Advanced small-cell colon carcinoma: a case report.

INTRODUCTION: Small-cell colon carcinoma is a very rare disease among colon neoplasms; it is difficult to achieve long-term survival due to its aggressive tumor behavior. Here we report the long-term survival of a patient with advanced small-cell colon carcinoma achieved by a combination of surgery and continuous chemotherapy. CASE PRESENTATION: A 67-year-old Japanese man underwent abdominal computed tomography in our institution for follow up after gastrectomy, and abnormal thickness of the sigmoid colon wall was revealed. An endoscopy demonstrated a 20mm Bormann 2 lesion with central ulceration located 20cm from the anal verge. A sigmoidectomy was performed. Histologically, the tumor deeply invaded the tissue and extended beyond the serosa, and was diagnosed as small-cell carcinoma. Cisplatin plus irinotecan was administered for adjuvant chemotherapy. Nine months after surgery, a follow-up computed tomography showed an enlarged lymph node behind the inferior vena cava and a 15×8mm nodule located at the ventral side of the cecum. Under consideration of progressive disease, cisplatin plus irinotecan therapy was performed again using the same regimen. After nine cycles of cisplatin plus irinotecan therapy, a follow-up gastric endoscopy demonstrated external tumor invasion to the duodenum wall. Carboplatin plus etoposide therapy was selected as a third-line regimen. After six cycles of carboplatin plus etoposide therapy, the recurrence sites were maintained in a stable condition, and the survival time reached approximately 30 months after the initial surgery. CONCLUSIONS: We report the long-term survival of a patient with advanced small-cell colon carcinoma. In the future, the accumulation and analysis of rare cases that obtain a better survival time will contribute to clarifying neuroendocrine carcinoma biology, and help to improve the prognosis.

Formulation design of a novel fast-disintegrating tablet.

As our society is becoming increasingly aged, the development of an appropriate dosage form for the elderly patients is mostly desirable. A novel fast-disintegrating tablet was investigated in this study as a user-friendly dosage form for the aged. Advantages of this formulation have sufficient hardness and can be manufactured by commonly used equipment. Saccharides can be divided into high- and low-compressibility categories, and an appropriate material for fast-disintegrating tablets was created by taking advantage of this fact. To improve the compressibility of low-compressibility saccharides, particle modification was conducted by coating and granulating a low-compressibility saccharide with a high one to enable the production of a fast-disintegrating tablet. Another discovery was that the high-compressibility saccharide used as a binder solution was present in an amorphous state after the granulation process. The crystal change from amorphous to crystal state intentionally by a conditioning process after compression enabled to increase tablet hardness by strengthening adhesion between particles. The conditioning process made it possible to achieve sufficient hardness while maintaining the fast disintegration time. As a result, this fast-disintegrating tablet that can be manufactured by commonly used equipment, can be used for the dosing of a wide range drugs.

Scintigraphic evaluation of a novel colon-targeted delivery system (CODES) in healthy volunteers.

The purposes of this study are to investigate the gastrointestinal transit and release properties of a novel, colon-targeted delivery system (CODES) administered to healthy volunteers using gamma scintigraphy and to confirm that lactulose functions to promote disintegration in the colon. Two placebo formulations were studied: one was CODES, which consisted of a lactulose containing core overcoated with both Eudragit E and Eudragit L designed to rapidly disintegrate in the colon, the other was lactulose-free reference formulation (LFRF) that consisted of lactulose-free tablet core overcoated with the same materials. Transit and disintegration of the radiolabeled formulations were followed by gamma scintigraphy. In the fasted state, scintigraphic images indicated that CODES started to disintegrate in the ascending colon in the majority of subjects at 7.11 +/- 2.01 h post-dose. Disintegration was complete within 1 h following commencement of in vivo release. In contrast, LFRF presented with prolonged in vivo disintegration properties. In the fed state, the disintegration period of CODES was almost comparable to that observed in the fasted state. Gamma scintigraphic studies clearly showed that CODES provides for rapid target site release in the colon regardless of the ingestion of food.

Studies on lactulose formulations for colon-specific drug delivery.

A novel, colon-targeted delivery system (CODES), which uses lactulose, was investigated in this study. Lactulose is not absorbed in the upper GI tract, but degraded to organic acids by enterobacteria in the lower gastrointestinal tract, especially the colon. A CODES consists of three components: a core containing lactulose and the drug, an inner acid-soluble material layer, and an outer layer of an enterosoluble material. When a CODES containing a pigment was introduced into the rat cecum directly after shaking in JP 2nd fluid for 3 h, pigment release was observed 1 h after introduction. A CODES containing 5-aminosalicylic acid (5-ASA) was orally administered to fasting and fed dogs to evaluate its pharmacokinetic profiles. 5-ASA was first detected in plasma after 3 h, which is the reported colon arrival time for indigestible solids, after dosing to fasting dogs. The T(max) in fed dogs was delayed by 9 h when compared to fasting dogs. This corresponds to the gastric emptying time. However, the C(max) and AUC under fed conditions were almost as same as those under fasting conditions. The results of this study show that lactulose can act as a trigger for drug release in the colon, utilizing the action of enterobacteria.