[Two Cases of Bowel Perforation during Chemotherapy with Bevacizumab to Metastatic Rectal Cancer].

Case 1: A male patient in his 60's who had rectal cancer and liver metastases underwent Hartmann's operation in January 2009. In April 2009, he received chemotherapy with modified FOLFOX6 plus bevacizumab as second-line treatment. Thirteen days later, he complained of abdominal pain and visited the emergency department. Computed tomography(CT)revealed gastrointestinal tract perforation. He underwent emergency surgery. However, dirty brownish ascites was observed, and the perforation point of the gastrointestinal tract could not be found. We suspected perforation of the colon and created an artificial anus in the terminal ileum. After the surgery, his condition improved. Case 2: A male patient in his 60's who had rectal cancer underwent Miles' operation in March 2005. In February 2010, CT revealed local recurrence in the presacral region. After radiotherapy, he received chemotherapy with CapeOX plus bevacizumab. During the course of the chemotherapy, he was admitted for upper abdominal pain and fever. He was diagnosed with a perforation of the transverse colon and underwent emergency surgery. After the surgery, drainage was needed for peritonitis, for about 1 month. At 93 days after the surgery, he was discharged. Gastrointestinal tract perforation is one of the most serious adverse events associated with bevacizumab. To avoid death caused by serious adverse events, medical staff and patient orientation or education on the possible serious adverse event is very important.

[Palliative care during chemotherapy for advanced colon cancers].

BACKGROUND: The median survival time following chemotherapy for unresectable metastatic colorectal cancer (mCRC) is approximately 2 years. Although palliative care during the chemotherapy period is very important, it has not been reported in detail. PATIENTS AND METHODS: Information on the palliative care of 110 patients with Stage IV mCRC, who were treated from September 2007 to March 2011, was retrospectively examined. RESULTS: Following an explanation of their recurrence or metastases of mCRC, all the patients received mental care from nurses or psychiatrists. They also needed care to prevent the side effects of chemotherapy. Some patients experienced pain associated with tumor growth. Thus, they required NSAIDs or opioids to reduce the cancer-related pain. After they could not be taken chemotherapy, 87.5% of these patients consulted medical social workers to discuss where they would live. CONCLUSIONS: The patients required palliative care depending on the duration of chemotherapy for mCRC. Thus, we believe that palliative care is an important part of treatment for advanced cancer.

[Recurrent gastric cancer treated with fourth-line chemotherapy consisting of capecitabine and cisplatin leading to partial response].

A 70-year-old man with advanced gastric cancer was treated with neoadjuvant chemotherapy consisting of S-1 plus cisplatin( CDDP). He exhibited symptoms of cerebral infarction during the second course of chemotherapy. Distal gastrectomy was performed and the histological diagnosis was pT3N3aM0, pStage IIIB. Adjuvant chemotherapy was administered; however, after the second course, gastric cancer recurred in the lymph nodes. Second-line chemotherapy with irinotecan (CPT-11) and CDDP was initiated. Thereafter, third-line chemotherapy with docetaxel was performed. However, the response to treatment was progressive disease (PD). Subsequently, fourth-line chemotherapy was performed with capecitabine and CDDP (XP chemotherapy). After the fourth course of XP chemotherapy, the response was partial response (PR). Moreover, PR was maintained after 20 courses of chemotherapy.

[A case of superior sulcus tumor treated with carbon ion radiotherapy].

Superior sulcus tumor( SST) is a rare type of lung cancer. Treatment usually consists of surgical resection after chemoradiotherapy. We report a case of a woman in her fifties who underwent carbon ion radiotherapy for SST. The patient complained of left shoulder pain, and imaging studies revealed a 5.2×3.5-cm local solid tumor at the apex of the left lung, invasion to the ribs, and no lymph node swelling. The level of tumor marker, carcinoembryonic antigen (CEA), was 5.7 ng/mL. Needle biopsy specimen revealed adenocarcinoma. The diagnosis was SST, T3N0M0, stage IIB. We did not detect Horner syndrome. Carbon ion radiotherapy at 66 Gy equivalent dose per 10 fractions was administered to the SST site. Subsequently, the tumor size decreased to 4.5×1.9-cm. The adverse effect was Grade 1 skin and pulmonary toxicity. Six months later, Grade 2 left shoulder connective tissue toxicity was observed; it was difficult to differentiate this from tumor recurrence. After 2.5 years from radiotherapy, the patient is free from recurrence. Carbon ion radiotherapy is effective and safe and can be considered as an important treatment option for SST.

[Fluoropyrimidines with oxaliplatin(L-OHP) as an adjuvant chemotherapy for Stage III colon cancer].

As an adjuvant treatment for Dukes B2 and C colon cancer, adding oxaliplatin (L-OHP) to a regimen of fluorouracil and Leucovorin improved disease-free survival in Western countries. In Japan, however, adjuvant chemotherapy with L-OHP is not commonly used to treat Stage III colon cancer. We report the present condition of adjuvant treatment for colon cancer in our hospital. Between September 2009 and December 2011, 66 patients with Stage III colon cancer were enrolled after curative surgery. The details of adjuvant therapy with fluoropyrimidines with and without L-OHP were explained to the patients. After the explanation, 33.3% of the patients(IIIa: 18.9%, IIIb: 55.5%) selected L-OHP chemotherapy. Regardless of the side effects, adjuvant chemotherapy including L-OHP is expected to protect against cancer recurrence in patients with Stage IIIb colon cancer.

[A case of advanced gastric cancer with Trousseau syndrome and pulmonary embolism].

A 60-year-old man showed symptoms associated with pulmonary embolism and anemia in June 2011, and was subsequently diagnosed with stage IV gastric cancer. Following frequent multiple cerebral infarctions and the development of symptoms, the patient was diagnosed with Trousseau syndrome. A total gastrectomy was performed to control bleeding. After the surgery, oral ingestion became possible. The patient was discharged and a hypodermic injection of heparin was given by the home doctor.

[Chemotherapy-mediated tumor regression in a patient with stage IV stomach small cell cancer].

Gastrointestinal tract endoscopy revealed the presence of a 5-cm-diameter type 3 tumor in the cardiac portion of the stomach. The tumor was chromogranin positive, and stomach small cell cancer was diagnosed by immunostaining and biopsy pathology. S-1+CDDP therapy was administered as the first-line treatment. A switch to S-1 monotherapy was made after the patient experienced grade 4 hyponatremia. However, following 7 courses of therapy the disease had progressed. Second-line chemotherapy of CPT-11+CDDP was initiated and after 2 courses the disease stabilized.

[A case of bilateral 3-lung lesion (metastatic and primary tumour, tumourlet) resected simultaneously].

A 70-year-old male patient underwent right nephrectomy for renal clear cell carcinoma. After 8 years an X-ray showed a nodule on the left lung, and CT scan detected it to be a 15 × 12 mm mass in S1+2 segment of the left lung. CT also detected another 15 × 7 mm mass in the right S3 segment. These lesions had a high FDG accumulation. Pre-operative diagnosis is bilateral pulmonary metastases from renal cell carcinoma, and bilateral lung segmentectomy was performed. Left S1+2 resected tumor was histologically clear cell carcinoma by intra-operative examination, then right S3 segmentectomy was done. And that time, small tumor was found in the middle lung lobe, and a wedge resection was performed. These specimens revealed a primary lung carcinoma of right S3, and tumourlet of middle lobe. It is very rare that three different histlogical types of lung tumor were found.

[A case of advanced transvers colon cancer with inguinal lymph node metastasis].

An 80-year-old woman complaining of a right inguinal induration and pain was performed an inguinal lymph node resection. Histological examination with immnohistochemistry revealed that the lymph node was metastasis of colon carcinoma. With total colonoscopy, she was diagnosed as advanced transvers colon cancer with right inguinal lymph node metastasis. She was performed a right hemi-colectomy. She was dead with peritoneal metastasis of colon cancer 2 years and 1 month later. We report this case that was diagnosed having transverse colon cancer with inguinal lymph node metastasis.

[A case of unresectable gastric cancer with pyloric stenosis which was resectable by chemotherapy after gastrojejunostomy].

A man in his fifties was referred to our hospital for anorexia and vomiting. Upper gastrointestinal endoscopy showed a gastric cancer (Borrmann Type 3) with pyloric stenosis. We performed gastrojejunostomy to allow oral intake for a tumor invading the pancreas head (cT4bN1H0P0CY1, Stage IV). After the operation, systemic chemotherapy with S-1 (120 mg/m²) was administered from July 2007, which caused grade 3 mucositis oral and drug rash after one week. Then, bi- weekly administration of CPT-11 (60 mg/m²) and CDDP (30 mg/m²) was started from August 2007 as second-line chemotherapy. The treatment was repeated for 14 courses till an allergic reaction happened. A weekly paclitaxel (PTX) therapy (80 mg/m²) was started from January 2009 as third-line. After 6 courses, CT showed that direct invasion to the pancreas was not clear any more, so a distal gastrectomy with D1 lymphadenectomy was performed on August 2009 (ypT3N- 1P0CY0, Stage IIB). The patient received 9 courses of weekly PTX therapy and after that the treatment has been discontinued. Recurrence was not observed for 48 months after an initial treatment.

[A case of pneumocystis pneumonia during chemotherapy for gastric cancer].

We report a death case of a man in his sixties with pneumocystis pneumonia during chemotherapy for gastric cancer. He was diagnosed with cStage IIIB (T4a, N2, H0, P0, M0). Because of bulky N2, systemic chemotherapy of S-1 and CDDP was performed from April 2009. But no reductions were noted after 2 courses. We next treated this patient with S-1 and CPT-11. He had also received corticosteroid treatment for nausea. Because of high fever and choke, he came to our hospital at day 12 in 3 courses, and a severe respiratory failure occurred. CT of the chest showed diffuse ground-glass bilateral opacities, and we immediately started a treatment with trimethoprim-sulfamethozazole and corticosteroid for the possibility of pneumocystis pneumonia. We finally deduced pneumocystis pneumonia from markedly elevated serum beta-D-glucan and PCR positive after hospitalization. In spite of early treatments, he died of bacterial pneumonia and gastric cancer. We should be careful of pneumocystis pneumonia during chemotherapy and corticosteroid treatment.

[A successful case with CPT-11 + CDDP chemotherapy for recurrent gastric cancer of the remnant stomach].

We report a successful case with irinotecan (CPT-11 60 mg/m2) + cisplatin (CDDP 30 mg/m2) chemotherapy (once in 2 weeks) for recurrent gastric cancer of the remnant stomach. A 77-year-old man was performed a distal gastrectomy for duodenal ulcer 42 years ago. He had a total gastrectomy for gastric cancer of remnant stomach when he was at 73 years old. After the surgery, we treated this patient with S-1 mono-therapy for five courses. However, we finished this treatment for lymph-node metastases. Next we treated him with CPT-11 + CDDP. An abdominal CT revealed a CR after 6 courses. We finished this treatment after 12 courses for anemia (grade 3). After the treatment, the metastatic lymph-nodes appeared in no change. So we considered that CR was continued for 3.5 years.

[A case of a 14-month survival patient on advanced esophageal cancer with uncontrolled brain metastasis completely responding to nedaplatin, adriamycin, plus 5-FU (NAF) therapy].

This case was a male patient, about 50 years old. He received a curative operation for advanced esophageal carcinoma [poorly differentiated squamous cell carcinoma type, Lt, pT3 (pAd) pN3, pstage III] in March 2005. He also received adjuvant chemotherapy of 5-FU plus cisplatin (CDDP). Fourteen months later (May 2006) from surgery, metastases to the left lung and left subclavian lymph nodes were diagnosed, so he received first-line triplet combination chemotherapy (NAF regimen; nedaplatin 60 mg/m2: day 1, adriamycin 50 mg/m2: day 1, 5-FU 700 mg/m2: day 1-5). According to the 9 courses of treatment of this regimen, complete response for these metastases was observed and first-line chemotherapy was finished. However, a severe headache appeared 3 months later, and he had a diagnosis of solitary 5 cm brain metastasis by MRI. Excision of the metastasis was performed with sequential whole-brain radiation therapy (30 Gy). Five months later, diffuse and multiple brain metastases relapsed, and second-line chemotherapy did not respond well, and finally he was died 3 months after palliative care. But, completely controlled metastases (lung and lymph node) by first-line chemotherapy did not relapse again in all his clinical period. If an anticancer therapy goes in complete response in an advanced esophageal carcinoma patient, we should consider about a rare brain metastasis in order to find out as small and solitary state.

[A case of liver metastasis of rectal cancer demonstrating complete response for more than two years to mFOLFOX6].

A man in his fifties with rectal cancer underwent low anterior resection in another Hospital in January 2006. He was finally diagnosed with Stage III a (pA, pN1, H0, P0). The patient who had postoperative complication such as ruptured suture left the hospital in May 2006, when he was detected with multiple liver metastases and was referred to our hospital for systemic chemotherapy. Systemic chemotherapy with mFOLFOX6 was performed from May 2006. Grade 3 diarrhea and grade 2 peripheral neuropathy, nausea and vomiting were observed. After 6 courses of mFOLFOX6, MRI revealed metastasis had been disappeared and levels of CEA and CA19-9 were decreased below normal. The treatment has been discontinued. Recurrence was not observed for 30 months.

[A case of successful management of recurrent intrahepatic cholangiocarcinoma by repeated radiofrequency ablations].

A 67-year-old man with intrahepatic cholangiocarcinoma (ICC) underwent an extended right hepatectomy. Approximately, during the next 20 months after the operation, the patient underwent 6 times of radiofrequency ablation for solitary recurrence of ICC. He has survived for 26 months after hepatic resection with PS 0. Radiofrequency ablation for solitary recurrence of ICC may be effective for a good prognosis.

[Three-case reports--a program of strength training for home health care on frail elderly patients with protein rich supplement just after the training].

We have a program of strength training for home health care with protein rich supplement just after the training on frail elderly patients. Three cases (80-90 years old) received a new good taste protein rich supplement. They were also frail patients after acute clinical treatments, and were able to go home directly against their physical moving problems for daily life. We performed cardio-pulmonary and swallowing function, energy intake, parameters of muscle strength and the status for daily life before and after the training. Practical results were very different among the patients. But, the status for daily life of all was better than before. It was not clear that the new supplement was effective for the parameters of muscle strength, or not. But a trial for programs with thus foods should be an option for promoting to home health care after hospitalization in frail elderly.

[Third-line treatment of intermittent hepatic arterial infusion for unresectable liver metastases from colorectal cancer].

We report 6 cases of liver metastases from colorectal cancer with third-line treatment of intermittent hepatic arterial infusion and systemic chemotherapy for unresectable liver metastases with clinical signification of direct invasion to adjacent organs in Stage IV colorectal cancer. Subjects were 19 consecutive patients who underwent R0 surgery to the primary tumor for colorectal carcinoma, pT4, M1 in 1995-2003. We studied the relationship of pathological invasion to adjacent organs of tumor to other clinicopathological factors to prognosis. Of the 19 patients, 11 (57.8%) were R0 surgery to the tumor of metastases. Only 4 (36.7%) patients survived more than 3 years. The patient without excision did not survive for three years. The median survival time was only 8.5 months. Multivariate analysis indicated that only R0 surgery to the tumor of metastases was an independent prognostic factor. The optimum resection for adjacent organs may prolong a survival. But the extended resection is a possibility of shortening the survival time.

[Surgical resection of pulmonary metastases from colorectal carcinoma in our hospital].

Pulmonary metastases from colorectal carcinoma are not rare next to liver metastases. Lung resection has been widely accepted, but postoperatively local lung recurrence has been seen in the wedge resection procedures. In our hospital, specimen of the wedge resection was histologically reviewed and revealed floating cancer cell clusters around the main tumor. The cause of the recurrence was supposed to be floating clusters or a technical problem of surgical margin in the video-associated thoracic surgery. Since 2004, we used 3-dimensional CT and identified the pulmonary segmental area of peripheral metastatic tumor less than 2.0 cm in diameter. From 1986 to 2003, we performed 18 cases of lung resection and found that recurrent cases were 25 to 64%. On the other hand, we detected 0 to 16% recurrence cases in 12 patients during the period of 2004-2007. We recommend segmentectomy to metastatic tumor less than 2.0 cm in diameter from colorectal carcinoma.

Gene expression of colorectal cancer: preoperative genetic diagnosis using endoscopic biopsies.

In colorectal cancer, to predict the response to chemo- and/or radio-therapy or the existence of lymph node metastasis preoperatively, a more competent diagnostic system is required, in addition to conventional diagnosis based on morphology and pathology. The application of gene expression profiling to preoperative cancer diagnosis using endoscopic biopsies could enable the selection of a more appropriate therapy for patients. In this study, we evaluated the feasibility of gene expression profiling using preoperative biopsies of colorectal tumors in a clinical setting, by investigating the influence of intra-tumor heterogeneity on the profiles and testing the prediction ability of tumor malignancy. Under endoscopic examination, two biopsies were sampled from each of 10 colorectal cancers and 10 adenomas, and their gene expression data were obtained using cDNA microarrays. The intra- and inter-tumor heterogeneities of the profiles were compared with unsupervised clustering analysis. Molecular prediction of tumor malignancy using biopsies was performed with the supervised classification algorithm. In clustering analysis, almost all paired biopsies from the same tumors joined each other. Pearson's correlation coefficients of the profiles between biopsies from the same tumors (mean, 0.83) were significantly greater than those of the profiles between biopsies from other cancers (mean, 0.58) (p<0.0001). In the supervised classification method, malignancy was correctly predicted in 39 out of 40 biopsies with 8-71 informative genes. Gene expression profiling using endoscopic biopsies of colorectal tumors revealed that the intra-tumor heterogeneity was smaller than the inter-tumor heterogeneity and tumor malignancy was correctly predicted. Our findings suggest that the technique of gene expression profiling accurately represents the biological properties of colorectal cancer and could help the preoperative diagnosis of this disease.

[A 14-month surviving patient on advanced esophageal cancer with big lymph node metastasis to cardia responding to S-1 plus cisplatin (CDDP) therapy at home].

This case was a 70s male patient. He was hospitalized with some dysphasia and a severe body weight loss since August 2004. The diagnosis was the esophageal cancer (type 2, 11 cm) with big lymph node metastasis on cardia (8 cm), and also pathologically poorly differentiated squamous cell carcinoma from two legions. He wanted a home chemotherapy for it. We administered a combination chemotherapy of S-1 plus cisplatin (CDDP) therapy. An eight-day admission within an each course to CDDP treatment and nutritional support were required for adverse events of anorexia (grade 3), but for other days home chemotherapy was done with good compliance of S-1 up to 6 courses. After 2 courses, endoscopic findings showed a pathological complete response of esophageal mass, and CT findings also showed a partial response of the lymph node. After 6 courses of S-1 + plus cisplatin in May 2005, a home S-1 single therapy which was not needed the admission started at will. But the lymph node mass of cardia progressed again in September 2005, and his therapy moved to the terminal care at home.