Should Lymph Nodes Be Retrieved in Patients with Intrahepatic Cholangiocarcinoma? A Collaborative Korea-Japan Study.

BACKGROUND: This study was performed to investigate the oncologic role of lymph node (LN) management and to propose a surgical strategy for treating intrahepatic cholangiocarcinoma (IHCC). METHODS: The medical records of patients with resected IHCC were retrospectively reviewed from multiple institutions in Korea and Japan. Short-term and long-term oncologic outcomes were analyzed according to lymph node metastasis (LNM). A nomogram to predict LNM in treating IHCC was established to propose a surgical strategy for managing IHCC. RESULTS: A total of 1138 patients were enrolled. Of these, 413 patients underwent LN management and 725 did not. A total of 293 patients were found to have LNM. The No. 12 lymph node (36%) was the most frequent metastatic node, and the No. 8 lymph node (21%) was the second most common. LNM showed adverse long-term oncologic impact in patients with resected IHCC (14 months, 95% CI (11.4-16.6) vs. 74 months, 95% CI (57.2-90.8), p < 0.001), and the number of LNM (0, 1-3, 4≤) was also significantly related to negative oncologic impacts in patients with resected IHCC (74 months, 95% CI (57.2-90.8) vs. 19 months, 95% CI (14.4-23.6) vs. 11 months, 95% CI (8.1-13.8)), p < 0.001). Surgical retrieval of more than four (≥4) LNs could improve the survival outcome in resected IHCC with LNM (13 months, 95% CI (10.4-15.6)) vs. 30 months, 95% CI (13.1-46.9), p = 0.045). Based on preoperatively detectable parameters, a nomogram was established to predict LNM according to the tumor location. The AUC was 0.748 (95% CI: 0.706-0.788), and the Hosmer and Lemeshow goodness of fit test showed p = 0.4904. CONCLUSION: Case-specific surgical retrieval of more than four LNs is required in patients highly suspected to have LNM, based on a preoperative detectable parameter-based nomogram. Further prospective research is needed to validate the present surgical strategy in resected IHCC.

A case of a malignant serous neoplasm of the pancreas with synchronous vascular invasion and metachronous metastases.

Serous neoplasms (SNs) of the pancreas are usually considered benign tumors. However, they rarely manifest malignant behaviors. Here we present a case of malignant SN and review the literature of malignant SN. A 71-year-old woman presented to our hospital with a palpable abdominal mass. Imaging studies revealed a 7 cm mass with a cluster of microcysts having a honeycomb appearance in the head of the pancreas, which invaded the superior mesenteric vein (SMV). After being clinically diagnosed with SN, pancreaticoduodenectomy was performed with resection of limited SMV. Microscopically, the tumor was diagnosed as an SN concomitant with the tumor thrombus in the SMV. Four years after the surgery, two liver tumors and two peritoneal nodules were detected and three of them were surgically resected. All of those lesions had a honeycomb appearance in their cut surfaces and they were microscopically indistinguishable from the originally resected SN. A review of the literature identified 22 cases of malignant metastatic SNs published to date. Even though extremely rare, metachronous metastasis could occur in SNs of the pancreas. Local invasion indicated an increased likelihood of future metastasis. Thus, periodic surveillance should be considered for SNs after resection, especially when they have a local invasion.

Mitral valve nonbacterial thrombotic endocarditis: a rare multi-surgery-tolerant survivor of Trousseau's syndrome.

BACKGROUND: Few previous reports have documented cases of nonbacterial thrombotic endocarditis associated with Trousseau's syndrome for which surgery proved possible for both the primary tumor and the cardiac lesion. The effectiveness of direct oral anticoagulants in patients with Trousseau's syndrome has also received scant attention. CASE PRESENTATION: A 69-year-old man with repeated episodes of cerebral infarction was diagnosed as having nonbacterial thrombotic endocarditis after mitral valve replacement surgery. Stroke recurred preoperatively under apixaban administration. A stomach biopsy also identified gastric adenocarcinoma, and gastric surgery was performed on the 40th postoperative day. The patient was discharged from the hospital and has been free of thromboembolism under a regime of subcutaneous heparin self-injection thereafter. CONCLUSIONS: We have reported a rare multi-surgery-tolerant survivor of Trousseau's syndrome in whom subcutaneous heparin injection was useful for preventing thromboembolic events over a long period.

Comparative outcomes of elderly and non-elderly patients receiving first-line palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND AND AIM: Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes of palliative chemotherapy for advanced biliary tract cancer in elderly patients. METHODS: We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non-elderly group (< 75 years old; n = 309). RESULTS: Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non-elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non-elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non-elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy.

Patients with recurrent biliary tract cancer have a better prognosis than those with unresectable disease: retrospective analysis of a multi-institutional experience with patients of advanced biliary tract cancer who received palliative chemotherapy.

BACKGROUND: Prognostic factors for patients with advanced biliary tract cancer (BTC) who received palliative chemotherapy have not been fully established. Especially, the status of unresectable/recurrent disease has not been well studied because of a small number of patients with recurrent BTC in previous studies. METHODS: This multicenter retrospective study was conducted in 18 institutions in Japan. We retrospectively reviewed data regarding 403 patients with pathologically proven BTC who received palliative chemotherapy between April 2006 and March 2009. One hundred and ninety-two patients with recurrent BTC were included. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: The median overall survival was significantly longer in the recurrent BTC patients than in the unresectable BTC patients (398 days vs. 323 days, P = 0.004). After adjustment using multivariate analysis, the status of recurrent/unresectable disease remained an independent prognostic factor (hazard ratio 1.33, 95% confidence interval 1.04-1.70, P = 0.022) in addition to performance status, extent of disease, carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels. CONCLUSIONS: The status of unresectable/recurrent disease was shown as an independent prognostic factor in the BTC patients. This result may help to predict life expectancy of BTC patients and design future clinical trials evaluating palliative chemotherapy in BTC.

[Resection of cholangiolocellular carcinoma successfully responding to neoadjuvant hepatic arterial infusion chemotherapy - report of a case].

A 78-year-old man who had hepatitis C was examined by computed tomography(CT)because of prostate cancer, and was found to have a liver tumor 8. 0 cm in size at S4/S8. The view of the liver tumor was enhanced by CTHA image and washed out by CTAP image. It was suspected to have invaded the RHV and MHV. The pathological examination of the liver biopsy sample revealed cholangiocellular carcinoma or cholangiolocellular carcinoma. Hepatic arterial infusion chemotherapy with gemcitabine and cisplatin was performed. The size of the tumor reduced to 6. 0 cm and the invasion to the RHV was no longer evident. Hepatic resection for the middle two segments was performed after 3 months of chemotherapy. After a histological examination of the resected specimen, the patient was given the final diagnosis of cholangiolocellular carcinoma. Over 50% of the tumor was estimated as necrosis by chemotherapy, indicating that the gemcitabine and cisplatin regimen was remarkably effective. The patient is alive with no evidence of recurrence.

Ovarian mucinous cystadenoma of borderline malignancy in a premenarchal girl.

Ovarian mucinous cystadenomas are benign epithelial neoplasms that occur most often in the third to sixth decade of life. Ovarian mucinous cystadenoma can be classified into 3 categories (benign, borderline malignancy, malignancy) based on histopathologic evaluation. Premenarchal cases of ovarian mucinous cystadenoma of borderline malignancy are exceedingly rare. To the best of our knowledge, there have been only 4 reported cases of borderline ovarian mucinous cystadenoma prior to 2009. Here we report a 13-year-old premenarchal girl with a giant mass occupying almost the whole of the abdomino-pelvic cavity.

Umbilical cyst containing ectopic gastric mucosa originating from an omphalomesenteric duct remnant.

An umbilical cyst originating from an omphalomesenteric duct remnant is extremely rare, and to the best of our knowledge, it has scarcely been reported in medical literature. We present ultrasonographic manifestations and computed tomographic findings of an umbilical cyst originating from an omphalomesenteric duct remnant in a 6-year-old girl. In cases of umbilical cyst, radiographic evaluation alone may not differentiate an omphalomesenteric duct remnant with heterotopic gastric mucosa from a urachal remnant, and surgical intervention is required.

[A case of interstitial pneumonitis induced by FOLFIRI+bevacizumab combination therapy for liver and lung metastasis of colon cancer].

A 64 -year-old female received oral S-1 chemotherapy followed by mFOLFOX6 chemotherapy for postoperative liver and lung metastasis of sigmoid colon cancer. The tumor progression was observed after twelve courses of mFOLFOX6 chemotherapy, and then FOLFIRI+bevacizumab chemotherapy was performed. After two courses of FOLFIRI+bevacizumab chemotherapy, leucopenia was observed. The chemotherapy was then discontinued and G-CSF was administered. Two days later she complained of high fever and dry cough, and was admitted to the hospital. A diffuse ground-glass appearance of bilateral lung was observed on chest X-ray and CT. Drug-induced interstitial pneumonitis was suspected, and Pneumocystis carini pneumonia was considered in the differential diagnosis. Oral administration of prednisolone and sulfamethoxazole/trimethoprim did not improve the symptoms, so steroid pulse therapy was performed. Steroid pulse therapy improved respiratory symptoms, but CT findings did not change remarkably. After nine weeks in the hospital, she was discharged with home oxygen therapy. Interstitial pneumonitis induced by FOLFIRI+bevacizumab chemotherapy is rare, but the number of cases may increase with increased use of this regimen. The possibility of interstitial pneumonitis should always be considered when the patient presents with a respiratory disorder while receiving systemic chemotherapy.

[A successfully resected case of liver metastasis of gastrointestinal stromal tumor responding to neoadjuvant chemotherapy with imatinib mesylate and interventional radiology].

A 75-year-old woman underwent resection of gastrointestinal stromal tumor (GIST) of small intestine in 1999. In January 2006, she suffered liver dysfunction and abdominal CT revealed she had a large liver metastasis. At first the tumor in the right lobe progressed to the medial segment and seemed unresectable. She twice underwent transarterial embolization and treatment with 400mg/day of imatinib mesylate. Then percutaneous transhepatic portal embolization was performed. As a result, liver metastasis markedly decreased in size, and extended right lobectomy of the liver was performed in June 2006. A large portion of the liver metastasis showed necrosis, but histopathological examination revealed focal remnants of viable tumor cells. In March 2007, radiofrequency ablation was performed for recurrence of remnant liver. The patient has been treated by imatinib mesylate and is alive with no evidence of tumor recurrence.

Risk factors for recurrence of primary sclerosing cholangitis after living donor liver transplantation: a single center experience.

We retrospectively reviewed our 10-year experience with living donor liver transplantation (LDLT) in 30 consecutive patients with end-stage primary sclerosing cholangitis (PSC) to determine long-term patient and graft survival and risk factors for recurrence of PSC. For strict diagnosis of recurrence, patients with hepatic artery thrombosis (n = 2), ABO blood type incompatible transplantation (n = 3), and postoperative survival shorter than 1 year (n = 5) were excluded from the study, leaving 20 patients for analysis. Recurrence was diagnosed in 11 patients 26-71 months after transplantation. Multivariate analysis showed that cytomegalovirus diseases within 3 months after transplantation and related donors were independent risk factors for recurrence. When the effects on recurrence were compared among donor-recipient relationships, there were significant differences, especially between nonrelated donors and parents. Multivariate analysis showed that age was an independent risk factor for time to graft loss. Cytomegalovirus prophylaxis and avoidance of related donors are important in reducing PSC recurrence, although this is a preliminary report with limitations due to the small number of patients. LDLT for young patients with PSC using grafts from their parents might have to be avoided where deceased donor liver transplantation is available.

Intrahepatic bile duct dilatation with a liver cyst and hemangioma: report of a case.

We report a case of intrahepatic bile duct dilatation with a liver cyst and hemangioma. A 58-year-old woman was referred for investigation of a cystic lesion and peripheral intrahepatic bile duct dilatation in the left lateral segment of the liver. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed dilatation of the intrahepatic bile ducts in the left lateral segment, near a 4.5-cm cystic lesion. Early enhancement into the delayed phase was seen in the dorsal part of the cystic lesion. Celiac angiogram showed a belt-shaped hypervascular area, but no encasement or irregularity of the artery. To exclude malignancy, we performed a left lobectomy. Microscopically, the cyst was lined with a single layer of flattened epithelial cells and a spongy tumor was diagnosed as cavernous hemangioma, which compressed the bile duct. The histopathological diagnosis was biliary stenosis associated with cavernous hemangioma of the liver. Invasive surgery may be avoided by awareness of this unusual benign pathology.

The impact of meticulous management for hepatic artery thrombosis on long-term outcome after pediatric living donor liver transplantation.

To analyze the risk factors in the development of hepatic artery thrombosis (HAT) and assess the impact of our perioperative management for HAT on the long-term outcome after pediatric living donor liver transplantation (LDLT), we reviewed 382 patients under 12 yr of age who underwent 403 LDLT from January 1996 to December 2005. One- and 10-yr patient survival rates were 78% and 78% in the patients with HAT (27 patients; 6.7%), and 84% and 76% in the patients without HAT, respectively (p = n.s.). Univariate analysis showed gender (female), body weight (lower), and graft-to-recipient weight ratio (higher) were significant risk factors in the patients with HAT (p < 0.05). Patients with Doppler ultrasound signal loss of the hepatic artery (HA) accompanied by an increase of liver enzymes underwent thrombectomy and reanastomosis (S-group, n = 13), and patients with a weak HA signal underwent anticoagulant therapy (M-group, n = 13). One patient underwent re-LDLT. One- and five-yr patient survival rates were 83% and 83% in the S-group, and 77% and 77% in the M-group (p = n.s.). The incidence of biliary complications in the S-group (58%) was significantly higher than that of the M-group (15%). For a successful long-term outcome, the early detection of HAT and prompt medical and surgical intervention are crucial to minimize the insult of HAT.

Anterior approach for left-sided hepatic resection.

Complete mobilization of the liver before parenchymal transection has been a standard approach during major hepatectomy. This safe approach is not always feasible for the cases in which it is difficult to mobilize the hepatic lobe involved by large tumors with diaphragmatic invasion. Recently, anterior approach for the right-sided hepatic resection was reported as an alternative method without mobilization of the right lobe. The approach might be adaptive to left hepatectomy without mobilization of the left lobe. We demonstrated here the technique of anterior approach for left-sided hepatic resection to propose the surgical indication of this procedure.

Histological recurrence of autoimmune liver diseases after living-donor liver transplantation.

BACKGROUND: The effects of living donor liver transplantation (LDLT) on the recurrence of autoimmune liver diseases have not been well documented. Genetic similarities may be beneficial to avoid severe rejection but may facilitate the recurrence of autoimmune diseases. Because familial occurrence of autoimmune liver diseases has been documented, there is a possibility that candidates for living-related donors may have the same disease as that of the recipients. METHOD: Between November 1994 and June 2004, 50 patients with primary biliary cirrhosis (PBC) (16-non-blood-relative donors and 34 blood-relative donors), and 28 patients with primary sclerosing cholangitis (PSC) underwent LDLT in Kyoto University Hospital. RESULTS: Among 35 patients with PBC who survived more than 1 year, 10 patients (29%) showed recurrent PBC, and nine of 10 patients with recurrent PBC (90%) were associated with blood-relative donors (mean follow-up period, 30 months; range, 2-68). Two recipients had donors with some clinical or histological characteristics of PBC, and their grafts developedrecurrent PBC. Cirrhosis or graft failure was not observed in any patients with recurrent PBC. For PSC patients who survived more than 1 year after LDLT, 13 of 22 (59%) showed PSC-compatible histology and radiological findings (mean follow-up period, 31 months; range, 22-71), and five died or underwent retransplantation. Human leukocyte antigen-DR15 was positively associated with susceptibility to PSC with ulcerative colitis. One donor was revealed to have retroperitoneal fibrosis without evidence of sclerosing cholangitis. CONCLUSIONS: Blood-relative donors may be associated with susceptibility to recurrent autoimmune diseases. Recurrence of PSC, but not PBC, adversely affected the outcome of LDLT. Caution should be taken as blood-relative donors can be at risk of autoimmune liver diseases.

Living donor liver transplantation with reduced monosegments for neonates and small infants.

BACKGROUND: In pediatric living donor liver transplantation, left lateral segment or monosegmental graft is used to overcome size discrepancies between adult donors and pediatric recipients. For neonates and extremely small infants, however, problems related to large-for-size graft are sometimes encountered even when using such grafts. The reduced monosegmental graft, in which the caudal part of the monosegmental graft is resected, has been introduced to address this problem. METHODS: Of 566 children who underwent transplant between June 1990 and September 2004, reduced monosegment living donor liver transplants were used for nine patients (median age, 144 days; median weight, 4.1 kg). This technique was used for infants with estimated graft-to-recipient weight ratio (GRWR) > or =4.0% when using the left lateral segment. RESULTS: Graft and patient survival was 66.7%. GRWR was reduced from 7.45+/-2.70% to 3.39+/-0.89% using this modification. Transaminase levels at days 1 and 2 after transplantation were significantly higher in reduced monosegmental transplantation than in left lateral segmental transplantation. Hepatic artery thrombosis and portal vein thrombosis were observed in one case each. CONCLUSION: Reduced monosegmental living donor liver transplantation represents a feasible option for neonates and extremely small infants with liver failure.

Liver transplantation without isoniazid prophylaxis for recipients with a history of tuberculosis.

Tuberculosis remains one of the most serious infections after organ transplantation. Isoniazid prophylaxis for liver transplant recipients with a history of tuberculosis is generally recommended. However, its benefit is controversial because of potential hepatotoxicity of isoniazid. It is crucial to determine appropriate post-transplant managements for the recipients with a history of tuberculosis. The purpose of this study was to investigate the necessity of isoniazid prophylaxis for liver transplant recipients who had a history of tuberculosis. The medical records of 1116 liver transplant recipients were studied, of whom seven had a history of tuberculosis (0.63%). One who underwent living-donor liver transplantation for fulminant hepatic failure was excluded from evaluation because of early death, caused by bacterial sepsis two months after transplantation, although reactivation of tuberculosis was not observed. The median observation period after transplantation was 25.5 months (range 12-82). Reactivation of tuberculosis did not occur in any of these six patients. In conclusion, we could not find rationale for isoniazid prophylaxis in liver transplant recipients with past diagnosis of tuberculosis, when the disease is considered to be inactive. Tuberculosis should be considered as cause of post-transplant infections, and careful post-transplant observations are essential for an early diagnosis.

Single center experience of 39 patients with preoperative portal vein thrombosis among 404 adult living donor liver transplantations.

Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) involves technical difficulty. The aim of this research was to analyze their preoperative diagnosis of PVT, operative procedures, and postoperative courses of patients with preoperative PVT. Thirty-nine patients of 404 adult patients (9.7%) undergoing LDLT in our hospital from 1996 June to 2004 December had PVT at their transplantation. Twenty-nine patients had intractable ascites, 21 had gastrointestinal bleeding, and 18 had encephalopathy. The thrombus was located in the portal trunk in 23, in the portal trunk and superior mesenteric vein (SMV) in 7, and developed into the SMV and the splenic vein in 8. The occlusive grade was partial in 29, and complete in 10 patients. The thrombus was removed by a simple technique, and eversion and/or incision technique, or total removal of the portal vein (PV). The PV was reconstructed with the thrombectomized native PV, with an interposed vein graft, or porto-caval hemitransposition. Advanced PVT had a significant impact on blood loss and hospital mortality. Three out of 10 patients with residual PVT required radiological and/or surgical intervention after transplantation. In conclusion, thorough planning is essential for a successful LDLT outcome for patients with preexisting PVT.

Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: the Kyoto experience.

Smaller-size infants undergoing living-donor liver transplantation (LDLT) are at increased risks of vascular complications because of their smaller vascular structures in addition to vascular pedicles of insufficient length for reconstruction. Out of 585 child patients transplanted between June 1990 and March 2005, 64 (10%) weighing less than 6 kg underwent 65 LDLTs. Median age and weight were 6.9 months (range: 1-16 months) and 5 kg (range: 2.8-5.9 kg), respectively. Forty-five lateral segment, 12 monosegment, and 8 reduced monosegment grafts were adopted, and median graft-to-recipient weight ratio was 4.4% (range: 2.3-9.7). Outflow obstruction occurred in only 1 patient (1.5%). Portal vein complication occurred in 9 (14%) including 5 with portal vein thrombosis. Hepatic artery thrombosis (HAT) occurred in 5 (7.7%). Patient and graft survivals were 73% and 72% at 1 yr, and 69% and 68% at 5 yr after LDLT, respectively. Thirteen of 22 grafts (58%) lost during the follow-up period occurred within the first 3 months posttransplantation. Overall graft survival in patients with and without portal vein complication was 67% and 65%, respectively (P = 0.54). Overall graft survival in patients with and without HAT was 40% and 67%, respectively. HAT significantly affected graft survival (P = 0.04). In conclusion, our surgical technique for smaller-size recipients resulted in an acceptable rate of vascular complications. Overcoming early posttransplantation complications will further improve outcomes in infantile LDLT.

Development of pulmonary hypertension in 5 patients after pediatric living-donor liver transplantation: de novo or secondary?

The development of portopulmonary hypertension (PH) in a patient with end-stage liver disease is related to high cardiac output and hyperdynamic circulation. However, PH following liver transplantation is not fully understood. Of 617 pediatric patients receiving transplants between June 1990 and March 2004, 5 (median age 12 yr, median weight 24.5 kg) were revealed to have portopulmonary hypertension (PH) after living-donor liver transplantation (LDLT), as confirmed by echocardiography and/or right heart catheterization. All children underwent LDLT for post-Kasai biliary atresia. In 2 patients with refractory biliary complications, PH developed following portal thrombosis; 2 with stable graft function, who had had intrapulmonary shunting (IPS) before LDLT, were found to have PH in spite of overcoming liver dysfunction due to hepatitis. PH developed shortly after distal splenorenal shunting in 1 patient, who suffered liver cirrhosis due to an intractable outflow blockage. The onset of PH ranged from 2.8 to 11 yr after LDLT, and mean pulmonary artery pressure (mPAP) estimated by echocardiography at the time of presentation ranged from 43 to 120 mmHg. Three of the 5 patients are alive under prostaglandin I2 (PGI2) treatment. Of these, 1 is prepared for retransplantation for an intractable complications of liver allograft, while the other 2 with satisfactory grafts are being considered for lung transplantation. Even after LDLT, PH can develop with portal hypertension. Periodic echocardiography is essential for early detection and treatment of PH especially in the recipients with portal hypertension not only preoperatively but also postoperatively.