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.

[A Case of Gastrointestinal Perforation in Gastric Cancer during Chemotherapy with Paclitaxel plus Ramucirumab].

A 54-year-old man underwent distal gastrectomy with D2 lymph node dissection in our institution in March 2017 due to the presence of advanced gastric cancer. The pathological diagnosis was signet ring, poorly differentiated, and moderate differentiated adenocarcinoma, which was pT4aN3aM0, pStage Ⅲc and HER2-negative. After surgery, he received adjuvant chemotherapy with S-1, however, he was diagnosed with dissemination and lymph node recurrence in June. Tumor marker, CEA level decreased after the introduction of the next treatment(capecitabine plus cisplatin), however the tumor marker level rose again in September, and the chemotherapy regimen was changed to weekly paclitaxel(PTX). Furthermore, ramucirumab was added to the weekly PTX regime in January 2018, as the tumor marker level rose again. One week after the last ramucirumab administration he visited our hospital with abdominal pain, and emergency surgery was performed after the diagnosis of a gastrointestinal perforation using CT. The surgery revealed dirty fluid and countless dissemination nodes throughout the abdominal cavity, and a small intestinal perforation on a white dissemination node was identified 70 cm proximal to the end of the ileum. We performed small bowel segmental resection and functional end-to-end anastomosis. No complications were observed, and an oral diet was able to be started after surgery; however, he was introduced to the best supportive care(BSC)as his general condition gradually deteriorated.

[Curative Resection of Locally Advanced Rectal Cancer with Synchronous Liver Metastasis after Long-Term Chemotherapy].

A 60s man was diagnosed with unresectable advanced rectal cancer with synchronous solitary liver metastasis. Chemotherapy was administered and the primary tumor shrank immediately. However, he still demonstrated dorsal extension; therefore, chemotherapy was continued for approximately 1 year. After long-term chemotherapy, the primary tumor was deemed to be resectable because the dorsal extension had decreased. We achieved curative resection by performing a primary tumor and liver resection and he has shown no recurrence without adjuvant chemotherapy. Although the primary tumor was initially diagnosed as unresectable, it is important to consider the potential for curative resection after long-term chemotherapy.

[Curative Resection of Locally Advanced Rectal Cancer with Para-Aortic Lymph Node Swelling after Long-Term Chemotherapy].

A 60s man was diagnosed as having unresectable advanced rectal cancer with swelling of the para-aortic lymph nodes. Chemotherapy was administered, and the primary tumor immediately shrank. He still had para-aortic lymph node swelling; therefore, chemotherapy was continued for approximately 2 years. After long-term chemotherapy, we diagnosed his tumor as resectable because the para-aortic lymph node swelling had shrunk. We achieved curative resection, and he has shown no recurrence without adjuvant chemotherapy. Although chemotherapy is the main treatment for unresectable advanced colorectalcancer, it is important to consider curative resection, as in this case with long-term chemotherapy.

Decreased Positive Fecal Occult Blood Tests and Delayed Medical Presentation for Colorectal Cancer during the Initial COVID-19 Pandemic Period: A Single-center Experience.

Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on the examination and treatment of colorectal cancer (CRC) and on the behaviors of patients and practitioners. Methods: This is a retrospective analysis of the CRC patients who presented to our department between April 2019 and March 2021 and underwent surgery. Clinical presentation of CRC and time from symptom onset to medical presentation were compared between the control (April 2019 to March 2020, n=124) and COVID-19 pandemic periods (April 2020 to March 2021, n=111). Results: Two hundred and thirty-five patients were reviewed. The rate of positive fecal occult blood tests was significantly lower during the COVID-19 pandemic period (13.5 vs. 25.0%, P = 0.027). Among the symptomatic patients who had melena and abdominal symptoms, the time from symptom onset to medical presentation was significantly longer during the COVID-19 period (115 vs. 31 days, P < 0.001). In addition, the interval between presenting to a practitioner and being referred to our department was similar between the two periods (19 vs. 13 days, P = 0.092). There were no significant differences in the stage of cancer between the two periods. The rate of preoperative sub-obstruction was significantly higher during the COVID-19 period (41.4 vs 23.4%, P = 0.003). There was no significant difference in overall survival and recurrence-free survival between two periods. Conclusions: Hesitation to seek examination and treatment for CRC was observed in patients but not in practitioners during the COVID-19 pandemic period. The prognosis did not change.

Liver metastases of a neuroendocrine tumor arising from a tailgut cyst treated with interventional locoregional therapies: a case report and review of the literature on recurrent cases.

A tailgut cyst is a rare, developmental cyst occurring in the presacral space. Although primarily benign, malignant transformation is a possible complication. Herein, we report a case of liver metastases after resection of a neuroendocrine tumor (NET) arising from a tailgut cyst. A 53-year-old woman underwent surgery for a presacral cystic lesion with nodules in the cyst wall. The tumor was diagnosed as a Grade 2 NET arising from a tailgut cyst. Thirty-eight months after surgery, multiple liver metastases were identified. The liver metastases were controlled with transcatheter arterial embolization and ablation therapy. The patient has survived for 51 months after the recurrence. Several NETs derived from tailgut cysts have been previously reported. According to our literature review, the proportion of Grade 2 tumors in NETs derived from tailgut cysts was 38.5%, and four of the 5 cases of Grade 2 NETs (80%) relapsed, while all eight cases of Grade 1 NETs did not relapse. Grade 2 NET may be a high-risk group for recurrence in NETs arising from tailgut cysts. The percentage of Grade 2 NETs in tailgut cysts was higher than that of rectal NETs, but lower than that of midgut NETs. To the best of our knowledge, this is the first case of liver metastases of a neuroendocrine tumor arising from a tailgut cyst that was treated with interventional locoregional therapies, and the first report to describe about the degree of malignancy of neuroendocrine tumors originating from tailgut cysts in terms of the percentage of Grade 2 NETs.

Spontaneous colonic perforation with collagenous colitis in an elderly patient.

Collagenous colitis (CC) is a variant of microscopic colitis that causes chronic, non-bloody, and watery diarrhea. The natural history of CC is generally benign and serious complications are rare. Perforation, especially spontaneous perforation, is a particularly rare complication. A 90-year-old woman presented with acute abdominal pain. She was diagnosed with peritonitis due to colonic perforation, and partial colectomy was performed. Macroscopic findings showed well-circumscribed longitudinal ulcer, and a pathological examination revealed descending colon perforation with CC. She had no history of examination and the case was considered to be spontaneous. The postoperative course was uneventful and she had no recurrence of CC after changing from the suspected drug (lansoprazole) to an H2-blocker. The characteristics of perforation by CC are characteristic longitudinal ulcer and micro-perforation. If it can be diagnosed accurately, conservative treatment may be an option. In spontaneous cases, the history of medication and the site of perforation may assist in this decision.

A case of Cronkhite-Canada syndrome with repeated linked color imaging observation of the subepithelial capillary network in the colon.

Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic gastrointestinal polyposis and ectodermal changes. While corticosteroids are considered effective, some cases are refractory. A 48-year-old woman presented with diarrhea, anorexia, and epigastralgia lasting for 3 months. She suffered from alopecia and nail dystrophy. Gastrointestinal endoscopy with histological examination confirmed non-neoplastic polyposis from the stomach to the rectum, confirming the diagnosis of CCS. Linked color imaging (LCI) with magnified endoscopy revealed a ribbon-like proliferation of capillaries surrounding the pits in the colonic mucosa. Histologically, the polyps had dilated glands, edematous stroma with inflammatory cell infiltrates and increased capillaries just beneath the epithelium. Immunohistochemical examination confirmed the expression of vascular endothelial growth factor (VEGF), mainly in the superficial epithelial and crypt cells. Steroid therapy was ineffective, and concomitant infliximab therapy provided symptomatic relief. Although symptoms rapidly improved with combination therapy, capillary hyperplasia and slight inflammation persisted in the colon mucosa after polyp resolution. Withdrawal of steroid treatment resulted in flare-ups of symptoms and polyps. Repeated magnified observations at LCI during post-relapse retreatment clearly captured the resolution process of both neovascularization and inflammation. Once the capillary hyperplasia and inflammation subsided, the steroid could be tapered off without relapse. To our knowledge, this is the first report describing the involvement of VEGF-induced angiogenesis and LCI findings in CCS; LCI observations are useful not only in the active phase of CCS, but also in determining subtle capillary hyperplasia and residual inflammation in remission, which may be an indicator of continued treatment.

The Prognosis and Recurrence Pattern of Right- and Left-Sided Colon Cancer in Stage II, Stage III, and Liver Metastasis After Curative Resection.

PURPOSE: Primary tumor location of colon cancer has been reported to affect the prognosis after curative resection. However, some reports suggested the impact was varied by tumor stage. This study analyzed the prognostic impact of the sidedness of colon cancer in stages II, III, and liver metastasis after curative resection using propensity-matched analysis. METHODS: Right-sided colon cancer was defined as a tumor located from cecum to splenic flexure, while any more distal colon cancer was defined as left-sided colon cancer. Patients who underwent curative resection at Nara Medical University hospital between 2000 and 2016 were analyzed. RESULTS: There were 110 patients with stage II, 100 patients with stage III, and 106 patients with liver metastasis. After propensity matching, 28 pairs with stage II and 32 pairs with stage III were identified. In the patients with stage II, overall survival (OS) and recurrence-free survival (RFS) were not significantly different for right- and left-sided colon cancers. In the patients with stage III, OS and RFS were significantly worse in right-sided colon cancer. In those with liver metastasis, OS of right-sided colon cancer was significantly worse than left-sided disease, while RFS was similar. Regarding metachronous liver metastasis, the difference was observed only in the patients whose primary colon cancer was stage III. In each stage, significantly higher rate of peritoneal recurrence was found in those with right-sided colon cancer. CONCLUSION: Sidedness of colon cancer had a significant and varied prognostic impact in patients with stage II, III, and liver metastasis after curative resection.

Long-Term Survival After Pelvic Exenteration for Locally Recurrent Rectal Cancer Associated With Crohn's Disease With, Adjuvant Chemotherapy, and Immunosuppressive Therapy.

Crohn's disease (CD) is associated with an increased risk of developing colorectal cancer. In particular, cases in which long-term survival is achieved by patients with local recurrence of CD-associated rectal cancer are rare. We report a case in which curative resection was achieved for a 47-year-old man with long-standing CD and locally recurrent rectal cancer. In this case, the patient obtained a long-term survival without recurrence after surgical resection with adjuvant chemotherapy and immunosuppressive therapy. In the management of inflammatory bowel disease patients with cancer, the management of both cancer and inflammatory bowel disease treatment is important for the long-term prognosis.

Spontaneous pneumoperitoneum with duodenal diverticulosis in an elderly patient: a case report.

BACKGROUND: Pneumoperitoneum commonly occurs as a result of a viscus perforation and usually presents with peritoneal signs requiring emergent laparotomy. Spontaneous pneumoperitoneum is a rare condition characterized by intraperitoneal gas with no clear etiology. CASE PRESENTATION: We herein report a case in which conservative treatment was achieved for an 83-year-old male patient with spontaneous pneumoperitoneum that probably occurred due to duodenal diverticulosis. He had stable vital signs and slight epigastric discomfort without any other signs of peritonitis. A chest radiograph and computed tomography showed that a large amount of free gas extended into the upper abdominal cavity. Esophagogastroduodenoscopy showed duodenal diverticulosis but no perforation of the upper gastrointestinal tract. He was diagnosed with spontaneous pneumoperitoneum, and conservative treatment was selected. His medical course was uneventful, and pneumoperitoneum disappeared after 6 months. CONCLUSION: In the management of spontaneous pneumoperitoneum, recognition of this rare condition and an accurate diagnosis based on symptoms and clinical imaging might contribute to reducing the performance of unnecessary laparotomy. However, in uncertain cases with peritoneal signs, spontaneous pneumoperitoneum is difficult to differentiate from free air resulting from gastrointestinal perforation and emergency exploratory laparotomy should be considered for these patients.

Laparoscopic Percutaneous Endoscopic Gastrostomy Is Useful for Elderly.

BACKGROUND: In recent years, enteral nutrition has become relatively easy to perform through the penetration of percutaneous endoscopic gastrostomy (PEG). However, there have been reports of complications, such as mispuncture of other organs at the time of performing PEG. Previously, we had constructed a gastrostomy under the laparotomy for difficult PEG cases, and 2 years ago, we introduced laparoscopically assisted PEG. This study aimed to clarify the feasibility and safety of LAPEG for elderly people over 65 years old. METHODS: We evaluated the perioperative outcomes in 7 elderly patients who underwent LAPEG during these 2 years. In these subjects, the safety of LAPEG was evaluated retrospectively based on the surgical outcomes, perioperative complications, and postoperative course using the clinical archives. RESULTS: The subjects' mean age was 81.1 ± 8.03 years. LAPEG was successful in all 7 patients. The median operation time was 38 minutes (range, 31-71 minutes). Intraoperative and postoperative early or late complications from LAPEG were not observed in our cases. Enteral nutrition was commenced 2 days after PEG placement in all cases without complications. CONCLUSION: We summarized the LAPEG cases performed at our institution for the elderly, and have reported its feasibility and safety. The strongest advantage of LAPEG was that it allowed placement of the PEG without any complication under direct observation of the intraperitoneal cavity to confirm the safety of each organ.