[A Case of Liver Metastasis of Colorectal Cancer Successfully Treated with Hepatic Arterial Infusion Chemotherapy after Systemic Chemotherapy Was Difficult to Administer].

The patient underwent partial sigmoid colon resection for sigmoid colon cancer with hyper CEA blood(1,110.6 ng/mL) and concurrent liver metastases mostly in the right lobe of the liver, followed by systemic chemotherapy(SOX plus BEV). Seven courses of chemotherapy resulted in PR on imaging, and CEA was reduced to 5.0 ng/mL, which was within reference values. As he continued chemotherapy, frequent hematologic toxicities and adverse events forced frequent dose reductions and changes in the chemotherapy schedule. About 2 years after surgery(19 courses of SOX plus BEV), the liver metastases became slightly enlarged on imaging, and the CEA was also increasing. The patient did not wish to undergo systemic chemotherapy and requested hepatic arterial infusion chemotherapy(HAIC), which has relatively few side effects and adverse events. HAIC with pyrimidine fluoride alone is ongoing for 22 courses, and tumor markers have decreased again with PR on imaging. Performance status has been good without hematologic toxicity or adverse events for approximately 1 year during the course of HAIC. HAIC is a weakly recommended therapy in the colorectal cancer treatment guidelines, but it is considered one of the most effective therapies with relatively few side effects.

[A Case of Complete Remission in a Patient with Synchronous Double Cancers of the Breast and Lung].

The patient is a 74-year-old woman. She had breast cancer(invasive ductal carcinoma, ER[+], PgR[+], HER2[-], Ki-67: 30-40%)and primary right lung cancer with lumbar metastasis, which led to the diagnosis synchronous double cancers of the breast and the lung. We decided to precede surgery for lung cancer because breast cancer was indicated hormonal receptor positive. Breast cancer is treated with anastrozole, thoracoscopic right upper lobectomy was performed for the lung cancer. Radiation therapy was performed for metastatic bone tumors. 13 months later, partial mastectomy sentinel lymph node biopsy performed. The histopathological diagnosis of breast cancer was pT2, pN0, cM0, pStage ⅡA, and histological response was Grade 2a. The remaining breast was treated radiation therapy. The breast cancer has not recurred and is doing well 6 months after surgery. As for primary lung cancer, 19 months have passed since surgery, and the patient is in complete remission without recurrence.

[A Case of Small Intestinal Metastasis from Lung Cancer].

An 88-year-old man underwent thoracoscopic lower lobectomy for left lung cancer at the age of 87. Ten months later, he was examined closely for abdominal distention, frequent constipation, and anemia with a decreased Hb of 6.1 g/dL. The CT scan revealed an irregular tumor with contrast effect. The patient was diagnosed with malignant tumor of small intestine. At laparotomy, a tumor of 5 cm in diameter was found in the jejunum, and small bowel resection was done. Pathological examination revealed that the tumor was a metastasis of lung cancer. Seven months later, the patient is currently an outpatient, with no evidence of cancer recurrence.

[The Short-Term and Long-Term Outcomes of Laparoscopic and Open Distal Gastrectomy].

We compared laparoscopic gastrectomy and open gastrectomy for the early gastric cancer. Laparoscopic surgery was comparable to laparotomy in terms of operation time and number of lymph node dissections, significantly less bleeding volume, postoperative hospital stay, and lower postoperative complication rate. As a result of E-PASS, surgical invasion was significantly low and the overall risk score was also significantly low. There was no difference in cancer-specific survival, and overall survival was significantly better with laparoscopic distal gastrectomy. Based on the above, laparoscopic gastrectomy is considered to be superior to open gastrectomy as a surgical technique for the early gastric cancer.

[A Case of Rectal GIST under Long-Term Follow-Up with Oral Imatinib].

The patient was a 79-year-old man with complaints of defecation difficulties and constipation. CT scan showed a 7.5 cm diameter mass in the lower rectum, and biopsy revealed GIST. MRI findings suggested prostate invasion, and the patient was started treatment with imatinib. Six months later, the tumor shrank to 4.5 cm in diameter. However, the patient refused surgery and continued taking Imatinib. The tumor continued to shrink gradually. Currently, 7 years later at the age of 86, it is only 2 cm in diameter and its inside has almost completely been replaced with calcifications.

[A Case of Colon Cancer with Synchronous Multiple Metastases Successfully Treated with Combined Chemotherapy].

A 68-year-old man having a descending colon cancer with multiple metastases of up to 9.5 cm in the right lobe of the liver(T3, N0, M1a)underwent laparoscopic colon resection for anemia control. Chemotherapy with mFOLFOX6 plus Bmab was administered postoperatively. Because this treatment had little effect, FOLFIRI plus Pmab was initiated 3 months later. A significant reduction in the tumor size was observed. Therefore, we performed laparotomy. However, the liver metastasis had invaded the inferior vena cava, which was not resectable. After the second surgery, we introduced the 5-FU hepatic arterial injection port ia plus Pmab iv, which was effective for 8 months. We then restarted chemotherapy with FOLFIRI plus Pmab. However, the tumor became more enlarged; therefore, we changed the chemotherapy regimen to SOX plus Bmab. Partial reduction in the tumor size was observed again, and the effects lasted for a while. The patient continued visiting the outpatient clinic with almost no symptoms for more than 1 year. He died of the primary cancer 3 years and 8 months after the first visit. We report a case of liver metastasis of colon cancer that could have been controlled successfully by repeatedly using the same pharmacotherapy.

[A Case of Hyaline Vascular-Type Castleman's Disease].

The patient was a 29-year-old female with a chief complaint of transient right-sided abdominal pain. A CT scan revealed homogenously contrasted tumor of 4 cm in diameter with smooth margins and clear borders in the lower part of the pancreatic head. The tumor was contrast-enhanced on MRI and stained on abdominal angiography using the proximal branch of the right colonic artery as a feeding vessel. PET scan showed moderate accumulation. Malignancy could not be ruled out, and tumor resection including the ascending colon was performed. The pathological diagnosis was hyaline vascular-type Castleman's disease in the mesentery of the colon.

[Study on Gastric Cancer Surgery in an Aged Society].

We examined the occurrence of complications following gastric cancer surgery in the elderly and its influence on the prognosis of reduction surgery.The study included 805 surgical cases of gastric cancer; elderly, middle-aged, and young patients were examined.In the elderly patients, there was a tendency to undergo reduction surgery.According to the gastric cancer treatment guidelines, 28.9% of the elderly patients, 5.3% of the middle-aged patients, and 0% of the young patients did not satisfy the criteria for lymph node dissection. The incidences of postoperative complications were 25.6%, 23.0%, and 13.4%in the elderly, middle-aged, and young patients, respectively, with a higher tendency seen in elderly patients.In elderly patients, the survival rate was examined separately for each postoperative complication, but no significant difference was noted.Additionally, the survival rate was assessed for the limited surgery and standard surgery groups; however, no significant difference was noted.Therefore, it is recommended that the optimal lymph node dissection range be determined in the elderly with respect to the general condition.

[Comparison of Laparoscopic Gastrectomy and Open Gastrectomy Outcomes in the Elderly].

In this study, we compared the outcomes of laparoscopic gastrectomy and open gastrectomy in the elderly. Laparoscopic surgery was comparable to laparotomy in terms of the operation time and number of lymph node dissections and was significantly associated with less bleeding volume, duration of postoperative hospital stay, and a lower postoperative complication rate. Surgical invasion and overall risk scores were significantly low as assessed by the Estimation of Physiologic Ability and Surgical Stress(E-PASS)system. Based on these findings, laparoscopic gastrectomy can be considered to be superior to open gastrectomy as a surgical technique for the elderly.

[A Case of Unresectable Sigmoid Colon Cancer with Peritoneal Dissemination Treated with Chemotherapy after an Unintended Emergency Jejunostomy Formation].

A 33-year-old man was diagnosed with bowel obstruction due to advanced sigmoid colon cancer and underwent an emergency laparotomy. The sigmoid colon cancer turned out to be unresectable because of firm invasion to the retroperitoneum with severe adhesions and diffuse dissemination. Therefore, unplanned jejunostomy was performed, which was complicated by high-output stoma and short bowel syndrome. His condition was stable enough to receive chemotherapy via parenteral nutrition and parenteral electrolyte solution infusion added to the diet. mFOLFOX6 plus cetuximab therapy was started 4 weeks postoperatively. Although oxaliplatin was discontinued because of worsening numbness, he was sustained without cancer progression by receiving chemotherapy for a year. Chemotherapy was interrupted by a Candida fungemia 13months postoperatively, and he died 4 months later. Patients with jejunostomy may have difficulty absorbing enough water and nutrients in the intestine; therefore, they are at risk of dehydration and electrolyte depletions due to high stomal output, and malnutrition due to the short bowel. These complications may prevent colorectal cancer patients with jejunostomy to be indicated for chemotherapy.

[Stage â £ Breast Cancer with Difficulty in Initiating Chemotherapy-A Case Report].

We report a case of breast cancer(T4b[skin], N1, M1[lung], ER-, PR-, HER2 3+)in a 63-year-old woman with liver dysfunction of unknown cause(T-Bil 3.6mg/dL, ALP 3,483 U/L, AST 214 U/L, ALT 320 U/L, g / -GTP 1,943 U/L). Further- more, serum CA19-9(4,670 U/mL)and HbA1c(8.8%)levels were both elevated. First, she underwent chemotherapy with trastuzumab and capecitabine. Subsequently, liver dysfunction relieved gradually. CA19-9 and HbA1c levels were also decreased, but the tumor size was NC. Subsequently, trastuzumab, pertuzumab, and docetaxel were administered, as liver function became normal. The tumor shrank significantly after this treatment. Finally, she underwent mastectomy. Five years after the first visit, she has continued chemotherapy, with lung metastases almost scarred(CR).

[A Case of Successful Treatment with Gemcitabine plus Nab-Paclitaxel Therapy for Nonresected Pancreatic Body Cancer(Stage IVb)].

A 61-year-old woman was introduced for consultation with a chief complaint of frequent vomiting. CT revealed a pancreatic body cancer approximately 40mm in size; an invading stenosis from the horizontal part of the duodenum to the jejunum, superior mesenteric artery, and portal vein, splenic vein obstruction, lymphadenopathy, and some ascitic fluid. We diagnosed a passage disorder due to the invasive stenosis from the horizontal part of the duodenum of the pancreatic body cancer to the jejunum, and subsequently performed a duodenum and jejunum bypass operation. We controlled cancer pain with opioid analgesia, and S-1 monotherapy was chosen as the primary chemotherapy. A tendency to increase and the cancer pain of the tumor was aggravated when 5 courses took effect, so gemcitabine plus nab-paclitaxel(GEM plus nab-PTX)therapy was chosen as the second-line chemotherapy because of adverse Grade 3 events due to difficulties with S-1 internal use. We tapered off the opioid analgesia dosage because the cancer pain was relieved after 1 course. The imaging top indicated stable disease at the end of 5 courses, but the pain was relieved so opioid pain killers were unnecessary. Foreign continuation is under treatment with 10-course GEM plus nab-PTX therapy after initial diagnosis. Currently, the patient has undergone 5 courses of S-1 for approximately 18 months, and has achieved stable disease. The only adverse events were nausea, fatigue, Grade 1 malaise, and Grade 2 alopecia, as detected with imaging.

[A Case of Advanced Rectal Cancer in Which Long-Term Disease-Free Survival Was Achieved by Multidisciplinary Therapy].

The is a case involving a 55-year-old man with advanced rectal cancer(type 3). MRI showed urinary tract and regional lymph node metastases without distant metastasis. The tumor was reduced(PR)after neoadjuvant chemotherapy(mFOL FOX6 plus Bmab, 4 courses). The patient underwent an abdominoperineal resection. Because infiltration of the tumor into the lower urinary tract was deep, it was also resected and repaired. The clip was placed to mark the repaired region. Pathological examination revealed that excision stump at the anterior wall of the urethra was cancer positive without lymph node metastasis. He was then administered chemotherapy(mFOLFOX6 4 courses)and irradiated 60 Gy in both sides of the inguinal lymph node to prevent metastasis to the pelvicdomain. One year and 6 months postoperatively, as the left inguinal lymph node swelled at 3.7 cm irregularly, he further received chemotherapy(FOLFIRI 8 courses). The size of the lymph node became normal with a good response to FOLFIRI. Six years postoperatively, he remains alive and well with no evidence of recurrence.

[Two Cases of Lung Metastasis from Breast Cancer Successfully Treated with Endocrine Therapy].

We report 2 cases of lung metastasis from breast cancer that were successfully treated with endocrine therapy.Case 1 is a 69-year-old woman with cirrhosis of the liver caused by hepatitis C.She underwent surgery for left breast cancer at the age of 58, and surgery for right breast cancer at the age of 65.Four years later, she was diagnosed with lung metastasis of breast cancer.She received letrozole and the treatment was effective.Because the severity of the pleural effusion increased 3 years later, fulvestrant was subsequently administered.As a result, the patient remained in good health for 1 year.She died 5 years later.Case 2 is a 72-year-old woman who underwent right breast cancer surgery 12 years previously.She complained of respiratory discomfort as a result of right pleural effusion from lung metastasis.She was hospitalized for cancer lymphangitis that had deteriorated.The patient was immediately treated with fulvestrant and her symptoms improved significantly; the pleural effusion also disappeared.Sixteen months later, no recurrence has been observed.

[A Case of Gastric Cancer with Adrenal Metastasis That Responded to Chemotherapy].

A 69-year-old man complained of abdominal pain and appetite loss. Advanced gastric cancer with bilateral adrenal metastases( stage Ⅳ)was revealed via an examination. XP(cisplatin and capecitabine)chemotherapy was administered. As a result, the tumor was reduced prominently, and his symptoms disappeared 3 months later. However, the cancer recurred 7 months later. Because of the tumor growth, the stent was detained for a passage obstacle by local increase of the tumor 12 months later. The patient died 14 months later.

The rs6983267 SNP is associated with MYC transcription efficiency, which promotes progression and worsens prognosis of colorectal cancer.

BACKGROUND: The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC. METHODS: Array comparative genomic hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157 primary CRC tissues. Expression profiles were analyzed by means of extraction expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and microsatellite instability were also examined in 107 of the 157 cases. RESULTS: aCGH analysis revealed two clusters; more frequent genomic copy number alteration (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster A. The average CNA was higher in samples containing the major allele (GT/TT) of rs6983267 than in those containing the minor allele (GG). Additionally, MYC expression was the highest in samples containing the GG allele (n = 18), followed by the GT and TT alleles (n = 41 and 48, respectively). EEM analysis revealed dominant up-regulation of MYC in samples containing the minor allele. Moreover, the presence of the minor allele in a MYC-positive, CNA-negative context predicted a poorer prognosis than the presence of the major allele in a MYC-negative, CNA-positive context in CRC. CONCLUSIONS: The presence of the minor allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up-regulation of MYC transcription. Furthermore, progression of CRC may require global CNA in the presence of the major allele and with lack of MYC transcription.

Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer: clinical significance.

This study focused on a cell cycle regulatory gene, FBXW7, which ubiquitinates c-Myc and cyclin E and promotes exit from the cell cycle. We determined the expression level of FBXW7 in colorectal cancer (CRC) cases, correlated those values with clinicopathologic features, and characterized the molecular mechanism of reduced expression of FBXW7 in CRC cells in vitro. FBXW7 mRNA and protein expression were evaluated in 93 CRC cases. Using CGH array, the copy number aberrations of the flanking region of FBXW7 were evaluated in another 130 CRC specimens. In vitro analysis of FBXW7 gene silencing in CRC cells was conducted. FBXW7 mRNA expression was significantly lower in tumor tissues than the corresponding normal tissues. The low FBXW7 expression group showed a significantly poorer prognosis than patients in the high expression group. A concordant relationship was observed between the incidence of FBXW7 repression and the genetic alteration. The incidence of genetic alteration was associated with the stage of disease progression. In vitro, FBXW7-specific siRNA enhanced expression of c-MYC and cyclin E proteins and up-regulated cell proliferation. Genetic alterations in tumors led to the loss of FBXW7 expression and increased cell proliferation. FBXW7 expression provides a prognostic factor for patients with CRC.

Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells.

BACKGROUND: We previously determined that cancer stem-like cells may influence the susceptibility of colorectal cancer (CRC) cells to chemotherapeutic agents. Although Takahashi and Park identified a set of induced pluripotent stem cell (iPS)-related genes required for normal stem cell maintenance, the precise role of iPS-related gene expression in CRC pathogenesis remains to be determined. The purpose of this study was to clarify the clinical relevance of "stemness"-regulating gene expression in CRC cases. MATERIALS AND METHODS: Cancer cells were excised from tissues of 79 CRC cases by laser microdissection (LMD), and quantitative RT-PCR was used to evaluate expression levels of the iPS-related genes c-MYC, SOX2, OCT3/4, LIN28, KLF4, and NANOG, and to identify any associations between their expression and clinicopathological CRC progression. RESULTS: We found that LIN28 expression is significantly associated with lymph node metastasis (p = 0.018) and Dukes stage (p = 0.0319). SOX2expression is also correlated with lymph node metastasis. Furthermore, the ten cases with Dukes D disease expressed significantly higher levels of SOX2transcript than the other 69 cases (p = 0.0136). In contrast, KLF4 expression was inversely related to Dukes stage. Expression of c-MYC, OCT3/4, and NANOG did not appear to have clinical relevance in CRC cases. CONCLUSION: The present analysis strongly suggests that altered expression of several iPS-related genes plays a role in CRC pathogenesis.

Over- and under-expressed microRNAs in human colorectal cancer.

MicroRNAs (miRNAs) constitute a class of small (21-23 nucleotides) noncoding RNAs that function as post-transcriptional gene regulators. It is becoming increasingly clear that altered miRNA expression correlates with the pathogenesis of cancers. The purpose of this study was to determine the up-regulated miRNAs in human colorectal cancer. Total RNA was isolated from cancer tissues and corresponding noncancerous tissues from surgically resected colorectal cancers. The expression profiles of miRNAs were determined using a miRNA microarray containing 455 human miRNA probes. The expression status of selected miRNAs in paired clinical samples was then investigated by real-time RT-PCR. Twenty-one miRNAs were identified by miRNA array analysis as overexpressed in colorectal cancer tissues compared to normal epithelial tissues. Among them, the expression of miR-31, miR-183, miR-17-5p, miR-18a, miR-20a and miR-92 were confirmed to be significantly higher in cancer tissues than in normal tissues (P<0.05). In contrast, the expression of miR-143 and miR-145 in cancer tissues were significantly lower than in normal tissues (P<0.05). The miR-18a overexpression group tended to have a poorer clinical prognosis than the low expression group (P=0.07). We identified miRNAs that were overexpressed or under-expressed in colorectal cancers and which may be correlated with colorectal carcinogenesis.

A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases.

BACKGROUND: Recently, a marker for predicting metastasis or recurrence precisely in solid cancers has been focused on instead of the identification of isolated tumor cells detected by epithelial genes in circulating system. We identified a candidate marker in gastric cancer by microarray and validated it through a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: To identify metastasis-related genes, we performed cDNA microarray analysis of total RNA from whole bone marrow blood from six cases with metastasis and three cases without metastasis. We determined clinical significance of the identified gene by microarray analysis with quantitative real-time RT-PCR in bone marrow and peripheral blood from 810 cases of gastric cancer. RESULTS: We focused on membrane type 1 matrix metalloproteinase (MT1-MMP) as a candidate marker to predict distant metastasis among identified genes. MT1-MMP-positive expression in peripheral blood was associated with incidence of peritoneal dissemination, lymphatic permeation, vascular permeation, and lymph node metastasis. MT1-MMP-positive expression in bone marrow was also significantly related to the incidence of distant metastasis and peritoneal dissemination. CONCLUSION: The expression of MT1-MMP in peripheral blood from gastric cancer cases was a powerful indicator of distant metastasis especially for peritoneal dissemination. The presence of MT1-MMP-expressing cells in bone marrow indicated higher risk for distant metastasis in gastric cancer cases.