Kenzo Koh

Functional outcome after low anterior resection with low anastomosis for rectal cancer using the colonic J-pouch. Prospective randomized study for determination of optimum pouch size.

PURPOSE: Functional outcome after low anterior resection with ultralow coloanal anastomosis for rectal cancer is improved by construction of a colonic J-pouchvs.straight anastomosis. Optimum size of this pouch has yet to be determined. Therefore, we initiated a prospective, randomized trial using 5-cm and 10-cm pouches to determine this size. METHODS: Patients with tumors 5 to 10 cm from the anal verge were included in the study. Before a low anterior resection anastomosis was performed, patients were randomized to either a 5-cm J-pouch group (5-J group) or a 10-cm J-pouch group (10-J group). Functional assessments were performed one year postoperatively. Clinical functions were evaluated using a functional scoring system. Physiologic functions, such as sphincter and reservoir function, were evaluated by anorectal manometry and evacuation function by the balloon expulsion and saline evacuation tests. RESULTS: Forty patients among 43 randomized patients were assessed for functional outcome one year postoperatively (5-J group, n=20; 10-J group, n=20). The functional score was similar for the two groups, although reservoir function in the 5-J group was significantly less than in the 10-J group. Sphincter function was similar between the two groups. Evacuation function in the 5-J group was significantly superior to that in the 10-J group. CONCLUSIONS: The 5-cm J-pouch conferred adequate reservoir function without compromising evacuation.

Comparison of controlled and Glisson's pedicle transections of hepatic hilum occlusion for hepatic resection.

BACKGROUND For hepatic resection, intraoperative bleeding is reduced by clamping the afferent blood flow. Selective clamping at the hepatic hilum can be accomplished using the standard controlled method or Glissons pedicle transection method. The safety and efficacy of these two methods have not previously been compared. STUDY DESIGN The intraoperative findings and complications were retrospectively reviewed in 90 patients who underwent major hepatectomy with selective inflow clamping between 1988 and 1997. RESULTS Blood loss and operative time did not differ between the two groups. Bile leakage was observed in 3 of 43 patients (7.0%) in the standard controlled method group and 11 of 47 patients (23.4%) in the Glissons pedicle transection method group (p = 0.031). In the Glissons pedicle transection method group, bile leakage occurred more frequently in patients who underwent left lobectomy than in those who underwent right lobectomy (p = 0.023). CONCLUSIONS There were no differences in intraoperative findings and postoperative complications analyzed between the standard controlled method and Glissons pedicle transection method for major hepatectomy except for the rate of bile leakage. In particular, attention must be paid to the bile duct injuries when the Glissons pedicle is dissected.

Longterm effects of hepatic arterial interleukin-2-based immunochemotherapy after potentially curative resection of colorectal liver metastases.

BACKGROUND Our previous study of hepatic arterial infusion of interleukin-2 (IL-2)-based immunochemotherapy demonstrated a high response rate of patients with unresectable liver metastases. In this study, we applied this therapy to the prevention of liver recurrence in patients who underwent potentially curative resection of liver metastases. STUDY DESIGN A pilot study was conducted of 18 patients with liver metastases from primary colorectal cancer who underwent potentially curative liver resection followed by adjuvant immunochemotherapy. The regimen consisted of a weekly hepatic arterial infusion of IL-2 (1.4-2.1 X 10(6) U) and 5-fluorouracil (250 mg) and a bolus of mitomycin C (2-4 mg) for 6 months. RESULTS Among 18 patients, 14 are still alive with a median postoperative survival of 52 months (as of April 1998). The 5-year overall survival rate was 75%. Although recurrent cancer developed in 6 of the 18 patients, no patients had recurrence in the residual liver. This complete prevention of liver recurrence is believed to have contributed to the high 5-year survival rate (75%) as compared with the survival rate of patients treated with surgery alone (average, 30%-40%) or with several other forms of adjuvant therapy. CONCLUSIONS Interleukin-2-based immunochemotherapy is useful in combination with liver resection for the prevention of liver recurrence in colorectal cancer patients with liver metastases. A multicenter randomized trial is recommended.

Functional Outcome After Low Anterior Resection for Rectal Cancer Using the Colonic J-Pouch

The functional outcome after low anterior resection (LAR) using the colonic J-pouch was compared with that after LAR using straight anastomosis. Colonic J-pouch construction was performed in 58 patients who underwent resection of tumors located 5–10 cm from the anal verge (J-pouch group). Functional assessment was performed 1 year postoperatively. Clinical function was evaluated using a scoring system, while physiologic sphincter and reservoir function were evaluated by anorectal manometry. The historical control group consisted of 20 patients who underwent LAR with straight anastomoses (straight group). The functional score of the J-pouch group was significantly better than that of the straight group. Although sphincter function was similar in the two groups, reservoir function was significantly better in the J-pouch group than in the straight group. These results demonstrated that the functional outcome following LAR for rectal cancer is improved by the colonic J-pouch construction.

Complete remission of liver metastases from colorectal cancer by treatment with a hepatic artery infusion (HAI) of interleukin-2-based immunochemotherapy: reports of three cases.

In an attempt to improve the therapeutic efficacy against liver metastases, a hepatic arterial infusion (HAI) of interleukin-2 (IL-2)-based immunochemotherapy for anticipating the regional potentiation of hepatic lymphokine-activated killer (LAK)/tumor-infiltrating lymphocytes (TIL) was initiated. We present herein the cases of three patients with multiple liver metastases from colorectal cancer in whom complete remission was achieved by treatment with an HAI of IL-2 in combination with mitomycin C (MMC) and 5 fluorouracil (5-FU). These patients received an HAI of IL-2 at 8 x 105 JRU, 5-FU at 250 mg daily, and MMC at 4 mg once weekly for 3 weeks, being the induction regimen, after which they were discharged on maintenance therapy consisting of IL-2 at 2 X 106 JRU, 5-FU at 250 mg twice weekly, and MMC at 4 mg once weekly. It was evident from the liver CT scan taken after 2–3 months that the metastatic foci seen before therapy had clearly disappeared, while the serum carcinoembryonic antigen (CEA) had decreased to normal levels in all three patients. Pancytopenia was seen in one patient, but other laboratory studies of the hepatic and renal parameters were normal. The total lymphocyte count in the peripheral blood showed a mild decrease, while the lymphocyte phenotype study showed a notable increase in CD4+ cells and a decrease in CD8+ cells, with an elevation of a 4/8 ratio, in all cases during therapy. One patient relapsed with pelvic recurrence 14 months after the initiation of therapy, but the other two patients are still in remission 25 and 22 months after the initiation of therapy.

Clinical characteristics of hepatitis B core antibody-positive hepatocellular carcinoma.

The pathology and prognosis of hepatitis B surface antigen (HBsAg)-positive hepatocellular carcinoma (HCC) and hepatitis C virus antibody (HCVAb)-positive HCC is well documented. However, patients with HBsAg-negative/hepatitis B core antibody (HBcAb)-positive HCC are included with non-B non-C disease and have been characterized independently. A series of 125 patients who had undergone hepatectomy for HCC were divided into three groups and compared. The HBsAg group comprised 25 HBsAg-positive patients, the HCV group comprised 70 HCVAb-positive patients, and the HBcAb group comprised 22 HBcAb-positive/HBsAg-negative patients. Eight patients of negative virus markers were excluded in this study. Tumors were larger in the HBcAb group (6.2 cm) than in the HBsAg (4.4 cm) and HCV (3.7 cm) groups. Disease-free 1-, 3-, and 5-year survival rates were, respectively, 75.0%, 57.1%, and 57.1% in the HBcAb group; 60.9%, 41.8%, and 41.8% in the HBsAg group; and 88.0%, 54.0%, and 37.8% in the HCV group. HBcAb-positive HCC patients had larger tumors, but their prognosis was relatively good. Although HBsAg and HCVAb are used for conventional screening of patients with hepatic disorders, we believe that screening is also necessary in patients with positive HBcAb titers for early detection of HCC.RésuméLa pathologie et le pronostic du carcinome hépatocellulaire (CHC) en rapport avec le virus de l’hépatite B à antigène de surface positif (CHC HBsAg-positif) et le virus de l’hépatite C à anticorps (Ac) positif (CHC VHC Acpositif) sont bien documentés. Cependant, les patients porteurs d’un CHC secondaire à l’hépatite HBsAg-négative ou à l’hépatite B à Ac de HBc positif (HBcAc-positif) sont classés parmi les patients à maladie non-B, non-C et ont été caractérisés indépendamment. 125 patients ayant eu une hépatectomie pour CHC ont été divisés en trois groupes et comparés entre eux: le groupe HbsAg, comprenant 25 patients HBsAg-positifs, le groupe VHC comprenant 70 patients CHC VHC Acpositifs et le groupe HBcAc groupe comprenant 22 patients HBcAc -positifs avec HBsAg-négatifs. Huit patients avec des marqueurs viraux négatifs ont été exclus de cette étude. La taille tumorale était supérieure dans le groupe HBcAc (6.2 cm) que dans les groupes HBsAg (4.4 cm) et VHC (3.7 cm). La survie sans maladie à 1, à 3 et à 5 ans a été, respectivement, de 75.0, de 57.1 et de 57.1% dans le groupe HBcAc, de 60.9, de 41.8 et de 41.8% dans le groupe HBsAg et de 88.0, de 54.0 et de 37.8% dans le groupe VCH. Les patients porteurs d’un CHC HBcAc-positif avaient des tumeurs plus grandes, mais leur pronostic était relativement bon. Bien que l’HBsAg et l’HCVAc soient utilisés pour détecter les patients ayant des maladies hépatiques, nous pensons que le dépistage est également nécessaire chez les patients HBcAc positifs pour la détection précoce du CHC.ResumenLa patología y el pronóstico del carcinoma hepatocelular (CHC) con antígeno de superficie para hepatitis B positivo (HBsAg-positivo) y con anticuerpos contra virus de hepatitis C positivos (HCVAb-positivo) han sido bien documentados. Sin embargo, los pacientes con CHC y HBsAg-negativo y anticuerpo nuclear (core) positivo (HBcAb-positivo) se incluyen con los que tienen enfermedad no-B no-C y han sido caracterizados en forma independiente. Ciento veinticinco pacientes sometidos a hepatectomía por CHC fueron divididos en 3 grupos para efectos de comparación. El grupo HBsAg comprendió 25 pacientes HBsAg-positivos, el grupo HCV comprendió 70 pacientes HCVAb-positivos y el grupo HBcAb comprendió 22 pacientes HBcAb-positivos con HBsAg-negativo. Ocho pacientes con marcadores virales negativos fueron excluidos. El tamaño del tumor apareció mayor en el grupo HBcAb (6.2 cm) que en los grupos HBsAg (4.4 cm) y HCV (3.7 cm). Las tasas de supervivencia libre de enfermedad a 1, 3 y 5 años fueron 75.0, 57.1 y 57.1% en el grupo HBcAg, 60.9, 41.8 y 41.8% en el grupo HBsAg y 88.0, 54.0 y 37.8% en el grupo HCV, respectivamente. Los pacientes HBcAb-positivos presentaron tumores de mayor tamaño, pero su pronóstico fue relativamente bueno. Aunque los HBsAg y HCVAb son utilizados en el tamizaje convencional de pacientes con alteraciones hepáticas, nosotros creemos que el tamizaje también es necesario en pacientes con HBcAb positivo para la detección temprana del CHC.

Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer

We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 × 105 JRU/day) for 25–40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leull (CD16)+, OKMl(CD11)+ and OKIal(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment. We conclude that continuous IS-IL-2 administration can result in an increase of their therapeutic efficacy of IL-2 administration and in a decrease its toxicity.

Longterm effects of hepatic arterial interleukin-2–based immunochemotherapy after potentially curative resection of colorectal liver metastases11This work was supported in part by Grants-in-Aid for Scientific Research (B) from the Ministry of Education, Science and Culture (#06454390), Japan.

BACKGROUND Our previous study of hepatic arterial infusion of interleukin-2 (IL-2)-based immunochemotherapy demonstrated a high response rate of patients with unresectable liver metastases. In this study, we applied this therapy to the prevention of liver recurrence in patients who underwent potentially curative resection of liver metastases. STUDY DESIGN A pilot study was conducted of 18 patients with liver metastases from primary colorectal cancer who underwent potentially curative liver resection followed by adjuvant immunochemotherapy. The regimen consisted of a weekly hepatic arterial infusion of IL-2 (1.4-2.1 X 10(6) U) and 5-fluorouracil (250 mg) and a bolus of mitomycin C (2-4 mg) for 6 months. RESULTS Among 18 patients, 14 are still alive with a median postoperative survival of 52 months (as of April 1998). The 5-year overall survival rate was 75%. Although recurrent cancer developed in 6 of the 18 patients, no patients had recurrence in the residual liver. This complete prevention of liver recurrence is believed to have contributed to the high 5-year survival rate (75%) as compared with the survival rate of patients treated with surgery alone (average, 30%-40%) or with several other forms of adjuvant therapy. CONCLUSIONS Interleukin-2-based immunochemotherapy is useful in combination with liver resection for the prevention of liver recurrence in colorectal cancer patients with liver metastases. A multicenter randomized trial is recommended.

Longterm effects of hepatic arterial interleukin-2–based immunochemotherapy after potentially curative resection of colorectal liver metastases 1

BACKGROUND Our previous study of hepatic arterial infusion of interleukin-2 (IL-2)-based immunochemotherapy demonstrated a high response rate of patients with unresectable liver metastases. In this study, we applied this therapy to the prevention of liver recurrence in patients who underwent potentially curative resection of liver metastases. STUDY DESIGN A pilot study was conducted of 18 patients with liver metastases from primary colorectal cancer who underwent potentially curative liver resection followed by adjuvant immunochemotherapy. The regimen consisted of a weekly hepatic arterial infusion of IL-2 (1.4-2.1 X 10(6) U) and 5-fluorouracil (250 mg) and a bolus of mitomycin C (2-4 mg) for 6 months. RESULTS Among 18 patients, 14 are still alive with a median postoperative survival of 52 months (as of April 1998). The 5-year overall survival rate was 75%. Although recurrent cancer developed in 6 of the 18 patients, no patients had recurrence in the residual liver. This complete prevention of liver recurrence is believed to have contributed to the high 5-year survival rate (75%) as compared with the survival rate of patients treated with surgery alone (average, 30%-40%) or with several other forms of adjuvant therapy. CONCLUSIONS Interleukin-2-based immunochemotherapy is useful in combination with liver resection for the prevention of liver recurrence in colorectal cancer patients with liver metastases. A multicenter randomized trial is recommended.