Laparoscopic deroofing for a giant hepatic cyst with biliary communication: a case report.

Previous reports describing laparoscopic deroofing as a management modality for a hepatic cyst with biliary communication remain limited. We present the case of a 76-year-old woman who was monitored for 4 years for a giant hepatic cyst in the right lobe of the liver. She presented to our department with a chief complaint of abdominal distension. Moreover, imaging revealed a 24-cm giant hepatic cyst. During laparoscopic deroofing, minimal bile leakage from the intra-cyst wall was observed, which was laparoscopically closed with sutures. No bile leakage or cyst recurrence was observed 18 months postoperative. This highlights that laparoscopic surgery may be used in managing hepatic cysts with biliary communication. Intraoperative findings may reveal biliary communication, which requires careful observation of the cyst wall after deroofing.

Matrix Metalloproteinase 9 Induced in Esophageal Squamous Cell Carcinoma Cells via Close Contact with Tumor-Associated Macrophages Contributes to Cancer Progression and Poor Prognosis.

Tumor-associated macrophages (TAMs) contribute to disease progression in various cancers, including esophageal squamous cell carcinoma (ESCC). We have previously used an indirect co-culture system between ESCC cell lines and macrophages to analyze their interactions. Recently, we established a direct co-culture system to closely simulate actual ESCC cell-TAM contact. We found that matrix metalloproteinase 9 (MMP9) was induced in ESCC cells by direct co-culture with TAMs, not by indirect co-culture. MMP9 was associated with ESCC cell migration and invasion, and its expression was controlled by the Stat3 signaling pathway in vitro. Immunohistochemical analyses revealed that MMP9 expression in cancer cells at the invasive front ("cancer cell MMP9") was related to high infiltration of CD204 positive M2-like TAMs (p < 0.001) and was associated with worse overall and disease-free survival of patients (p = 0.036 and p = 0.038, respectively). Furthermore, cancer cell MMP9 was an independent prognostic factor for disease-free survival. Notably, MMP9 expression in cancer stroma was not associated with any clinicopathological factors or patient prognoses. Our results suggest that close interaction with TAMs infiltrating in cancer stroma or cancer nests induces MMP9 expression in ESCC cells, equipping them with more malignant features.

[A Case Report of Rectal MiNEN Surgical Resection].

A 56-year-old man with diarrhea and bloody stools was found to have a type 2 tumor in the rectosigmoid region. A biopsy revealed well-differentiated tubular adenocarcinoma(tub1), and laparoscopic high anterior resection was performed. The final diagnosis was MiNEN(NEC:adenocarcinoma=6:4), RS, type 2, Ly0, V0, pT3(SS), pN0, M0, and pStage Ⅱa. He has been followed up without postoperative adjuvant chemotherapy and has been alive without recurrence for 1 year and 4 months after surgery. MiNEN is a rare disease, and most of them are mixed with NEC components or high- grade NET G3 and have a poor prognosis. We present an important case of rectal MiNEN.

[Long-Term Survival after Resection of Two Lung Metastases That Appeared Five Years after Pancreatic Cancer Surgery-A Case Report].

A woman in her 70s was diagnosed with cancer of pancreatic head. She underwent subtotal stomach-preserving pancreatoduodenectomy. Moderately differentiated adenocarcinoma, positive peripancreatic exfoliation surface, and R1 resection was diagnosed by histopathological examination. She underwent adjuvant chemotherapy(S-1), but 5 years and 6 months after the operation, a single nodule(16×9 mm)appeared on anterior segment of left lung. She underwent thoracoscopic left upper lobectomy on suspicion of primary lung cancer. Adenocarcinoma consistent with pancreatic cancer metastasis was diagnosed by histopathological examination. She didn't choose chemotherapy after second operation. 1 year and 1 month after the left pneumonectomy, a single nodule(11×10 mm)reappeared in lateral basal segment of right lung. Although it was difficult to diagnose whether it was primary or metastatic, she decided to undergo thoracoscopic partial lung resection. Histopathological examination revealed that the histology was similar to that of the previous lung lesion and was consistent with pancreatic cancer metastasis. After that, she also didn't choose chemotherapy. She has been alive for 7 years and 7 months after her first pancreatic cancer surgery without any new obvious recurrence.

[A Case Report of Pancreatic Tail Carcinoma with Positive Periotoneal Washing Cytology with Recurrence-Free Survival after Surgery and Chemotherapy].

A woman in her 70s underwent distal pancreatectomy(D2 dissection)for a pancreatic tail carcinoma after a close examination of the cause of her poorly controlled diabetes mellitus. Intraoperative rapid peritoneal washing cytology showed no malignant findings, but histopathological examination revealed Ptb, TS2, tub2, pT3, ly1, v3, ne3, mpd0, pS0, pRP1, pOO0, pPCM0, pDPM0, pN0, pM0, pCY1, pStage ⅡA, R0(Pancreatic Cancer Treatment Protocol 7th Edition). The patient was treated with S-1 therapy for 6 months postoperatively and is alive 1 year and 9 months without recurrence. The prognosis after resection of pancreatic cancer with positive peritoneal washing cytology is said to be worse than that of patients with negative, because of the high recurrence rate of peritoneal metastasis. We report a case of pancreatic tail carcinoma with positive peritoneal washing cytology with recurrence-free survival after surgery and chemotherapy.

[A Case Report of Appendiceal NET G1 Diagnosed by Histopathological Examination after Appendectomy for Acute Appendicitis].

A 36-year-old woman was diagnosed with acute appendicitis after a close examination of her abdominal pain and nausea. Laparoscopic appendectomy was performed, and pathological examination revealed a NET G1. They were localized lesions on the tips and body of the appendix, with no additional resection because the tumor size was less than 2 cm and no risk factors for recurrence and metastasis(vascular invasion, NET G2 or higher, or invasion of the mesentery). The patient was followed up with contrast-enhanced CT every 6 months and has been recurrence-free for 2 years postoperatively.

[Laparoscopic Resection of a Liver and Ovarian Metastasis of Transverse Colon Cancer-A Case Report].

A 60s woman was diagnosed to transverse colon cancer and she underwent laparoscopic right hemicolectomy. Localized peritoneal dissemination surrounding tumor was detected during surgery. She was administrated to chemotherapy due to a hepatic metastasis in S2/3 postoperatively. Subsequently, PET-CT revealed a left ovarian metastasis in addition to a liver metastasis during chemotherapy. Laparoscopic hepatic left lateral segmentectomy and bilateral adnexectomy was performed at 1 year and 9 months after the first surgery and histopathological examination showed a metastasis of transverse colon cancer. The growth of liver and lung metastases and peritoneal disseminations was detected at 6 months later after the second surgery and the patient is currently receiving palliative treatment. Previous literatures described that ovarian metastasis of colon cancer showed bilateral metastasis and resistance to chemotherapy frequently and ruptured in some cases. We should consider to resect bilateral ovary even if unilateral metastasis alone was detected by imaging examination.

[A Difficult Case of a Huge Cystic Gastrointestinal Stromal Tumor of the Stomach with CA125-Level Elevation].

A 67-year-old woman presented with abdominal distention. Computed tomography and magnetic resonance imaging revealed a huge tumor measuring >30 cm with solid and cystic regions. The serum level of CA125 was elevated. An exploratory laparotomy was performed by a gastroenterologist and a gynecologist for the purpose of diagnosis and tumor removal. During laparotomy, the ovary and uterus were found to be intact. The tumor was found to originate from the greater curvature of the stomach and invade the mesentery of the transverse colon. Histopathologically, tumor cells were positive on c-kit immunohistochemical staining. A high-risk gastrointestinal stromal tumor of the stomach was diagnosed according to the modified-Fletcher classification. Because cystic GIST is relatively rare and CA125 was elevated similar to that in Pseudo-Meigs syndrome, preoperative diagnosis was difficult in this case.

Chemokine (C-C Motif) Ligand 1 Derived from Tumor-Associated Macrophages Contributes to Esophageal Squamous Cell Carcinoma Progression via CCR8-Mediated Akt/Proline-Rich Akt Substrate of 40 kDa/Mammalian Target of Rapamycin Pathway.

Tumor-associated macrophages (TAMs) promote tumor progression. The number of infiltrating TAMs is associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) patients; however, the mechanism underlying this phenomenon is unclear. cDNA microarray analysis indicates that the expression of chemokine (C-C motif) ligand 1 (CCL1) is up-regulated in peripheral blood monocyte-derived macrophages stimulated using conditioned media from ESCC cells (TAM-like macrophages). Here, we evaluated the role of CCL1 in ESCC progression. CCL1 was overexpressed in TAM-like macrophages, and CCR8, a CCL1 receptor, was expressed on ESCC cell surface. TAM-like macrophages significantly enhanced the motility of ESCC cells, and neutralizing antibodies against CCL1 or CCR8 suppressed this increased motility. Recombinant human CCL1 promoted ESCC cell motility via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway. Phosphatidylinositol 3-kinase or Akt inhibitors, CCR8 silencing, and neutralizing antibody against CCR8 could significantly suppress these effects. The overexpression of CCL1 in stromal cells or CCR8 in ESCC cells was significantly associated with poor overall survival (P = 0.002 or P = 0.009, respectively) and disease-free survival (P = 0.009 or P = 0.047, respectively) in patients with ESCC. These results indicate that the interaction between stromal CCL1 and CCR8 on cancer cells promotes ESCC progression via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway, thereby providing novel therapeutic targets.

[Surgical Resection of Gastric MANEC-Two Case Reports].

Case 1 was a 78-year-old woman with a tumor in the stomach on preoperative CT of an inguinal hernia. The patient was diagnosed with advanced gastric cancer at posterior wall of fornix and underwent total gastrectomy and splenectomy. Postoperative pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma(MANEC), T1b2, N1, M0, StageⅠB. She has been alive without recurrence for 3 years without postoperative adjuvant chemotherapy. Case 2 was a 78-year-old man who was admitted to the hospital with acute pancreatitis and had a thickened wall of the lesser curvature of the gastric antrum on CT. He was diagnosed with advanced gastric cancer and underwent distal gastrectomy and D2 dissection. Postoperative pathological diagnosis was gastric MANEC, T1b2, N1, M0, Stage ⅠB. Oral administration of S-1 was started as postoperative adjuvant chemotherapy, but he was very tired and ended in 1 course at his request. Computed tomography 6 months after the operation revealed multiple liver metastases, and he was transferred to best supportive care at his request. He died 1 year after surgery. We experienced 2 valuable cases of gastric MANEC.

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.

[A Case of Pancreatic Body Cancer with Peritoneal Dissemination Followed Up for 15 Months without Recurrence].

A 72-year-old woman was admitted to the gastroenterology division of our hospital due to abdominal pain and vomiting. Dynamic contrast-enhanced CT showed a tumor at the body of the pancreas and main pancreatic duct dilation. She was diagnosed with carcinoma of the body of the pancreas via EUS-FNA. There was no vascular invasion or distant metastasis on preoperative imaging. She was introduced to the Gastrointestinal Surgery division where a mesenteric nodule was found at the time of the surgery. Intraoperative frozen section confirmed the diagnosis of occult peritoneal metastases. After consulting with her family, we completed the pancreatosplenectomy. On histopathological examination, this case was TS2, tub2, pT3, mpd0, S1, RP1, PV0, A0, PL0, OO0, N0, M1(PER), CY1, PCM0, DPM0, R1, stage Ⅳ. After the operation, we treated the patient with gemcitabine(GEM)plus nab-paclitaxel for 3 months(4 courses). She then developed side effects such as anorexia and tiredness. After discussing with the patient, chemotherapy was discontinued. The patient remains alive without recurrence 19 months after the operation. Patients with metastatic pancreatic adenocarcinoma have poor prognoses because they are no longer candidates for surgical therapy. We encountered a case of pancreatic body cancer with peritoneal dissemination, followed up for 15 months without recurrence.

[A Case of Synchronous Triple Cancer of the Stomach, Intrahepatic Bile Duct, and Prostate].

A 73-year-old man presented with the chief complaint of hematemesis(bloody vomiting). Upon examination, he was diagnosed as having gastric cancer with liver metastasis. He consulted our hospital for a second opinion. Gastrointestinal endoscopy showed a 50 mm early stomach cancer. Contrast-enhanced CT showed a progressive contrast-enhanced tumor in the S7 segment of the liver. FDG-PET/CT showed increased FDG uptake in the prostate. High PSA levels were also observed. He was diagnosed as having gastric cancer and prostate carcinoma. Intrahepatic cholangiocarcinoma and metastatic liver cancer were mentioned as differential diagnoses of the liver tumor. Hormonal therapy for prostate carcinoma failed to reduce the size of the liver tumor. PSA staining of the liver biopsy revealed negative results. As gastric cancer rarely metastasizes, metastatic liver cancer was unlikely. The patient was diagnosed as having intrahepatic cholangiocarcinoma. He underwent distal gastrectomy with hepatic posterior sectionectomy. The treatment strategy for multiple cancers depends on the primary lesion and the stage of cancer progression. Therefore, adequate evaluation is necessary before initiating treatment.

ANXA10 induction by interaction with tumor-associated macrophages promotes the growth of esophageal squamous cell carcinoma.

Tumor-associated macrophages (TAMs) have important roles in the growth, angiogenesis and progression of various tumors. Although we have demonstrated the association of an increased number of infiltrating CD204+ TAMs with poor prognosis in esophageal squamous cell carcinomas (ESCCs), the roles of TAMs in ESCC remain unclear. Here, to study the effects of TAMs on the tumor microenvironment of ESCCs, we established a co-culture assay using a human ESCC cell line and TAM-like peripheral blood monocyte-derived macrophages and performed a cDNA microarray analysis between monocultured and co-cultured ESCC cell lines. Our qRT-PCR confirmed that in the co-cultured ESCC cell lines, CYP1A1, DHRS3, ANXA10, KLK6 and CYP1B1 mRNA were highly up-regulated; AMTN and IGFL1 mRNA were down-regulated. We observed that the high expression of a calcium-dependent phospholipid-binding protein ANXA10 was closely associated with the depth of invasion and high numbers of infiltrating CD68+ and CD204+ TAMs and poor disease-free survival (P = 0.0216). We also found ANXA10 promoted the cell growth of ESCC cell lines via the phosphorylation of Akt and Erk1/2 pathways in vitro. These results suggest that ANXA10 induced by the interaction with TAMs in the tumor microenvironment is associated with cell growth and poor prognosis in human ESCC tissues.

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.

[A Case Report of a Patient Over 90 Years of Age with Liver Metastasis after Sigmoid Colectomy Controlled by a Combination Oral UFT/LV Chemotherapy Regimen].

A92 -year-old woman underwent laparoscopic sigmoid colectomy with D3 lymphadenectomy. Histological examination confirmed a pT3(SS), pN0, pM0, pStageⅡ tumor. Abdominal CT 6 months after surgery revealed liver metastasis close to the right branch of the portal vein in the S6 region of the liver. There were no indications for transcatheter arterial embolization, radiofrequency ablation, or hepatectomy. Although she had Grade 3 neutropenia, the patient received 15 courses of oral UFT/LV. Three courses of UFT/LV plus bevacizumab were also administered. She was judged to have achieved stable disease (SD); however, Grade 4 proteinuria was observed. After she was administered 2 courses of TAS-102, we shifted to best supportive care. She died of a sigmoid cancer 32 months after UFT/LV initiation. Careful adaptation of chemotherapy can be used to control a patient's condition during certain periods, even in patients with super-advanced age.

Successful single-stage laparoscopic surgery using a preoperative self-expanding metallic stent in patients with obstructive colorectal cancer.

INTRODUCTION: Although a self-expanding metallic stent (SEMS) or a transnasal or transanal decompression tube is sometimes used as a bridge to surgery in patients with obstructive colorectal cancer, the optimal decompression procedure to achieve successful laparoscopic surgery remains unclear. METHODS: Forty-two patients with obstructive colorectal cancer who were preoperatively decompressed by using SEMS (the SEMS group, n = 20) or a decompression tube (the DT group, n = 22) between January 2010 and February 2017 were included in this retrospective study. RESULTS: In the SEMS group, 20 patients (100%) were able to eat and 17 patients (85%) were able to undergo total colonoscopy preoperatively, but no patients could do so in the DT group (P < 0.01 and P < 0.01, respectively). The serum albumin level increased in the time between admission and just before surgery in five patients in the SEMS groups (25%), whereas it decreased in all patients in the DT group (P = 0.037). Laparoscopic surgery was performed more frequently in the SEMS groups (19 patients, 95%) than in the DT group (13 patients, 59.1%) (P = 0.018). Primary anastomosis without stoma was also achieved more frequently in the SEMS groups (19 patients, 95%) than in the DT group (15 patients, 68.2%) (P = 0.047). Anastomotic leakage did not occur in the SEMS group, but it did occur in one patient in the DT group. The recurrence-free survival rate did not differ between the groups (median follow-up period: 21 months). CONCLUSION: In patients with obstructive colorectal cancer, SEMS appears to be more effective than a decompression tube as a preoperative treatment to achieve successful laparoscopic resection without stoma.

Recent updates in the surgical treatment of colorectal cancer.

Because of recent advances in medical technology and new findings of clinical trials, treatment options for colorectal cancer are evolutionally changing, even in the last few years. Therefore, we need to update the treatment options and strategies so that patients can receive optimal and tailored treatment. The present review aimed to elucidate the recent global trends and update the surgical treatment strategies in colorectal cancer by citing the literature published in the last 2 years, namely 2016 and 2017. Although laparoscopic surgery is still considered the most common approach for the treatment of colorectal cancer, new surgical technologies such as transanal total mesorectal excision, robotic surgery, and laparoscopic lateral pelvic lymph node dissection are emerging. However, with the recent evidence, superiority of the laparoscopic approach to the open approach for rectal cancer seems to be controversial. Surgeons should notice the risk of adverse outcomes associated with unfounded and uncontrolled use of these novel techniques. Many promising results are accumulating in preoperative and postoperative treatment including chemotherapy, chemoradiotherapy, and targeted therapy. Development of new biomarkers seems to be essential for further improvement in the treatment outcomes of colorectal cancer patients.

[A Case Report of Chylous Ascites after Laparoscopic Sigmoid Colectomy Treated with Conservative Therapy].

A man in his sixties with a medical history of diabetes and dyslipidemia was detected with a tumor with massive submucosal invasion on colonoscopy. He was diagnosed with sigmoid cancer and underwent laparoscopic sigmoid colectomy with D3 lymph node dissection. An electric surgical knife and an ultrasonically activated device was used to perform D3 lymph node dissection with preservation of the left colic artery(LCA)and division of the S1A and S2A. On postoperative day 4(POD4), 1 day after oral intake was started, chylous ascites began to develop. Owing to the small volume of ascites, oral feeding was continued, and chylous ascites was treated successfully with a low-fat diet. Chylous ascites immediately reduced on POD6, after which the drain was removed on POD7. He was discharged on POD9. Fasting and complete parenteral nutrition are not necessarily required in the treatment of chyle leakage after laparoscopic colorectal cancer surgery.

[A Case of Ruptured Gastrointestinal Stromal Tumor of the Stomach with Intraabdominal Bleeding].

A 50s man visited our hospital because of abdominal pain that initiated 1 day prior. An approximately 4.0×5.0×4.5c m tumor, which was in contact with the greater curvature of the gastric body, was detected on contrast-enhanced computed tomography. He was diagnosed with a ruptured gastrointestinal stromal tumor and underwent emergency surgery. During the operation, about 250mL of bloody ascites and a ruptured tumor measuring 6-7 cm in size was observed in the middle of the gastric body. Partial gastrectomy was performed. The histopathological diagnosis was GIST of the stomach. In the gene search, PDGFR-a mutation D842V was detected in exon 18. Therefore, he is undergoing a follow-up examination without postoperative adjuvant therapy even though he is classified as high-risk. Currently, the patient has survived for 8 months after surgery without recurrence. We should perform careful follow-up of the patient.