Pneumatosis Cystoides Intestinalis Secondary to Sunitinib Treatment for Gastrointestinal Stromal Tumor.

A 67-year-old man with liver and retroperitoneal metastases from a gastrointestinal stromal tumor arising in the jejunum had been administered oral sunitinib for 2 months. He presented to our department with right-sided lower abdominal pain. His general condition was good, with no high-grade fever, and the other vital signs were also stable. Contrast-enhanced computed tomography was promptly performed, and pneumatosis cystoides intestinalis (PCI) was detected in a wide area around the ileocecal lesion. There were no signs of acute abdomen requiring emergency surgery due to conditions such as intestinal perforation, ischemia, or obstruction. Sunitinib was discontinued and the patient was placed on nil orally with intravenous infusion. PCI resolved promptly and the patient was discharged on the 21st day after admission. PCI is a rare side effect of sunitinib with only 8 cases reported previously, which can complicate with acute abdomen or gastrointestinal perforation, in some cases. Thus, the early identification of sunitinib as the cause of PCI is important. Although PCI is a rare adverse effect of sunitinib, clinicians must be aware of it to promptly provide the correct diagnosis and treatment.

[One-stage resection of intravenous leiomyomatosis extending into the right atrium].

Intravenous leiomyomatosis (IVL) is a benign tumor that originates from a uterine myoma and rarely extends to the heart through the inferior vena cava (IVC). Echocardiography revealed an abnormal mass in the right atrium in a 63-year-old asymptomatic woman. Preoperative examination revealed a tumor extending from a myoma through the right internal iliac vein to the right atrium, and the patient was diagnosed with IVL. She underwent sternotomy combined with laparotomy, and the intravenous and intracardiac tumor was removed under normothermic cardiopulmonary bypass without cardiac arrest. Hysterectomy and bilateral adnexectomy were also performed. No additional therapy was required after surgery.

[An example of metastasis to the iliopsoas muscle from sigmoid colon cancer].

Even though skeletal muscle, making up about 40% of body weight, is the largest organ in the human body, metastasis from malignant lesions is rare. Among reports of metastasis, those involving the iliopsoas muscle are numerous but few reports involve resection. Reported here is one example we experienced where metastasis developed in the iliopsoas muscle following colectomy, resection was then made possible by radiotherapy and chemotherapy. The case involved a 71-year- old male in which a Hartmann procedure was performed for sigmoid colon cancer. The pathology was Type 3 (8 × 7 cm, adenocarcinoma( mod), ss or more, ly1, v1, n0, ow(-), aw or ew(+), stage II). Upon additional sampling, thermal degredation of neoplastic cells was shown and outpatient oral UFT was performed. Five years following surgery, lymphoadenopathy was noted in the area of the left iliac artery upon US and CT. PET showed a probable metastasis to the left iliopsoas muscle. Early esophageal and stomach cancer were diagnosed by GFT. The esophageal cancer was located 30-32 cm from the incisors, unstained, Borrmann type 1, penetrating deeper than the muscularis propria. Biopsy revealed a diagnosis of tubular adenocarcinoma. ESD was performed for the esophageal cancer and one month later, a total gastrectomy D1+ß was performed. During surgery, the iliopsoas muscle tumor was determined to be large and impossible to resect. Radiotherapy of 10MV X-ray, 8 fields, 65-70 Gy/26 times for 6 . 5 weeks was performed for residual tumor but had no effect on tumor size. Fifteen courses of FOLFOX+bevacizumab were then performed. The tumor was markedly reduced in size, unidentifiable upon CT but showed slight uptake on PET and resection of the suspected residual tumor was performed. Histologically, atypical cells were shown in scarred muscle and connective tissue, however, degradation by chemotherapy was high. Residual tumor at resection margins was found, findings consistent with metastasis form sigmoid colon cancer. Taking into account the age and condition of the patient following surgery, chemotherapy was changed to S-1. Currently, 5 months after resection, there has been no recurrence.

[Preoperative S-1/CDDP combination chemotherapy was effective in a case of local advanced gastric cancer].

INTRODUCTION: The prognosis of type 4 advanced gastric cancer is extremely poor, even the use of multidisciplinary treatment cannot provide satisfactory results. Presented here is a case of highly advanced gastric cancer in which preoperative chemotherapy was effective and resection possible. CASE: A 64-year-old female complained of epigastric distress. Current medical history included: hypertension, hyperlipemia, diabetes, chronic heart disease and development of epigastric distress. Endoscopy was performed upon examination in the Gastroenterology Department. Visual inspection showed a lesion extending from the greater curvature of the fundus to the antrum. Type 4 advanced gastric cancer was strongly suspected. Biopsy samples taken from the antral lesser curvature and from the ulcer border on the upper anterior wall of the body were diagnosed as Group V, adenocarcinoma. Abdominal CT revealed no hepatic mass, but overall thickening of the gastric wall was noticeable and the lymph nodes in the area of the lesser curvature of the stomach and celiac artery were identified. Abdominal ultrasound showed an overall thickening of the gastric wall, and invasion into a portion of the left hepatic lobe and pancreas was suspected. Swelling of the lymph nodes surrounding the stomach was suspected. TREATMENT: Because of gastric cancer with suspected invasion of the left hepatic lobe and pancreas, it was decided to perform preoperative chemotherapy (S-1 + CDDP) and then perform a total gastrectomy. Four courses were performed. RESULTS: Endoscopy revealed no change in the lesion within the stomach. Only scarring in the body and antrum was found, the enlargement was greatly reduced and visual inspection revealed no esophageal infiltration. Biopsy samples were taken from 2 sites, the body center on the lesser curvature side and the greater curvature of the antrum. Scar-like fibrosis was significant and it was not possible to distinguish an increase in poorly differentiated adenocarcinoma. Abdominal CT showed a reduction in gastric wall thickening. These findings showed preoperative chemotherapy to be effective. Following the chemotherapy, a total gastrectomy in addition to splenectomy and cholecystectomy were performed. Histopathological findings showed MLU, type 5, approx. 8.5 × 13 cm, poorly differentiated adenocarcinoma (por 2), INF γ, sci, pT2 (SS), ly2, v0, pN2 (#1: 2/8, #6: 1/6, #11p: 2/5), pPM (-), pDM (-), Stage IIIA. Along with the formation of fibrous scar tissue, an invasive growth of por 2 poorly differentiated adenocarcinoma was found from the submucosal layer to just beneath the serosal layer. Therapeutic effect of the chemotherapy was Grade 2. Post operative S-1 + CDDP was begun but nausea developed and S-1 was reduced. Because of a decrease of neutrophils and nausea, the therapy was changed to UFT. It is currently 6 months after surgery and there are no signs of recurrence. CONCLUSION: Preoperative chemotherapy (S-1 + CDDP) is a therapy which shows promise in reducing tumor size even in highly advanced gastric cancer.

[A case in which intra-arterial chemotherapy for simultaneous hepatic metastases markedly improved AFP-producing gastric cancer].

The prognosis of most hepatic and lymph node metastases in AFP-producing gastric cancer is poor, and despite the use of multimodal therapy, the average survival period is reported to be approximately one year. Described here is one example in which intra-arterial chemotherapy for simultaneous hepatic metastases in AFP-producing gastric cancer achieved a marked improvement. The patient is a 65-year-old female. Distal gastrectomy was performed for Type II gastric cancer. L, type 2, 5.5x2.4 cm, tub 2>por 1, pT2 (MP), int, INF b, ly2, v1, pN1, pPM (-), pDM (-), pH1: stage IV. The AFP level before surgery was 801.4 ng/mL and lowered to 65.8 ng/mL after surgery, AFP-producing gastric cancer and simultaneous hepatic metastases (S4, single lesion) was diagnosed based upon imaging examinations. 5-FU+epirubicin+MMC (FEM)intra-arterial chemotherapy was started one month following surgery, but because CT showed multiple new hepatic lesions(S4, S5)four months following surgery, DSM therapy was performed with hepatic arterial injections of MMC 10 mg, DSM 300 mg. Dynamic CT showed a reduction in size of the tumors in both S4 and S5, and at five months following surgery, hepatic arterial infusion chemotherapy FP (CDDP 5 mg+5-FU 250 mg weekly) was started and performed 45 times in a 14-month period. During therapy, CR was achieved for the hepatic metastases and tumor marker levels were also normal. Because an introduction of contrast medium into the hepatic reservoir showed a narrowing of the hepatic artery and inflow of contrast medium into the splenic artery, arterial infusion was terminated. Following this, from the 20th month following surgery, S-1 (100 mg/day: 4 weeks administration, 2 weeks rest) was started and from the third course (50 mg/ day: 4 weeks administration, 2 weeks rest), and the patient is currently undergoing a sixth course. Currently, 2 years and 4 months after surgery, there have been no recurrences. This suggests the possibility that intra-arterial chemotherapy is an effective treatment method for hepatic metastases in AFP-producing gastric cancer.

[S-1+gemcitabine (GEM) therapy was effective in a case of unresectable pancreatic head carcinoma].

OBJECTIVE: Treatment results of pancreatic head carcinoma are not good and long-term survival, especially in nonresectable cases is extremely difficult to obtain. The case reported here is of nonresectable pancreatic head carcinoma in which S-1+gemcitabine (GEM) proved to be effective. CASE: A 70-year-old male. The patient initially complained of epigastralgia. Jaundice was also noted and upon further study, pancreatic head carcinoma, portal vein and common hepatic artery infiltration along with duodenal infiltration were diagnosed. Gastrojejunostomy and cholecystectomy were performed with a preoperative diagnosis of Phb, TS2 infiltrative type T4, CH (+), DU (+), S (+), RP (-), PV (+), Ach (+), PLX, OO (-), N0, M0, and Stage IVa. Perioperative findings showed no hepatic or peritoneal metastases. Following surgery, S-1+ GEM (S-1 100 mg/day, day 1-14; GEM 1,000 mg/m(2) was administered on day 8 and day 15 for 2 weeks followed by one week of no administration) was started. After completing 2 courses, there was no change in the tumor, but after finishing the sixth course, there was a notable reduction in tumor size, and after finishing the 10th course, a further reduction was noted. Currently at the end of the 14th course, the tumors are unidentifiable upon imaging. At 1 year and 5 months from the initial diagnosis, there has been no recurrence and chemotherapy is being continued. In the case reported here, there have been no adverse side-effects from the S-1+GEM therapy, it is a safe method which does not lower QOL in patients with unresectable pancreatic carcinoma, and we can look forward to the possibility of extended survival times. CONCLUSION: In the case of unresectable pancreatic carcinoma, S-1+GEM therapy may be able to provide an improved long-term prognosis.

[Peroral direct cholangioscopy for diagnosis and treatment].

Peroral direct cholangioscopy (PDCS) is endoscopic method for diagnosis in the common bile duct (CBD) utilizing an ultra-slim upper endoscope. Clinical utility and problem of this method were investigated in ten patients who had stenosis or obstruction in the CBD with stones or a tumor. Scope shaft had to become the form of a U loop by counterclockwise rotation, to advance the scope in the direction of intrahepatic bile duct. As for one case, although the scope was formed alpha loop without U loop, direct observation of total CBC was possible. Large working channel of the endoscope could take adequate tissue sample by large biopsy forceps. Electrohydraulic lithotripsy and stone extraction with a basket could be accomplished easily and safely by direct visualization with a clear image. Pneumobilia was noted in all cases with insertion of PDCS. Although the abdominal pain and pyrexia with regard to PDCS did not occur, transient leukocytosis was noted.

[Complete recovery obtained with combined S-1 + CDDP therapy in a patient with multiple lung metastases from esophageal cancer].

PURPOSE: There are numerous reports on the subject of effectiveness in radio-chemotherapy with regard to esophageal cancer, suggesting especially the combination therapy of 5-FU + CDDP aimed for recovery. Treatment becomes difficult when distal metastases appear during an adjuvant therapy followed by surgery. Our report here is a case in which a complete recovery was obtained after changing to S-1, a prodrug of 5-FU, in response to multiple lung metastases which appeared during the combined 5-FU + CDDP therapy followed by surgery for esophageal cancer. CASE: The patient was a 71-year-old male. Endoscopy during a physical examination showed a Type 1 tumor 27-30 cm from the anterior teeth. Detailed tests provided a preoperative diagnosis of esophageal cancer: Ut Type 1, T2-T3, N2, MO, IMO. A right thoracolaparotomic subtotal esophagectomy and retrosternal reconstruction were performed. Pathological findings showed well-differentiated squamous cell carcinoma, pT1b (sm), pN1 (106-rec R), pStage II. Postoperative combination of 5-FU + CDDP (day 1-5, 5-FU 500 mg; CDDP 10 mg/body) was started. Because of the appearance of multiple lung metastases after the completion of 3 courses, 2 courses of S-1 + CDDP (S-1 120 mg/body day 1-14; CDDP 5 mg/body day 1-5, day 8-12) were performed. After completing the chemotherapy, CT revealed the resolution of the lung metastases and complete recovery was diagnosed. Following this, a treatment with S-1 alone was continued until the appearance of bone metastases at which time radiotherapy was performed. The treatment is currently ongoing and no recurrence of the lung metastases has been shown. CONCLUSION: There have been numerous reports of the combination of S-1 + CDDP in esophageal cancer for NAC or in inoperable cases. However, our report suggests that this method may be effective in cases of recurrence or distal metastases.

[Two cases of inoperable gastric cancer successively treated with TS-1+CDDP as neoadjuvant chemotherapy].

CASE 1: A 30-year-old male with a loss of appetite and hematemesis was diagnosed with scirrhous gastric cancer upon detailed examination. Laparoscopic biopsy showed it to be Group V. Pre-operative diagnosis was T3N3P1HOM1, Stage V. Three courses of pre-operative chemotherapy (NAC) of TS-1+CDDP were performed. Laparoscopic examination as well as imaging showed a clear reduction in tumor size. Total gastrectomy, resection of the small intestine and cholecystectomy were performed. Pathological findings were type 4, por 2, pT3 (ss), ly1, v0, pN0, pM1 (gall bladder, small intestine): pStage IV. CASE 2: A 55-year-old male with epigastric pain was diagnosed with scirrhous gastric cancer upon detailed examination. Pre-operative diagnosis was T3N1P1H0M0, Stage IIIA. Upon surgery, gastro-jejunal anastomosis was performed as resection was not an optional. Three courses of TS-1+CDDP were performed. A clear reduction of tumor size was noted upon laparoscopic examination as well as imaging and distal gastrectomy was performed. The pathological findings shown were type 4, por 2, pT3 (ss), ly2, v1, pN1, p1, pStage IV. The prognosis for inoperable gastric cancer is not promising and there is no established treatment guideline, however, there are cases in which TS-1+CDDP therapy has made surgery possible, and with the anticipation of extended survival, can be considered a useful therapy method.

[Radiofrequency ablation (RFA) in colorectal cancer with hepatic metastases].

We considered the appropriateness of RFA, which was performed in three cases of colorectal cancer with hepatic metastases accompanied by liver cirrhosis. Case 1 involved a patient with sigmoid colon cancer ss, n1 (+) with severe hepatic dysfunction and synchronous hepatic metastases (S5, S6, S8) in which RFA was performed. After 1 year and 6 months, recurrence (S3, S4) was detected in the residual liver, and the patient is currently undergoing the IFL (CPT-11/5-FU/Leucovorin) treatment. In case 2, following a partial hepatic resection, RFA was performed for cecal cancer ss, n2(+) with synchronous hepatic metastases (S5, S6, S8). After 11 months, recurrence (S5, S6, S7) occurred in residual liver and again RFA was performed following a partial hepatic resection. Lung metastases have occurred and currently IFL (CPT-11/5-FU/Leucovorin) and WHF treatments are underway. In case 3, 4 years and 8 months after cancer of the descending colon ss, n1 (+), RFA was performed on asynchronous hepatic metastases (S5, S7, S8). The patient died of peritonitis carcinomatosa one year after RFA. In all three cases, metastases were identified by dynamic CT as low density masses with no blood flow. Necrosis in all three metastases and local control had been achieved. There were no severe complications. Under the current conditions, local coagulation methods including RFA are appropriate in those cases in which resection are not possible such as multiple metastases with severe hepatic dysfunction, etc.

[The use of radio frequency ablation (RFA) for colorectal liver metastases in one patient].

We studied one case in which the application of RFA was used for colorectal liver metastases with cirrhosis. The patient was a 51-year-old male. Sigmoid colon cancer and hepatocellular cancer (S5, S6, S8) were diagnosed before surgery. RFA was planned, as resection was determined to be impossible, because of reduced reserve liver function due to hepatitis B and cirrhosis. Resection of the Sigmoid colon was performed. Rapid pathological diagnosis was performed on the liver tumor and it was determined to be metastases from the sigmoid colon cancer. RFA was performed on the liver tumor with the expectation of local control. After the operation, WHF arterial infusion was performed as an outpatient, but the blood platelet count decreased and that resulted in impaired liver function making the continuation of WHF arterial infusion at a regular pace difficult. After 11 months from the operation, multiple recurrences appeared and the infusion was restarted. Consequently, the tumor size was reduced. Following the infusion, however, the liver function became impaired and there was no choice but to discontinue the infusion. After one year and 9 months from the operation, multiple recurrences appeared in the residual liver and WHF arterial infusion was restarted. The tumor size gradually reduced after the infusion and only S3 currently remains with good local control. Because this example was a case with multiple metastases along with a high level of liver function impairment, RFA was tested and good local control was achieved. In cases such as these where liver resection is not possible, local ablation therapies including RFA are applicable.

[Evaluation of intraarterial infusion chemotherapy for liver metastasis from gastric cancer FEM: combination therapy of 5-FU, epirubicin and MMC].

OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, epirubicin, MMC) therapy. SUBJECTS: Data for 111 patients with liver metastasis from gastric cancer were collected from January 1977, until June 2003 (synchronous: 74 cases, asynchronous: 37 cases). Thirty patients were H1, 20 were H2 and 61 were classified as H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 10), Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intraarterial infusion (5 cases). Group B: Resection of the primary lesion (n = 67), Group B1: Resection of the primary lesion only (46 cases), Group B2: Intraarterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (4 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: 1-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%. 4.8 months; and Group C: 6%, 3.9 months, respectively. One case from Group A2a and 2 cases from Group B2a have survived for 3 years or longer. CONCLUSION: 1) We treated 3 patients with liver metastasis from gastric cancer who survived for 3 years or longer. 2) Resection of the primary lesion along with hepatic intraarterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended length of survival.

[Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer FEM--combination therapy of 5 FU, Epirubicin and MMC].

OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, Epirubicin, MMC) therapy. SUBJECTS: One hundred ten cases of liver metastasis from gastric cancer were collected from January, 1977 until June, 2001 (synchronous: 74 cases, asynchronous: 36 cases). Twenty-nine cases were H1, 20 cases were H2 and 61 cases were H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 9); Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intra-arterial infusion (4 cases). Group B: Resection of the primary lesion (n = 67); Group B1: Resection of the primary lesion only (46 cases), Group B2: Intra-arterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (3 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: One-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%, 4.8 months; and Group C: 6%, 3.9 months, respectively. Five patients from Groups A2a and B2a survived for one year or longer. CONCLUSION: 1. The prognosis with liver metastasis from gastric cancer, even with a number of therapies, is not promising. 2. Resection of the primary lesion along with hepatic intra-arterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended survival.

[Resection made possible following hepatic arterial infusion in 2 cases of hepatic metastases from colorectal cancer].

Of 66 examples of hepatic metastases from colorectal cancer, 30 cases in which resection was performed had 3- and 5-year cumulative survival rates of 66.7% and 56.8%, while in 36 cases in which resection was not possible, the percentages were 8.7% and 2.9%, respectively. In two of the latter cases, resection was possible following WHF (5-FU 1,000 mg/m2 5 h qw). Case 1: A 58-year-old male, with rectal cancer and multiple metastases (H3, synchronous). Arterial infusion was performed 21 times, with the total volume of 5-FU administered being 31.5 g. The size of the lesions was reduced and hepatic resection was performed. The patient later died due to local recurrence and intra-abdominal lymph node metastases. He had survived 2 years and 11 months following hepatic resection and was free from recurrence of hepatic metastases. Case 2: An 82-year-old female, with cancer of the ascending colon, sigmoidal colon and multiple hepatic metastases (H3, metachronous). Arterial infusion was performed 16 times, with the total amount of 5-FU administered being 20 g. A lowering of CEA levels and reduction of tumor size were achieved, and hepatic resection was performed. Seven months following hepatic resection, CEA levels are normal and no distant metastases or recurrence in the residual liver have been found: possibly a complete cure. Even among cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible following hepatic arterial infusion chemotherapy, with the possibility of complete cure.