[A Case of HER2 Positive Unresectable Gastric Cancer Leading to Conversion Therapy with Chemotherapy].

A 72‒year‒old man visited our hospital with a chief complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer at the body of the stomach. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2‒positive gastric cancer with invasion to the pancreas as well as the paraaortic lymph node, and multiple liver metastases were also observed. The cancer was judged to be cT4a, N2M1(H1 LYM: No. 16), cStage Ⅳ and thus was considered suitable for chemotherapy. We performed capecitabine plus cisplatin plus trastuzumab therapy. After 3 courses, the primary lesion and swollen lymph nodes decreased in size. After 20 chemotherapy courses, the primary lesion relapsed, so conversion surgery was performed. The patient underwent total gastrectomy, distal pancreatectomy, and partial resection of the liver. We planned to perform adjuvant chemotherapy, but the patient declined it because of anorexia. At 18 months after the operation, recurrence of the tumor was detected at the celiac artery. Chemotherapy was performed as follows: capecitabine plus trastuzumab 10 courses, ramucirumab plus paclitaxel, irinotecan, and nivolumab. However, the patient eventually died 71 months after the first visit.

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab].

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.

[A Case Report of Sigmoid Colon Cancer with Para-Aortic Lymph Node Metastases and Multiple Liver Metastases Resected after FOLFOX Therapy].

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.

[Two Cases of Advanced Gastric Cancer Diagnosed as Pathological Complete Response after Preoperative Chemotherapy with S-1 and Oxaliplatin].

We herein report 2 cases of gastric cancer treated by S-1 and oxaliplatin combination therapy before later undergoing gastrectomy. The pathological results of both cases demonstrated complete response. Case 1 had a giant tumor which was suspected to have invaded the pancreas. Case 2 was associated with extensive lymph node metastasis. Based on the findings of these 2 cases, preoperative chemotherapy with S-1 and oxaliplatin for advanced gastric cancer shows sufficient efficacy.

Peristomal Moisture-Associated Skin Damage and Independence in Pouching System Changes in Persons With New Fecal Ostomies.

PURPOSE: The purpose of this study was to evaluate factors related to peristomal moisture-associated skin damage (MASD) in patients who underwent ostomy surgery because of colorectal cancer, and their independence in pouching system changes. Findings were used to determine pre- and postsurgical care for these patients. DESIGN: Retrospective review of medical records. SUBJECTS AND SETTING: The study setting was an 800-bed hospital in metropolitan Tokyo, Japan. The sample comprised 89 patients (median age: 65 years; male vs female: 58 vs 31) who visited a stoma clinic within 8 weeks of ostomy surgery. Fifty-two subjects had ileostomies and 37 had colostomies; data were collected between January 2008 and July 2014. METHODS: Data were collected from outpatient and inpatient records. Potential relationships between MASD and independence in pouching system changes were evaluated via univariate tests to identify possible associations, followed by logistic regression analysis. RESULTS: Patients living with an ileostomy were more likely to experience peristomal MASD than were patients living with a colostomy (odds ratio [OR] = 3.782; 95% confidence interval [CI]: 1.34-10.64; P = .012). Analysis also found that patients with postsurgical chemotherapy were more than 2.5 times more likely to experience peristomal MASD than patients who did not require postoperative chemotherapy (OR = 2.702; 95% CI: 1.02-7.18; P = .046). We also found that patients 65 years or older were significantly more likely to have difficulty in changing their pouching system than were younger patients (OR = 7.193; 95% CI: 2.21-23.41; P = .001), as were those with diabetes mellitus (OR = 11.842; 95% CI: 2.56-54.77; P = .002). CONCLUSIONS: Patients undergoing ileostomy and those receiving postoperative chemotherapy are more likely to experience peristomal MASD. Older patients (>65 years) and those with diabetes mellitus are less likely to achieve independence. These findings influenced our management of persons undergoing ostomy surgery for management of colorectal cancer in our clinic. We recommend additional research using a larger and more diverse sample to confirm our findings.

[Long-Term Survival of Gastric Cancer with Multiple Liver and Lymph Node Metastases-A Case Report].

Currently, chemotherapy against unresectable advanced gastric cancer is progressing with the development new drugs and due to results of several clinical trials. Here, we reported a case of long-term survival of gastric cancer with multiple liver and lymph node metastases. A 68-year-old man was diagnosed with gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple liver metastases at another hospital. He was referred to our hospital from Yamashita Naika Syokakika. We administrated 4 courses of S-1 plus CDDP. The main tumor and all metastatic lesions were significantly reduced. Subsequently, total gastrectomy, partial liver resection, and left neck and para-aortic lymph node resection(conversion surgery)were performed. The cancer cell was remnant at the main tumor and para-gastric lymph node. No cancer cells were detected in another lesion(R0 resection). Postoperatively, only S-1 was administered. However, 28 months after undergoing gastrectomy, liver metastasis occurred. Therefore, S-1 plus oxaliplatin, paclitaxel plus ramucirumab, and CPT-11 plus CDDP were administered. Liver metastases again increased and decreased, respectively. However, 46 months after gastrectomy, liver metastasis recurred and nivolumab was administered. Subsequently, liver metastases disappeared. At 55 months after gastrectomy, rectal resection was performed against rectal cancer and partial liver resection against liver metastases. Cancer cells were not detected in the resected specimens.

[Neoadjuvant Chemoradiotherapy for Locally Advanced Carcinoma Associated with Anal Fistula].

The patient was a 59-year-old man. He was admitted to our hospital because of increasing anal pain with induration of the perianal region. There were large secondary orifices with mucous discharge on the left side of the perineal resion and buttock. We diagnosed adenocarcinoma on analysis of a biopsy specimen from induration of the perianal region. Pelvic CT and MRI showed that the tumor spreaded within the pelvis, with invasion of the prostate and sacrum. We performed neoadjuvant chemoradiotherapy preoperatively. After chemoradiotherapy, the tumor reduced in size greatly. We performed abdominoperineal resection and massive resection of skin of the perianal region. The defect of the pelvic floor and perianal skin was repaired using skin flap. The surgical margin was tumor free. Neoadjuvant chemoradiotherapy was considered effective for locally advanced carcinoma associated with anal fistula.

Overexpression of the S100A2 protein as a prognostic marker for patients with stage II and III colorectal cancer.

We aimed to identify a novel prognostic biomarker related to recurrence in stage II and III colorectal cancer (CRC) patients. Stage II and III CRC tissue mRNA expression was profiled using an Affymetrix Gene Chip, and copy number profiles of 125 patients were generated using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving recurrence were extracted as candidate biomarkers. The protein expression of the candidate gene was assessed using immunohistochemical staining of tissue from 161 patients. The relationship between protein expression and clinicopathological features was also examined. We identified 9 candidate genes related to recurrence of stage II and III CRC, whose mRNA expression was significantly higher in CRC than in normal tissue. Of these proteins, the S100 calcium-binding protein A2 (S100A2) has been observed in several human cancers. S100A2 protein overexpression in CRC cells was associated with significantly worse overall survival and relapse-free survival, indicating that S100A2 is an independent risk factor for stage II and III CRC recurrence. S100A2 overexpression in cancer cells could be a biomarker of poor prognosis in stage II and III CRC recurrence and a target for treatment of this disease.

Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.

BACKGROUND: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). METHODS: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. RESULTS: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. CONCLUSION: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients.

Diagnostic performance of multidetector row computed tomography for assessment of lymph node metastasis in patients with distal rectal cancer.

BACKGROUND: The accurate preoperative diagnosis of depth of tumor invasion and nodal status in distal rectal cancer is important because neoadjuvant chemotherapy or lateral pelvic lymph node dissection is indicated for patients with T3-T4 tumor or nodal involvement. This study aimed to determine the optimal cutoff value for predicting lymph node metastasis in patients with distal rectal cancer using multidetector row computed tomography (MDCT). METHODS: The study investigated 77 patients who had undergone surgery for distal rectal cancer at a single institution between 2008 and 2011. Diagnostic performance for depth of tumor invasion and mesorectal and lateral pelvic lymph node metastases was evaluated. The optimal cutoff value was determined by receiver operating characteristic curve analysis. RESULTS: For predicting mesorectal and lateral pelvic lymph node metastasis, MDCT had a sensitivity of 0.36 and 0.89 and a specificity of 0.78 and 0.97, respectively. The optimal cutoff values of major and minor axes lengths for predicting mesorectal lymph node metastasis were 6.5 mm and 5.7 mm, respectively. The areas under the curve (AUCs) were 0.82 and 0.88, respectively. For predicting lateral lymph node metastasis, the optimal cutoff values were 9 mm for the major axis and 6 mm for the minor axis. Both AUCs were 1. CONCLUSIONS: Using MDCT, the optimal cutoff value of minor axis length for predicting mesorectal and lateral pelvic lymph node metastases in patients with distal rectal cancer was 6 mm. The accuracy of MDCT was satisfactory for predicting lateral pelvic lymph node metastasis.

Over-the-scope-clipping system for anastomotic leak after colorectal surgery: report of two cases.

An anastomotic leak is one of the major complications following colorectal surgery. Standard treatments for anastomotic leak are total parenteral nutrition or temporary ileostomy. The over-the-scope-clipping (OTSC) system was originally developed to treat intestinal perforation or to close the tissue after natural orifice transluminal endoscopic surgery. Two cases of successful management of an anastomotic leak after colorectal surgery using the OTSC system are reported. One patient avoided a temporary ileostomy. In the other, hospitalization was shortened by the use of the OTSC system. The OTSC system can be a potential option in the management of anastomotic leaks after colorectal surgery.

[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.

[Three cases of anal squamous cell carcinoma treated with chemoradiotherapy].

We reviewed the clinical records of 3 patients with anal squamous cell carcinoma treated with chemoradiotherapy (CRT). Case 1: The patient was diagnosed with StageI (T1N0M0) and treated with cisplatin (CDDP)+5-FU+radiation. Chemotherapy was discontinued after the second course because of adverse effects. She achieved partial response(PR), and underwent a salvage surgery. Seven months after the surgery, she died from other comorbidities. Case 2: The patient was diagnosed with Stage I (T1N0M0) and treated with CDDP+5-FU+radiation. Chemotherapy was discontinued after the second course because of adverse effects. He achieved PR, and underwent a salvage surgery. Three years and 7 months after the surgery, he died from other comorbidities. Case 3: The patient was diagnosed with Stage IIIB (T4N1M0) and treated with MMC+S-1+radiation. Chemotherapy was discontinued after the first course because of adverse effects. She achieved complete response (CR) and is still surviving without cancer recurrence. We conclude that CRT is an effective treatment for anal squamous cell carcinoma.

Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis.

We identified a novel prognostic biomarker for the distant metastasis of colorectal cancer (CRC) using comprehensive combined copy number and gene expression analyses. Expression of mRNA in CRC tissue was profiled in 115 patients using an Affymetrix Gene Chip, and copy number profiles were generated for 122 patients using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving distant CRC metastasis were extracted as candidate biomarkers. Expression of the candidate gene mRNA was validated in 86 patients using quantitative reverse transcription polymerase chain reaction assays. Expression of the protein encoded by the candidate gene was assessed using immunohistochemical staining of tissue from 269 patients. The relationship between protein expression and clinicopathologic features was also examined. Following combined copy number and gene expression analyses, three genes linked to distant metastasis of CRC were extracted as candidate biomarkers. The expression of NUCKS1, reportedly overexpressed in several cancers other than CRC, was significantly higher in CRC tissue than in normal tissue. Overexpression of the NUCKS1 protein in CRC cells was found to be associated with significantly worse overall survival and relapse-free survival, indicating that NUCKS1 is an independent risk factor for CRC recurrence. The overexpression of NUCKS1 in cancer cells could be used as a CRC prognostic marker and might also be a target for treatment of this disease.

[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 case report of stage IV cecal cancer exhibiting a complete response to multidisciplinary therapy].

A 52-year-old man underwent ileocecal resection for cecal cancer, followed by left hepatectomy and S6 partial resection for liver metastasis. A month later, abdominal computed tomography revealed metastases in the mediastinal lymph nodes, para-aortic lymph nodes, and left adrenal gland. After 4 courses of the capecitabine plus oxaliplatin(CapeOX) regimen and 4 courses of CapeOX plus bevacizumab, a complete response was observed regarding the lymph nodes metastasis. Then, left adrenalectomy was performed for the residual left adrenal metastasis. CapeOX plus bevacizumab was administered as a postoperative chemotherapy for 8 courses, Capecitabine was started due to adverse reactions, such as peripheral neuropathy (grade 2) and a gastric ulcer. After the gastric ulcer healed, capecitabine plus bevacizumab was administered for 5 courses. The patient has had no recurrence for almost 2 years since the resection of the adrenal metastasis.