[A Case of Noninvasive Ductal Carcinoma Arising in Benign Phyllodes Tumor].

A 70-year-old woman underwent a partial mastectomy with preoperative diagnosis of phyllodes tumor. Histopathological examination of the resected specimen revealed noninvasive ductal carcinoma of up to 20 mm in the phyllodes tumor. We note the possibility of a situation in which a phyllodes tumor is accompanied by cancer, and detailed pathological examination is necessary.

[A Case of Intussusception Due to Ileal Malignant Lymphoma of AYA Generation].

The case is a 17-year-old man. He had complained of right lower abdominal pain for a week. He had no symptoms such as fever, weight loss, or night sweats. He was diagnosed with intussusception by abdominal contrast-enhanced CT and was hospitalized. The day after hospitalization, lower gastrointestinal endoscopy was performed, and a tumor 25 mm in size was found in the invagination of the ileum. Intussusception was recovered by intestinal scope insufflation, and the tumor was found to be a type 1 tumor located approximately 5 cm proximal to the Bauhin's valve. On day 17 of hospitalization, he had intussusception again at the time of surgery, and performed laparoscopic reduction before performing laparoscopy-assisted partial resection of the small intestine and appendectomy. The postoperative course was good and he was discharged on POD12(on day 29 of hospitalization). Histopathological diagnosis was diffuse large B-cell lymphoma(DLBCL), and chemotherapy was to be administered at the referral hospital. In intussusception of the adolescents and young adults(AYA)generation, such as this case outside of childhood, it is necessary to treat the patient with consideration for the presence of neoplastic lesions such as malignant lymphoma. We report our case with some literature considerations.

[A Case of Unresectable Colorectal Cancer with Complete Remission after Palliative Surgery Due to Continued Pharmacotherapy].

A 50s-year-old man was admitted to our hospital because of abdominal pain and vomitting. CT showed a thickened wall of the sigmoid colon, marked enlargement of the oral side, and a 30 mm tumor on the left lateral section of the liver. We diagnosed colonic obstruction due to sigmoid colon cancer with liver metastasis. We failed to place a colonic stent for decompression, so we performed a colostomy using the cecum. An exploratory laparoscopy was performed instead of curative surgery due to peritoneal disseminations, followed by chemotherapy and molecular targeted therapy. Although primary lesion, liver metastatic lesion and disseminated lesions were reduced by pharmacotherapy the patient developed a grade 2 skin disorder around the colostomy. Therefore, it was determined that molecular targeted therapy could not be continued. The resection of the primary lesion and closure of the colostomy were performed to continue pharmacotherapy. Pharmacotherapy was resumed after operation. The patient is currently getting complete remission, undergoing maintenance therapy with no skin disorders. In this case, surgery was performed as part of the multidisciplinary treatment. It suggested that palliative surgery might be an effective option in multidisciplinary treatment.

[A Case of Effective Peritoneo-Venous Shunt for Refractory Malignant Ascites in a Gastric Cancer Patient with Peritoneal Dissemination].

This paper reports a case of refractory ascites in a patient with gastric cancer. A peritoneo-venous shunt(PVS)was inserted in the patient, which contributed to extending the duration of home-based care as well as improving the patient's quality of life. The patient was a female in her 70s. She was diagnosed with gastric cancer and underwent total gastrectomy. Five years and 7 months after the surgery, she was diagnosed with peritoneal recurrence. Ascites temporarily decreased following chemotherapy, but gradually worsened thereafter. Since the patient required frequent puncture drainage for the ascites, cell-free concentrated ascites reinfusion therapy(CART)was performed. However, on the day prior to the scheduled second course of CART, marked abdominal distension was observed. Therefore, a PVS was inserted. No PVS-associated complications were observed. Following the insertion of the PVS, the patient's abdominal circumference and body weight markedly improved. Best supportive care(BSC)was provided to the patient as she became weak after undergoing several courses of chemotherapy on an outpatient basis. On the other hand, the PVS was working properly. The patient was able to continue her daily life activities at home. She died from the cancer after 164 days of the PVS insertion.

[A Case of Rectal Cancer with Collet-Sicard Syndrome].

The case was a woman in her 50s. Total pelvic resection was performed for advanced rectal cancer(cT4b[vagina]N3M0, cStage Ⅲc), after neoadjuvant chemoradiation therapy. Five months after the operation, she was unable to stand due to severe back pain. Spinal MRI revealed multiple bone metastases and lumbar fractures. In addition, dysphagia and dysarthria rapidly progressed almost simultaneously with back pain. Initially, brain metastasis was suspected, but head MRI revealed Collet-Sicard syndrome due to skull base metastasis. Irradiation to the skull base and high cervical spine, thoracolumbar spine was started. After irradiation, her back pain and cranial nerve symptoms improved. She was discharged and received palliative treatment. About a month after discharge, she was hospitalized for recurrent dysphagia and died on day 5 of hospitalization. Collet-Sicard syndrome is caused by damage to the cranial nerves Ⅸ to Ⅻ and is often caused by a tumor. Trauma, vasculitis, and internal carotid artery dissection have been reported as other causes. Symptoms such as hoarseness, dysarthria, tongue atrophy, dysphagia, and headache have been reported. Collet-Sicard syndrome due to bone metastasis of colorectal cancer were very rare, and we found only one other report. We report our case with some literature considerations.

[A Case of Rapidly Growing Breast Spindle Cell Carcinoma].

We report a case of rapidly growing breast spindle cell carcinoma. The case was a 69-year-old female. Her chief complaint was right breast pain. She was being followed after surgery for left breast cancer but was seen because of right breast pain. In the right mammary gland CD area, a 27×27 mm large unclear mass lesion was observed, which had not been seen half a year prior. Right mastectomy and axillary dissection were performed following a preoperative diagnosis of pT2N1M0, pStage ⅡB ductal carcinoma. Currently, 2 years and 2 months have passed since the operation, and recurrence has not been observed. Case reports of rapidly growing breast spindle cell carcinoma are occasionally found, but no literature specifically defines acute growth. Here, we defined rapid growth using the tumor doubling time(DT)proposed by Gerstenberg et al. Of all the reported cases of breast spindle cell carcinoma, the DT was fewer than 90 days in most cases. Breast spindle cell carcinoma demonstrates rapid grown compared to normal breast cancer.

[A Case of Gallbladder Jejunal Anastomosis and Duodenal Jejunal Anastomosis to Maintain QOL for an Elderly Patient with Pancreatic Cancer].

An 87-year-oldwoman was admittedto our hospital with abdominal pain andfever. Computedtomography showeda 25 mm tumor mass in the pancreatic headandshowedd ilatation of the pancreatic duct andcommon bile duct. She was diagnosed with obstructive cholangitis due to pancreatic head cancer. An endoscopic naso-biliary drainage(EUS)tube was inserted, and an endoscopic ultrasound(ENBD)examination was performed. At this time, duodenal perforation occurred, and an emergency operation was performed. During the laparotomy, perforation was found in the anterior wall of the duodenum. The contamination in the abdominal cavity and the degree of tissue damage in the duodenum were mild. Gall bladder jejunal andd uodenal jejunal anastomoses were performedfor biliary bypass andto close the perforation andbypass the gastrointestinal tract, respectively. She hadno postoperative complications andwas discharged 13 days postoperatively. Oral intake was possible after discharge, andthe patient returnedhome without complications. She died 5 months postoperatively. In this case, we performedbile duct andgastrointestinal bypass surgery prophylactically. Although this surgery will not be effective for all patients, we thought that it wouldbe useful for predicting the patient's future condition and for increasing the procedural options, even in case of emergency surgery.

[Long-Term Survival of a Rectal Cancer Patient with Virchow Lymph Node Metastasis, Liver Metastasis, and Para-Aortic Lymph Node Metastasis].

A 67-year-old female was diagnosed with Stage Ⅳ rectal cancer with paraaortic lymph node metastasis. The patient underwent Hartmann's operation with D3 lymph node and paraaortic lymph node dissection. Postoperative chemotherapy with FOLFIRI was then administered for 1 year. However, liver metastasis developed, for which partial hepatectomy was performed. Postoperative chemotherapy with S-1(20 courses)was then administered. Three years and 11 months following the first operation, lymph node metastases developed and resection of lymph nodes(No. 12p, No. 16b1int)was performed. Postoperative chemotherapy with capecitabine(Cape)(8 courses)was then administered. Five years and 7 months following the first operation, Virchow lymph node metastasis developed. Despite chemotherapy with Cape and bevacizumab (Bmab), Virchow lymph node swelling recurred, and resection was performed. Nine years and 4 months following the first operation, lymph node metastases developed, and resection of lymph nodes(Virchow, No. 16b1int)was performed. Postoperative chemotherapy with S-1(8 courses)was then administered. At present, 11 years and 4 months after the first operation, the patient, whose chemotherapy has been discontinued, is alive without recurrence.

[Pulmonary Metastasis Resection Twice after Curative Resection of Esophageal Cancer-A Long-Term Survival Case].

The prognosis of patients with esophageal cancer recurrence is poor, and surgical treatment is rarely performed. Here, we report on a patient with long-term survival who underwent pulmonary metastasis resection twice after curative resection of esophageal cancer. A 62-year-old male underwent curative resection of esophageal cancer after preoperative chemoradiotherapy. The histopathological diagnosis was poorly differentiated squamous cell carcinoma(pT2N1M0, fStage Ⅱ). Five months after the operation, right lung metastasis(right-S2)was detected. Accordingly, pulmonary metastasis resection was performed. Fourteen months after the initial operation, left lung metastases(left-S3/S6)were detected. The patient underwent resection again for the pulmonary metastases. The patient died of pneumonia without recurrence 8 years 3 months after the initial operation. In selected cases, surgical resection seems effective for treating distant esophageal cancer metastasis, suggesting that surgery should be an option in cases of accumulation of numerous distant metastases in esophageal cancer.

[A Comparison of the Treatment Methods for Obstructive Colorectal Cancer].

PURPOSE: Emergency surgery for obstructive colorectal cancer is considered to be associated with a high degree of risk, and surgery may after decompression is considered to be safer. In cases of obstructive colorectal cancer, decompression can be achieved with surgery, an ileus tube, or a stent, depending on the disease condition. We herein compare the treatment methods for obstructive colorectal cancer. METHODS: Forty-two patients with obstructive colorectal cancer underwent emergency treatment between January 2012 and December 2016. RESULTS: Among the patients with obstructive colorectal cancer, 18 receiveda stent, 10 receiveda nasal ileus tube, 6 receiveda transanal ileus tube, 5 underwent stoma construction, and 3 underwent emergency surgery without decompression. The stent group showed the highest laparoscopic operation rate. There was no significant difference in the overall survival of the treatment groups. One patient in the stent group developed duplicated cancer. CONCLUSION: Stent placement can be considered to be a viable option in the emergency treatment for obstructive colorectal cancer because laparoscopic surgery anda preoperative examination can be performed.

[A case of recurrent rectal cancer with idiopathic thrombocytopenic purpura showing rapid progression, suggesting disseminated intravascular coagulopathy].

A 64-year-old female with idiopathic thrombocytopenic purpura(ITP)was admitted to our hospital under the diagnosis of rectal cancer. Intersphincteric resection and splenectomy were performed after high-dose gamma globulin therapy. Thirteen months after the surgery, she suffered from a local recurrence and groin and pelvic lymph node metastases. Radiotherapy was planned before curative resection. During radiation, she complained of severe back pain and high fever with severe thrombocytopenia, and was admitted to our hospital. The examinations revealed disseminated intravascular coagulopathy(DIC), probably induced by multiple bone and hepatic metastases. Although anti-DIC therapy and chemotherapy with FOLFIRI were performed, thrombocytopenia did not improve, and she died of cancer progression about 2 months after admission. We report a case ofDIC induced by cancer progression with ITP. Since thrombocytopenia may be induced by either DIC or ITP, selecting a treatment for such a patient is difficult. We report the present case in detail and discuss findings from the literature.

Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma.

BACKGROUND: Diagnosis of esophageal squamous cell carcinoma (SCC) may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. RESULTS: Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning) using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of these antigens were similar in amino acid sequences, and they were designated as ECSA (esophageal carcinoma SEREX antigen)-1, -2 and -3. The ECSA family was also similar to an EST clone, hepatocellular carcinoma-associated antigen 25a (HCA25a). Serum antibody levels to ECSA-1, -2 and -3 were significantly higher in patients with esophageal SCC than in healthy donors. Based on the conserved amino acid sequences, three peptides were synthesized and used for enzyme-linked immunosorbent assays (ELISA). The serum antibody levels against one of these peptides were significantly higher in patients with esophageal SCC. This peptide sequence was also conserved in FAM119A, GOSR1 and BBS5, suggesting that these are also ECSA family members. Reverse transcription followed by quantitative PCR analysis showed that the mRNA expression levels of ECSA-1, -2 and -3 and FAM119A but not of HCA25a, GOSR1 and BBS5 were frequently elevated in esophageal SCC tissues. CONCLUSIONS: We have identified a new gene family designated ECSA. Serum antibodies against the conserved domain of the ECSA family may be a promising tumor marker for esophageal SCC.

Decrease in chemosensitivity against anticancer drugs by an esophageal squamous cell carcinoma SEREX antigen, AISEC.

We performed SEREX (serological identification of antigens by recombinant cDNA expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and examined whether some of the SEREX antigens can affect chemosensitivity against anticancer drugs. We isolated a novel gene which was designated as AISEC (antigen identified by SEREX for esophageal carcinoma). RT-PCR analysis showed that the mRNA expression levels of AISEC were higher in esophageal SCC tissues than in their normal counterparts. By transfection into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts, we isolated a clone, FAISEC-3, which stably expressed AISEC. FAISEC-3 cells were more resistant to anticancer drugs, such as mitomycin C, ifosfamide, vincristine, camptothecin and etoposide, than parental ras-NIH cells. Luciferase reporter assay after a transient transfection with AISEC cDNA or the control vector revealed that the transactivity of p53 was suppressed by AISEC in a dose-dependent manner. These results suggested that esophageal SCC tissues produce AISEC in increased amounts, which can reduce the chemosensitivity against anticancer drugs possibly by suppressing the p53 transactivation ability.

Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. METHODS: Tumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. RESULTS: MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1). CONCLUSION: MKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of esophageal SCC with high specificity. It is plausible that MKRN1 is involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of L-FILIP.

Serum anti-myomegalin antibodies in patients with esophageal squamous cell carcinoma.

In order to identify new serum markers of esophageal squamous cell carcinoma (SCC), we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX). E. coli was transformed with a lambdaZAPII phage cDNA library prepared from mRNA of an esophageal cancer cell line (T.Tn), and IPTG-induced cDNA products were screened for interaction with antibodies in allogeneic sera of patients with esophageal SCC. We identified myomegalin (MMGL, phosphodiesterase 4D interacting protein/PDE4DIP) as a new SEREX antigen for esophageal SCC. Western blot analysis revealed that serum anti-myomegalin antibodies (s-MMGL-Abs) were present in 43 (47%) of 91 patients, but in only one (2.2%) of 45 healthy controls. Of the 21 patients with stage I disease, 8 (38%) were sero-positive. The positive rate of s-MMGL-Abs was greater than those of other conventional tumor markers. Reverse transcription-PCR analysis suggested that alternative splicing from myomegalin variant 1 to variant 5 may explain, in part, the development of s-MMGL-Abs. Although the presence of s-MMGL-Abs was not related to any clinicopathological features of the patients, multivariate analysis indicated that the presence of s-MMGL-Abs was significantly associated with a favorable prognosis. Consequently, s-MMGL-Abs may be a useful tumor marker to diagnose and establish a prognosis in patients with esophageal SCC.

Sensitization against anticancer drugs by transfection with UBE2I variant gene into ras-NIH3H3 mouse fibroblasts.

We previously performed SEREX (serological identification of antigens by recombinant expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and isolated a variant clone (AK093616) of ubiquitin-conjugating enzyme E21 (UBE2I). This clone was tentatively designated as UBE2I-v5 and analyzed for biological function by transient transfection of the cDNA into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts. Chemosensitivity to 92 cytotoxic drugs was compared between UBE2I-v5-transfected cells and the parental ras-NIH cells. The UBE2I-v5-transfected cells were more sensitive than the parental cells to anticancer drugs such as vincristine (VCR), mitoxantrone (MIT) and etoposide (VP16). The regression analysis of the total chemosensitivity pattern of UBE2I-vS-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor a), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-I), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPalpha (CCAAT/enhancer binding protein a) and the tumor suppressor p53. Thus, it is possible that UBE21-v5 plays a role in carcinogenesis by suppressing the function of CIEBPa and/or p53 via RPA2-like activity.

Identification of a novel SEREX antigen, SLC2A1/GLUT1, in esophageal squamous cell carcinoma.

We have carried out SEREX (serological identification of antigens by recombinant cDNA expression cloning), and identified SLC2A1 (solute carrier family 2/facilitated glucose transporter, member 1) as an antigen recognized by serum IgG antibodies in patients with esophageal squamous cell carcinoma (SCC). The levels of serum anti-SLC2A1 antibodies (s-SLC2A1-Abs), examined by enzyme-linked immunosorbent assay using bacterially expressed glutathione-S-transferase-SLC2A1 fusion protein, were significantly higher in patients with esophageal SCC than in healthy donors. When using a cut-off level as the mean + 2x standard deviations of healthy donors, a total of 12 (21%) out of 57 SCC patients were revealed as positive for s-SLC2A1-Abs. The presence of s-SLC2A1-Abs was not associated with either clinicopathological factors or survival. Because s-SLC2A1-Abs were not associated with the positivity of other conventional serum markers, a combination assay of s-SLC2A1-Abs with these conventional serum markers may be useful for the diagnosis and monitoring of esophageal SCC.

Assessment for diagnosis of lymph node metastasis in esophageal cancer using endoscopic ultrasound elastography.

BACKGROUND: We performed endoscopic ultrasound real-time tissue elastography to more accurately diagnose lymph node metastasis of esophageal cancer. The aim of this study was to evaluate the ability of EUS elastography to distinguish benign from malignant lymph nodes in esophageal cancer patients. METHODS: The present study had two steps. As the first step (study 1), we developed diagnostic criteria for metastatic lymph nodes using elastography and verified the validity of the criteria. Three hundred and twenty-two lymph nodes from 35 patients treated by surgical resection were included in the study. As the second step (study 2), we preoperatively examined the lymph nodes of esophageal cancer patients with EUS elastography and compared its diagnostic performance with that of the conventional B-mode EUS images. A total of 115 lymph nodes from 31 patients were included. RESULTS: In study 1, lymph nodes were considered malignant if 50 % or more of the node appeared blue, or if the peripheral part of the lesion was blue and the central part was red/yellow/green. The sensitivity and specificity of the elastography were 79.7 and 97.6 % with an accuracy of 93.8 %, which was significantly higher than the values for conventional B-mode imaging. In study 2, the sensitivity and specificity of the EUS elastography were 91.2 and 94.5 % with an accuracy of 93.9 %, which was also significantly higher than the values for conventional B-mode EUS imaging. CONCLUSIONS: The present study demonstrated that EUS elastography is useful for diagnosing lymph node metastasis of esophageal cancer.

Presence of serum tripartite motif-containing 21 antibodies in patients with esophageal squamous cell carcinoma.

SEREX has been applied to esophageal SCC, and the TRIM21 gene was identified as a novel SEREX antigen of esophageal SCC. The presence of s-TRIM21-Abs was confirmed by Western blotting using bacterially expressed TRIM21 gene product and was evaluated for clinicopathological significance in patients with esophageal SCC. s-TRIM21-Abs were detected in 18 (20%) of 91 patients with esophageal SCC but not in 42 healthy donors. The presence of s-TRIM21-Abs was partly associated with tumor size (P = 0.063) and poor survival (P = 0.067). To measure serum antibody levels, ELISA using purified recombinant TRIM21 protein was developed. The levels of s-TRIM21-Abs were significantly higher in patients with esophageal SCC than in healthy donors (P = 0.013). s-TRIM21-Abs may be a useful tumor marker to diagnose and predict disease progression in patients with esophageal SCC.

Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma.

We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers.