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Here, I examined the efficacy of neoadjuvant chemotherapy( NAC) with S-1/CDDP( SP) in my hospital. The subjects were 8 patients with advanced gastric cancer who had undergone NAC since 2007 (7 men and 1 woman; median age, 70 years). The staging before the treatment was Stage II A: 1 patient, II B: 2 patients, III B: 3 patients, III C: 1 patient, and IV: 1 patient. The macroscopic type of 3 and 5 patients was large type 3 and type 4, respectively. Gastrectomy was performed following the NAC with SP. The NAC response rate was 62.5%. In the histological response criteria, 1 patient was grade 0, 2 patients were grade 1a, 2 patients were grade 1b, and 3 patients were grade 2. Adverse events following the NAC were in the acceptable range. We noted that the presence of Stage IV or grade 0 histological response criteria to NAC indicated poor prognosis. Thus, I believe that preoperative surgery after NAC in Stage III gastric cancer should be considered to be curative.

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.

A jejunum partial resection was performed on a 49-year-old female for jejunum leiomyosarcoma of 7 cm in 1990. She was resected four times for recurrent tumors from 1993 to 2004. We started an internal use of imatinib in 2003, because we could get a diagnosis of GIST. After the surgery of 2004, she stopped taking the internal use of imatinib, but an intraabdominal recurrence occurred in 2006 and she restarted taking the internal use of imatinib.

A 74-year-old female was performed distal gastrectomy (f-T3N0H0P0CY0M0, Stage II) for gastric cancer in 2003. After 14 months, CT scan showed a metastasis in S7 segment of the liver. We performed chemotherapies until seventh-line and radio-frequency ablation (RFA). It finally got a long-term survival of 36 months postoperatively. RFA may be one of the useful therapies of liver metastasis from gastric cancer.

A-57-year-old male was performed a total gastrectomy (f-T3N2H0P1CY1M0, Stage IV) for gastric cancer in 2004. We kept performing chemotherapies until the seventh-line, and the patient at last had a long-term survival of 46 months after surgery. If we recognized a tumor that had a tendency to be progressive, the long-term survival may be obtained by changing a regimen as early as possible.

The dawn of chemotherapy for gastrointestinal cancers including colorectal cancer was the inception of 5-fluorouraci (l 5-FU), produced by Dr. Heidelberger in 1957. 5-FU had been playing the leading role in chemotherapy for colorectal cancer for four decades until the Nineties. The second wave of chemotherapy was biochemical modulation. For the enhancement of 5-FU effects, the sequential combination with methotrexate and leucovorin (LV) was devised. Among them, 5-FU/LV was established in standard chemotherapy for colorectal cancer, due to several meta-analyses. Oral 5-FU such as UFT, TS-1 and capecitabine derivatives are gaining an important position in chemotherapy for colorectal cancer based on the accumulation of evidence. The third wave enveloped chemotherapy. Irinotecan was developed for gastrointestinal cancer. In 2000, CPT-11+5-FU/LV became the standard and first-line chemotherapy for colorectal cancer in the U.S. and Europe. Unfortunately, we in Japan have lagged behind the U.S. and Europe, because, 5-FU with LV was not approved here until 1999. Oxaliplatin was accepted in Europe first. FOLFOX, including continuous infusion of 5-FU, and LV were approved in 1998. In 2004, oxaliplatin + 5-FU/LV, named FOLFOX 4, was approved as the first-line chemotherapy treatment for colorectal cancer in the U.S. Oxaliplatin was the synthesized in Japan. At last, it was approved with usage restrictions the past March. We are now able to use FOLFOX 4, and this chemotherapy strategy for colorectal cancer in Japan is spreading rapidly. Recently, several new molecular targeted agents, which we call the fourth wave of chemotherapy, have been available in clinical studies,and promising data have been presented. Among them, evacizumab and cetuximab were tested in large phase III studies, their efficacies were upheld, and the drugs were approved in the U.S. Median survival time(MST) has been gradually prolonged through 5-FU/LV with irinotecan and oxaliplatin. Now, with the addition of molecular targeted agents, over 20 months of MST was reported.

This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

We report a 77-year-old patient with gastric cancer who has survived 5 years after multidisciplinary treatment for both liver and brain recurrences. He underwent a D2 distal gastrectomy for macroscopically type 2 cancer at the lower third of the stomach on May 1997. The histopathological findings were as follows: O-IIc (SM2), poorly differentiated adenocarcinoma, pN2, ly2, v2, stage II. One year after surgery, a follow-up abdominal CT scan revealed multiple liver metastases. He received both hepatectomy and prophylactic hepatic arterial infusion of mitomycin C with induced hypertensive chemotherapy (IHC), a drug delivery system using the difference in blood flow between normal and tumor vessels by intravenously injected angiotensin-II. IHC was carried out monthly and the total dose of MMC was 74 mg (6 courses). Although he was disease-free for about 2 years, brain metastases were found on December 2000. He then underwent excision of the brain metastases and consecutive radiation by X-knife. Although he had a relapse of liver metastases on April 2002, he is still alive now. We consider multidisciplinary treatment including complete surgical resection as effective, even for recurrent or highly malignant gastric cancer.

We report 2 patients with metastatic ovarian tumors of gastric origin who underwent oophorectomy with paraaortic and intrapelvic lymph node dissection, and showed a relatively good outcome. Case 1 A 40-year-old female with gastric cancer located in the MULE area underwent total gastrectomy with D3 lymph node dissection on June 2, 1989. Pathological Stage was IIIB and curability was B according to the JGCA classification. In month 56 after surgery, a left ovarian tumor was detected, and bilateral oophorectomy with paraaortic and intrapelvic lymph node dissection was performed. Signet ring cell carcinoma from the stomach was confirmed in both left ovary and lymph node around the left external iliac artery. In month 51 after the oophorectomy, the patient died from carcinomatous peritonitis. Case 2 A 23-year-old female with gastric cancer located in the M area underwent distal gastrectomy with D3 lymph node dissection on November 1, 2000. Pathological Stage was IV and curability was B according to the JGCA classification. In month 19 after surgery, a left ovarian tumor was detected, and left oophorectomy with paraaortic and intrapelvic lymph node dissection was performed. Poorly differentiated adenocarcinoma from the stomach was confirmed in both left ovary and paraaortic lymph nodes. Chemoradiation therapy was performed for the bone metastasis in lumbar vertebra, which was detected in month 4 after the oophorectomy, and partial response was achieved. As of June 2003, no other malignant lesion has been detected.

The case was a 63-year-old male with the chief complaint of hematuria. A local doctor made the diagnosis of a bladder tumor (egg-sized) on the basis of the results of ultrasonography. CT-scan and cystoscopy. He was thus referred to our Department for treatment. Histopathological study of the biopsied tumor specimen revealed that the tumor was a squamous cell carcinoma. The bilateral internal iliac arteries were occluded for 48 hours, and 100 mg of CDDP and 40 mg of THP were arterially infused. After 7 days, hematuria disappeared, as did the tumor 5 weeks after treatment. No malignancy was noted from histological examination of a biopsy specimen obtained from the cured cancer region using a cystoscope. Since then, there was no recurrence for 12 months. Thus, this approach is thought to be an effective treatment for primary bladder cancer.