Toshiomi Kusano

Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma

BACKGROUND In order to elucidate the predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma (ICC), we evaluated 7 patients who survived for more than 5 years (5-year survivors). METHODS We examined the clinicopathologic and biologic factors of the 5-year survivors, and these findings were then compared with those in 20 patients who died within 5 years after surgery (control group). RESULTS In the 5-year survivors, the gross appearance of the tumors included a mass-forming (MF) type in 5 cases, an intraductal growth (IG) type in 1, and another type (microcarcinoma with hepatolithiasis) in 1. No case demonstrated a periductal infiltrating (PI) type. Except for 1 case with an IG type tumor, no lymph node metastasis was seen in any patients. All of the 5-year survivors were classified from stage I to III, and all also underwent a curative resection. The clinicopathologic factors demonstrating significant differences between the 5-year survivors and the control group included the gross type of the tumor, lymph node involvement, the surgical margin, curability, and pTNM stage. CONCLUSION The predictive factors for long-term survival in patients with ICC are thus suggested to include not only tumor staging and curability, but also lymph node metastasis and the gross type of the tumors.

Natural progression of untreated hepatolithiasis that shows no clinical signs at its initial presentation

Goals To elucidate the natural progression of hepatolithiasis that showed no signs at the time of initial presentation. Study Over a 17-year period, we observed 122 of 311 patients with hepatolithiasis who reported no symptoms and, thus, who received no treatment at initial presentation. The follow-up period was for up to 15 years (mean, 10.08 years). Results Fourteen of 112 patients (11.5%) developed some symptoms attributed to hepatolithiasis. The interval until the onset of symptoms ranged from 9 months to 7.33 years (mean, 3.42 years ). The developing symptoms included abdominal pain, hepatic abscess, cholangitis, and cholangiocarcinoma. Nine of the 14 patients (64.3%) developed stone migration to the extrahepatic bile duct at the onset of clinical symptoms. The incidence of lobar liver atrophy on computed tomography in the patients with symptomatic hepatolithiasis (13 of 14 patients; 92.9%) was significantly higher than that in the patients with asymptomatic hepatolithiasis (14 of 108 patients; 13.0%). The prognosis of the patients with symptomatic hepatolithiasis were as follows: 2 died of cholangiocarcinoma, 1 died of hepatic failure, and 11 survived. Fifteen of asymptomatic patients died, but none of these deaths were attributed to hepatolithiasis. Conclusions Close observation is an alternative management at initial presentation for patients with asymptomatic hepatolithiasis without extrahepatic stones or lobar liver atrophy.

Radiation-Associated Rectal Cancer: Report of Four Cases

Background/Aims: Radiation-associated rectal cancer is a remarkable clinical entity. We demonstrate 4 patients (mean age 68 years, range 63–74) who had undergone pelvic radiotherapy for cervical cancer. We indicate some characteristics of radiation-associated rectal cancer. Results: Two patients had received intracavitary and external pelvic radiotherapy, while the remaining 2 had external pelvic radiotherapy following hysterectomy. The mean total radiation dose was 63 Gy, though radiation dose information was not available for 1 patient. Colorectal cancer developed at a mean time of 20.7 years (range 11–30) after radiation therapy. All patients presented with chronic radiation colitis, and 3 demonstrated abnormal tumor markers. Colonoscopy revealed an ulcerative, localized well-differentiated adenocarcinoma of the rectosigmoid colon in 1 patient, and diffusely infiltrating cancers of the lower rectum, one signet-ring cell carcinoma and two mucinous carcinomas in the remaining 3. One case was stage I, 2 were stage IIIa, and the remaining case was stage IV. Three patients underwent abdominoperineal resection. The remaining patient was felt to be inoperable. The colorectal wall demonstrated the changes of chronic radiation injury. Two patients died within a short time because of their advanced cancers. Conclusion: Radiation-associated rectal cancer has a tendency to be diagnosed in the advanced stage and to have a poor prognosis. A literature review and our case report suggest that since there are no reliable clinical or laboratory indicators of the presence of a curable colorectal cancer in the setting of chronic radiation proctocolitis, surveillance with a colonoscope should be done 10 years after irradiation in patients with previous pelvic radiotherapy.

Radiation Enterocolitis: Overview of the Past 15 Years

AbstractFrom April 1980 to April 1995 a total of 54 patients (53 women, 1 man) were hospitalized in our department for the surgical treatment of radiation enterocolitis. Two surgical protocols were applied for these patients: intestinal decompression procedures alone (intestinal bypass, colostomy, or both; n= 18) or an intestinal resection in addition to decompression (n= 36). The clinical factors contributing to survival after irradiation were retrospectively reviewed by a multiple variate proportional hazards model. As a result, patients treated with decompression procedures alone had an 11 times higher risk for death than those treated with the addition of intestinal resection. In the former group, 5 of 18 patients died of bleeding from the remaining intestine after operation. We concluded that surgical resection of the diseased intestine is a useful procedure for treating radiation enterocolitis to reduce intestinal bleeding from the irradiated intestine.

Characteristics of Hepatocellular Carcinoma in Patients with Negative Virus Markers: Clinicopathologic Study of Resected Tumors

n= 11), hepatitis C virus antibody positive (HC, n= 21), and non-BC (both HbsAg and HCVAb negative, n= 12). Seven patients were excluded from the study because of operative death (n= 3), a history of alcohol abuse (n= 3), or the presence of dual positive HB and HC virus markers (n= 1). The data were analyzed by either an analysis of variance (ANOVA) or a contingency table. The age of the non-BC patients was higher (63.0 ± 4.1, ± SE) than that of HB patients (54.0 ± 3.2, p < 0.05) but was identical to that of the HC group (62.0 ± 1.8). Among the preoperative laboratory data, the serum glutamic oxaloacetate and glutamate pyruvate transaminoses (GOT, GPT) levels were statistically lower in the non-BC patients (32.8 ± 4.8 and 28.0 ± 4.4 IU/L, respectively) than in the HB and HC patients. The pathologic features of the resected specimens in the non-BC patients showed more invasive growth than in specimens from the HB or HC patients. The clinical stages (defined based on the criteria of the Japanese Association of Hepatocellular Carcinoma) were also more advanced in the non-BC patients than in the other groups. Postoperative survival time showed no significant difference among the groups. In conclusion, the non-BC patients had comparatively greater invasive growth and more advanced clinical stages than the HB and HC patients, despite the absence of liver cirrhosis, and so demonstrated the same poor survival data as observed in the HB and HC patients.

Perforation Due to Metastatic Tumors of the Ileocecal Region

Abstract. We reviewed our department’s medical records between April 1986 and April 1994 to identify patients who showed acute abdominal symptoms requiring surgical treatment due to metastatic tumors of the small intestine. In group A, seven patients (30%) were treated for acute peritonitis, and all were found to have an intestinal perforation due to hematogenous metastases (group A). In group B, 16 patients (70%) were treated for an intestinal obstruction, and all were found to have disseminated tumors of the small intestine (group B). In group A all tumors were isolated and located exclusively in the ileocecal region, whereas all tumors in group B showed peritoneal dissemination, with no predominant anatomic localization. In general, the intestinal tumors in group A originated from cancers of the upper aerodigestive tract, whereas those in group B originated from advanced cancers in the abdominal cavity. The tumors were significantly smaller and the period between the onset of symptoms from the original malignancy and the onset of abdominal symptoms (perforation or obstruction) was significantly shorter in group A. In conclusion, intestinal metastases located in the ileocecal region have unique clinicopathologic features and so should be recognized as a distinct disease entity. Therefore when patients with a known upper aerodigestive malignancy exhibit acute abdominal symptoms, intestinal metastasis to the ileocecal region, necrotic changes, and perforation should be considered in the differential diagnosis.

Adenovirus-Mediated Gene Transfer Using Ex Vivo Perfusion of the Heart Graft

A replication-deficient adenovirus was used for ex vivo gene transfer into rat heart grafts under conditions simulating clinical transplantation. The adenoviral vector, AdHCMVsp1LacZ, containing an expression cassette of Escherichiae coli lacZ, was used to perfuse heart grafts during cold ischemia before transplantation. Heart grafts were perfused with University of Wisconsin (UW) solution containing either 0 pfu, 5×1010 pfu, or 1×1011 pfu of viral vector, and were preserved for either 2 or 4 h and then transplanted into syngeneic recipients. The animals were killed at 1, 7, and 14 days after transplantation. The infection rate was assessed by histochemical staining for β-galactosidase. Using polymerase chain reaction (PCR), viral DNA presence was confirmed in every graft perfused with viral vectors. The protein production from the transfected gene was confirmed by a functional protein assay. An efficient gene transfer was achieved with an infection rate of 1%–1.5% for all cardiac myocytes, as assessed by 5-bromo-4-chloro-indolyl-β-d-galactopyranoside (X-gal) staining. All studies were negative in the control grafts. Gene expression persisted for at least 10 days after transplantation. We thus conclude that an efficient adenovirus-mediated gene transfection and expression of gene products can be achieved in ex vivo perfusion of the heart graft during cold preservation.

Synchronous double cancers of the remnant stomach and pancreas: report of a case.

We present here in the case of a 75-year-old man who developed synchronous double cancers of the remnant stomach and pancreas 12 years after undergoing distal gastrectomy for gastric carcinoma. The patient was referred to our hospital in March, 1993, with a provisional diagnosis of carcinoma of the remnant stomach. Laboratory data on admission showed an abnormal level of CA19-9 (116.1 U/ml) and positive occult blood in the stools. An upper gastrointestinal series and gastroendoscopy demonstrated an ulcerative polypoid tumor in the gastric stump proximal to the gastroduodenostomy anastomosis, and a biopsy confirmed the findings of mucinous adenocarcinoma. Abdominal computed tomography (CT) scan revealed a low-density nodule anterior to the abdominal aorta, suggestive of a nodal metastasis. A laparotomy was performed which also disclosed a low-density mass located within the head of the pancreas. The patient was subsequently diagnosed as having double carcinomas of the remnant stomach and pancreas, and total gastrectomy and pancreatoduodenectomy were carried out. The histologic sections from the remnant stomach showed mucinous adenocarcinoma, whereas those from the pancreas showed tubular adenocarcinoma. Double carcinomas in this association are extremely rare and this case may in fact be the first observation of synchronous double cancers of the remnant stomach and pancreas.

Clinicopathologic features of resected primary adenosquamous carcinomas of the liver.

Four cases of resected adenosquamous carcinoma of the liver were clinicopathologically reviewed, together with immunohistochemical findings. Although no lymph node metastases were seen and a curative resection was achieved in all cases, two patients had recurrences in the peritoneum and distant organs such as the pericardium and pleura relatively soon after the operation. Of the remaining two cases, one patient died during the postoperative period and the other died of coexistent hilar cholangiocarcinoma. Together these findings suggest that this disease tends to spread locally and distantly in the early phase of tumor growth and shows aggressive biological behavior. In an immunohistochemical study, involucrin was a specific marker for the squamous component and CA19-9 was a marker for the adenomatous component.

Common bile duct exploration—Primary closure of the duct with retrograde transhepatic biliary drainage—

A new method of retrograde transhepatic biliary drainage (RTBD) using and RTBD tube with primary closure of the common duct was investigated with special reference to the usefulness and feasibility of this procedure. At operation, an atraumatic vinyl chloride tube was inserted from a choledochotomy incision and in most cases advancedvia the left hepatic duct to the liver surface, which was then penetrated. After the choledochotomy incision had been primarily sutured, the RTBD tube was fixed to the abdominal wall. This drainage method was applied to 71 patients as an alternative to the conventional T-tube drainage and its effect on bile drainage was prominent. The insertion of an RTBD tube did not influence liver function tests and an RTBD tube cholangiography revealed no severe deformity at the primary closure site of the bile duct. The most common complication was movement of the optimal site for stenting of the bile duct, however, no serious complications were encountered. On average, the RTBD tube was removed on the 16th postoperative day, the mean postoperative stay in hospital being 22 days. These findings suggest the need for a prospective randomized clinical trial to prove the usefulness and feasibility of primary bile duct closure using our drainage method.