence supports the theory that tumor cell clusters efficiently metastasize to distant organs. However, the roles of epithelial-to-mesenchymal transition (EMT) in metastasizing tumor cell clusters have not yet been fully elucidated. To investigate this issue, tumor fragments were dissected from 40 colorectal cancer (CRC) patients and implanted subcutaneously into immunodeficient mice. We observed that tumors developed from the tumor fragments obtained from 28 of the 40 CRC patients. The tumors were then dissociated into cell suspensions to be orthotopically injected into secondary mice. The tumors from 13 of the 28 patients progressed. Furthermore, metastases formed spontaneously in the liver and lungs from the tumor fragments obtained from 8 of these 13 patients. Moreover, employing a mathematical analysis, we showed that tumor cell clusters seeded these metastases significantly more often than did single tumor cells. Membrane E-cadherin- and nuclear ZEB1-positive tumor cells indicating the hybrid epithelial/mesenchymal state were also detected in primary tumors of various CRC patients, and in the corresponding patient-derived xenografts (PDXs) and circulating tumor cell clusters in the bloodstreams of mice. In contrast, ZEB1 staining was barely detectable in the patient-matched liver metastases presumably developing through mesenchymal-to-epithelial transition. Inhibition of E-cadherin or ZEB1 expression by shRNA notably prevented the PDX-derived tumor organoids from colonizing the liver, when injected intrasplenically into mice, indicating E-cadherin and ZEB1 expressions to be required for their metastatic colonization. Taken together, these findings suggest that the epithelial/mesenchymal state mediates metastatic seeding of human CRC cell clusters into distant organs.

Experience in the use of a device to attach an anti-adhesion-absorption barrier film to the abdominal cavity in laparoscopic colorectal surgery.

The use of laparoscopic surgery is widespread worldwide and is becoming the standard procedure. Postoperative adhesion, which is one of the typical postoperative complications, is considered to be less likely to occur compared with open surgery. However, once complications, such as small bowel obstruction or chronic abdominal pain, occur due to adhesion, the minimal invasiveness can be greatly impaired, and it can also become costly from a medical economics perspective. In the past, anti-adhesion absorption barrier films have been used to prevent adhesion, but there are many cases in which laparoscopic techniques are required, depending on the site of intraperitoneal attachment. Herein, we report a device that can easily attach an absorbent barrier preparation.

Effects of Receptor for Advanced Glycation End-Products (RAGE) Signaling on Intestinal Ischemic Damage in Mice.

OBJECTIVE: Superior mesenteric artery ischemia and nonocclusive mesenteric ischemia are representative diseases of the vascular emergency known as irreversible transmural intestinal necrosis (ITIN). The receptor for advanced glycation end-products (RAGE) belongs to the immunoglobulin superfamily of extracellular ligands, which also includes high-mobility group box 1 (HMGB-1) and proteins of the S100 family. The HMGB-1 ligands have been implicated in the pathogenesis of various inflammatory disorders. This study was designed to investigate the relation between RAGE and ITIN in a murine acute intestinal ischemic model. MATERIALS AND METHODS: ITIN was induced by clipping the cranial mesenteric artery and the peripheral blood vessels. Mucosal and blood samples were collected and analyzed by reverse-transcription PCR and immunohistochemistry for mucosal inflammation and levels of RAGE-related proteins. The influence of RAGE signaling on intestinal cell reproduction was investigated using the cell scratch test, an in vitro wound-healing assay. Finally, RAGE-related proteins and their respective inhibitors were administered intraperitoneally to ITIN model mice to determine their effects. RESULTS: RAGE-expressing cells were located at the base of the intestinal crypts at day 0. As ITIN progressed, most of the damaged intestinal cells expressed RAGE, and ligands of RAGE such as HMGB-1, S100 A8/A9, and S100ß were present in the crypt cells from the bottom to the top. The quantities of S100 A8/A9 and S100ß were particularly high, above the levels found in other diseases. When S100 A8/A9 and S100ß were applied to small intestinal epithelial cells in vitro, regeneration was significantly impeded. Inflammatory Gr1+ neutrophils and F4/80+ macrophages are involved in tissue ischemia. S100 A8/A9 enhances inflammatory myeloid cell influx. CONCLUSIONS: RAGE-related proteins are elevated in ITIN model mice and impede intestinal regeneration in vitro. RAGE-related proteins may be a new therapeutic target or a new marker for ITIN.

[A Case of Good Quality of Life(QOL)and Favorable Response to Transarterial Chemoembolization(TACE)against Synchronous Multiple Liver Metastases].

We report a case of good quality of life(QOL)and favorable response to transarterial chemoembolization(TACE)against synchronous multiple liver metastases. An 85-year-old man was admitted to our hospital because of melena. Colonoscopy showed multiple type 2 tumors in the sigmoid colon and upper rectum. CT and EOB-MRI examinations revealed that there were multiple liver metastases. Because of his age and surgical stress, he underwent a laparoscopic Hartmann's procedure. After the resection of the primary tumor, he received tegafur/uracil for his liver metastases. However, he discontinued receiving the drugs 2 weeks later because of the development of adverse events. Instead of systemic chemotherapy, he chose to undergo TACE. He underwent TACE with irinotecan and HepaSphereTM(BioSphere Medical)8 times for his multiple liver metastases. Consequently, all multiple liver metastases disappeared. Therefore, TACE may be useful for patients who are not suitable for systemic chemotherapy.

[A Case of Systemic Chemotherapy Combined with Molecular Drug Treatment Following Biliary Stent Implantation for Obstructive Jaundice Due to Metastases of Liver Gland Lymph Node after Colorectal Cancer Surgery].

We report a case of systemic chemotherapy after biliary stent placement for obstructive jaundice due to hepatic portal lymph node metastasis after colorectal cancer surgery. The patient was a 40s woman. Laparoscopic anterior resection for rectosigmoidRS cancer was performed. The pathological diagnosis was T3N0M0PUL0R0, pStage Ⅱ according to the 8th edition of colorectal cancer handling regulations. Because multiple liver metastases were observed 8 months after the surgery, partial resection of the posterior region of the liver was performed. Multiple lung metastases were observed 1 year after hepatectomy, but she wantedto undergo follow-up observation. Jaundice was observed 1 year after the diagnosis of lung metastasis, and obstructive jaundice due to hepatic portal lymph node metastasis was diagnosed. Endoscopic retrograde biliary drainage(ERBD)was performed, and a bile duct stent was placed. After improving jaundice, 12 courses of mFOLFOX6 plus cetuximab therapy were performed. Currently, because of the exacerbation of lung metastasis, FOLFIRI plus bevacizumab therapy is being administered. Systemic chemotherapy containing a molecular-targeted drug is being administered in our case, but complications relatedto the biliary stent have not been observed. There are few reports on similar cases, andfollow - up observation with careful attention to long-term safety is necessary.

Endoscopic Submucosal Dissection Decreases Additional Colorectal Resection for T1 Colorectal Cancer.

BACKGROUND There are 3 methods of treating T1 colorectal cancer (T1 CRC), which include endoscopic resection, endoscopic resection followed by additional colorectal resection, and surgical resection. In this retrospective study, changes in the management of T1 CRC after introduction of endoscopic submucosal dissection (ESD) were investigated by comparison with the 10-year period before introduction of ESD. MATERIAL AND METHODS During a 20-year period from 1996 to 2015, 835 patients with T1 CRC were treated, including 331 patients before introduction of ESD (Group A) and 504 patients after introduction of ESD (Group B). Clinicopathological findings and treatment methods were compared between these 2 groups. RESULTS As the initial treatment, endoscopic treatment was performed in 185 patients (55.9%) in Group A and 288 (57.1%) in Group B. In Group B, ESD was performed in 161 patients (55.9%), accounting for more than half of the T1 CRC patients receiving endoscopic treatment. In Groups A and B, observation after endoscopic resection was selected for 54.2% and 67.3% of T1a patients, respectively (p=0.04). A similar trend was noted for T1b patients, and there was no significant difference of the treatment approach. Among all T1 CRC patients, the percentage undergoing observation after endoscopic resection was significantly higher in Group B than in Group A (34.3% vs. 26.9%, p=0.02), and the percentage of patients undergoing additional colorectal resection was significantly lower in Group B (22.8% vs. 29.0%, p=0.04). CONCLUSIONS After introduction of ESD, it was performed in more than half of all patients with T1 CRC undergoing endoscopic treatment. The percentage of patients undergoing observation following endoscopic resection of T1 CRC increased after introduction of ESD.

[A Study of Treatment for Pathological T1(SM)Colorectal Cancer Patients after Endoscopic Resection at Our Department].

Approximately 10% of pathological T1(SM)colorectal cancer patients develop lymph node metastases. Therefore additional colectomy with lymph node dissection is recommended when it applies to the specific criteria in the current JSCCR guidelines. However, additional colectomy would not be done in some cases, because surgery is too invasive for some patients. Endoscopic treatment(ESD or EMR)for T1(SM)cancer was performed in 324 cases between 2008 and 2016. Of those, 231 cases had satisfied the criteria for additional colectomy. Among them, 74 cases(32.0%)did not undergo, and additional colectomy(+)groupwas 153 cases(66.2%). Between the 2 groups, no difference in prognosis could be found. We considered there was no difference, because the prognosis of SM cancer is relatively good. In consideration of patient background, the treatment policy has to be chosen according to feasibility.

[A Case of Pelvic Metastasis of Rectal Cancer That Developed Ten Years after Curative Resection].

We report a case of pelvic metastasis of rectal cancer that developed 10 years after curative resection. An 81-year-old woman underwent intersphincteric resection for lower rectal cancer 10 years previously. The tumor was pathologically diagnosed as T2N0M0, Stage Ⅰ. Nine years after the curative resection, serum carcinoembryonic antigen(CEA)levels were slightly elevated, but no recurrence was found on computed tomography(CT). Eleven months after CT, serum CEA levels elevated to 15.9 ng/mL. Pelvic metastasis in the piriformis muscle was detected on positron emission tomography(PET)-CT. Following CT-guided biopsy, she was pathologically diagnosed with metastatic rectal cancer. Radiotherapy (60 Gy/30 Fractions) was administered. Ten months after radiotherapy, PET-CT revealed no relapse in the pelvis with lung metastases.

Repeated laparoscopic resection of extra-regional lymph node metastasis after laparoscopic radical resection for rectal cancer.

Here, we report a case of repeated laparoscopic resection of extra-regional lymph node metastases in a patient after laparoscopic surgery for rectal cancer. A 72-year-old woman was diagnosed with upper rectal cancer and underwent laparoscopic low anterior resection and D3 dissection. The pathological stage was considered as T3, N2b, M0, Stage IIIC. Six months after the operation, positron emission tomography-computed tomography (PET-CT) showed fluorodeoxyglucose (FDG) accumulation in the infra-renal para-aortic lymph nodes (PALNs). Systemic chemotherapy was administered; however, chemotherapy was discontinued due to hemoptysis related to her pulmonary disease. Therefore, we performed laparoscopic PALN resection. Pathologically, one lymph node was diagnosed with a metastasis. Three months after the second operation, PET-CT identified FDG accumulation in the left lateral pelvic lymph nodes (LPLNs) and a PALN. Laparoscopic LPLN dissection and PALN resection through minilaparotomy were performed. Pathologically, lymph node metastases were diagnosed in both fields. Sixteen months after the 3rd operation, there is no recurrence.

A case of total laparoscopic sigmoidectomy involving the use of needle forceps and transanal specimen extraction for sigmoid colon cancer.

A 76-year-old male underwent endoscopic mucosal resection for a stage T1 tumour of the sigmoid colon. We performed laparoscopic sigmoidectomy through 5 ports using needlescopic instruments. The resected specimen was extracted from the abdominal cavity transanally. After attaching an anvil to the sigmoidal stump, the rectal stump was reclosed using an endoscopic linear stapler, and then, colorectal anastomosis was conducted using the double stapling technique. Performing transanal specimen extraction using needlescopic forceps improves aesthetic outcomes and reduces post-operative pain and the risk of abdominal incisional hernias. This method is an easy to introduce a form of reduced-port surgery because of its feasibility and conventional port arrangement. Hence, we consider that it is an option for minimally invasive surgery.

Development of Amylose- and ß-Cyclodextrin-Based Chiral Fluorescent Sensors Bearing Terthienyl Pendants.

Phenylcarbamate derivatives of amylose and ß-cyclodextrin show excellent chiral recognition when used as chiral stationary phases (CSPs) for high-performance liquid chromatography. To open up new possibilities of carbohydrate-based materials, we developed chiral fluorescent sensors based on amylose and ß-cyclodextrin (Am-1b and CyD-1b, respectively) by attaching fluorescent π-conjugated units on their side chains. Their recognition abilities toward chiral analytes containing a nitrophenyl unit were evaluated by measuring the enantioselective fluorescence quenching behavior. Both sensors showed the same degree of enantioselective fluorescence response for various aromatic nitro compounds. However, in some cases, their enantioselectivities were different depending on the analytes. The difference in the chiral recognition abilities between Am-1b and CyD-1b seems to be based on the structural difference of their inherent backbones, that is, the one-handed helical structure and cyclic structure, respectively. The study on the resolution ability of the Am-1b-based CSP revealed that the terthienyl-based pendant of Am-1b provides not only a fluorescent functionality but also a different chiral recognition site from that of amylose tris(phenylcarbamate).

[A case of cecum colon cancer with lymph node metastasis successfully treated with XELOX plus bevacizumab].

A 65-year-old woman with a history of constipation presented at our hospital and was subsequently diagnosed with advanced cecum cancer. We performed laparoscopic right hemicolectomy in January 2009, with pathological findings reveal- ing the presence of Stage III b (pT3, pN3, cM0, Cur A) disease. The patient was treated with a uracil/tegafur plus Leucovorin (UFT/LV) adjuvant chemotherapy regimen for six months. In June 2010, bold examination indicated an elevated level of tumor marker CA19-9. Computed tomography (CT) and positron emission tomography (PET)/CT revealed Virchow's and para-aortic lymph node metastasis. Therapy with XELOX and bevacizumab (Bmab) was administered and continued for 10 cycles. Capecitabine+Bmab treatment was also administered for 11 courses due to an adverse event of peripheral neuropathy. Follow-up revealed both the Virchow's and para-aortic lymph node metastasis had disappeared upon completion of treatment. In November, 2011 the patient was considered to have achieved a clinical complete response (CR) and continues to be followed with no further disease progression.

Laparoscopic intersphincteric resection using needlescopic instruments.

Intersphincteric resection (ISR) is a procedure designed to preserve anal function in cases with very low rectal cancer. We report our clinical experience with laparoscopic ISR (Lap ISR) performed using needlescopic instruments. First, a camera port is created at the umbilicus. Two 5-mm ports are then inserted at the right upper and lower quadrants. Two needlescopic forceps (Endo-Relief(™) Hope Denshi Co., Chiba, Japan) are inserted at the left upper and lower quadrants. We then perform the following procedures; ligation of the inferior mesenteric artery and vein, total mesorectal excision and dissection of the intersphincteric space. After the transanal intersphincteric dissection, the specimen is extracted through the anus and a hand -sewn coloanal anastomosis is performed. The covering ileostomy is finally created at the right upper port. We performed Lap ISR using needlescopic forceps in two patients with very low rectal cancer. In both cases, we were able to perform this procedure without insertion of an additional port or to change the needlescopic forceps to conventional 5-mm forceps. Lap ISR with needlescopic instruments is a feasible procedure for minimally invasive surgery.