Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

[A Case of Laparoscopic Uterine and Vaginal Resection for Local Recurrence after Abdominoperineal Resection for Anal Canal Cancer].

The patient was an 80s woman. She visited our hospital with chief complaint of melena, and further evaluation revealed anal canal cancer. We performed robot-assisted abdominoperineal resection(D3 lymphadenectomy)and lateral lymph node dissection. The pathological diagnosis was anal canal cancer, muc>por1>tub2, T3N1bM0, pStage Ⅲb. One year after the surgery, she had a mass in the soft tissue of perineum on CT scan and PET-CT showed abnormal accumulation, which was diagnosed as local recurrence. At the same time, she also had a mass with abnormal accumulation in ascending colon, and it was diagnosed as ascending colon cancer. In both cases, we judged radical resection was possible, and the policy of surgery was decided. First, laparoscopic ileocecal resection was performed. The local recurrence lesion became a mass, invading the soft tissue of the perineum, the posterior wall of the vagina, and the cervix. So, we performed laparoscopic excision of local recurrent region together with the uterus and the posterior wall of the vagina. Based on the result of pathological examination, the patient was diagnosed with ascending colon cancer(tub1, pT1bN1aM0, pStage Ⅲa), and recurrence of anal canal cancer. The postoperative course is good and there are no signs of recurrence for 6 months after the operation.

[A Case of Robotic-Assisted Total Pelvic Exenteration for Locally Advanced Rectal Cancer Invading the Prostate].

The patient was a 60s man, whose chief complaint of melena and weight loss. He visited our hospital, and further evaluation revealed rectal cancer(Rb)invading the prostate with obturator lymph node metastasis. The clinical diagnosis was T4b (prostate)N3M0, Stage Ⅲc. He was administered 4 courses of CAPOX plus bevacizumab. After chemotherapy the primary tumor and lymph nodes showed PR, the diagnosis of ycT4bN1bM0, Stage Ⅲc. We performed robot-assisted total pelvic exenteration. He has been cancer-free for 5 months.

[A Case of Laparoscopic Total Pelvic Exenteration for Sigmoid Colon Cancer Using Infrared Illumination System (IRIS)].

The patient was 80s woman, whose chief complaint of fever and abdominal pain. She visited our hospital, and further evaluation revealed sigmoid colon cancer invading the uterus and abdominal wall. The pooling of pus in the uterus was formed and we diagnosed as pyometra. The clinical diagnosis was T4b(uterus, abdominal wall)N0M0, cStage Ⅱc. We performed laparoscopic sigmoidectomy, uterus and bilateral ovaries. We report a case in which the intraoperative infrared illumination system(IRIS)was used to support the identification of the ureter by near-infrared light and total pelvic exenteration could be safely performed.

[A Case of Early Appendiceal Adenocarcinoma Coexisting with High-Grade Appendiceal Mucinous Neoplasm].

We report a case of a female in her fifties with early appendiceal adenocarcinoma coexisting with high-grade appendiceal mucinous neoplasm(HAMN)with a review of the literature. The patient presented to our hospital because of an enlarged appendix noted by contrast-enhanced CT performed for hematuria. Contrast-enhanced CT showed that the appendix had swollen to 10 mm and mucus had accumulated inside, which had no evidence of obvious malignancy. She was followed up on CT once a year. Four years after her first visit, she underwent laparoscopic appendectomy for a definitive diagnosis. There were no adhesions or inflammation in her abdominal cavity, and the appendix root was dissected with an automatic anastomosis device. Her resected specimen macroscopically showed mild wall thickening, but no obvious neoplastic lesion. Pathological examination revealed that in many areas centered on the tip of the appendix, highly columnar atypical epithelium with enhanced mucus production was densely proliferated in the form of glandular tubular and papillary. The nuclei of the proliferating epithelium were large and the fission image was conspicuous, but they remained in the mucosa. Pathological examination diagnosed as HAMN according to the WHO classification. The atypical epithelium in a small area at the tip was particularly strong in nuclear atypia, and showed a strong positive diffusely in p53, which was an image of well-differentiated tubular adenocarcinoma. The pathological diagnosis was V, Type 0-Ⅱb, 2 mm, tub1 in HAMN, pTis, Ly0, V0, Pn0, pPM0, pDM0, pRM0, R0. Six months have passed since the operation, but no recurrence has been observed.

[A Case of Giant Intestinal GIST That Was Resected Just after TAE].

A 42-year-old woman visited our hospital complaining of fever and diarrhea. She had abdominal swelling and muscular defense. CT revealed a lobulated tumor occupying the lower abdomen. The tumor contained solid and cystic areas. The main artery vascularizing the tumor was the ileocecal artery, so we considered the tumor to be derived from the intestine or mesentery. We anticipated massive bleeding due to resection, and immediately after the embolization of the artery just before the operation. A vascular bundle from the terminal ileum and mesentery was found on the dorsal side of the tumor, and an outflow from the inferior mesenteric vein was also observed. We ligated each vessel and performed ileocecal resection. The operation lasted 4 hours and 18 minutes, with an estimated blood loss of 2,585 mL, requiring the transfusion of 6 units of concentrated red blood cells. According to histopathological findings, tumor cells with spindle-shaped to ellipsoidal nuclei proliferated in bundles and intricately, and immunostaining was positive for c-kit and DOG-1. We identified the tumor as high-risk GIST. The clinical course after the operation was uneventful. She continued to take imatinib for 3 years and is currently alive and without recurrence for 6 years after the operation.

Bridge to surgery using a self-expandable metallic stent for stages II-III obstructive colorectal cancer.

BACKGROUND: Bridge to surgery (BTS) using a self-expandable metallic stent (SEMS) for the treatment of obstructive colorectal cancer improves the patient's quality of life. This study aimed to examine prognostic factors of obstructive colorectal cancer. METHODS: We analyzed stage II-III resectable colon cancer cases (Cur A) retrospectively registered between January 2005 and December 2017. Overall, 117 patients with Cur A obstructive colorectal cancer were evaluated: 67 of them underwent emergency surgery (ES Group) and 50 of them after BTS with SEMS placement (BTS group). We compared surgical results and prognoses between the two groups. RESULTS: A total of 50 patients underwent endoscopic SEMS placement, which technical success of 96% and morbidity rate of 18%. Primary anastomosis rates were 77.6% in ES and 95.7% in BTS (p <  0.001); postoperative complication, 46.3% in ES and 10.5% in BTS (p <  0.001); pathological findings of lymphatic invasion, 66.7% in ES and 100% in BTS (p <  0.001); venous invasion were 66.8% in ES and 92% in BTS (p = 0.04); and recurrence of 25.4% in ES and 39.1% in BTS. The 3-year overall survival was significantly different between two groups (ES, 86.8%:BTS, 58.8%), BTS is worse than ES (log-rank test; p <  0.001). Venous invasion independently predicted worsened recurrence-free and overall survival. CONCLUSIONS: The vascular invasiveness was correlated with tumor progression after SEMS placement, and the survival rate was lower in BTS. SEMS potentially worsens prognostic outcomes in stage II-III obstructive colorectal cancer.

[A Case of Early Rectal Cancer Accompanied by Multiple Liver Abscesses].

An 81-year-old female who suffered from headache and general fatigue was diagnosed multiple liver abscesses by abdominal computed tomography(CT). Antibiotics and percutaneous transhepatic abscess drainage(PTAD)were performed, liver abscesses were improved. During the treatment, followed abdominal CT indicated lower rectal tumor. An early rectal cancer accompanied by multiple liver abscesses was diagnosed and performed surgery. The histological diagnosis was Rb, type 1, tub2, pT1b(SM 8,000 µm), Ly0, V1a, pN0, pStage Ⅰ. After surgery, the patient remains free from liver abscess. We report early colorectal cancer with multiple liver abscesses in Japanese literature.

[A Case of Locally Advanced Appendiceal Cancer with Radical Resection after CAPOX plus Bevacizumab].

We report a case of a male in his sixties with appendiceal cancer who underwent radical resection following CAPOX plus bevacizumab neoadjuvant chemotherapy. The patient presented to our hospital with a chief complaint of chronic low abdominal pain. Contrast-enhanced CT before neoadjuvant chemotherapy revealed an inhomogeneous tumor in the ileocecal region. Invasion to the bladder and the sigmoid colon was also observed. A colonoscopy showed an elevated lesion, which was caused by extramural invasion to the sigmoid colon. Pathological examination of the sigmoid colon tumor revealed well differentiated tubular adenocarcinoma and KRAS codon13 G13D. Hence, we diagnosed the patient with locally advanced appendiceal cancer with invasion to the bladder and sigmoid colon. We administered CAPOX plus bevacizumab as neoadjuvant chemotherapy. Contrast-enhanced abdominal CT after neoadjuvant chemotherapy revealed shrinkage of the primary tumor and reduction in the invasion to the bladder and sigmoid colon. We performed ileocecal resection(+D3), a partial sigmoidectomy, and partial bladder resection on the 135th day from the diagnosis. The resected specimen showed an appendiceal tumor with invasion to the bladder and sigmoid colon. The pathological diagnosis was Ⅴ, yType 5, tub2>tub1, ypT4b, ypN0, ycH0, ycM0, ycPUL0, Ly1b, V1b(VB), Pn01b, pStage Ⅱa, and the histological treatment effect of preoperative therapy was Grade 1b. Our experience indicates that in patients with locally advanced appendiceal cancer, multimodal treatment with neoadjuvant chemotherapy is an effective option.

[Clinical Significance of Palliative Esophageal Stent Placement for Esophageal Cancer].

BACKGROUND: Since the introduction of the guideline for the diagnosis and treatment of esophageal carcinoma in 2007, the indication for placing an esophageal stent has changed, especially with respect to the treatment of esophageal stricture after chemoradiotherapy(CRT). For CRT cases, irradiation after stent placement and stent placement after CRT are not recommended due to the risk of perforation. METHODS: Thirty-eight patients who underwent esophageal stenting in our department between January 2007 and December 2018 and who were diagnosed with thoracic esophageal cancer were included in this study. We retrospectively examined the safety and treatment effect of esophageal stent placement. RESULTS: Prior cancer therapy was observed in 16 cases(8 cases of chemotherapy and 8 cases of CRT). In the no prior therapy group, 13 cases were treated with BSC and 9 cases with chemotherapy. Esophageal stent placement after CRT was performed in 8 cases. Esophageal stent was placed 9(6-14)months after CRT. The stent patency period was 5(1-11)months, and the survival period after stent placement was 6(1-12)months. There was no difference in the frequency of complications and treatment outcomes of the CRT group compared with the non-CRT group. CONCLUSION: Cases undergoing esophageal stent placement after CRT can expect therapeutic effects similar to those of other cases. However, complications such as perforation can be fatal; thus, careful consideration should be given to each individual case for esophageal stent placement after CRT.

[A Case of Brain, Lung, and Adrenal Metastasis from Colorectal Cancer Controlled by Loco-Regional Surgery].

A 64-year-old man presented with the chief complaint of weakness in the left half of his body. He fell down on the road while riding a bicycle and was transported to the emergency room. A contrast-enhanced brain MRI revealed a 28mm ringshaped mass in the right frontal lobe. A craniotomy was performed 14 days later. The histopathological diagnosis showed the tumor as a well-differentiated tubular adenocarcinoma. Postoperative examination revealed a rectal cancer and a left lung mass. A low-anterior resection was performed 1 month after the craniotomy, and a partial lung resection was performed 2 months after the rectal excision. Metachronous solitary metastasis of the left adrenal gland was noticed 10 months after the removal of the lung metastasis and we subsequently performed a left adrenalectomy. The patient is not undergoing any active treatment 13 months after the adrenalectomy, but has no signs of recurrence. The loco-regional surgery was enabled for local control of multi-relapsed lesions from rectal cancer.

Prognostic factors for cytology-positive gastric cancer.

PURPOSE: Positive peritoneal lavage cytology for gastric carcinoma cells (CY1) is considered distant metastasis and is classified as Stage IV. However, patients with CY1 comprise a heterogeneous population, and their prognosis varies greatly. The prognostic factors for gastric cancer patients with CY1 were retrospectively reviewed. METHODS: The participants were 80 gastric cancer patients with CY1 in our institution encountered between 2005 and 2017. Prognostic factors were analyzed using univariate and multivariate analyses. RESULTS: The operative procedure was distal gastrectomy for 30 patients, total gastrectomy for 27 patients, staging laparoscopy for 10 patients, gastrojejunostomy for 8 patients, and probe laparotomy for 5 patients. Other distant metastases were recognized in 36 patients. A multivariate analysis revealed that other distant metastases were the strongest independent risk factor for the overall survival (p < 0.0001). When the cohort was limited to CY1 patients without other distant metastases, cN2-3 (p = 0.01), the prognostic nutritional index (PNI) < 40 (p = 0.02) and Type 4 (p = 0.03) were independent risk factors according to a multivariate analysis. The survivals of patients with cN2-3 or PNI < 40 after gastrectomy were equivalent to those with other distant metastases, as assessed by log-rank analyses. CONCLUSIONS: The prognoses of CY1 gastric cancer patients with cN2-3 or PNI < 40 were poor, even after gastrectomy.

Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The involvement of epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Here, we aimed to identify EMT-related genes associated with TGF-ß in ESCC and to clarify the role of these genes in the progression of ESCC. METHODS: EMT-related genes associated with TGF-ß expression were identified in patients with ESCC using microarray analysis and public datasets. The effects of ubiquitin-like with PHD and ring finger domains 2 (UHRF2) expression were analyzed in ESCC cell lines. Cell proliferation and invasion were measured using MTT and invasion assays, respectively. UHRF2 mRNA expression was also analyzed in 75 ESCC specimens to determine the clinical significance of UHRF2 in ESCC. RESULTS: Treatment of ESCC cell lines with TGF-ß increased UHRF2 expression. UHRF2 overexpression increased CDH1 (E-cadherin) expression and decreased invasive capacity. The 75 ESCC specimens were divided into the UHRF2 high-expression group (n = 61) and the UHRF2 low-expression group (n = 14). Low UHRF2 expression was significantly correlated with vascular invasion (p = 0.034) and was an independent prognostic factor for poor prognosis (p = 0.005). CONCLUSION: UHRF2 may be a negative regulator of EMT and a novel prognostic biomarker for ESCC.

[Clinical Outcome of Eight Patients with Perforated Colorectal Cancer].

We studied the clinicopathological findings of 8 patients with perforated colorectal cancer. Four patients were male. In 7 patients, the primary cancer site was left side colon. Chief complaints were abdominal pain in 7 patients and diarrhea in 1 patient. The emergent operation was performed in all cases. The final stages of 8 patients were as follows: 5 patients with Stage II, 2 patients with Stage III, 1 patient with Stage IV. All patients were discharged from our hospital. Postoperative chemotherapy was performed for 5 patients. Of these 8 patients, 1 patient had peritoneal dissemination and 1 patient had local recurrence. Two patients were died of cancer and 6 patients were alive. In conclusion, patient with perforated colorectal cancer were high risk cases for recurrence.

[An Analysis of Perforated Gastric Cancer with Acute Peritonitis in Our Hospital].

Perforated gastric cancer is relatively rare and the incidence is reported about 1% of all the cases of gastric cancer. We retrospectively analyzed the clinical data of the consecutive 12 patients with perforated gastric cancer who underwent operation in our hospital between January 2005 and December 2016. There were 5 men and 7 women, with an average age of 65.8 years old(34-87). Perforated gastric cancer occurred in the region U(1 cases), M(6 cases), L(5 cases). There were 11 cases with distant metastasis. We could successfully diagnosed as perforated gastric cancer in 8 cases before emergency operation. Gastrectomy was performed in 5 cases. However, the curative resection was performed only 1 case. Prognosis of perforated gastric cancer is poor. We considered as an appropriate two-step surgical strategy that the first step of surgery is an acute peritonitis treatment followed by radical gastrectomy with lymphadenectomy.

[A Case of Anal Canal Adenocarcinoma Locally Controlled by Rectal Amputation after Chemoradiotherapy].

A 73-year-old man was admitted to our hospital with anal pain. The 10 cm tumor was observed externally at the 3 o' clock side of his anus. He was unable to maintain the sitting position because of pain and had fecal incontinence and erosive skin inflammation. We identified this anal stenosis as anal canal adenocarcinoma(moderately differentiated). Thereby, no distant metastasis was found; we decided to treat the patient with conventional therapy. We made a double-hole colostomy in the sigmoid colon, and then the patient received preoperative chemoradiotherapy(CRT). Radiation therapy(RT)was adminis- tered at 40 Gy/20 Fr and oral capecitabine of 825mg/m / 2/time was administered twice a day on the RT days. The tumor shrinkage was good, and then we performed a laparoscopy-assisted abdominoperineal resection of the rectum. Pathologically therapeutic effect was Grade 1b. His activity of daily living was dramatically improved, and he can now main tan the sitting position. Twelve months postoperatively, he has no sign of recurrence. In this case, we experienced an anal canal adenocarcinoma that was possibly locally controlled by preoperative CRT and rectal amputation.

[A Case of Transverse Colon Cancer in Which Long-Term Chemotherapy Was Performed after Palliative Colonic Stent Placement].

We report a case involving a 76-year-old woman with transverse colon cancer undergoing long-term chemotherapy following palliative colonic stent placement. She visited our hospital with a diagnosis of colonic obstruction. Her abdomen was evidently distended and tender. CT revealed the apple core sign in the transverse colon-hepatic flexure area, and then bowel obstruction. The disseminated lesion occluded the superior mesenteric vein. Multiple masses were found on both lungs; a single tumor was detected in liver S6. Hence, we diagnosed her with unresectable obstructive transverse colon cancer. A colonic stent was inserted to remove the obstruction. Because primary tumor resection was rendered impossible, mFOLFOX6 was initiated with the colonic stent intact. After 5 courses, CT revealed that the liver metastasis disappeared, and lung metastases exhibited SD of a therapeutic effect. She further received 5 courses of mFOLFOX6 and 20 courses of maintenance therapy using FU. However, single liver metastasis recurred, exhibiting PD of a therapeutic effect. Histological diagnosis of liver metastasis was a consistent finding due to metastatic colorectal cancer; RAS mutation was not detected. Currently, 2 years after the diagnosis, FOLFIRI and panitumumab are being administered as the second-line treatment, with no colonic stentrelated complications.

[A Case of Sister Mary Joseph's Nodule from Multiple Colon Cancers].

A 94-year-old woman, who had been treated for multiple colon cancers 4 years ago, complained of umbilicus induration and had been followed up in a previous hospital with a diagnosis of periumbilical inflammation. Four years and 3 months postoperatively, the umbilical induration was enlarged, and umbilical metastasis of adenocarcinoma was diagnosed on biopsy. Umbilical resection was performed, and multiple peritoneal metastases were revealed. Umbilical metastases may worsen the patient's quality of life; thus, local resection was recommended positively.

Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). METHODS: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. RESULTS: In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. CONCLUSIONS: Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC.

[Cell-Free and Concentrated Ascites Reinfusion Therapy for Malignant Intractable Ascites from Colorectal Cancer].

Malignant intractable ascites worsens not only patient symptoms but also their daily activities. It often leads to a patient discontinuing or postponing chemotherapy. In the present study, we introduced cell-free and concentrated ascites reinfusion therapy(CART)for malignant intractable ascites from colorectal cancer. Six patients underwent 12 CART treatments using AHF-WMO as the ascites filterand AHF-UP as the concentrator(Asahi Kasei Medical Co., Ltd.)from January 2014 to January 2017. The patients included 2 men and 4 women aged 67-89 years. Primary locations were 3 rectums, 1 transverse colon, 1 descending colon, and 1 cecum. Five patients had peritoneal dissemination, and 1 patient had liver metastasis. All the patients were administrated diuretics, but they were all refractory to the treatment. The median punctured ascites volume was 3,850 mL, and the ascites reinfusion after CART was 485 mL, the median concentration was 7.5. Only one patient had a fever. Performance status(PS)improved significantly after the treatment, and appetite score also improved. One patient was fit to undergo chemotherapy after the treatment. In summary, we found that CART is a safe and acceptable procedure for malignant intractable ascites in colorectal cancer patients.