A case report of a gastrobronchial fistula and lung abscess caused by leakage from the staple line of a gastric tube after esophagectomy for esophageal cancer.

BACKGROUND: Gastrobronchial fistulas are rare, but life-threatening, complications of esophagectomy. They are caused by anastomotic leakage and mainly occur around anastomotic sites. In the present paper, we report a rare case of leakage from the staple line of a gastric tube after esophagectomy for esophageal cancer, which was successfully treated using an intercostal muscle flap and lung resection. CASE PRESENTATION: A 61-year-old male underwent subtotal esophagectomy with regional lymphadenectomy for esophageal cancer. The sutures along the staple line of the gastric tube failed 11 days after surgery, and a pulmonary abscess was also found on imaging. The abscess did not heal after conservative treatment; therefore, right lower lobectomy, gastrobronchial fistula resection, primary closure, and patching of the leaking portion of the gastric tube with an intercostal muscle flap were performed 9 months after the first operation. The patient's postoperative course was uneventful, and he was discharged on the 354th day. CONCLUSIONS: We experienced a case involving a gastrobronchial fistula caused by leakage from the staple line of a gastric tube and successfully treated it by performing right lower lobectomy and patching the leak with an intercostal muscle flap.

Does anastomotic leakage after rectal cancer resection worsen long-term oncologic outcome?

PURPOSE: The influence of anastomotic leakage on long-term survival in patients with rectal cancer is debatable. The aim of this study was to evaluate relationships between anastomotic leakage and long-term survival. METHODS: In this multicenter retrospective cohort study, 395 consecutive stage I to III rectal cancer patients underwent anterior resection between 2007 and 2012. Five-year overall survival, 5-year disease-free survival, and 5-year local recurrence-free survival were compared between patients with leakage (Leakage (+)) and patients without leakage (Leakage (-)). RESULTS: Of 395 patients, 50 (12.7%) had anastomotic leakage. Of these 50, 34 (68.0%) required urgent surgery and 16 (32.0%) could be managed by watchful waiting or with percutaneous drainage. The median follow-up period was 62.6 months. Five-year overall survival did not differ between the two groups (Leakage (+) 93.8% vs. Leakage (-) 89.0%, P = 0.121). Five-year disease-free survival also did not differ between the two groups (81.6% vs. 80.3%, P = 0.731), and neither did 5-year local recurrence-free survival (91.9% vs. 86.1%, P = 0.206). In a multivariable Cox regression model, BMI > 25, preoperative CA19-9 > 37, pathological T stage, pathological N stage, and circumferential resection margin (CRM) positive were independent predictors of disease-free survival. Moreover, pathological T stage, pathological N stage, and CRM positive were the only independent predictors of overall survival and local recurrence-free survival. Anastomotic leakage was not a risk factor for overall survival, disease-free survival, or local recurrence-free survival. CONCLUSION: Anastomotic leakage is not associated with a significant decrease in long-term survival in rectal cancer patients.

Non-placement versus placement of a drainage tube around the cervical anastomosis in McKeown esophagectomy: study protocol for a randomized controlled trial.

BACKGROUND: Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal cancer. Currently, transthoracic and abdominal esophagectomy with cervical anastomosis (McKeown esophagectomy) is a frequently used technique in Japan. However, cervical anastomosis is still an invasive procedure with a high incidence of anastomotic leakage. The use of a drainage tube to treat anastomotic leakage is effective, but the routine placement of a closed suction drain around the anastomosis at the end of the operation remains controversial. The objective of this study is to evaluate the postoperative anastomotic leakage rate, duration to oral intake, hospital stay, and analgesic use with nonplacement of a cervical drainage tube as an alternative to placement of a cervical drainage tube. METHODS: This is an investigator-initiated, investigator-driven, open-label, randomized controlled parallel-group, noninferiority trial. All adult patients (aged ≥20 and ≤85 years) with histologically proven, surgically resectable (cT1-3 N0-3 M0) squamous cell carcinoma, adenosquamous cell carcinoma, or basaloid squamous cell carcinoma of the intrathoracic esophagus, and European Clinical Oncology Group performance status 0, 1, or 2 are assessed for eligibility. Patients (n = 110) with resectable esophageal cancer who provide informed consent in the outpatient clinic are randomized to either nonplacement of a cervical drainage tube (n = 55) or placement of a cervical drainage tube (n = 55). The primary outcome is the percentage of Clavien-Dindo grade 2 or higher anastomotic leakage. DISCUSSION: This is the first randomized controlled trial comparing nonplacement versus placement of a cervical drainage tube during McKeown esophagectomy with regards to the usefulness of a drain for anastomotic leakage. If our hypothesis is correct, nonplacement of a cervical drainage tube will be recommended because it is associated with a similar anastomotic leakage rate but less pain than placement of a cervical drainage tube. TRIAL REGISTRATION: UMIN-CTR, 000031244. Registered on 1 May 2018.

Long-Term Outcomes of Thoracoscopic Esophagectomy in the Prone versus Lateral Position: A Propensity Score-Matched Analysis.

BACKGROUND: Several studies have suggested that thoracoscopic esophagectomy (TE) in the prone position (TEP) may be more feasible than TE in the lateral position (TEL); however, few studies have compared long-term survival between the two procedures. We evaluated whether TEP is oncologically equivalent to TEL. METHODS: Surgical outcomes of TEs performed from January 2006 to December 2013 at our hospital were retrospectively analyzed. Propensity score matching was used to control for confounding factors. RESULTS: TE was performed in 200 patients diagnosed with esophageal squamous cell carcinoma; 78 patients were matched in two procedures. The mean thoracic operative time in TEL was shorter than in TEP (228.9 min vs. 299.1 min; p < 0.001); however, the mean thoracic blood loss in TEL was higher than in TEP (186.9 ml vs. 76.5 ml; p < 0.001). The mean number of thoracic lymph nodes harvested in TEL was lower than in TEP (23.5 vs. 26.9; p < 0.05), and the pulmonary complication rate in TEL was higher than in TEP (30.8% vs. 15.4%; p < 0.05). The 5-year overall survival rates in pathological stage I (81.2% vs. 81.6%; p = 0.82), stage II (65.3% vs. 80.9%; p = 0.21), stage III (26.7% vs. 24.2%; p = 0.86) and all stages (63.6% vs. 62.3%; p = 0.88), and the 5-year progression-free survival rates in pathological stage I (78.0% vs. 81.8%; p = 0.54), stage II (53.5% vs. 77.6%; p = 0.13), stage III (10.5% vs. 12.8%; p = 0.81) and all stages (53.6% vs. 57.9%; p = 0.50) were not significantly different between the two procedures. CONCLUSION: TEP and TEL provide equal oncological efficiency.

Optimal monitor positioning and camera rotation angle for mirror image: overcoming reverse alignment during laparoscopic colorectal surgery.

Mirror image is one of the most difficult situations that the assistant surgeon encounters in laparoscopic colorectal surgery. The aim of the present study was to investigate whether task performance with mirror images improves by changing the position of the monitor and the rotation angle of the camera. Twenty-four surgeons performed the task under different conditions: Coaxial image (C), Mirror image (M), Mirror image + Monitor on the left side of participants (M + Mon), Mirror image + Camera rotated 90 degrees to the right (M + Cam), and Mirror image + Monitor on the left side + Camera rotated to the right (M + Mon + Cam) in a training box. The outcome measure was the mean time for completing the task. The mean time for completing the task, in decreasing order, was M (111.4 ± 58.9 seconds) > M + Mon (70.5 ± 29.4 seconds) > M + Cam (47.1 ± 17.1 seconds) > M + Mon + Cam (33.4 ± 10.3 seconds) > C (20.5 ± 3.5 seconds). (multivariable analysis of variance (MANOVA), p = 7.9 × 10-7) Task performance with mirror images improved by changing the monitor positioning and camera rotation angle. This novel method is a simple way to overcome mirror image in laparoscopic colorectal surgery.

Current status of minimally invasive esophagectomy for esophageal cancer: Is it truly less invasive?

Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal cancer. However, it is one of the most invasive procedures with high morbidity. To reduce invasiveness, minimally invasive esophagectomy (MIE), which includes thoracoscopic, laparoscopic, mediastinoscopic, and robotic surgery, is becoming popular worldwide. Thoracoscopic esophagectomy in the prone position is ergonomic for the surgeon and has better perioperative arterial oxygen pressure/fraction of inspired oxygen (P/F) ratio. Thoracoscopic esophagectomy in the left decubitus position is easy to introduce because it is similar to standard right posterolateral open esophagectomy (OE) in position. It has a relatively short operative time. Laparoscopic approach could potentially have a substantial effect on pneumonia prevention under the condition of thoracotomy. Mediastinoscopic surgery has the potential to reduce pulmonary complications because it can avoid a transthoracic procedure. In robotic surgery, in the future, less recurrent laryngeal nerve palsy will be expected as a result of polyarticular fine maneuvering without human tremors. In studies comparing MIE with OE, mediastinoscopic surgery and robotic surgery are usually not included; these studies show that MIE has a longer operative time and less blood loss than OE. MIE is particularly beneficial in reducing postoperative respiratory complications such as atelectasis, despite no dramatic decrease in pneumonia. Reoperation might occur more frequently with MIE. There is no significant difference in mortality rate between MIE and OE. It is important to recognize that the advantages of MIE, particularly "less invasiveness", can be of benefit at facilities with experienced medical personnel.

Laparoscopic Complete Mesocolic Excision for Double Flexural Colon Cancers.

BACKGROUND: Laparoscopic complete mesocolic excision (CME) for hepatic or splenic flexural colon cancer is considered technically demanding. The double (hepatic and splenic) flexural colon cancers are rare, and the laparoscopic CME procedure for such disease is not standardized. METHODS: This video presents laparoscopic CME for double (hepatic and splenic) flexural colon cancers using a medial and cranial approach. RESULTS: The patient was a 60-year-old woman with the diagnosis of splenic flexure cancer (cT4N1M0) and hepatic flexure cancer (cT3N0M0). Laparoscopic subtotal colectomy was performed. First, the left colic artery was divided at its origin, and the inferior mesenteric vein also was divided at the same level. The descending mesocolon was widely separated from the retroperitoneal tissues using a medial approach. Then, lymph node dissection along the surgical trunk was performed using a cranial approach. Finally, the transverse mesocolon was divided at the inferior border of the pancreas, and CME was achieved. The specimen was extracted through a small incision at the umbilicus, and side-to-side ileo-sigmoid anastomosis was performed extracorporeally. CONCLUSIONS: The approach presented in the video might be useful for standardization of laparoscopic CME for double flexural colon cancers.

Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with frequent recurrence even after curative resection. The tumor microenvironment, which consists of non-cancer cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), was recently reported to promote several cancers, including ESCC. However, the role of CAF as a coordinator for tumor progression in ESCC remains to be elucidated. In our immunohistochemical investigation of ESCC tissues, we observed that the intensity of expression of two CAF markers-alpha smooth muscle actin (αSMA) and fibroblast activation protein (FAP)-in the tumor stroma was significantly correlated with the depth of tumor invasion, lymph node metastasis, advanced pathological stage, and poor prognosis. We co-cultured human bone marrow-derived mesenchymal stem cells (MSCs) with ESCC cells and confirmed the induction of FAP expression in the co-cultured MSCs. These FAP-positive MSCs (which we defined as CAF-like cells) promoted the cell growth and migration of ESCC cells and peripheral blood mononuclear cell-derived macrophage-like cells. CAF-like cells induced the M2 polarization of macrophage-like cells. A cytokine array and ELISA revealed that CAF-like cells secreted significantly more CCL2, Interleukin-6, and CXCL8 than MSCs. These cytokines promoted the migration of tumor cells and macrophage-like cells. The silencing of FAP in CAF-like cells attenuated cytokine secretion. We compared cell signaling of MSCs, CAF-like cells, and FAP-silenced CAF-like cells; PTEN/Akt and MEK/Erk signaling were upregulated and their downstream targets, NF-κB and ß-catenin, were also activated with FAP expression. Silencing of FAP attenuated these effects. Cytokine secretion from CAF-like cells were attenuated by inhibitors against these signaling pathways. These findings indicate that the collaboration of CAFs with tumor cells and macrophages plays a pivotal role in tumor progression, and that FAP expression is responsible for the tumor promotive and immunosuppressive phenotypes of CAFs.

Review of the literature laparoscopic surgery for metastatic hepatic leiomyosarcoma associated with smooth muscle tumor of uncertain malignant potential: Case report.

Metastatic hepatic leiomyosarcoma is a rare malignant smooth muscle tumor. We report a case of metastatic hepatic leiomyosarcoma associated with smooth muscle tumor of uncertain malignant potential (STUMP). A 68-year-old female presented with a liver mass (60 mm × 40 mm, Segment 4). She underwent left salpingo-oophorectomy for an ovary tumor with STUMP in a broad ligament 6 years ago. Though FDG-PET showed obvious metabolically active foci, abnormal metabolically active foci other than the lesion were not detected. A malignant liver tumor was strongly suspected and laparoscopic partial liver resection was performed with vessel-sealing devices using the crush clamping method and Pringle maneuver. Immunohistochemical findings revealed metastatic liver leiomyosarcoma associated with STUMP in a broad ligament. This case is an extremely rare case of malignant transformation from primary STUMP to metastatic hepatic leiomyosarcoma. It provides important evidence regarding the treatment for metastatic hepatic leiomyosarcoma associated with STUMP.

CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.

Tumor-associated macrophages (TAMs) are involved in tumor progression and poor prognosis in several malignancies. We previously demonstrated the interaction between high numbers of infiltrating TAMs and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To investigate the significance of TAMs in ESCC, we conducted a cDNA microarray analysis of peripheral blood monocytes (PBMo)-derived macrophages and PBMo-derived macrophages stimulated with conditioned media of TE-series ESCC cell lines (TAM-like PBMo-derived macrophages). C-X-C motif chemokine ligand 8 (CXCL8) was up-regulated in the TAM-like PBMo-derived macrophages. Here we confirmed a high expression level of CXCL8 in TAM-like PBMo-derived macrophages and the expression of CXCR1/2, known as CXCL8 receptors, in TE-series ESCC cell lines. Recombinant human CXCL8 induced the ESCC cell lines' migration and invasion by the phosphorylation of Akt and Erk1/2. In indirect co-cultures, not only signal pathway inhibitors but also neutralizing antibodies against CXCL8, CXCR1 and CXCR2 suppressed these phenotypes induced by TAM-like PBMo-derived macrophages. Immunohistochemical analysis of 70 resected ESCC samples showed that high expression levels of CXCL8 in ESCC tissues were significantly associated with lymph node metastasis and poor prognosis. These results suggest that CXCL8 up-regulated in the microenvironment may contribute to ESCC progression by promoting cancer cells' migration and invasion.

Preoperative detection and localization of small bowel hemangioma: Two case reports.

Among the various diagnostic modalities for small bowel hemangioma, video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) can be recommended as part of the work-up in patients with obscure gastrointestinal bleeding (OGIB). DBE is superior to VCE in the accuracy of diagnosis and therapeutic potential, while in most cases total enteroscopy cannot be achieved through only the antegrade or retrograde DBE procedures. As treatment for small bowel bleeding, especially spout bleeding, localization of the lesion for the decision of DBE insertion facilitates early treatment, such as endoscopic hemostatic clipping, allowing patients to avoid useless transfusion and the worsening of their disease into life-threatening status. Applying endoscopic India ink marking prior to laparoscopic surgical resection is a particularly useful technique for more minimally invasive treatment. We report two cases of small bowel hemangioma found in examinations for OGIB that were treated with combination of laparoscopic and endoscopic modalities.

Local advanced rectal cancer perforation in the midst of preoperative chemoradiotherapy: A case report and literature review.

Standard chemoradiotherapy (CRT) for local advanced rectal cancer (LARC) rarely induce rectal perforation. Here we report a rare case of rectal perforation in a patient with LARC in the midst of preoperative CRT. A 56-year-old male was conveyed to our hospital exhibiting general malaise. Colonoscopy and imaging tests resulted in a clinical diagnosis of LARC with direct invasion to adjacent organs and regional lymphadenopathy. Preoperative 5-fluorouracil-based CRT was started. At 25 d after the start of CRT, the patient developed a typical fever. Computed tomography revealed rectal perforation, and he underwent emergency sigmoid colostomy. At 12 d after the surgery, the remaining CRT was completed according to the original plan. The histopathological findings after radical operation revealed a wide field of tumor necrosis and fibrosis without lymph node metastasis. We share this case as important evidence for the treatment of LARC perforation in the midst of preoperative CRT.

NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells.

Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAM_Ls revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs.

Software-assisted morphometric and phenotype analyses of human peripheral blood monocyte-derived macrophages induced by a microenvironment model of human esophageal squamous cell carcinoma.

Human macrophages play important roles in tumor promotion and are called tumor-associated macrophages (TAMs). We previously demonstrated that human esophageal squamous cell carcinomas (ESCCs) contain TAMs and that these TAMs tend to have tumor-supporting features. Here we exposed human macrophages to conditioned media of TE-series human ESCC cell lines (TECMs) to generate an ESCC extracellular stimuli-influenced TAM model. CD14(+) peripheral blood monocytes (PBMos) from healthy donors were treated with M-CSF and with additional IL-4 or TECM exposure. Morphological changes of the cells and the induction of CD163/CD204 proteins were detected in the TECM-exposed model TAMs by immunofluorescence. A software-assisted immunofluorescent cell image analysis showed increased CD163/CD204 positivity in the model TAMs and a weak to moderate positive correlation between the cytoplasmic area and the sum fluorescent intensity of CD204. Morphological changes of the cells were significantly reflected by several cytomorphometric parameters. PBMos were elongated with M-CSF treatment, then enlarged with TECM exposure. The cytoplasmic aspect ratio was decreased by M-CSF treatment and slightly increased by TECM exposure. The nuclear-cytoplasmic ratio decreased during the whole process of cell differentiation. This system is useful for quantitative assessments of TAM-like morphological changes of macrophages and the induction of CD163/CD204 in a model ESCC microenvironment.

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways.

Tumor-associated macrophages (TAMs) are known to be involved in the progression, angiogenesis, and motility of various cancers. We previously reported the association between an increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study the roles of TAMs in ESCC, we first exposed peripheral blood monocyte (PBMo)-derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of the expression of the M2 macrophage marker CD204 and the protumorigenic factors interleukin (IL)-10, VEGFA, and MMPs. Next, we compared gene expression profiles between PBMo-derived macrophages stimulated with or without TECM by cDNA microarray and focused on growth differentiation factor 15 (GDF15) among the highly expressed genes including IL-6, IL-8, and CXCL1. Our immunohistochemical study of 70 surgically resected ESCCs revealed that GDF15 was present not only in cancer cells but also in macrophages. The high expression of GDF15 in the ESCCs was significantly correlated with several more malignant phenotypes including vessel invasion, lymph node metastasis, and clinical stages. Patients with high GDF15 expression showed significantly poorer disease-free survival (P=0.011) and overall survival (P=0.041). We also found that recombinant human GDF15 promotes cell proliferation and the phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in the tumor microenvironment and is associated with aberrant growth and a poor prognosis in human ESCC.

Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma.

Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned media of ESCC cell lines induced CD204 expression in THP-1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells stimulated with TPA (macrophage [MΦ]-like THP-1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment.

[A case of AFP-producing gastric carcinoma, in which liver metastases were eliminated successfully underwent total gastrectomy after chemotherapy].

A 64-year-old man was admitted to our hospital for severe anemia, and a thorough examination revealed an AFP-producing gastric cancer with multiple liver metastases. He was treated with S-1, and liver metastases were reduced. However, the originalgastric tumor did not disappeare. We administered paclitaxelas second-line treatment, and CDDP/CPT-11 as thirdline treatment, intravenously. In August 2006, liver metastases were not detected, so he underwent total gastrectomy and lymph node dissection. The final stage was StageIB(mp, n0). He has had no recurrence as of 36 months postoperatively.