The effect of staple height and rectal-wall thickness on anastomotic leakage after laparoscopic low anterior resection.

BACKGROUND: The aim of this study was to evaluate the effect of staple height and rectal wall thickness on the development of an anastomotic leak after laparoscopic low anterior resection performed with the double stapling technique. METHODS: One hundred ninety-nine patients treated from 2013 to 2021 were enrolled. Patients were divided into two groups: those who developed an anastomotic leak (AL (+)) and those who did not (AL (-)). Clinicopathological factors were compared between the groups. RESULTS: Anastomotic leaks were observed in 8/199 patients (4%). A 1.5 mm linear stapler was used for 35/199 patients (17%), 1.8 mm for 89 (45%), and 2 mm for 75 (38%). In the AL (+) group (n = 8), lower staple height (1.5 mm or 1.8 mm) was used more frequently than in the AL (-) group (n = 191). Rectal wall thickness and the rectal wall thickness to staple height ratio was significantly (p < .05) greater in the AL (+) group. However, rectal wall thickness was significantly (p < .05) greater in patients who received neoadjuvant treatment and those with advanced T stage (T3,4) lesions. CONCLUSION: Linear stapler staple height and rectal wall thickness are significantly associated with the development of an anastomotic leak after laparoscopic low anterior resection. Larger staples should be selected in patients with a thicker rectal wall due to neoadjuvant treatment or adjacent advanced rectal tumors.

Metachronous Krukenberg tumor from adenocarcinoma in a Meckel's diverticulum: a case report.

Adenocarcinoma in a Meckel's diverticulum is rare and difficult to diagnose preoperatively. We report the first case of a metachronous Krukenberg tumor from adenocarcinoma in a Meckel's diverticulum. A 45-year-old woman was admitted for recurrent abdominal pain. Computed tomography scan showed a lesion with contrast enhancement, and a Meckel's diverticulum-associated tumor was suspected. Double-ballon enteroscopy revealed intestinal stenosis and biopsy showed adenocarcinoma. Operative findings showed a Meckel's diverticulum with tumor. Histopathological evaluation revealed well-differentiated adenocarcinoma, interrupted by ectopic gastric mucosa, diagnosed as adenocarcinoma in a Meckel's diverticulum. Two years postoperatively, a multi-cystic mass with contrast enhancement was observed in the pelvis on imaging evaluation and oophorectomy performed. Histological examination of the resected ovary showed proliferation of atypical glandular ducts, consistent with metastatic adenocarcinoma. This case demonstrates that adenocarcinoma in a Meckel's diverticulum may result in distant metastases and requires appropriate follow-up.

Delayed mesh infection after inguinal hernia repair: a case report.

Delayed deep mesh infection is a rare complication and the precise mechanism of its development is unknown. We report a case of delayed deep mesh infection after inguinal hernia repair. A 65-year-old man was admitted for treatment of colon cancer. He had a history of bilateral hernioplasty repaired with mesh-plugs 6 years previously. Fluorine-18 fluorodeoxyglucose positron emission tomographic scan showed positive findings in the right inguinal region similar to cancer. He had no complaints or findings to suspect mesh infection. Postoperative computed tomography scan over time revealed a fluid collection with inflammation. Eleven years after hernia repair, the patient presented with inflammation in the right inguinal region and emergency operation was performed. An abscess cavity was found and the mesh-plug covered with granulation tissue was removed. The patient remains free of recurrence of inguinal hernia or inflammatory changes after 3 years of follow-up.

The inflammatory role of dysregulated IRS2 in pulmonary vascular remodeling under hypoxic conditions.

Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown previously that insulin receptor substrate 2 (IRS2), a molecule highly critical to insulin resistance and metabolism, has an anti-inflammatory role in Th2-skewed lung inflammation and pulmonary vascular remodeling. Here, we investigated the hypothesis that IRS2 has an immunomodulatory role in human and experimental PH. Expression analysis showed that IRS2 was significantly decreased in the pulmonary vasculature of patients with pulmonary arterial hypertension and in rat models of PH. In mice, genetic ablation of IRS2 enhanced the hypoxia-induced signaling pathway of Akt and Forkhead box O1 (FOXO1) in the lung tissue and increased pulmonary vascular muscularization, proliferation, and perivascular macrophage recruitment. Furthermore, mice with homozygous IRS2 gene deletion showed a significant gene dosage-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy in response to hypoxia. Functional studies with bone marrow-derived macrophages isolated from homozygous IRS2 gene-deleted mice showed that hypoxia exposure led to enhancement of the Akt and ERK signaling pathway followed by increases in the pro-PH macrophage activation markers, vascular endothelial growth factor-A and arginase 1. Our data suggest that IRS2 contributes to anti-inflammatory effects by regulating macrophage activation and recruitment, which may limit the vascular inflammation, remodeling, and right ventricular hypertrophy that are seen in PH pathology. Restoring the IRS2 pathway may be an effective therapeutic approach for the treatment of PH and right heart failure.

NLRP3 Inflammasome Activation in Lung Vascular Endothelial Cells Contributes to Intestinal Ischemia/Reperfusion-Induced Acute Lung Injury.

Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. The NLRP3 inflammasome regulates the caspase-1-dependent release of IL-1ß, an early mediator of inflammation after I/R injury. In this study, we investigated the role of the NLRP3 inflammasome in mice with intestinal I/R injury. Deficiency of NLRP3, ASC, caspase-1/11, or IL-1ß prolonged survival after intestinal I/R injury, but neither NLRP3 nor caspase-1/11 deficiency affected intestinal inflammation. Intestinal I/R injury caused acute lung injury (ALI) characterized by inflammation, reactive oxygen species generation, and vascular permeability, which was markedly improved by NLRP3 deficiency. Bone marrow chimeric experiments showed that NLRP3 in non-bone marrow-derived cells was the main contributor to development of intestinal I/R-induced ALI. The NLRP3 inflammasome in lung vascular endothelial cells is thought to be important to lung vascular permeability. Using mass spectrometry, we identified intestinal I/R-derived lipid mediators that enhanced NLRP3 inflammasome activation in lung vascular endothelial cells. Finally, we confirmed that serum levels of these lipid mediators were elevated in patients with intestinal ischemia. To our knowledge, these findings provide new insights into the mechanism underlying intestinal I/R-induced ALI and suggest that endothelial NLRP3 inflammasome-driven IL-1ß is a novel potential target for treating and preventing this disorder.

GSDME-Dependent Incomplete Pyroptosis Permits Selective IL-1α Release under Caspase-1 Inhibition.

Pyroptosis is a form of regulated cell death that is characterized by gasdermin processing and increased membrane permeability. Caspase-1 and caspase-11 have been considered to be essential for gasdermin D processing associated with inflammasome activation. In the present study, we found that NLRP3 inflammasome activation induces delayed necrotic cell death via ASC in caspase-1/11-deficient macrophages. Furthermore, ASC-mediated caspase-8 activation and subsequent gasdermin E processing are necessary for caspase-1-independent necrotic cell death. We define this necrotic cell death as incomplete pyroptosis because IL-1ß release, a key feature of pyroptosis, is absent, whereas IL-1α release is induced. Notably, unprocessed pro-IL-1ß forms a molecular complex to be retained inside pyroptotic cells. Moreover, incomplete pyroptosis accompanied by IL-1α release is observed under the pharmacological inhibition of caspase-1 with VX765. These findings suggest that caspase-1 inhibition during NLRP3 inflammasome activation modulates forms of cell death and permits the release of IL-1α from dying cells.

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis.

Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol. Fer-1 also inhibited hepatic I/R-induced inflammatory responses. Furthermore, hepatic I/R injury was attenuated by iron chelation by deferoxamine and exacerbated by iron overload with a high iron diet. These findings demonstrate that iron overload is a novel risk factor for hepatic I/R injury in LT, and ferroptosis contributes to the pathogenesis of hepatic I/R injury.

Role of TLR5 in inflammation and tissue damage after intestinal ischemia-reperfusion injury.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice. METHODS AND RESULTS: Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury. CONCLUSION: These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.

Crucial Role of NLRP3 Inflammasome in the Development of Peritoneal Dialysis-related Peritoneal Fibrosis.

Long-term peritoneal dialysis (PD) therapy leads to peritoneal inflammation and fibrosis. However, the mechanism underlying PD-related peritoneal inflammation and fibrosis remains unclear. NLRP3 inflammasome regulates the caspase-1-dependent release of interleukin-1ß and mediates inflammation in various diseases. Here, we investigated the role of NLRP3 inflammasome in a murine model of PD-related peritoneal fibrosis induced by methylglyoxal (MGO). Inflammasome-related proteins were upregulated in the peritoneum of MGO-treated mice. MGO induced parietal and visceral peritoneal fibrosis in wild-type mice, which was significantly reduced in mice deficient in NLRP3, ASC, and interleukin-1ß (IL-1ß). ASC deficiency reduced the expression of inflammatory cytokines and fibrotic factors, and the infiltration of macrophages. However, myeloid cell-specific ASC deficiency failed to inhibit MGO-induced peritoneal fibrosis. MGO caused hemorrhagic ascites, fibrin deposition, and plasminogen activator inhibitor-1 upregulation, but all of these manifestations were inhibited by ASC deficiency. Furthermore, in vitro experiments showed that MGO induced cell death via the generation of reactive oxygen species in vascular endothelial cells, which was inhibited by ASC deficiency. Our results showed that endothelial NLRP3 inflammasome contributes to PD-related peritoneal inflammation and fibrosis, and provide new insights into the mechanisms underlying the pathogenesis of this disorder.

Four-directional approach to the meso-transverse attachment combined with preoperative radiological vascular simulation facilitates short-term surgical outcomes in laparoscopic transverse colon cancer surgery.

INTRODUCTION: Transverse colon resection is one of the most difficult laparoscopic procedures because of anatomic hazards such as variations in the mesenteric vascular anatomy and the complex structure of organs and surrounding membranes. METHODS: We evaluated the short-term surgical outcomes of laparoscopic transverse colon resection using a creative approach. This approach included preoperative surgical simulation using virtual surgical anatomy by CT, a four-directional approach to the mesentery, and 3-D imaging during laparoscopic surgery. RESULTS: A total of 45 consecutive patients who underwent laparoscopic resection for transverse colon cancer from June 2013 to December 2017 were enrolled in this study. All procedures were completed safely, with minor postoperative complications, including two patients with anastomotic stenosis, two with intra-abdominal phlegmon, one with delayed gastric emptying, and one with pneumonia, all treated non-operatively. There were no conversions to open resection. Operation time was 203 min (range, 125-322 min), and the estimated blood loss during surgery was 5 mL (range, 0-370 mL). The mean postoperative hospital stay was 10 days (range, 7-21 days), and no patients required readmission. CONCLUSION: Short-term surgical outcomes after laparoscopic transverse colon resection demonstrated that this creative approach was safe and feasible. The four-directional approach to the meso-transverse attachment combined with preoperative radiological simulation can facilitate laparoscopic transverse colon surgery.

Utility of preoperative 3-D simulation of laparoscopic lateral pelvic lymph node dissection for advanced rectal cancer: Surgical outcomes of 10 initial cases.

INTRODUCTION: Laparoscopic lateral pelvic lymph node dissection (LPLD) is technically challenging because of the complicated anatomy of the pelvic wall. To overcome this difficulty, we introduced preoperative 3-D simulation. The aim of the study is to investigate the usefulness of preoperative 3-D simulation for the safe conduct of laparoscopic LPLD for rectal cancer. METHODS: After undergoing colonoscopy, patients were brought to the radiology suite where multi-detector row CT was performed. Three-dimensional images were constructed at a workstation and showed branches of the iliac artery and vein, ureter, urinary bladder, and enlarged lymph nodes. All members of the surgical team participated in preoperative simulation using the 3-D images. RESULTS: A total of 10 patients with advanced lower rectal cancer and enlarged lateral pelvic lymph nodes underwent laparoscopic unilateral LPLD after total mesorectal excision, tumor-specific mesorectal excision, or total proctocolectomy. Four of the 10 patients (40%) had variations in pelvic vascular anatomy. The median operative time for unilateral LPLD was 91 min (range, 66-142 min) and gradually declined, suggesting a good learning curve. The median number of lateral pelvic lymph nodes harvested was nine (range, 3-16). The median estimated blood loss was 13 mL (range, 10-160 mL). No conversion to open surgery or intraoperative complications occurred. No patient had major postoperative complications. CONCLUSION: Preoperative 3-D simulation may be useful for the safe conduct of laparoscopic LPLD, especially for surgeons with limited prior experience.

Metachronous solitary metacarpal bone metastasis from rectal cancer.

Metachronous solitary metacarpal bone metastasis from rectal cancer has not been reported previously. Here, we describe a 54-year-old woman who underwent abdominoperineal resection for rectal cancer following neoadjuvant chemoradiotherapy. The resected specimen contained adenocarcinoma with no lymph node metastases (Stage II, T3N0M0); no adjuvant chemotherapy was administered. Fifteen months after surgery, the patient presented with pain and swelling of the right thumb. Radiography revealed metacarpal bone destruction, and fluorine-18 fluorodeoxyglucose positron emission tomography showed uptake only in the metacarpal bone. Open biopsy revealed an adenocarcinoma, and a right thumb resection was performed. Histological examination indicated features of adenocarcinoma similar to the findings of a rectal lesion, leading to a diagnosis of metachronous solitary metacarpal bone metastasis from rectal cancer. The patient remains free of disease after 6 years of follow-up. Our findings suggest that surgical resection may lead to favorable outcomes in patients with resectable solitary bone metastases.

Interaction of Neutrophils with Macrophages Promotes IL-1ß Maturation and Contributes to Hepatic Ischemia-Reperfusion Injury.

Accumulating evidence suggests that IL-1ß plays a pivotal role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury; however, the mechanism by which I/R triggers IL-1ß production in the liver remains unclear. Recent data have shown that neutrophils contribute to hepatic I/R injury independently of the inflammasomes regulating IL-1ß maturation. Thus, we investigated the role of neutrophils in IL-1ß maturation and tissue injury in a murine model of hepatic I/R. IL-1ß was released from the I/R liver and its deficiency reduced reactive oxygen species generation, apoptosis, and inflammatory responses, such as inflammatory cell infiltration and cytokine expression, thereby resulting in reduced tissue injury. Depletion of either macrophages or neutrophils also attenuated IL-1ß release and hepatic I/R injury. In vitro experiments revealed that neutrophil-derived proteinases process pro-IL-1ß derived from macrophages into its mature form independently of caspase-1. Furthermore, pharmacological inhibition of serine proteases attenuated IL-1ß release and hepatic I/R injury in vivo. Taken together, the interaction between neutrophils and macrophages promotes IL-1ß maturation and causes IL-1ß-driven inflammation in the I/R liver. Both neutrophils and macrophages are indispensable in this process. These findings suggest that neutrophil-macrophage interaction is a therapeutic target for hepatic I/R injury and may also provide new insights into the inflammasome-independent mechanism of IL-1ß maturation in the liver.

Synchronous metastatic squamous cell carcinoma to the colon and cervical lymph nodes from a carcinoma of unknown primary site: A case report.

Metastatic squamous cell carcinoma (SCC) from an unknown primary site to the colon has not been reported previously. A 75-year-old woman presented with a mass in the left submandibular region. Biopsy revealed a Class V lesion, but the histologic type was undetermined. Surgical resection of the left submandibular gland with cervical lymph node dissection was performed. However, SCC was seen in the lymph nodes only, with no tumor in the submandibular gland. Three months after surgery, computed tomography revealed that the preoperatively diagnosed lesion in the transverse colon had grown considerably. A laparoscopic right hemicolectomy was performed. Histological examination showed features of SCC, similar to the findings in the cervical lymph nodes. We report a rare case of synchronous metastatic SCC to the colon and cervical lymph nodes from a carcinoma of unknown primary site.

Diagnosis of a submucosal mass at the staple line after sigmoid colon cancer resection by endoscopic cutting-mucosa biopsy.

A 48-year-old man underwent laparoscopic sigmoid colon resection for cancer and surveillance colonoscopy was performed annually thereafter. Five years after the resection, a submucosal mass was found at the anastomotic staple line, 15 cm from the anal verge. Computed tomography scan and endoscopic ultrasound were not consistent with tumor recurrence. Endoscopic mucosa biopsy was performed to obtain a definitive diagnosis. Mucosal incision over the lesion with the cutting needle knife technique revealed a creamy white material, which was completely removed. Histologic examination showed fibrotic tissue without caseous necrosis or tumor cells. No bacteria, including mycobacterium, were found on culture. The patient remains free of recurrence at five years since the resection. Endoscopic biopsy with a cutting mucosal incision is an important technique for evaluation of submucosal lesions after rectal resection.

Endocrine cell carcinomas of the colon and rectum: a clinicopathological evaluation.

PURPOSE: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. METHODS: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. RESULTS: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. CONCLUSION: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.

Reduction in the size of enlarged pelvic lymph nodes after chemoradiation therapy is associated with fewer lymph node metastases in locally advanced rectal carcinoma.

PURPOSE: We hypothesized that a reduction in the size of the lymph nodes after neoadjuvant therapy for locally advanced rectal carcinoma would be associated with decreased lymph node metastases and/or a better prognosis. METHODS: Between March 2006 and April 2012, 71 patients with primary rectal cancer received neoadjuvant chemoradiation therapy (CRT). For all lymph nodes 5 mm or larger in size, the major and minor axes were measured on CT scan images, and the product was calculated. The lymph node size was determined before and after CRT. The patients were divided into three groups based on the lymph node size before and after treatment. Group A exhibited a reduction in size of 60% or more, Group B a reduction of less than 60% and Group C had no lymph node enlargement before treatment. RESULTS: The incidence of lymph node metastases on pathological examination was 15% in Group A and 50% in Group B (p = 0.006). The five-year disease-free survival in Group A was 84% compared with 78% in Group B (log rank p = 0.34). The five-year overall survival in Group A was 92% compared with 74% in Group B (log rank p = 0.088). CONCLUSIONS: A reduction in the size of enlarged lymph nodes after neoadjuvant therapy may be a useful prognostic factor for recurrence and survival.

Extensive bowel necrosis related to bevacizumab in metastatic rectal cancer patient: a case report and review of literature.

Recently, bevacizumab has become a key drug for treatment of metastatic colorectal cancer. Molecularly targeted agents such as bevacizumab can cause life-threatening adverse effects, though they are generally considered less toxic than cytotoxic drugs. Here, we review the case of a 76-year-old male rectal cancer patient with liver metastasis who suffered extensive bowel necrosis after administration of 5-fluorouracil-based chemotherapy with bevacizumab, and required a subtotal colectomy and end-ileostomy. Microscopic findings revealed extensive mucosal necrosis in the resected colon specimen and necrosis at the muscularis propria of the descending colon. Pathological findings suggested that the mucosal damage induced by chemotherapy may be exacerbated by treatment with bevacizumab, resulting in extensive necrosis.

Ileosigmoid knot at week 13 of pregnancy: report of a case.

The ileosigmoid knot (ISK) is a rare cause of intestinal obstruction. ISK is a condition in which the ileum wraps around the base of the sigmoid colon and forms a knot, leading to high mortality with rapid progression to bowel gangrene. We herein report a rare case of ISK at week 13 of pregnancy. The ISK was diagnosed by computed tomography, and the patient underwent emergency surgery for acute abdomen. Laparotomy showed segmental gangrenous change in the sigmoid colon, which was twisted around the distal ileal loop. The gangrenous bowel was resected, and primary anastomosis was performed. To our knowledge, the present case involves the first and earliest pregnancy in which a preoperative diagnosis of ISK was made and successful treatment was performed with surgery. A radiologic approach should be undertaken for prompt diagnosis and optimal management, even in early pregnancy.

Prolapse of the small intestine from the uterine perforation at dilatation and curettage.

Dilatation and curettage (D&C) sometimes causes uterine perforation, which usually does not cause a serious problem. Here, we report uterine perforation caused by D&C, in which the small intestine prolapsed from the uterus, requiring intestinal resection. D&C was performed for missed abortion at 9 weeks. After dilating the cervix, forceps grasped tissue that, upon being pulled, resulted in the intestine being prolapsed into the vagina. Laparotomy revealed a perforation at the low anterior uterine wall, through which the ileum had prolapsed. The mesentery of the prolapsed ileum was completely detached and the ileum was necrotic, which was resected. The uterus and the intestine were reconstructed. Although intestinal prolapse is considered to be caused by "unsafe" D&C performed by inexperienced persons or even by nonphysicians in developing countries, this occurred in a tertiary center of a developed country. We must be aware that adverse events such as uterine perforation with intestinal prolapse can occur even during routine D&C.