[A Case of Pelvic Desmoid-Type Fibromatosis Treated by Radiation and Medication Therapies].

The treatment for desmoid-type fibromatosis involves surgical resection and medication therapy, but the standard treatment has not yet been established. In the West, the usefulness of radiation therapy has been reported. We encountered a patient with desmoid-type fibromatosis in the pelvis who was treated by radiation and medication therapies and achieved a good tumor reduction effect. The patient was a 70-year-old man. He had a 6-year history of pain in the right leg and had a palpable mass on the right side of the anus; he was admitted to our department. CT showed a 12×7×12 cm mass in the pelvis, and CT-guided needle biopsy revealed a desmoid-type fibromatosis. Because tumor exclusion resulted in obstruction of the rectum, radiation therapy(60 Gy in 30 Fr)was started after performing transverse colon colostomy; simultaneous medication therapy with a COX-2 inhibitor and the anti-allergic agent tranilast was administered. Cystic degeneration was observed 5 months after the end of radiation therapy, and after 12 months, the tumor volume had halved. Around 28 months after the end of radiation therapy, medication treatment has been continued with slow contraction.

Methylation of bone morphogenetic protein 2 is associated with poor prognosis in colorectal cancer.

The present study investigated aberrant methylation in colorectal cancer (CRC) and its impact on characteristics and prognosis of patients with CRC. Bone morphogenetic protein 2 (BMP2) was identified as a target gene in oligonucleotide microarray expression profiling in a previous study. Subsequently, the BMP2 methylation status was assessed in 498 patients with stage I-III CRC using methylation-specific polymerase chain reaction, and the association between BMP2 methylation status, patient characteristics and prognosis was assessed. BMP2 methylation was observed in 302/498 (60.6%) patients and was associated with positive lymph nodes and venous invasion (P<0.05). In the stage III subgroup, overall survival (OS) was significantly worse in the methylated BMP2 group compared with in the unmethylated BMP2 group (P=0.012). BMP2 methylation was identified as an independent factor for poor OS in stage III patients (P=0.041). Notably, in the left-sided stage III CRC subgroup, relapse-free survival and OS were significantly worse in the methylated BMP2 group than in the unmethylated group (P=0.048 and P=0.031, respectively). In conclusion, DNA hypermethylation of BMP2 was a poor prognostic factor in patients with stage III disease, particularly in those with left-sided stage III CRC. BMP2 methylation may be a biomarker for prognosis prediction and treatment decision-making.

[A Case of Metastatic Colorectal Cancer with Hyperammonemic Encephalopathy Induced by mFOLFOX6 and SOX Therapy].

A 77-year-old man was given a diagnosis of pT4aN0M1a(PUL2), stage Ⅳ, RAS mutant type, after the operation for advanced ascending colon cancer. He was administered mFOLFOX6 plus Bmab as first-line chemotherapy. He showed consciousness disturbance on the 2nd day during the 6 cycles. Because of head computed tomography and magnetic resonance imaging showing no abnormal findings, we diagnosed convulsive seizure. His consciousness level gradually improved after intravenous infusion. He showed consciousness disturbance on the 2nd day during the 7 cycles again. Because blood ammonia level were high at 400µg/dL, he was diagnosed as hyperammonemic encephalopathy. His consciousness level rapidly recovered after branched chain amino acid(BCAA)infusion. SOX plus Bmab therapy was started as a post-treatment, he developed hyperammonemia(NH3 288µg/dL)again, on the 4th day during the 3 cycles. After taking of oral administration of BCAA and lactulose, the recurrence of hyperammonemic encephalopathy was not found. Therefore, 3 cycles of SOX plus Bmab therapy and 12 cycles of IRIS plus Bmab therapy were administered.

[A Case of HER2 Positive Occult Breast Cancer Presenting as Swollen Axillary Lymph Nodes].

Occult breast cancer, which develops as a metastatic lesion with no primary tumor detected in the breast, is a rare breast cancer. A 68-year-old female patient particularly complained of the presence of a right axillary mass. The mass in the right axilla was palpable, but no tumor was found in both the breasts on palpation, ultrasound examination, or MRI. Partial breast resection and axillary lymph node dissection were performed following a diagnosis of invasive ductal carcinoma by core needle biopsy. There was no mammary gland tissue present around the tumor due to the pathology of the disease, and the tumor was diagnosed as occult breast cancer. As the cancer was ER negative and HER2 positive, treatment with a combination of FEC, docetaxel, and trastuzumab was initiated. Radiotherapy, which irradiated the right supraclavicular fossa and the right mammary gland, was administered. No disease recurrence and mammary tumor has been reported in the patient till date. Treatment of occult breast cancer generally includes local therapy such as radiation and surgery. However, in the present case, we did not operate upon the breast; instead we treated the right breast and the right supraclavicular fossa with radiation therapy. As the tumor was HER2 positive, we reasoned that local control of disease would be likely if treatment with chemotherapy and trastuzumab was performed effectively.

Carcinoembryonic antigen testing after curative liver resection for synchronous liver metastasis of colorectal cancer: a Japanese multicenter analysis.

PURPOSE: To identify the possible roles of carcinoembryonic antigen (CEA) testing after liver resection for synchronous colorectal liver metastasis (CLM). METHODS: The subjects of this retrospective study were patients who underwent complete resection of primary tumors and synchronous CLM between 1997 and 2007 at 20 institutions in Japan. We studied the associations between perioperative CEA levels and the characteristics of recurrence. RESULTS: Recurrence was detected during the median follow-up time of 52 months in 445 (73.7%) of the total 604 patients analyzed. A postoperative CEA level >5 ng/ml was an independent predictor, with the highest hazard ratio (2.25, 95% confidence interval 1.29-3.91, P = 0.004). A postoperative CEA level >5 ng/ml had a specificity of 86.2% and a positive predictive value of 84.2% for recurrence. Patients with a high postoperative CEA level had a significantly higher recurrence rate, with a shorter time until recurrence and a higher frequency of multiple metastatic sites than those with a low postoperative CEA level. Among the patients with recurrence, 173 (52.7%) had an elevated CEA level (>5 ng/ml) when recurrence was detected. CONCLUSIONS: A postoperative CEA level >5 ng/ml was an independent predictor of recurrence; however, CEA testing was not a reliable surveillance tool to identity recurrence after liver resection.

Clinical Significance of Methylation and Reduced Expression of the Quaking Gene in Colorectal Cancer.

BACKGROUND: This study investigated abnormal methylation in colorectal cancer (CRC) and the potential role of the Quaking RNA-binding protein (QKI) gene in tumorigenesis. MATERIALS AND METHODS: Oligonucleotide microarray expression profiling was carried out on a panel of primary CRC specimens (n=17) and CRC cell lines (n=5), followed by methylation analysis using methylation-specific polymerase chain reaction. QKI expression levels were assessed in 156 primary CRCs by qRT-PCR and immunohistochemistry. RESULTS: Low QKI expression was observed in 47.7% in CRCs. QKI promoter methylation was detected in 32.1% of patients with CRC, and in these patients mRNA expression in tumor tissue was significantly down-regulated compared to matched normal tissues (p=0.049). There was a significant relationship between low QKI expression and recurrence after surgery (p=0.004). Low QKI expression was an independent risk factor for recurrence after surgery in 153 patients with CRC without distant metastases (p=0.036). CONCLUSION: Patients with tumors expressing low levels of QKI experienced significantly higher rates of tumor recurrence after curative surgery and worse prognoses. Methylation of the QKI promoter and concomitant reduced expression of QKI mRNA may be important for CRC initiation and progression. Loew QKI expression may be a useful clinical biomarker for predicting recurrence and prognosis.

[A Case of Noninvasive Ductal Carcinoma of the Breast in a Male].

Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.

Identification of SATB1 as a Specific Biomarker for Lymph Node Metastasis in Colorectal Cancer.

BACKGROUND/AIM: The integration of gene expression analysis and genomic profiling represents an efficient approach to the discovery of cancer-related genes. Lymph node metastasis (LNM) is a significant prognostic factor in colorectal cancer (CRC). Detection and analysis of factors related to LNM will help develop new diagnostic methods or therapies. In this study, we aimed to identify genes that are significantly related to LNM in CRC through integrated copy number analysis (CNA) and gene expression analysis. MATERIALS AND METHODS: Genes showing both up-regulated expression and copy number gains in cases involving CRC with LNM were extracted as candidate biomarkers. Expression of the mRNA of the final candidate was validated in 124 patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Expression of the protein encoded by this candidate gene was assessed using immunohistochemical (IHC) staining of tissueσ from 328 patients. The association between protein expression and clinicopathological features was also examined. RESULTS: Special AT-rich sequence-binding protein 1 (SATB1) was extracted from integrated microarray analysis. SATB1 mRNA expression in cancer tissue was significantly higher in patients with LNM than without LNM. SATB1 protein overexpression was significantly associated with LNM. Moreover, overexpression of SATB1 was an independent poor prognostic factor in stage I-III, especially in stage II CRC. CONCLUSION: SATB1 may play an important role in LNM of CRC. SATB1 may be a biomarker of LNM and of recurrence after surgery for CRC.

[Evaluation of Bevacizumab in Combination with Weekly Paclitaxel for Locally Advanced Breast Cancer].

Locally advanced breast cancer that exhibits bleeding, has a foul odor, and expresses an exudate often reduces the quality of life(QOL). Bevacizumab(Bv)in combination with weekly paclitaxel(PTX)therapy has a high response rate. To date, we have used this combination for 8 cases of locally advanced breast cancer in our hospital. The patients' mean age was 62.1 years. The tumors were T4b in 6 cases, T4c in 1 case and T4d in 1 case. The clinical stage was Stage III B in 1 case and Stage IV in 7 cases. The subtype was Luminal A in 2 cases, Luminal B in 4 cases, and triple negative in 2 cases. The mean dosage duration was 5.8 months. Five cases underwent local control operations after chemotherapy. One case showed a complete response, 4 cases had a partial response, 2 cases had a stable disease and 1 case had progressive disease. Four cases with Grade 2-3 hypertension and 4 cases with Grade 2 neutropenia were identified. Bvin combination with weekly PTX therapy had a high response rate, and 5 patients were able to undergo surgery. As QOL improved after treatment and the safety did not have any problem, Bv in combination with weekly PTX therapy is one of the effective treatments for locally advanced breast cancer.

Unusual bleeding from hepaticojejunostomy controlled by adult variable stiffness colonoscopy: report of a case and literature review.

We herein present a case of a 59-year-old man who had undergone pylorus preserving pancreaticoduodenectomy with regional lymph node dissection prior to episodes of melena. Series of conventional endoscopic investigations failed to identify the bleeding source. Enhanced computed tomography scan revealed complete obstruction of the main portal vein with numerous collateral veins running towards the hepatic hilus. Comprehensively, hemorrhage from the jejunal varices caused by postoperative portal hypertension was highly suspected. As the jejunal loop was out of reach, adult variable-stiffness colonoscope (AVSC) was utilized to solve the Roux-en-Y anatomy. Numerous telangiectasis and small varices at hepaticojejunostomy were observed and in the mean time, bleeding was noticed and endoclips were placed without any delay. Ectopic variceal bleeding in jejunal loop after pancreaticoduodenectomy is difficult to manage. We believe that AVSC is an alternative device when specialized jejunal endoscopy is not available.

Intra-abdominal desmoid tumor difficult to distinguish from a gastrointestinal stromal tumor: report of two cases.

Desmoid tumors are benign fibroblastic neoplasms with no metastatic potential, but a propensity for local recurrence even after complete surgical resection. These lesions can develop at any site in the body, and commonly occur in the intra-abdominal area. Intra-abdominal desmoid tumors usually occur at the mesentery or retroperitoneum, and may morphologically mimic gastrointestinal stromal tumors (GISTs). Distinguishing between these tumors is important, because the therapies differ substantially, but is often difficult even with the use of CD117 staining. We herein report the cases of two patients with sporadic intra-abdominal desmoid tumors that were differentiated from GIST by immunohistological examination using beta-catenin and CD34. Desmoid tumors specifically express nuclear beta-catenin, and show no expression of CD34. We recommend staining for beta-catenin and CD34 when an intra-abdominal desmoid tumor is suspected.

[A case of postoperative colon cancer with peritoneal dissemination in which a long-term response was achieved using panitumumab maintenance therapy].

A 66-year-old man underwent a sigmoidectomy for advanced sigmoid colon cancer. The pathological examination revealed that the tumor was T3, N0, M0, and KRAS wild type. Fifteen months after surgery, the patient was hospitalized with stenosis of the anastomosis due to recurrent disease that had disseminated to the peritoneum, and which was unresectable. After transverse colostomy, the patient received 8 courses of mFOLFOX6+panitumumab (Pmab), and 39 courses of infusional 5-fluorouracil (5-FU) + Leucovorin (LV)+ Pmab. A partial remission (PR) was maintained for 27 months. The utility of maintenance therapy with an anti-epidermal growth factor receptor (EGFR) antibody-based regime has not previously been demonstrated. In this case, a long PR was achieved using infusional 5-FU+LV+Pmab, suggesting that this is a useful maintenance therapy following mFOLFOX6 + Pmab. However, the side effects resulting from Pmab treatment reduced the patient's quality of life (QOL). We suggest that Pmab maintenance therapy can be established by controlling the side effects of the anti-EGFR antibody.

[Resection for the treatment of bleeding caused by ovarian metastasis after hepatectomy for metachronous liver metastasis from sigmoid colon cancer].

We describe the case of a 75-year-old woman who underwent bilateral oophorectomy for bleeding due to right ovarian metastasis after hepatectomy for metachronous liver metastasis from sigmoid colon cancer. She underwent curative resection for sigmoid colon cancer( T4a, N2, M0, Stage IIIC). She received adjuvant chemotherapy of tegafur/uracil(UFT) plus leucovorin for 6 months. The patient underwent hepatectomy for liver metastasis 13 months after the primary resection for sigmoid colon cancer. One year after liver resection, the patient underwent emergency surgery for the treatment of bleeding due to ovarian metastasis. She received adjuvant capecitabine chemotherapy for 6 months after oophorectomy. The patient was alive with no evidence of disease 36 months after her oophorectomy. In the present report, we describe the case of a patient who underwent repeated resection for distant metastases after sigmoidectomy. These findings suggest that therapeutic strategies including surgical resection will be very important in the future.

[A case of advanced rectal cancer treated with leucovorin, fluorouracil, and oxaliplatin plus panitumumab preoperative chemotherapy].

A 58-year-old woman had a very large advanced rectal cancer( with wild-type K-RAS expression). Abdominal computed tomography( CT) revealed a space-occupying lesion in the pelvis and an enlarged lymph node. We established a diagnosis of unresectable rectal cancer and subsequently performed transverse colostomy. The patient received 6 courses of Leucovorin, fluorouracil, and oxaliplatin( mFOLFOX6) plus panitumumab( Pmab), 2 courses of simplified Leucovorin plus 5-fluorouraci(l sLV5-FU) plus Pmab, and 1 course of Pmab. The size of the primary tumor decreased remarkably after chemotherapy. Low anterior resection was performed. The pathological stage was T4a, N0, M1, Stage IVa. The results from this case suggest that mFOLFOX6 plus Pmab preoperative chemotherapy is a useful regimen for the treatment of locally advanced K-RAS wild-type rectal cancer.

[A case of advanced rectal cancer with bone metastasis successfully treated with chemo-radiation therapy].

A 62-year-old man presented to a hospital with left buttock pain, and sacral neoplasia was suspected. He was referred to our hospital. Colonoscopy( CS) and bone biopsy showed rectal cancer with metastasis to the sacrum. There was no bleeding or ileus associated with the primary lesion, and the sacral metastasis was unresectable; therefore, we decided to provide palliative care for pain relief. Radiation therapy( 40 Gy) was performed on the sacral metastasis and included the primary lesion, and zoledronate was administered concomitantly. Both CS and computed tomography (CT) showed tumor regression of both the primary and metastatic lesions, and the patient's carcinomatous pain was alleviated. Irinotecan, 5- fluorouracil, and Leucovorin (FOLFIRI)+cetuximab was administered to reduce the progression of the primary lesion. After 3 months, CT showed significant tumor regression of both the primary and metastatic lesions. The sacral metastasis was no longer evident on the CT images, and positron emission tomography( PET)-CT did not show fluorodeoxyglucose (FDG) accumulation. The primary lesion had shrunk and become flat, but biopsy indicated residual lesion. Although clinically the frequency of bone metastasis of colon cancer has been reported to be 8.6 to 10.7%, single metastasis is not often seen. In this report, we present a case of advanced rectal cancer with bone metastasis, which was successfully treated with chemo-radiation therapy.

[A case of recurrent rectal cancer successfully treated for a long period with capecitabine plus oxaliplatin and bevacizumab therapy].

A 62-year-old woman was diagnosed as having rectal cancer and underwent low anterior resection. The final pathological diagnosis was RS, type 3, circ, mod>muc>por>,pSE, ly1, v1, pN2, sH0, sP0, cM0, fStage IIIb, with KRAS mutation. Adjuvant chemotherapy with tegafur-uracil( UFT) plus Leucovorin( LV) was administered for 6 months. Ten months after surgery, right internal iliac and common iliac lymph node metastasis and peritoneal dissemination were diagnosed. In October 2009, capecitabine plus oxaliplatin (CapeOX) plus bevacizumab (Bmab) therapy was initiated. In May 2010, diagnostic imaging revealed a complete response after 42 months. In the present report, we describe the case of a patient with rectal cancer who experienced postoperative recurrence and achieved long-term complete response with CapeOX plus Bmab therapy. We also include a brief review of the literature.

[A case of neuroendocrine carcinoma of the anal canal with multiple bone metastases successfully treated with combined modality therapy].

Neuroendocrine carcinoma (NEC) of the anal canal is a comparatively rare tumor with a poor prognosis. We report herein a case of NEC of the anal canal with multiple bone metastases that was successfully treated with combined therapy. A 63-year-old man was referred to our hospital with the chief complaint of anal and back pain. A tumor was found in the anal canal, and pathologic examination revealed it to be NEC( Ki-67 expression>50%); fluorodeoxyglucose( FDG) positron emission tomography (PET)-computed tomography (CT) showed multiple bone metastases. Initially, a l-leucovorin/5- fluorouraci(l 5-FU)/oxaliplatin( L-OHP)(: mFOLFOX6)/bevacizumab( Bmab) regimen and octreotide were administered to treat the unresectable and advanced NEC. Strontium-89 and zoledronate were used to treat pain related to the bone metastases. After 3 months, the tumor and bone metastases became difficult to identify. The patient experienced grade 2 neurotoxicity after 5 months, and thus, we stopped L-OHP administration. After 10 months, we reintroduced L-OHP because of additional progression of the bone metastases.

[A patient with unresectable progressive advanced rectal cancer maintained in a state of remission by using combination therapy].

We report the case of a patient with unresectable progressive advanced rectal cancer, who has been able to maintain a good quality of life because of combination therapy, including chemoradiotherapy. A 52-year-old woman was diagnosed with progressive locally advanced rectal cancer and invasion of the adnexa of the uterus and the left ureter. No distant metastasis was detected. Colostomy was performed, followed by chemoradiotherapy combined with S-1; then, mFOLFOX6 +bevacizumab (BV) therapy was administered. Aggravation of bilateral hydronephrosis was detected upon completion of 2 courses of treatment, and therefore, percutaneous nephrostomy of the right kidney was performed. After the patient underwent 20 courses of treatment, imaging showed a reduction in the size of the lesion, and the CEA level returned to normal. Later, remission was sustained by sLV5FU2+BV therapy and oral administration of S-1. As a result, we were able to remove the nephrostomy tube from the right kidney in February 2011. Four years after initiation of the treatment, the patient has shown no indication of recurrence.

[A case of simultaneous resection of pancreatic tail and transverse hematogenous metastasis].

CASE: A 51-year-old male patient visited our hospital after a positive result for a stool test for occult blood. Subsequent lower gastrointestinal endoscopy showed a neoplastic lesion in the transverse colon, and abdominal computed tomography revealed a tumor in the tail of the pancreas. Since there was the possibility of multiple cancers with pancreatic cancer and transverse colon cancer, resection of pancreatic tail and transverse colectomy were performed. Histopathological findings: The pancreatic lesion was found to be a moderately differentiated tubular adenocarcinoma, and the lesion in the transverse colon was mainly located in the submucosal layer. In light of the principal lesion having the same histopathological characteristics as the pancreatic lesion, it was diagnosed as hematogenous metastasis of pancreatic cancer to transverse colon. Postoperative course: After 9 courses of 3-week administration of gemcitabine(GEM) and 1-week cessation, he developed hepatic metastasis. The treatment with GEM+S-1 was additionally repeated 7 times, but the patient was not responsive to the treatment, and died 1 year and 6 months after his first visit to our hospital. CONCLUSION: Surgery is not generally indicated in patients with pancreatic cancer with hematogenous metastasis. In this case, a comparatively long-term survival period was achieved after simultaneous resections.

[A case of vaginal metastasis of rectal cancer post -operation].

Vaginal metastasis is extremely rare, as is metastatic colorectal cancer. A 78-year-old woman was diagnosed with rectal cancer and uterine fibroid. Low anterior resection and simple hysterectomy was performed and the final diagnosis was fStage IIIa. Adjuvant chemotherapy was not performed. One year after the surgery, she was referred to our hospital with the chief complaint of hematuria. A tumor was observed in the posterior wall of the vagina. We performed vaginal mucosal resection and the pathological diagnosis was metastasis of rectal cancer. One year and 5 months after the surgery, we performed left inguinal node dissection and the pathological diagnosis was metastasis of rectal cancer. The patient has remained disease-free for 3 years and 5 months without adjuvant chemotherapy after resection of the vaginal metastasis.