Prognostic Significance of Biologic Factors in Patients with a Modest Radiologic Response to Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancers: Impact of the Combination Index of Sialyl-Lewis Antigen-Related Tumor Markers.

BACKGROUND: Appropriate re-evaluation after neoadjuvant treatment (NAT) is important for optimal treatment selection. Nonetheless, determining the operative eligibility of patients with a modest radiologic response remains controversial. This study aimed to assess the prognostic significance of biologic factors for patients showing a modest radiologic response to NAT and investigate the tumor markers (TMs), CA19-9 alone, DUPAN-II alone, and their combination, to create an index that combines these sialyl-Lewis antigen-related TMs associated with treatment outcomes. METHODS: This study enrolled patients deemed to have a "stable disease" by RECIST classification with slight progression (tumor size increase rate, ≤20%) as their radiologic response after NAT. A sialyl-Lewis-related index (sLe index), calculated by adding one fourth of the serum DUPAN-II value to the CA19-9 value, was created. The prognostic significances of CA19-9, DUPAN-II, and the sLe index were assessed in relation to postoperative outcomes. RESULTS: An sLe index lower than the cutoff value (45.25) was significantly associated with favorable disease-free survival. Moreover, the post-NAT sLe index had a higher area under the curve value for recurrence within 24 months than the post-NAT levels of CA19-9 or DUPAN-II alone. Multivariable analysis showed that a post-NAT sLe index higher than 45.25 was the single independent predictive factor for recurrence within 24 months. CONCLUSIONS: Additional evaluation of biologic factors can potentially enhance patient selection, particularly for patients showing a limited radiologic response to NAT. The authors' index is a simple indicator for the biologic evaluation of multiple combined sialyl-Lewis antigen-related TMs and may offer a better predictive significance.

The clinical significance of the lymph node ratio as a recurrence indicator in ampullary cancer after curative pancreaticoduodenectomy.

BACKGROUND: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer. METHODS: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined. RESULTS: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions. CONCLUSION: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer.

The preliminary analysis of lymphatic flow around the connective tissues surrounding SMA and SpA elucidates patients' oncological condition in borderline-resectable pancreatic cancer.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood. MATERIALS AND METHODS: From 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined. RESULTS: HEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%. CONCLUSIONS: Our preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy.

INTRODUCTION: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. METHODS: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. RESULTS: Twenty-seven patients (51%) were treatment-naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival (OS) for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months, and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. CONCLUSION: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

Clinicopathological characteristics and survival outcomes in patients with advanced esophageal squamous cell carcinoma who were intraoperatively diagnosed non-curative.

INTRODUCTION: Curative esophagectomy is not always possible in patients with locally advanced esophageal cancer. However, few studies have investigated patients who underwent non-curative surgery with intraoperative judgment. This study aimed to investigate patient characteristics and clinical outcomes for patients undergoing non-curative surgery and compare them between non-resectional and non-radical surgery. METHODS: Among 989 consecutive patients with thoracic esophageal squamous cell carcinoma (ESCC) who were preoperatively expected for curative esophagectomy, 66 who were eligible for non-curative surgery were included in this study. RESULTS: Intraoperative diagnosis of T4b accounted for 93% of the reasons for the failure of curative surgery. In those patients, esophageal cancer locally invaded into the aortobronchial constriction (70%), trachea (25%), or pulmonary vein (5%). LN metastasis mainly invaded into the trachea (50%), or bronchus (28%).The overall survival of patients with non-curative surgery was 51.5%, 25.7%, and 10.4% at 6, 12, and 24 months after surgery, respectively. Although there were no differences in preoperative patient characteristics between non-resectional and non-radical surgery, distant metastasis, especially pleural dissemination, was significantly observed in T4b patients due to esophageal cancer with non-radical surgery than those with non-resectional surgery (35% vs. 15%, P=0.002). Even in patients with non-curative surgery, R1 resection and postoperative CRT were identified as independent factors for survival 1 year after surgery (P=0.047, and 0.019). CONCLUSIONS: T4b tumor located in aortobronchial constriction or trachea/bronchus makes it difficult to diagnose whether it is resectable or unresectable. Moreover, surgical procedures and perioperative treatment were deeply associated with the clinical outcomes.

Prognostic Value of a Novel Index Combining the Prognostic Nutritional Index and D-Dimer Levels for Gastric Cancer after Gastrectomy.

INTRODUCTION: The prognostic nutritional index (PNI) and D-dimer level are two useful measures for gastric cancer prognosis. As they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a PNI-D score - which combines the PNI and D-dimer level - and validate its usefulness as a prognostic marker. METHODS: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three PNI-D score groups based on the following criteria: score 2, low-PNI (≤46) and high D-dimer levels (>1.0 µg/mL); score 1, either low-PNI or high D-dimer levels; and score 0, no abnormality. We defined the PNI-D score as low (score 0 or 1) and high (score 2), respectively. RESULTS: The PNI-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank p < 0.0001). The 5-year overall survival rates of patients with PNI-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high-PNI-D score was an independent, statistically significant prognostic factor for poor overall (p = 0.01) survival in patients with gastric cancer. CONCLUSIONS: The PNI-D is an independent prognostic factor for patients with gastric cancer.

DUPAN-II normalisation as a biological indicator during preoperative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). METHODS: This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. RESULTS: Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039). CONCLUSION: Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.

Modified Collard technique is more effective than circular stapled for cervical esophagogastric anastomosis in prevention of anastomotic stricture: a propensity score-matched study.

The anastomotic technique after esophagectomy is of great interest in the prevention of anastomotic complications that adversely affect postoperative recovery. This study aimed to compare the clinical outcomes of modified Collard (MC) and circular stapled (CS) anastomoses after esophagectomy. A total of 504 consecutive patients with thoracic esophageal cancer who underwent esophagectomy and cervical esophagogastric CS or MC anastomosis from January 2013 to December 2019 were enrolled. Out of 504 patients, 134 and 370 underwent CS and MC anastomoses. The frequency of anastomotic leakage and stricture was significantly lesser in the MC group than in the CS group (3.0 vs. 10.5%, P = 0.0014 and 11.1 vs. 34.3%, P < 0.001, respectively). CS anastomosis was an independent risk factor for anastomotic stricture (odds ratio, 4.89; P < 0.001). Oral intake was significantly higher in the group without anastomotic stricture than in the group with anastomotic stricture at 2, 3, and 6 months postoperatively (P < 0.001, P = 0.013, and P < 0.001, respectively). The percentage body weight loss (%BWL) was -12.2% in the group with anastomotic stricture and -7.5% in the group without anastomotic stricture at 3 months postoperatively (P = 0.0012). Anastomotic stricture was an independent factor associated with %BWL (odds ratio, 4.86; P = 0.010). Propensity score-matched analysis, which included 88 pairs of patients, confirmed a significantly lower anastomotic stricture rate in the MC group than in the CS group (10.2 vs. 35.2%, P < 0.001). MC anastomosis is better than CS anastomosis for reducing the frequency of anastomotic stricture, which may be useful for maintaining early postoperative nutritional status.

Recurrence Pattern Comparing Preoperative Chemoradiotherapy and Preoperative Chemotherapy with Docetaxel plus 5-Fluorouracil and Cisplatin for Advanced Esophageal Cancer.

BACKGROUND: Preoperative chemoradiation therapy (CRT) or chemotherapy (CT) followed by surgery is currently being administered for advanced esophageal cancer. However, few studies have directly compared CRT and CT for treating locally advanced esophageal carcinoma. This study aimed to assess postoperative recurrence patterns and post-recurrence outcomes in patients with radical esophagectomy after CRT or triplet CT regimen with docetaxel, cisplatin, and 5-fluorouracil (DCF). METHODS: This study included 325 consecutive patients with thoracic esophageal cancer who received preoperative CRT or DCF followed by curative esophagectomy between January 2010 and December 2019. We compared recurrence patterns after surgery and post-recurrence treatments between CRT and DCF. Locoregional recurrence was defined as recurrences at the primary tumor site or regional lymph nodes. Distant recurrence was defined as non-regional lymph node recurrences, systemic metastases, malignant pleural effusions, or peritoneal metastases. RESULTS: Among 325 patients, 74 received preoperative CF + RT and 251 received preoperative DCF. A propensity score-matched cohort of 53 with CRT and 53 with DCF was included. CRT patients had tumors located in the upper esophagus and had more advanced cancer than DCF patients; however, no differences in patient characteristics were observed in the matched cohort. CRT patients had better histopathological responses and control of locoregional recurrence than DCF patients. On the other hand, distant recurrence, especially in the non-regional lymph node, lung, and pleural dissemination, significantly developed more frequently in CRT patients. Furthermore, CRT patients may have received insufficient post-recurrence treatment, owing to fewer treatment options. Therefore, although there was no difference in recurrence rate in the two groups, CRT patients had significantly poorer post-recurrence survival than DCF patients. CONCLUSIONS: Preoperative DCF could reduce distant recurrence after surgery compared to preoperative CRT. The differences in recurrence patterns can be related to the selection of post-recurrence treatment and their prognosis after recurrence.

Clinical importance of carcinoembryonic antigen messenger RNA level in peritoneal lavage fluids measured by transcription-reverse transcription concerted reaction for advanced gastric cancer in laparoscopic surgery.

BACKGROUND: Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer. METHODS: We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity. RESULTS: A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence. CONCLUSIONS: TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy.

Postoperative aggressive diuresis prevents postoperative tissue edema and complications in patients undergoing distal pancreatectomy.

PURPOSE: Intraoperative fluid restriction is reported to be associated with reduced postoperative tissue edema and decreased incidence of postoperative pancreatic fistula (POPF) in pancreatic surgery. However, there is limited information regarding the postoperative approach to prevent postoperative tissue edema and reduce POPF. METHODS: Patients undergoing distal pancreatectomy from 2013 to 2018 in our institute were retrospectively enrolled (n = 128). The patients were classified into the two groups: an early diuresis group (ED group: patients administered diuretic agents on postoperative day 2 or earlier between 2016 and 2018, n = 69) and a conventional diuresis group (CD group: patients administered diuretic agents on postoperative day 3 or later between 2013 and 2015, n = 59). Postoperative tissue edema assessed by CT imaging and the incidence of clinically relevant POPF (CR-PF; grade B or C) were compared. RESULTS: Postoperative tissue edema was significantly reduced in the ED group (p < 0.0001). The incidence of CR-PF was lower in the ED group (19% vs. 32%, p = 0.082), especially in patients with postoperative diuresis on POD 1 (12%, p = 0.044). CONCLUSION: Early and aggressive postoperative diuresis potentially reduced postoperative visceral tissue edema. This postoperative approach to prevent tissue edema may reduce the incidence of CR-PF in pancreatic surgery.

Robotic total gastrectomy with thrombectomy and portal vein reconstruction for gastric cancer and portal vein tumor thrombus.

BACKGROUND: Gastric cancer with portal vein tumor thrombus (PVTT) is poor prognosis, and the treatment remains challenging. Regarding surgery, there are only reports of highly invasive laparotomy. We report some techniques of the completely robotic total gastrectomy with thrombectomy and portal vein reconstruction for the patient with gastric cancer and PVTT for the first time. CASE PRESENTATION: A 79-year-old man was diagnosed with a 5-cm gastric cancer on the side of the lesser curvature from the middle of the gastric body to the cardia. Computed tomography revealed a massive PVTT extending from the left gastric vein to the portal trunk (28 x 16 mm). There were no other distant metastases. After 3 cycles of the chemotherapy, the PVTT shrank to 19 x 12 mm. After obtaining informed consent from the patient, robotic total gastrectomy with regional lymphadenectomy and thrombectomy were performed. We used the da Vinci Xi Surgical System. A 3-cm incision was made at the umbilicus, and a wound retractor was placed. Five additional ports were placed. The right side suprapancreatic lymph nodes were performed at the time of the thrombectomy. It was important to identify the precise extent of the PVTT with intraoperative ultrasonography before the thrombectomy. After PVTT identification, the portal trunk was clamped above and below the tumor thrombus with vascular clips. The membrane on the anterior wall of the portal trunk around the PVTT was carefully incised with da Vinci Scissors. The tumor thrombus was completely enucleated without separation. The incised part of the portal trunk was reconstructed with continuous 5-0 synthetic monofilament nonabsorbable polypropylene sutures. After removing the vascular clamps, we made sure there was no leakage from the portal vein and no tumor thrombus remnants with intraoperative ultrasonography. Robotic total gastrectomy with lymphadenectomy and Roux-en-Y reconstruction were performed. The patient was discharged without complications. The patient has remained alive for 30 months after surgery. CONCLUSIONS: Robotic total gastrectomy with thrombectomy and portal vein reconstruction is a safe, minimally invasive, and precise surgery. It may contribute to improved prognosis of gastric cancer with PVTT when combined with chemotherapy.

Establishment and implementation of Cancer Genomic Medicine in Japan.

Approximately 1 in 2 Japanese people are estimated to be diagnosed with cancer during their lifetime. Cancer still remains the leading cause of death in Japan, therefore the government of Japan has decided to develop a better cancer control policy and launched the Cancer Genomic Medicine (CGM) program. The Ministry of Health, Labour, and Welfare (MHLW) held a consortium at their headquarters with leading academic authorities and the representatives of related organizations to discuss ways to advance CGM in Japan. Based on the report of the consortium, the CGM system under the national health insurance system has gradually been realized. Eleven hospitals were designated in February 2018 as core hospitals for CGM; subsequently, the MHLW built the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) as an institution to aggregate and manage genomic and clinical information on cancer patients, and support appropriate secondary use of the aggregated information to develop research aimed at medical innovation. As the first step in Japan's CGM in routine practice, in June 2019 the MHLW started reimbursement of 2 types of tumor profiling tests for advanced solid cancer patients using the national insurance system. Japan's CGM has swiftly been spreading nationwide with the collaboration of 167 hospitals and patients. The health and research authorities are expected to embody personalized cancer medicine and promote CGM utilizing state-of-the-art technologies.

Laparoscopic-assisted disinvagination and polypectomy for multiple intussusceptions induced by small intestinal polyps in patients with Peutz-Jeghers syndrome: a case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a very rare autosomal dominant genetic disorder characterized by hamartomatous polyps in the gastrointestinal tract and hyperpigmentation of the lips, hands, and feet. The hamartomatous polyps in the small intestine often cause intussusception and bleeding. CASE PRESENTATION: A 62-year-old male was hospitalized for treatment of deep vein thrombosis and pulmonary embolism. In the small intestine, computed tomography showed three small polyps with intussusceptions. Since the patient had gastrointestinal polyposis and pigmentation of his lips, fingers, and toes, he was diagnosed with PJS. After an inferior vena cava filter was placed, he underwent laparoscopic-assisted surgery. The polyps causing intussusception were resected as far as possible without intestinal resection, since they had caused progressive anemia and might cause intestinal obstruction in the future. The patient was discharged from the hospital on postoperative day 9 without complications. CONCLUSIONS: Laparoscopic-assisted disinvagination and polypectomy is a useful, minimally invasive treatment for multiple intussusceptions caused by small intestinal polyps in patients with PJS.

Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy.

BACKGROUND: The cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) are well known to play a dominant role in distant metastasis. Nevertheless, the effect on CAFs with current chemoradiation therapies remains uncertain. OBJECTIVE: This study aimed to reveal the role of CAFs under current chemoradiation therapy (CRT) and investigate the factors regulating CAFs. METHODS: α-SMA-positive cells in 86 resected PDAC specimens with/without preoperative CRT were evaluated by immunohistochemistry. Various factors, including the plasma levels of vitamin D, were investigated for association with the number of CAFs or distant metastasis-free survival (DMFS). Human pancreatic satellite cells (hPSCs) extracted from clinical specimens were used to validate the factors. RESULTS: All PDAC samples contained CAFs but the number varied widely. Multivariate analysis for DMFS indicated a larger number of CAFs was a significant risk factor. Univariate analysis for the number of CAFs identified two clinical factors: preoperative CRT and lower plasma levels of vitamin D. In subgroup analysis, the higher plasma level of vitamin D was a dominant factor for longer DMFS in PDAC patients after preoperative CRT. These results were validated by using extracted hPSCs. Irradiation activated stromal cells into CAFs facilitating malignant characteristics of PDAC and the change was inhibited by vitamin D supplementation in vitro. CONCLUSION: In conjunction with established current therapies, vitamin D supplementation may be an effective treatment for PDAC patients by inactivating CAFs.

Patients Treated with Preoperative Chemoradiation for Pancreatic Ductal Adenocarcinoma have Impaired Bone Density, a Predictor of Distant Metastasis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm that spreads to surrounding tissue or distant sites. This study investigated distant metastases in PDAC patients with or without preoperative chemoradiation therapy (CRT), focusing on vitamin D levels and bone density. METHODS: This study included 146 patients with PDAC who underwent surgery from 2007 to 2014. Bone density was evaluated using computed tomography, and the preoperative vitamin D level was calculated by enzyme-linked immunosorbent assay (ELISA) for patients with available plasma (48 cases). RESULTS: When the patients were divided into two groups according to the change in bone density, the group with decreased bone density had a shorter distant metastasis-free survival time (DMFS) after surgery than the other group (p < 0.05). Low vitamin D was a weak predictor of DMFS, but the difference was not significant (p = 0.08), perhaps because of the sample size. Multivariate analysis indicated three significant factors associated with distant metastasis: a decrease in bone density (hazard ratio [HR], 2.17; p = 0.04), normalization of the Dupan-2 value after surgery (hazard ratio [HR], 0.39; p = 0.02), and completion of adjuvant chemotherapy (HR, 0.29; p < 0.01). Univariate analysis showed that a low vitamin D concentration (<20 pg/ml) was a risk factor (p = 0.04) for bone density change. Multivariate analysis found that preoperative CRT was the only factor associated (±, OR, 5.8; p = 0.04) with bone density change, suggesting that preoperative CRT significantly decreases bone density in patients with insufficient vitamin D. CONCLUSION: Patients treated with preoperative CRT tend to have impaired bone density, which is a predictor of distant metastasis. Thus, vitamin D supplementation may decrease distant metastasis.

[Complete Surgical Resection of a Huge Hepatocellular Carcinoma Invading the Diaphragm and Lung after Transcatheter Arterial Chemoembolization (TACE) and Sorafenib--A Case Report].

We report a case of locally advanced huge hepatocellular carcinoma (HCC) invading the diaphragm and the right lung, which was controlled by sorafenib, thereby allowing curative resection. A 72-year-old man was diagnosed with advanced HCC invading the diaphragm and the right lung. At the time of diagnosis, his tumor was considered unresectable and he underwent transarterial embolization (TAE)/transcatheter arterial chemoembolization (TACE) 3 times. Assessment with enhanced CT after TAE/TACE showed that a viable lesion remained. Subsequently, he was treated with sorafenib for 15 months. Reassessment showed that the main tumor remained stable in size, and he was admitted to our hospital for surgery. Preoperative evaluation by enhanced CT and MRI detected an intrahepatic metastasis in segment 4 of the liver. After TACE was performed for this nodule, extended right hemihepatectomy with right diaphragmatic and right lung partial resection was performed. He had no postoperative complications and was discharged 27 days after surgery. He remains alive without recurrence 10 months after surgery.

[Efficacy and safety of eribulin for metastatic breast cancer patients].

In the EMBRACE trial, eribulin was reported to significantly increase overall survival compared to treatment of the physician 's choice when given to patients with recurrent or metastatic breast cancer who had received prior treatment, including an anthracycline and a taxane. In April 2011, eribulin was approved in Japan for the treatment of inoperable or recurrent breast cancer. In this article, we report on the efficacy and safety of eribulin in cases we encountered. Twenty patients with advanced and recurrent breast cancer were administered eribulin in our hospital during the period from August 2011 to December 2012. The median age was 62 years(range, 42-76 years); 16 patients had the estrogen receptor(ER)(+)/human epidermal growth factor receptor 2(HER2)(-)subtype, whereas 4 patients had the triple-negative subtype. Following recurrence, the median number of chemotherapy regimens was 3(range, 0-5). Regarding the antitumor effects of eribulin, no cases showed complete response(CR), 5 cases showed partial response(PR), and 10 cases showed stable disease(SD); therefore, the response rate(CR+PR)was 25% and the clinical benefit rate(CR+PR+B6-month SD)was 35%. Median progression free survival was 146 days, and median overall survival was 482 days. In terms of adverse events(AEs), observed cases of hematotoxicity were of neutropenia(75%), leucopenia(75%), and anemia(80%). Cases of Grade 3 hematotoxicity or higher were of neutropenia(40%), leucopenia(20%), and febrile neutropenia(1 case, 5%). The observed non-hematotoxic AEs were peripheral neuropathy(30%)and general malaise(35%), although none were of Grade 3 or higher. The therapeutic efficacy of eribulin in the present study was relatively better than that in previous reports(EMBRACE trial, Japan Domestic 221 trial). The frequency of Grade 3 or higher AEs was low, and the drug was well tolerated. We believe that eribulin is a novel drug that provides therapeutic efficacy while maintaining quality of life(QOL).

[A bridge to surgery for colon cancer obstruction in a very elderly patient - a case report].

A 94-year-old woman with a distended abdomen was transferred to our hospital.Based on the enhanced abdominal computed tomographic (CT) finding, she was diagnosed with colonic obstruction due to sigmoid cancer. Colonoscopy was performed to make definitive and qualitative diagnoses, and to release the stenosis using a self-expanding metallic stent (SEMS). The SEMS was inserted without complication.On the fifth day after the decompression, the patient underwent laparoscope-assisted sigmoidectomy with lymph node resection.Despite the colon obstruction, a primary anastomosis was performed.The operation time was 163 min, and 3 mL of blood was lost.The patient was discharged without complications. We describe the case of a bridge to surgery in a very elderly patient. A bridge to surgery can be an effective option for the treatment of colon obstruction in non-elderly and very elderly patients.