Kazuhiro Mikagi

Metastatic Pulmonary Adenocarcinoma 13 Years After Curative Resection for Pancreatic Cancer: Report of a Case and Review of Japanese Literature

CONTEXT For the majority of patients, ductal adenocarcinoma of the pancreas remains a lethal disease. Currently, surgical extirpation for localized disease offers the only chance for long-term survival. CASE REPORT We report a patient who underwent successful resection of isolated lung metastasis occurring 13 years after pancreatic cancer resection. A 59-year-old woman underwent distal pancreatectomy for pancreatic cancer 13 years previously, followed by adjuvant chemotherapy, and was followed-up at the outpatient clinic of a local hospital. From around June 2010, she noticed bloody sputum, so she visited a local hospital. Since her chest X-ray and CT revealed a 1.5 cm mass shadow in the segment 10 of her right lung and she was referred to the Respiratory Disease Center of our hospital. As a result of through examinations, she was strongly suspected of having lung metastasis of pancreatic cancer, and underwent partial pneumonectomy. Postoperative histopathological examination of the resected specimen was consistent with lung metastasis of pancreatic cancer. She is still alive and currently receives third line of chemotherapy. CONCLUSION Patients who have achieved long-term survival after pancreatic cancer resection and can tolerate surgery may benefit from resection of a lung metastasis of pancreatic cancer in terms of survival, if it controls the metastasis.

Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases

Background Five or more colorectal liver metastases (CRLM) are considered marginally resectable and cannot be treated solely by hepatic resection (Hr). This study investigated the long-term effectiveness of surgical treatment using microwave coagulo-necrotic therapy (MCN) and/or Hr for marginally resectable or unresectable multiple CRLM. Methods This study retrospectively analyzed 82 consecutive CRLM patients with ≥5 CRLM who underwent MCN, Hr, or both, at our institution from 1994 to 2012. Presuming all CRLM were resected curatively, virtual remnant liver volume was calculated using preoperative computed tomography or magnetic resonance imaging. Virtual remnant liver volume <30% was defined as unresectable. Patients were divided into marginally resectable (Group Y; n=29) and unresectable (Group N; n=53). Overall and recurrence-free survival were assessed. Results Mean maximum tumor diameter and tumor number were 3.1 and 6.0 cm in Group Y and 3.3 and 11.3 cm in Group N. Surgical methods included MCN (n=16), MCN+Hr (n=9), and Hr (n=4) in Group Y, and MCN (n=28) and MCN+Hr (n=25) in Group N. One- and 2-year recurrence-free survival rates were 38.0% and 22.8% in Group Y, and 18.9% and 3.8% in Group N (P=0.01). However, 1-, 3-, and 5-year overall survival rates of Group N (86.8%, 44.6%, and 33.7%, respectively) were similar to those of Group Y (82.8%, 51.4%, and 33.3%, respectively; P= not significant each). Conclusion MCN may improve survival for patients with unresectable multiple CRLM, similar to that in patients with marginally resectable multiple CRLM.

Potential usefulness of mucin immunohistochemical staining of preoperative pancreatic biopsy or juice cytology specimens in the determination of treatment strategies for intraductal papillary mucinous neoplasm

We classified resected intraductal papillary mucinous neoplasms (IPMNs) into four subtypes (gastric, intestinal, pancreatobiliary and oncocytic) according to their morphological features and mucin expression, determined their clinicopathological characteristics and investigated the possibility of preoperatively diagnosing these subtypes. Sixty resected tumors, 4 preoperative tumor biopsies and 10 preoperative pancreatic juice cytology specimens were analyzed. The gastric and intestinal types accounted for the majority of IPMNs. Non-gastric type IPMNs were of high-grade malignancy. Many of the pancreatobiliary-type IPMNs were in an advanced stage and were associated with a poor prognosis. The results of mucin immunohistochemical staining of preoperative biopsy and surgically resected specimens were in agreement with each other, and in close agreement with those for pancreatic juice cytology specimens obtained from 10 patients during endoscopic retrograde cholangiopancreatography (ERCP). The immunostaining of preoperative biopsy specimens and ERCP-obtained pancreatic juice cytology specimens may be useful in the differential diagnosis of gastric and intestinal types of IPMN. If such techniques enable the preoperative diagnosis of IPMN subtypes, their use in combination with conventional preoperative imaging modalities may lead to surgical treatment best suited for the biological characteristics of the four subtypes.

Usefulness of lavage cytology during endoscopic transpapillary catheterization into the gallbladder in the cytological diagnosis of gallbladder disease.

Many studies have reported methods of cell collection involving percutaneous transhepatic cholangiodrainage (PTCD) and fine‐needle aspiration cytology for the diagnosis of gallbladder disease. However, few studies have described the use of a transpapillary approach, i.e., endoscopic transpapillary catheterization into the gallbladder (ETCG). In this study, we analyzed cells collected by ETCG to evaluate its usefulness in the cytological diagnosis of gallbladder disease.

Perioperative challenges associated with a pancreaticoduodenectomy and distal pancreatectomy for pancreatic cancer in patients with situs inversus totalis: Report of two cases

Situs inversus totalis is a rare anatomic variant of a complete mirror-image transposition of the thoracic and abdominal viscera. The performance of a pancreaticoduodenectomy and distal pancreatectomy in patients with situs inversus totalis is both rare and challenging. We herein present two cases of pancreatic cancer with situs inversus totalis. The abdominal anatomy was preoperatively assessed by multidetectorrow computed tomography, three-dimensional reconstruction, and angiography. We herein report that a pancreaticoduodenectomy and distal pancreatectomy with standard regional lymphadenectomy are feasible in patients with situs inversus totalis. Due to the transposition of the viscera and major blood vessels in such cases, preoperative knowledge of the exact anatomy, mapping of anomalies, and meticulous forward planning are essential for performing these technically difficult and complex hepatobiliary-pancreatic surgeries.

The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients.

Accuracy of differential diagnosis for pancreatic cancer is improved in the combination of RCAS1 and CEA measurements and cytology in pancreatic juice

Improvement of diagnostic accuracy for pancreatic cancer in pancreatic disease patients was investigated by examining the combination of three diagnostic methods, i.e., measurements of RCAS1 and CEA levels in pancreatic juice and pancreatic juice cytology. Pancreatic juice was collected from 12 pancreatic cancer (PC) and 26 non-PC patients. RCAS1 and CEA levels were measured by using ELISA. RCAS1 expression on surgically resected tissue was immunohistochemically examined for 2 PC patients. By setting the cutoff level of RCAS1 at 10 U/ml and that of CEA at 18.5 μg/ml, sensitivity of RCAS1 was 42% and that of CEA was 50%. On the other hand, sensitivity and specificity increased from 42% and 85% of RCAS1 alone to 75% and 85% in the examination of RCAS1 + CEA + cytology, and the false-negative rate was also reduced to 25% in this combination. Immunohistochemically, a patient with a high RCAS1 level in pancreatic juice had numerous RCAS1-positive tumor cells in the pancreatic juice. We concluded that RCAS1 and CEA measurements together with cytology in pancreatic juice would be a useful combination method for making a differential diagnosis of PC from non-PC.

Long-Term Maintenance of Complete Response after Sorafenib Treatment for Multiple Lung Metastases from Hepatocellular Carcinoma.

Sorafenib is an effective treatment for unresectable hepatocellular carcinoma (HCC) characterized by disease stabilization. However, the response rates are very low (<9%), and a complete response is rarely achieved. We report an extremely rare case of a HCC patient with multiple lung metastases treated with sorafenib who achieved a complete response for a long period. A 77-year-old woman was diagnosed with chronic hepatitis C in 1990. In 2007, a HCC detected in the liver was treated with percutaneous ethanol injection therapy. Subsequently, recurrence of HCC in the liver was treated with microwave coagulonecrotic therapy in 2010. In April 2011, a computed tomography (CT) scan revealed innumerable multiple metastases spread diffusely in both lungs. Tumor marker levels were extremely high [α-fetoprotein (AFP) 76,170 ng/ml, lens culinaris agglutinin-reactive fraction of AFP 7.5%, des-γ-carboxyprothrombin (DCP) 63,400 mAU/ml]. Sorafenib was administered at a reduced dose of 400 mg/day because of old age. Four months after sorafenib treatment, AFP and DCP had decreased to within normal levels, and the multiple lung metastases had disappeared. Currently, sorafenib is administered at a reduced dose of 400 mg/day, and the complete response has been maintained for 48 months.

Impact of more detailed categorization of shrinkage or progression ratio at initial imaging response after sorafenib treatment in advanced hepatocellular carcinoma patients.

Background Sorafenib therapy improves survival in unresectable hepatocellular carcinoma (HCC) patients without an objective response. The present study investigated whether the initial imaging response might be a prognostic indicator after administration of sorafenib therapy in HCC patients. Patients and methods This retrospective study reviewed unresectable HCC patients undergoing sorafenib therapy. Patients evaluated without complete response, partial response (PR), or progressive disease (PD) at the initial imaging response evaluation by modified Response Evaluation Criteria in Solid Tumors were divided into three groups according to more detailed categorization of the shrinkage/progression ratio in initial imaging response. A comparison of progression-free and overall survival among these groups was performed. Results Of the 43 non-PR non-PD patients with target lesions, ten (23.3%) exhibited mild response (MR; −30% to −5%), 14 (32.6%) exhibited no change (NC; −5% to +5%), and 19 (44.2%) exhibited mild-PD (MPD; +5% to +20%). There was no statistical difference in progression-free or overall survival between MR and NC patients. The median progression-free survivals in NC+MR and mild-PD patients were 15.0 and 5.3 months, respectively (P<0.01), and the median survival times were 31.9 and 17.1 months, respectively (P<0.001). In multivariate analysis, etiology (hepatitis C virus) and initial imaging response (MR+NC) was identified as an independently good prognostic factor. Conclusion More detailed categorization of shrinkage or progression at the initial imaging response evaluation may be a useful marker for predicting sorafenib treatment outcomes in HCC patients. If the initial imaging response is not progression but stability, sorafenib may have a survival benefit.