[A Case of Advanced Gastric Cancer with Synchronous Liver Metastases Responding to Preoperative Combination Chemotherapy with S-1 plus Oxaliplatin(SOX)].

A 67-year-old man was admitted to our hospital because of anemia and weight loss, and diagnosed with a type 3 tumor in the upper gastric body. Pathological examination suggested moderately differentiated adenocarcinoma with immunohistochemically negative staining for HER2. Abdominal CT revealed thickening of the gastric wall and multiple liver metastases. The clinical findings suggested Stage IV disease(T4aN0M1). Chemotherapy was administered with a combination of S-1 plus CDDP(SP). However, the level of CEA(ng/mL)increased from 49.2 to 634.6, and the treatment schedule was changed to a combination of S-1 plus oxaliplatin(SOX). After 3 courses of the SOX regimen, abdominal CT showed a reduction of liver metastases and the level of CEA decreased to 8.4 ng/mL. We performed total gastrectomy with D1 lymph node dissection in September 2016. Post-operative pathological findings were ypStage IV (T3N0M1)and chemotherapeutic effect was grade 2. CT scan revealed regrowth of the tumor in S2 3 months after the operation. The patient underwent transcatheter arterial chemoembolization(TACE)followed by a regimen of paclitaxel plus ramucirumab(PTX/RAM). At present, he is being treated with the PTX/RAM regimen in the outpatient department with no signs of tumor growth. Although the prognosis of gastric cancer with synchronous liver metastases is very poor, it is possible for survival to be prolonged with multimodality therapy.

[A Case of Successful Repeated Metastectomy for Peritoneal Recurrence of over 90 Years Old Colon Cancer Patient].

Treatment for cancer recurrence in elderly people over 90 years old is usually less advantageous in chemotherapy, and surgical resection is considered rather invasive if cure can be expected. We experienced a case of colon cancer in which recurrence of peritoneal dissemination was discovered and resected at the age of 90 years and at 92 years twice. Laparoscopic surgery for colon cancer at the age of 89 years was performed. At 13 months after primary surgery, CT revealed a nodule of 10mm in diameter in the abdominal cavity, and it was also positive in PET-CT. Because there was no other recurrent foci, radical resection was performed. After 14 months(2 years and 4 months after primary surgery), a 17mm large nodule was pointed out and radical resection was done again. Three years later(5 years and 6 months from primary surgery)have passed, she survives without recurrence at 95-years-old and 4 months without any decline in QOL. When recurrence of peritoneal dissemination can obtain radicality in resection, even for elderly persons, surgery should be considered if invasion is minor.

[Curative Resection for Metastatic Lower Rectal Tumor from Ovarian Cancer - Report of a Case].

We here report the case of a 56-year-old female patient who underwent curative resection for right ovarian cancer with intraperitoneal dissemination and liver metastases. She received following adjuvant chemotherapy, and had been visited hospital for regular follow-up since then. One and half a year after surgery, blood examination showed increasing value of CA125. Contrast-enhanced CT scan revealed a tumor whose long diameter was 5 cm at front side of lower rectum. Following MRI and PET-CT examinations indicated the pelvic tumor as recurrence of ovarian cancer, so that laparotomy was carried out. As the tumor was palped through Douglas cavum, we performed low-anterior rectal resection for en bloc tumor extirpation. Tumor cells mainly developed at peri-rectal wall and proper muscle by HE staining of pathological findings, and ER(positive), vimentin(positive), CD56(positive), synaptophysin(negative)and chromogranin A(negative)by immunostaining indicated the tumor as metastasis of ovarian cancer. Though rectal metastasis from ovarian cancer is basically rare, it might be necessary to rule out possibility of metastatic colon tumor from ovarian cancer when treating patient with rectal tumor who had underwent surgery for ovarian cancer before.

[An 85-Year-Old Man with Lymph Node Metastasis of Recurrent Rectal Cancer Treated UsingProton Beam Therapy].

There are few reports that describe the efficacy of proton beam therapy for lymph node metastasis of recurrent rectal cancer, and carbon ion radiotherapy yields higher local tumor control rates. Proton beam therapy needs a longer treatment period but is less toxic to adjacent healthy organs compared to carbon ion radiotherapy. Here we report an 85-year-old man who underwent curative surgery for rectal and sigmoid cancer at the age of 76 years. After 4 years and 2 months, he had liver metastases at S3 and S8, both of which were resected. Eight years and 6 months after primary resection, CT imaging revealed a solitary lymph node metastasis of 28mm in the minor axis, adjacent to the portal vein and IVC. Because of the location and patient's age, proton beam therapy was selected as the treatment strategy, rather than surgery or chemotherapy. A total of 67.5 GyE/25 fx proton beam therapy was applied. CT imaging 4months after irradiation revealed a partial response(PR)and the tumor had shrunk to 8mm. PR continued for 2 years and 1 month. Although the tumor relapsed after 3 years of irradiation and had grown to 16 mm, the patient had no adverse events or symptoms throughout this period. Proton beam therapy may be one of the options for tumors at difficult locations in fragile patients because of its reduced toxicity.

[A Case of Advanced Rectal Cancer Resulting in a Pathologically Complete Response after Neoadjuvant Chemotherapy].

A 61-years-old man was admitted to our hospital because of abdominal pain. Colonoscopy revealed a type 2 tumor in the rectum, which was diagnosed as low differentiated adenocarcinoma. At least 8 abdominal lymph adenopathies were enhanced on contrast-enhanced CT. We diagnosed stage cT3N2H0M0P0, cStage III b. Because of the risk of a poor prognosis, we tried neoadjuvant chemotherapy for the purpose of down staging. A CRT was prevented by Clostridium difficile enteritis, but we completed 80% of the regimen. Laparoscopic abdominoperineal resection was performed after 4 months of chemotherapy. The specimen contained no tumor lesion, and the pathology results were no residue of adenocarcinoma, status postchemoradiation therapy, Grade 3.

[A Case of T1a Early Gastric Cancer That Metastasized to the Right Femoral Muscles Six Years and Seven Months after Radical Surgery].

A 49-year-old woman presented to our hospital complaining of abdominal distension and right thigh edema 6 years and 7 months after undergoing total gastrectomy for early gastric cancer in December 2008. The histopathological type of the tumor was poorly differentiated adenocarcinoma. The pathological findings led to a diagnosis of T1aN2M0, Stage II A disease. In August 2015, abdominal CT and MRI revealed para-aortic lymph node swelling, ascites, and a tumor on the right femoral muscles. We performed a needle biopsy of the femoral muscle, and the final diagnosis was intramuscular metastasis from the primary gastric cancer. We initiated chemotherapy using TS-1 plus docetaxel. TS-1(80mg/m2/day)was orally administered for 2 weeks followed by a 1-week drug-free period, and 1 course of docetaxel(40mg/m2)was administered intravenously on day 1. After 2 courses of this regimen, the tumor on the right femoral muscles was reduced in size. However, diarrhea and leukopenia were observed, and the treatment schedule was changed to several other chemotherapy regimens. The patient died of progressive disease 6 months after the diagnosis of muscle metastasis. We report a rare case of late recurrence after curative resection in a patient treated for T1a early gastric cancer.

[Right Hemi-Colectomy for a Metastatic Transverse Colon Tumor from Breast Cancer Following Bilateral Breast Cancer Resection - A Case Report].

We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery. Colonoscopy revealed stenosis of the same lesion with an edematous mucosa and sclerosis. Using immunohistochemistry, a biopsy specimen from the lesion tested positive for CK AE1+AE3, and negative for CD20(-)and CD3 (-). As a result, the tumor was diagnosed as a poorly differentiated adenocarcinoma. We performed right hemicolectomy to avoid her intestinal obstruction. Tumor cells were mainly present at the subserosa, according to HEstaining. Using immunostaining, the cells were tested for the following markers: CDX2(-), GCDFP15(weakly positive), CK7(strongly positive), CD20(partially positive), E R(+), PgR(-), and HER2(1+), characterizing the tumor as metastasis of breast cancer. Although gastro-intestinal metastasis from breast cancer is rare, and colon metastasis is even rarer, it might be necessary to rule out the possibility of a metastatic colon tumor from breast cancer when treating patients with a colon tumor who have undergone surgery for breast cancer.

[Laparoscopic Surgery for T4b Colorectal Cancer].

BACKGROUND: It is considered difficult to perform laparoscopic surgery for colorectal cancer with T4b that is directly invades to adjacent organs. This retrospective study evaluated pT4b colorectal cancer in terms of the efficacy of laparoscopic surgery. METHODS AND RESULTS: Forty-six cases with pT4b colorectal cancer that occurred between 2006 and 2014 were investigated. Laparoscopic surgery (LAC) was performed in 20 cases, of which 5 were conversions, and open surgery (OC) was performed in 26 cases. Pathologically-proven invaded organs resected by LAC were the abdominal wall (n=6), greater omentum (n=5), small intestine or colon (n=3), bladder, appendix, or ovary (n=1). Organs resected by OC were the abdominal wall (n=8), bladder (n=5), colon, greater omentum, or small intestine (n=3), stomach, ovary, spermatic duct (concurrent with bladder), prostate, or sacrum (n=1). Operation time (median) was 275 min for LAC and 260 min for OC. Blood loss (median) was 100 mL for LAC and 410 mL for OC. The duration of hospital stay (median) was 15 days after LAC and 18 days after OC. There were 2 cases with morbidities greater than Grade 3 after LAC and 1 case after OC. There was 1 hospital death in the OC group. CONCLUSION: Laparoscopic surgery for T4b colorectal cancer can be feasible in select cases.

[Examination of the usefulness of the self-expanding metallic stent for ileus due to colorectal cancer].

Ileus due to colon cancer often develops from a timing and the method of the operation and perioperative care, comparing with ordinary cases. The use of self-expanding metallic stent (SEMS) was first authorized by insurance and became available nationwide in Japan in 2012. Insertion of SEMS for ileus due to colorectal cancer is useful as a bridge to surgery (BTS) approach and releases stenosis as palliative care. Here we report 5 successful cases of anastomosis performed during a laparoscopic operation for ileus due to colorectal cancer after BTS using SEMS. Successful SEMS insertion for colon cancer ileus enables observation of the proximal side. Because the decompression efficiency with SEMS is high, laparoscopic surgery becomes possible. SEMS insertion as a BTS is useful for ileus due to colorectal cancer.

[Response to neoadjuvant chemotherapy in breast cancer as assessed by subtype].

The aim of this study was to investigate the responses to neoadjuvant chemotherapy (NAC) in breast cancer according to subtype. The study included 69 women who received NAC at our hospital between January 2004 and January 2013. Complete response( CR) was achieved in 14 patients( 20.3%) and partial response( PR) was achieved in 37 patients (53.6%).CR and PR rates according to subtype were as follows: 0% and 57.1% for the luminal type, 0% and 66.7% for the luminal-human epidermal growth factor receptor (HER)-2 type, 16% and 56% for the triple negative type, and 58.8% and 41.2% for the HER2 type, respectively. The CR rate was the highest among patients with HER2-type breast cancer. Trastuzumab was additionally administered to 12 patients with HER2-type breast cancer, and the CR rate among these patients was significantly higher after trastuzumab treatment( 75%).Thus, it is important to select a treatment strategy for breast cancer on the basis of the subtype diagnosed.

[Resection and postoperative multidisciplinary treatment for hepatocellular carcinoma with massive portal venous tumor thrombus-a single-center experience].

BACKGROUND: Patients with advanced hepatocellular carcinoma( HCC) with massive portal venous tumor thrombus (PVTT) face a dismal prognosis as no standard therapy has been defined. A cancer board was established at our hospital 5 years ago. OBJECTIVE: The aim of this retrospective study was to evaluate our surgical and multidisciplinary treatment for HCC with massive PVTT. PATIENTS AND METHODS: From July 2007 to June 2012, 8 patients with HCC with PVTT extending into the main portal trunk were treated. Hemihepatectomy and PVTT removal were performed in 4 patients. Postoperative multidisciplinary treatment included transarterial chemoembolization, hepatic arterial infusion therapy, and administration of sorafenib. In 1 patient, intrahepatic recurrence and bilateral adrenal metastases were resected. RESULTS: There was no in- hospital mortality. The median postoperative hospital stay was 30 days. The overall median survival for patients who underwent surgery and who did not undergo surgery was 344.5 days and 67 days, respectively. CONCLUSIONS: Resection for HCC with PVTT extending into the main portal trunk is acceptable at medium-scale teaching hospitals in Japan. Surgery and postoperative multidisciplinary therapy may improve the outcome of patients with HCC with massive PVTT.

[Clinical significance of neutrophil to lymphocyte ratio in colorectal cancer patients receiving adjuvant chemotherapy combined with polysaccharide-K].

The neutrophil to lymphocyte ratio (N/L ratio) has been reported to be related to the prognosis of various types of cancer. In particular, a high N/L ratio has been suggested to be associated with poor outcome. We investigated the changes in N/L ratio during treatment in 12 patients who had undergone surgery for colorectal cancer and were receiving postoperative adjuvant therapy with a combination of chemotherapy and polysaccharide-K (PSK). The patients were stratified into 2 groups according to the preoperative N/L ratio (cut-off ratio was 2.5): high N/L (≥2.5) and low N/L (<2.5). The changes in N/L ratio and other clinical parameters over time were investigated. In patients with a high preoperative N/L ratio, the use of postoperative PSK-chemotherapy controlled the N/L ratio at low levels. The N/L ratio tended to remain low in patients with low preoperative N/L ratios. No difference in outcome was observed between patients with high and low N/L ratios. In patients who underwent colorectal cancer surgery, postoperative adjuvant therapy with a combination of chemotherapy and PSK succeeded in controlling the N/L ratio at low levels. Further studies with more patients are required to explore the outcomes associated with changing N/L ratios.

[A case of advanced gastric cancer exhibiting pathological complete response after neoadjuvant chemotherapy].

A 77-year-old woman diagnosed as having advanced gastric cancer with para-aortic lymph node metastasis received neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1. After 2 courses of chemotherapy, distal gastrectomy with D2 lymphadenectomy was performed. There were no viable cancer cells in the primary lesion and lymph nodes. Currently, the patient is visiting our hospital for treatment with S-1 as adjuvant chemotherapy, and shows no signs of recurrence.

[Two long-term survival cases of Stage IV colon cancer through multidisciplinary treatment].

We report the long-term survival in two cases of colon cancer through multidisciplinary treatment, including surgery. Case 1: A 67-year-old male patient underwent anterior rectal resection, partial hepatectomy(S4, S5, S5/8) and cholecystectomy for rectal cancer with liver metastasis in July 2006(pSS, pN0, sH1, sP0, sM0, Stage IV, Cur B). Liver metastasis, lung metastasis, and metastatic colon cancer occurred 5 times during the 59 months following the first operation. We performed surgery and adjuvant chemotherapy to treat each recurrence. Case 2: A 42-year-old male patient underwent sigmoidectomy for sigmoid colon cancer with multiple liver metastasis in May 2007 (pSS, pN0, sH2, sP0, sM0, Stage IV, Cur C). Recurrence occurred 7 times at the liver and lung during the 58 months after the first operation. We performed surgery and adjuvant chemotherapy to treat each recurrence.

[Three cases of sigmoid colon cancer accompanied by invagination].

Invagination in adults is rare compared to children. We experienced 3 sigmoid colon cancers in which symptoms of invagination were discovered. Because the tumors in 2 of the 3 cases could be reduced, operations were electively performed. The tumor in the remaining case could not be reduced and an urgent operation was required. Because all cases responded in the early stage, their postoperative progress was good. Invagination in adults is typically caused by an organic disease, particularly cancer. It is necessary to consider not only reduction of the invagination but also treatment of the primary disease causing invagination. It is important that the malignant symptoms be detected promptly in order to develop a suitable treatment strategy.

[A case of severe subcutaneous emphysema during laparoscopic right-hemicolectomy].

A 76-year-old woman, weighing 40 kg, was scheduled for laparoscopic right-hemicolectomy. Forty minutes after starting the laparoscopic procedure, PaCO2 increased to 64.3 mmHg. Massive subcutaneous emphysema from the anterior thorax to the abdomen was noted and we stopped the laparoscopic procedure. In the laparoscopic procedure for the treatment of colectomy, it is important to discover abnormalities such as snowball crepitation and arrhythmia, and to monitor ETCO2 continuously in order to avoid massive subcutaneous emphysema and hypercapnia. During a laparoscopic procedure, hypercapnia might cause acidosis, arrhythmia, hypotension, myocardial ischemia, and cardiac arrest.

[A resected case of signet-ring cell carcinoma of the rectum].

Here, we present the case of a 76-year-old woman who consulted us in April 2010, following a positive fecal occult blood test, and was diagnosed with lower rectal cancer. Signet-ring cell carcinoma was diagnosed by histology. Because hydronephrosis of both sides was considered the cause of dissemination of the tumor, only chemotherapy was performed. After the eighth course of XELOX+bevacizumab treatment, hydronephrosis of both sides improved and the tumor marker level became normal. An abdominoperineal rectal resection was performed in February 2011. The results of pathological examination of the resected specimen showed complete response. After the operation, the tumor marker level was elevated, and recurrence in the pelvic cavity and multiple bone metastases were detected by positron emission tomography/ computed tomography. Chemotherapy has now been resumed. Signet-ring cell carcinoma is rare in colorectal cancer. The frequency of multiple organ metastases is high, and the growth rate of the tumor is also high. Poor prognosis compared to the usual colorectal cancer has been reported.

Let-7 expression is a significant determinant of response to chemotherapy through the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma.

PURPOSE: Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer. EXPERIMENTAL DESIGN: Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity. RESULTS: The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway. CONCLUSIONS: Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer.

Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

BACKGROUND & AIMS: Enteral nutrition (EN) is provided for patients with cancer. However, Little is known about the clinical efficacy of EN support during chemotherapy in patients with cancer. METHODS: Ninety-one patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin and adriamycin) for esophageal cancer were enrolled to receive either EN (n = 47) or PN (n = 44) at random. The primary endpoint was the incidence of chemotherapy-related toxicities during chemotherapy. RESULTS: Total and dietary intake calories during chemotherapy were equal in the two groups. There were no significant differences in serum albumin level and body weight change after chemotherapy between the two groups. There was no significant difference in tumor response to chemotherapy between the two groups (EN: 51%, PN: 55%, p = 0.886). Leukopenia and neutropenia of grade 3 or 4, defined according to the Common Toxicities Criteria of the National Cancer Institute, were significantly less frequent in the EN group than PN group (leukopenia: 17% vs 41%, p = 0.011, neutropenia: 36% vs 66%, p = 0.005). Lymphopenia and thrombocytopenia tended to be less frequent in the EN group, albeit insignificantly. CONCLUSIONS: Compared with PN support, EN support during neoadjuvant chemotherapy reduced the incidence of chemotherapy-related hematological toxicities in patients with esophageal cancers.

[A case of refractory pancreatic fistula following pancreaticoduodenectomy treated successfully by intestinal decompression catheter insertion to jejunum under local anesthesia].

The case was an 80-year-old woman with inferior bile duct cancer. The patient had undergone subtotal stomach-preserving pancreaticoduodenectomy with end-to-side pancreaticojejunostomy. Postoperative pancreatic fistula was observed in a short period and was treated by somatostatin analog administration and abscess drainage. Despite these conservative therapies, pancreatic fistula resulted in abdominal bleeding from the branch of dorsal pancreatic artery, which stopped by emergent transcatheter arterial embolization. Because pancreatic fistula had become refractory, the intestinal decompression catheter insertion was performed under local anesthesia to the jejunum located directly below abdominal wall. After this surgery, pancreatic fistula was resolved over a few weeks. This technique could be safely performed and avoided the injury of drainage fistula, and was considered to be an option for treating refractory pancreatic fistula.