[Migration of Internal Pancreaticojejunostomy Stents into the Bile Ducts in Patients Undergoing Pancreaticoduodenectomy].

The patient was a 68-year-old male. Pancreaticoduodenectomy(PD)for papillary carcinoma was performed. Computed tomography(CT)3 months after surgery revealed the migration of a lost Pit-stent into the bile duct. However, there were no symptoms. On CT 2 years after surgery, the lost stent had spontaneously fallen off. However, hepaticolithiasis was observed, and lithotripsy was performed using endoscopic retrograde cholangiopancreatography(ERCP). A pancreatic fistula after PD is an important complication. To prevent pancreatic fistulae, pancreatic stenting at the site of PD is performed in many cases. The postoperative in vivo kinetics of a lost stent remains to be clarified. Several case reports on complications have been published. In this study, we report a patient in whom the migration of a lost Pit-stent into the intrahepatic bile duct after PD led to hepaticolithiasis, and review the literature.

[A Patient with Small Intestinal Leiomyosarcoma and Intussusception Who Underwent Single Port Surgery].

The patient was a 33-year-old female. She was referred to our hospital from a previous clinic with abdominal pain and vomiting. Contrast-enhanced abdominal CT revealed intussusception, leading to a diagnosis of intussusception with a small intestinal tumor as an advanced part. Intestinal obstruction symptoms were observed, and emergency surgery was performed on the same day. As a technique, single port surgery was selected, and laparoscopic reduction was attempted. However, it was ineffective. The site of intussusception was induced outside the body through a small laparotomy wound, and reduction was performed using Hutchinson's procedure. As an adjacent lymph node was markedly swollen, the mesentery involving this lymph node was dissected in a fan shape, and the tumor was extirpated. The tumor measured 40 mm in long diameter, being a hemicircular, protruding lesion. Histologically, disarray of short spindle tumor cells was observed. Immunostaining showed Kit- and DOG1-negtive reactions and partially α-SMA and desmin-positive reactions, suggesting leiomyosarcoma. With the establishment of an immunostaining-test-based classification, leiomyosarcoma is currently rare. In this study, we report a patient in whom single port surgery for intussusception related to small intestinal leiomyosarcoma was successful.

[A Case of Small Intestinal GIST Diagnosed by Intussusception].

The patient was a 34-year-old female. She consulted our hospital with epigastric pain. Abdominal computed tomography (CT)revealed a small intestinal tumor, measuring 30 mm in diameter, with contrast effects. For detailed examination, enteroscopy was scheduled, but abdominal pain suddenly occurred. CT showed marked dilatation of the small intestine and intussusception, and emergency surgery was performed on the same day. Intussusception was observed on the anal side 70 cm from Treitz' ligament. The intestinal wall was black, and fissures of the serosa were partially noted. It was difficult to release the intussusception, and a 55 cm area of the jejunum involving the site of intussusception was resected. The patient was discharged on the 8th postoperative day. At the tip of the intussusception, a submucosal tumor measuring 25 mm in maximum diameter was present. Pathologically, the proliferation of spindle-shaped cells originating from the muscularis propria was observed, comprising an intricate structure. On immunostaining, KIT-positive and CD34, S-100, α-SMA-negative reactions were detected, leading to the diagnosis of a gastrointestinal stromal tumor(GIST). Nuclear divisions were noted in <5/50 visual fields. According to the risk classification, the risk was evaluated as low. The patient is being followed-up in accordance with guidelines.

[A Case of Preoperatively Diagnosed Early Cystic-Duct Carcinoma].

A 88-year-old man presented with abdominal discomfort. Computed tomography(CT)images showed gallbladder tumor, and the patient was referred to our hospital. In addition to the above, CT images showed a tense gallbladder and EUS showed papillary raised lesions mainly from the cystic duct to the gallbladder neck. Based on the above, we diagnosed cystic duct cancer and performed full-thickness cholecystectomy, extrahepatic bile duct resection, regional lymph node dissection at our department. Macroscopic findings of the resected specimen showed a Villous ridge in the cystic duct. Histopathological findings revealed well-differentiated adenocarcinoma with an irregular papillary structure centered on the cystic duct. The depth of invasion remained within the epithelium, and a diagnosis of primary early cystic duct cancer was made. Primary cystic duct cancer is a relatively rare disease and often does not lead to preoperative diagnosis. This time, we experienced a case in which cystic duct cancer was diagnosed preoperatively due to complaints of abdominal discomfort and could be surgically resected.

[Patient with Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma with Small Intestinal Perforation Development during Chemotherapy].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is classified under type Ⅱ enteropathy-associated T-cell lymphoma(EATL). It is a rare disease with a low incidence rate. This study reports a case of a patient with MEITL who developed small intestinal perforation during chemotherapy. The patient was a 55-year-old woman who presented to a previous clinic with epigastric pain. Enteroscopy results showed a map-like ulcer in the jejunum. Examination of the tissue specimen collected from this site suggested T-cell lymphoma. The patient was referred to our hospital for chemotherapy. Seven days following the initiation of chemotherapy, an abdominal computed tomography(CT)revealed free air, leading to a diagnosis of gastrointestinal perforation. Emergency surgery was performed. Intraoperatively, bowel perforation and a degenerative ulcer were observed at 95 cm and 80 to 115 cm from the Treitz' ligament, respectively. In addition, all-layer intestinal necrosis was noted 150 and 90 cm from the terminal ileum. Total resection and anastomosis were performed. Postoperatively, the patient developed sepsis due to chemotherapy-related pancytopenia but recovered. She was discharged on postoperative day 24. Subsequently, positron emission tomography(PET)-CT revealed residual intestinal tumor cells and peritoneal dissemination. Chemotherapy was initiated, but there was no response. The patient died after 6.5 months. A radical treatment for MEITL has not yet been established. More case reports are needed to improve the prognosis of this disease.

[An Early Gastric Cancer with Sarcoid Reactions of the Regional Lymph Nodes].

The patient was a 73-year-old male who was referred to our hospital for detailed examination because computed tomography(CT)revealed lymph node swelling. Upper gastrointestinal endoscopy revealed a 0-Ⅱc lesion in the greater curvature of the middle gastric body. The periphery of the lesion site was not reached using endoscopy. CT revealed lymph node swelling, but positron emission tomography(PET)-CT did not show abnormal accumulation in any area other than the lesion site involving the lymph nodes. Under a diagnosis of cT2N0M0, Stage Ⅰ tumor, total gastrectomy via laparotomy and lymph node dissection(D2+No.10)was performed. The histopathological diagnosis suggested early gastric cancer pT1b (SM)N0M0, Stage ⅠA. Although lymph node metastasis was not observed, the outgrowth of non-caseating epithelioid cell granulomas was observed in all lymph nodes. There was no granulomatous lesion at any other site, including the lung, leading to a diagnosis of sarcoid reactions. The"sarcoid reaction"refers to non-caseating epithelioid cell granuloma formation in a local area or the regional lymph nodes of a malignant tumor through reactions to extraneous foreign bodies in the absence of the general condition or signs as sarcoidosis. Sarcoid reactions to early gastric cancer are rare. In this study, we report a patient with early gastric cancer who showed sarcoid reactions of the regional lymph nodes and review the literature.

[A Case of Elective Laparoscopic Resection for Sigmoid Colon Cancer with Irreducible Intussusception].

An 85-year-old man was hospitalized for a right greater trochanteric fracture. Rectal intussusception was found by diagnostic imaging but left untreated because of minor gastrointestinal symptoms. As a result of work-up for persistent mucous stool, he was diagnosed with sigmoid colon cancer with intussusception. The intussusception could not be reduced during barium enema examination but could undergo elective laparoscopic surgery with a good postoperative course. Adult intussusception may be asymptomatic and require no emergency treatment. In such a case, elective surgery can be performed. Many facilities employ laparotomy as a standard of care for intussusception. With the recent technological advances in endoscopic surgeries, laparoscopic surgery can be considered as a treatment option.

[A Case of Mesenteric Undifferentiated Pleomorphic Sarcoma].

Undifferentiated pleomorphic sarcoma develops in adult soft tissues and has a poor prognosis. It often recurs in the limbs and trunk, but is rare in the mesentery. Complete resection of the tumor is the first-line treatment, and there are previously reported cases of the usefulness of chemotherapy and radiation therapy; however, several factors remain to be clarified. We report a case of undifferentiated pleomorphic sarcoma originating in the ascending mesocolon.

[A Case of Goblet Cell Carcinoid].

The patient was a 26-year-old female who had undergone conservative treatment for acute appendicitis at another clinic and was referred to our hospital for interval appendectomy. We performed a single-incision laparoscopic appendectomy, and the patient was diagnosed with goblet cell carcinoid(GCC)based on the postoperative pathological examination. Since GCC is considered a high-grade tumor, we performed a laparoscopic ileocolic resection with D3 lymphadenectomy. There was no residual disease or lymph node metastasis detected in the resected specimen. Patients with advanced GCC typically have poor prognosis, because GCC is characterized by peritoneal dissemination and lymph node metastasis. However, our findings suggested that an additional laparoscopic surgery could be one of the curative and safe treatment options for selected pa- tients with GCC.

[Resection of Synchronous Liver Metastasis from Ascending Colon Cancer with Aplastic Anemia-A Case Report].

The aplastic anemia(AA)syndrome is characterized by pancytopenia and bone marrow hypoplasia. Although anemia, bleeding tendency, and susceptibility to infection are issues of concern during surgery, few reports have been published on the perioperative management, and management methods have not been established. A 77-year-old woman visited our hospital with chief complaints of melena and fatigability. Marked pancytopenia was observed at the first visit. After a detailed examination, she was diagnosed with ascending colon cancer accompanied by AA and solitary liver metastasis. As AA responded poorly to treatment, without improvement in pancytopenia, we decided to perform colectomy. The perioperative management, including blood transfusion and administration of a G-CSF preparation, was performed in collaboration with a hematologist, followed by right hemicolectomy and hepatic lateral segmentectomy. She was transferred to the department of hematology on hospital day 8 without complications. In conclusion, a highly invasive surgery, as in the present case, can be performed safely with an appropriate perioperative management even in cases complicated by AA.

[Spontaneous Disappearance of Undifferentiated Pleomorphic Primary Mesenteric Sarcoma-A Case Report].

The patient was a 49-year-old man with persistent fever since the introduction of hemodialysis(HD). Vomiting and abdominal swelling appeared 4 months after initiating hemodialysis. Computed tomography(CT)scan revealed a tumor measuring 9 cm, and disorders of passage from the jejunum. Surgery was performed, and resection was impossible because of peritoneal dissemination. Histopathological examination of the disseminated nodes suggested an undifferentiated pleomorphic sarcoma. Postoperatively, drainage from the gastric fistula was approximately 2,000mL/day. Chemotherapy was considered impossible because of HD, and palliative therapy was selected. However, the volume of drainage from the gastric fistula gradually decreased, and the disorders of passage reduced. CT scan confirmed marked reduction in the size of the intraperitoneal tumor and its subsequent disappearance. At the 2-year-and-5-month postoperative follow-up, no relapses were observed, and the course had been uneventful. Undifferentiated pleomorphic sarcomas develop in the soft tissue of adults and have a poor prognosis. However, mesenteric development is rare. Total tumorectomy is the first choice of treatment. A consensus on the usefulness of chemotherapy or radiotherapy has not been reached. Furthermore, no studies have reported spontaneous tumor disappearance in the absence of treatment. Here, we report a case of minor undifferentiated primary mesenteric sarcoma and its spontaneous disappearance and review the literature.

[Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with Transanal Minimally Invasive Surgery].

A46 -year-old man developed ulcerative colitis at the age of 19 years. Although the colitis was medically treated, it relapsed and repeated over time. Periodic lower gastrointestinal endoscopy revealed lower rectal cancer, and he was referred to our department of surgery. Previous steroid therapy induced diabetes, and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89 kg/m2, indicating that laparoscopic dissection near the anus would be difficult to perform. Therefore, the patient was scheduled for transanal minimally invasive surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as possible in the ventral to dorsal direction, followed by the TAMIS procedure. Dissection was started from the dentate line, and, after the closure of the anal stump, GelPOINT was placed, and made continuous with the previous dissection layer by applying the technique of down-to-up total mesorectal excision(TME)by TAMIS. The large intestine was excised through a small abdominal incision to create an ileal pouch, hand-sewn anastomosis was performed transanally to create a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several problems remain to be solved, including an understanding of its unique anatomy and the mastery of single-port surgical techniques. However, the herein reported patient with a high BMI had a definite indication for TAMIS-TME.

[A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

Efficacy and Safety of mFOLFOX6 as Perioperative Chemotherapy for Resectable Liver Metastases from Colorectal Cancer: A Case-Control Study.

BACKGROUND/AIM: Although resection is effective for managing resectable liver metastases from colorectal cancer, the clinical significance of chemotherapy for such metastases has remained undetermined. Therefore, we conducted a phase II trial of perioperative chemotherapy with mFOLFOX6 to examine its efficacy. PATIENTS AND METHODS: A total of 41 patients were examined. The liver resection rate was the primary endpoint, whereas the response rate, adverse events, completion rate, liver injury rate, R0 resection rate, and histological results were the secondary endpoints. RESULTS: Overall, 34 (82.9%) patients underwent liver resection, and 77.4% and 100% had synchronous and metachronous liver metastases, respectively. The seven remaining patients did not undergo resection because of progressive disease. Moreover, 2, 15, 17, and 7 patients had a complete response, partial response, stable disease, and progressive disease, respectively, which indicated that the response rate was 41.5%. Regarding adverse events, three patients exhibited Grade 3 myelosuppression and one patient had gastrointestinal symptoms. On the basis of histopathological examination, 27, 5, and 2 patients belonged to grades 1a:1b, 2, and 3, respectively. Regarding liver injury, 29.4% had liver sinusoidal injury, whereas 11.7% had steatohepatitis. Meanwhile, all patients underwent postoperative chemotherapy. CONCLUSION: mFOLFOX6 is safe and yields favorable therapeutic effects. The indication for liver resection after a certain waiting period is clinically significant.

Validation of Urinary Charged Metabolite Profiles in Colorectal Cancer Using Capillary Electrophoresis-Mass Spectrometry.

This study aimed to validate and reanalyze urinary biomarkers for detecting colorectal cancers (CRCs). We previously conducted urinary metabolomic analyses using capillary electrophoresis-mass spectrometry and found a significant difference in various metabolites, especially polyamines, between patients with CRC and healthy controls (HC). We analyzed additional samples and confirmed consistency between the newly and previously analyzed data. In total, we included 36 HC, 34 adenoma (AD), and 214 CRC samples, which were used for subsequent analyses. Among the 132 quantified metabolites, 16 exhibited consistent differences in both datasets, which included polyamines, etc. Pathway analyses of the integrated data revealed significant differences in many metabolites, such as glutamine, and metabolites of the TCA (tricarboxylic acid cycle) and urea cycles. The discrimination ability of the combination of multiple metabolites among the three groups was evaluated, which yielded higher sensitivity than tumor markers. The Mann-Whitney test was employed to evaluate the prognosis predictivity of the assessed metabolites and the difference between the patients with or without recurrence, which yielded 16 significantly different metabolites. Among these 16 metabolites, 11 presented significant prognosis predictivity. These data indicated the potential of metabolite-based discrimination of patients with CRC and AD from HC and prognosis predictivity of the monitored metabolites.

Prospective Multicenter Phase II Study of Biweekly TAS-102 and Bevacizumab for Metastatic Colorectal Cancer.

BACKGROUND: This study assessed the efficacy and safety of biweekly trifluridine and tipiracil hydrochloride (TAS-102) with bevacizumab combination therapy for patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We included 19 patients with mCRC who received TAS-102 and bevacizumab combination therapy biweekly as third-line chemotherapy. The primary endpoint was progression-free survival. RESULTS: Patients had a median age of 73 years and most (73.4%) were men. The median progression-free and overall survival were 5.6 and 11.5 months, respectively. Five (26.3%) patients achieved a response and the disease control rate was 12/19 (63.1%). One patient (5.2%) experienced neutropenia grade 3 or more. The median time from baseline performance status 0/1 to worsening to 2 or more was 10.3 months. CONCLUSION: Biweekly TAS-102 plus bevacizumab facilitates tumor shrinkage by reducing the incidence of grade 3 or more neutropenia, improving survival, and maintaining performance status. This combination may represent a treatment option for patients with late-stage mCRC receiving third- or later-line therapy.

Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis.

Vitamin K2 (menaquinone-4: MK4) has been reported to inhibit cell growth and induce apoptosis in various tumor cells. We examined the effects of MK4 using three types of colon cancer cell lines: PMCO1, COLO201, and DLD-1. Exposure to MK4 was at concentrations from 5 to 50 microM, growth inhibitory effects were observed dose-dependently in COLO201 and PMCO1, whereas the growth inhibition observed in DLD-1 was minimal. Comparison of COLO201 and PMCO1 cells exhibiting distinct growth inhibitory effects showed that cell death via apoptosis accompanied by activation of caspase-3 was induced in PMCO1, while apoptosis was not induced in COLO201. On the contrary, immunoblot assay using an anti-LC3B antibody showed autophagy induction by addition of MK4 and incubation in all three types of colon cancer cell lines. Addition of 3-methyladenine (3-MA) attenuated the growth inhibitory effect of MK4 in COLO201, whereas no influence of 3-MA was noted in PCMO1. Electron microscopy images of COLO201 showed that addition of MK4 induced an increased number of cytoplasmic autophagosomes and autolysosomes as well as morphological changes including scantiness of cytoplasm accompanied by loss of cell organelles, nuclear shrinkage, and fragmentation of cytoplasmic membrane in some cells, indicating the induction of cell death via autophagy not accompanied by the formation of apoptotic bodies in COLO201 cells. These results suggested that the response to MK4 and the way of induction of cell death vary in different colon cancer cell lines.

Collision Tumor of Adenocarcinoma and Gastrointestinal Stromal Tumor in the Small Bowel.

We report a very rare case of collision tumor composed of primary adenocarcinoma of the jejunum and gastrointestinal stromal tumor (GIST). The patient was a 63-year-old man who visited our hospital for epigastralgia and vomiting. Abdominal computed tomography revealed a mass in the upper jejunum, with gastric and duodenal dilatation. Endoscopy of the small bowel showed a circumferential tumor in the upper jejunum, which was diagnosed as primary adenocarcinoma by tissue biopsy. Thereafter, partial resection of the small bowel from the third part of the duodenum over the upper jejunum was performed. A tumor colliding with the primary adenocarcinoma was identified on the serosal side of the jejunum in the excised specimen and was histologically diagnosed as GIST. The annual incidence of primary adenocarcinoma of the small bowel (i.e., jejunum and ileum excluding the duodenum) has been reported to be 7 in 1 million people, and only 6 cases of collision tumor of the small bowel (i.e., duodenum: 5, ileum: 1) have been reported thus far. Although esophageal, gastric, and large intestinal collision tumors composed of primary cancer and GIST have been reported, to our knowledge, the present patient is the first case of the small bowel. The cause of or correlation between 2 tumors forming a collision tumor remains unclear. In the present patient, there was no pathological finding of infiltration between the 2 tumors. Although the collision of the 2 tumors was unclear, the findings indicate their independent development in closely located regions consistent with collision tumors.

Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines.

Vitamin K2 (MK4) has antitumor effects on various types of cancer cell lines in vitro, and its efficacy has also been reported in clinical applications for patients with leukemia, myelodysplastic syndrome, and hepatocellular carcinoma (HCC). However, details of the mechanism of the antitumor effects of MK4 remain unclear. In the present study, we examined the antitumor effects of MK4 on cholangiocellular carcinoma (CCC) cell lines and its mechanism of action using the HL-60 leukemia cell line that exerts MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest as a control. MK4 exerted dose-dependent antitumor effects on all three types of CCC cell lines. However, apoptosis occurred in a smaller percentage of cells and there was less cell cycle arrest compared with other cancer cell lines studied previously, which suggested slight MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest. On the contrary, histopathological fidings showed a large number of cells containing vacuoles in their cytoplasm, and electron microscopic findings showed a large number of cytoplasmic autophagosomes and autolysosomes. These findings suggested evidence of autophagy-related cell death. Fluorescence microscopy following acridine orange staining revealed an increase in the number of cytoplasmic acidic vesicular organelles characteristic of autophagy. Moreover, there were few cells forming autophagic vesicles in the control group, while the percentage of cells containing vacuoles in the MK4-treated group increased with the duration of culture. These results suggested that, unlike in leukemia, gastric cancer, HCC, and other cancer cells, the antitumor effects of MK4 on CCC cells are induced via autophagy formation.

Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity.

Synchronous or metachronous liver metastasis occurs in approximately 15% of colorectal cancer patients and is an important negative prognostic factor. We therefore need an effective therapy to prevent metastasis. It has become apparent that cyclooxygenase (COX)-2 plays an important role in cancer growth, invasion and metastasis and that there is potential for chemoprevention via inhibition of these processes. We injected colon 26, a colorectal cancer cell line, in CDF1 mouse spleen and, from the following day, two kinds of COX-2 inhibitor (etodolac and nimesulide) were administered orally. Two weeks later, the animals were sacrificed, the liver was excised, and we counted the number of metastatic nodules on the liver surface. In addition, COX-2 mRNA, matrix metalloproteinase (MMP)-9 mRNA, and tissue inhibitor of MMP (TIMP)-1 mRNA of cancer tissue were measured by means of real-time RT-PCR. The number of metastatic nodules on the liver surface was significantly lower in the etodolac-treated group than in controls (p=0.001), but no significant difference was noted in the nimesulide-treated group. The expression of COX-2 mRNA was also significantly lower in the etodolac-treated group than in controls (p=0.04), but not in the nimesulide-treated group. In addition, the expression of MMP-9 mRNA was significantly lower in the etodolac group than in controls (p=0.02), but not in the nimesulide group. Among the groups, there were no significant differences in TIMP-1 mRNA. Expression of COX-2 mRNA and MMP-9 mRNA correlated significantly (r=0.78, p=0.001), but there was no correlation between either COX-2 mRNA and TIMP-1 mRNA expression or between MMP-9 mRNA and TIMP-1 mRNA expression. These findings indicate that the selective COX-2 inhibitor, etodolac, suppresses liver metastasis by reducing MMP-9 activity.