Objective Definition and Optimized Strategy for "Biologically Borderline Resectable" Colorectal Liver Metastases.

BACKGROUND: The prognostic benefit of preoperative chemotherapy leading to conversion surgery for unresectable colorectal liver metastases (CRLM) is well recognized, while that of neoadjuvant chemotherapy (NAC) compared with upfront surgery (UFS) for resectable CRLM is negligible. This study aims to assess the prognostic benefit and search for optimal indication of NAC for resectable advanced CRLM by establishing an objective definition of biologically borderline resectable (bBR) CRLM. METHODS: A bicentric retrospective analysis of patients with CRLM undergoing curative-intent initial liver resection between 2007 and 2021 was performed. An original classification matrix was established, which reassessed technical resectability using virtual hepatectomy and oncological favorability using Beppu's nomogram. Patients with technically resectable but biologically unfavorable CRLM were classified into the bBR group. The propensity score matching analysis using preoperatively available factors was performed to assess long-term outcomes of the bBR-UFS and bBR-NAC groups. RESULTS: Of 831 patients reviewed, 240 were categorized into the bBR group: bBR -UFS (n = 139) and bBR-NAC (n = 101). Ten (10%) in the bBR-NAC group (n = 101) experienced biological status change from unfavorable to favorable after NAC (Biological Conversion) and showed significantly longer overall survival (hazard ratio 5.63, 95% confidence interval 1.37-23.1; P = 0.016) than the bBR-UFS group. However, after propensity score matching, no significant difference between the UFS and NAC groups (n = 67 for each) was found in long-term outcomes. CONCLUSIONS: NAC for bBR-CRLM did not enhance the prognostic impact of the following liver resection, except for a limited number of optimal candidates experiencing the Biological Conversion.

RRM1 is mediated by histone acetylation through gemcitabine resistance and contributes to invasiveness and ECM remodeling in pancreatic cancer.

The invasiveness of pancreatic cancer and its resistance to anticancer drugs define its malignant potential, and are considered to affect the peritumoral microenvironment. Cancer cells with resistance to gemcitabine exposed to external signals induced by anticancer drugs may enhance their malignant transformation. Ribonucleotide reductase large subunit M1 (RRM1), an enzyme in the DNA synthesis pathway, is upregulated during gemcitabine resistance, and its expression is associated with worse prognosis for pancreatic cancer. However, the biological function of RRM1 is unclear. In the present study, it was demonstrated that histone acetylation is involved in the regulatory mechanism related to the acquisition of gemcitabine resistance and subsequent RRM1 upregulation. The current in vitro study indicated that RRM1 expression is critical for the migratory and invasive potential of pancreatic cancer cells. Furthermore, a comprehensive RNA sequencing analysis showed that activated RRM1 induced marked changes in the expression levels of extracellular matrix­related genes, including N­cadherin, tenascin­C and COL11A. RRM1 activation also promoted extracellular matrix remodeling and mesenchymal features, which enhanced the migratory invasiveness and malignant potential of pancreatic cancer cells. The present results demonstrated that RRM1 has a critical role in the biological gene program that regulates the extracellular matrix, which promotes the aggressive malignant phenotype of pancreatic cancer.

Enhanced Recognition Confidence of Millimeter-Sized Intrahepatic Targets by Real-Time Virtual Sonography.

OBJECTIVES: Real-time virtual sonography (RVS) is an artificial-intelligence-assisted ultrasonographic navigation system that displays synchronized preoperative computed tomography (CT) images corresponding to real-time intraoperative ultrasonograms (IOUS). This study aimed to investigate whether RVS can enhance IOUS identification of small intrahepatic targets found in preoperative CT. METHODS: Patients with small intrahepatic targets detected by preoperative thin-slice dynamic CT before liver resection were included. The targets included millimeter-sized liver tumors or a third-order or more distal portal branch and were marked on CT images using 3D simulation software. After laparotomy, the targets were searched using fundamental IOUS, and participating liver surgeons subjectively scored the target identifying confidence on a scale of 1-5 (5 points for detection with the highest confidence and one point for undetectable). Then, the search procedure was repeated using the RVS, and the scores were compared. RESULTS: Totally, 55 patients with 117 small targets were investigated. The median target size was 6.0 mm, and the median registration time was 3.6 seconds. The target identification confidence score significantly increased from 2.78 to 4.52 points after using RVS. Seventeen targets (14.5%) were undetectable in fundamental IOUS, and 14 of them were identified by RVS. The detectability of small liver tumors (2-5 points of identification confidence) by IOUS was 81.1 and 96.7% by RVS. CONCLUSION: RVS enhanced surgeons' confidence in identifying millimeter-sized intrahepatic targets found in preoperative CT.

Chronological improvement of pancreatectomy for resectable but advanced pancreatic neuroendocrine neoplasms.

BACKGROUND: Progress of non-surgical treatments in the last decade has improved the prognosis of pancreatic neuroendocrine neoplasms (PanNEN). However, the improvement of surgery for advanced PanNEN remains unknown. This study aimed to investigate the chronological changes of the clinical impact of pancreatectomy for PanNEN. METHODS: Patients undergoing curative-intent pancreatectomy for PanNEN between 1991 and 2010 were categorized into the earlier period group, and those between 2011 and 2021 were into the later period group. Advanced PanNEN was defined as showing resectable synchronous liver metastases or invasion to portal venous systems or adjacent organs. The recurrence-free survival (RFS) and overall survival (OS) were analyzed among patients with non-advanced and advanced PanNENs. The independent prognostic risk factors were identified using a Cox proportional hazard model. RESULTS: A total of 189 patients (n = 54 in the earlier period and n = 135 in the later period) were included. The proportion of advanced PanNEN increased from 15% to 30% (P = 0.027). The RFS and OS of non-advanced PanNEN were similar between the periods. Whereas, among patients with advanced PanNEN, the later period group showed improved prognosis; The 5-year RFS of the earlier period vs. the later period was 0% vs. 27%, and the 5-year OS was 38% vs. 82% (p = 0.013). CONCLUSIONS: A radical surgical treatment for advanced PanNEN has shown prognostic improvement in this decade. However, more careful perioperative examinations and possibly, additional treatments are required for PanNEN with portal vein invasion.

International Expert Consensus on Precision Anatomy for minimally invasive distal pancreatectomy: PAM-HBP Surgery Project.

BACKGROUND: Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021). METHODS: Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. RESULTS: Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts. CONCLUSIONS: The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide.

International expert consensus on precision anatomy for minimally invasive pancreatoduodenectomy: PAM-HBP surgery project.

BACKGROUND: The anatomical structure around the pancreatic head is very complex and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD. METHODS: Studies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. RESULTS: Three clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection. CONCLUSIONS: MIPD experts suggest that surgical trainees perform resection based on precise anatomical landmarks for safe and reliable MIPD.

Curative Surgery and Ki-67 Value Rather Than Tumor Differentiation Predict the Survival of Patients With High-grade Neuroendocrine Neoplasms.

OBJECTIVE: To elucidate the role of surgery in patients with high-grade neuroendocrine neoplasms (hg-NENs) and Ki-67 more than 20%. BACKGROUND: Although surgery is the first treatment choice in patients with low-grade NENs, whether it increases the survival of patients with hg-NENs is debatable. METHODS: Between 2005 and 2018, 63 patients pathologically diagnosed with hg-NENs treated at our institution were retrospectively analyzed. The risk factors for overall survival (OS) and recurrence-free survival were analyzed, and OS was compared between each treatment group. RESULTS: The median observation time was 21.2 months, and the median Ki-67 value was 52%. Patients with hg-NENs were classified into low Ki-67 (Ki-67 <52%) and high Ki-67 (Ki-67 ≥52%) groups. Multivariate analysis for OS identified surgery (P = 0.013) and low Ki-67 value (P = 0.007) as independent risk factors, whereas morphological differentiation defined by the WHO 2017 criteria showed no association with OS. Patients with low Ki-67 value subjected to R0/1, R2, and chemotherapy had a median survival time of 83.8, 16.6, and 28.1 months, respectively. The median survival time for R0/1 group was significantly longer than that for chemotherapy group ( P = 0.001). However, no difference in survival was reported between patients from R0/1 and chemotherapy groups with high Ki-67. Ki-67 value could determine recurrence-free survival ( P = 0.006) in patients who underwent R0/1 surgery for pancreatic hg-NENs. CONCLUSIONS: R0/1 surgery predicted prognoses in the low Ki-67 group. The indication of surgery for patients with hg-NENs did not depend on tumor differentiation.

Hormonal tumor mapping for liver metastases of gastroenteropancreatic neuroendocrine neoplasms: a novel therapeutic strategy.

PURPOSE: In patients with metastatic functional gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), it is unknown what degree of tumor reduction is required to eliminate hormonal symptoms. We aimed to reduce hormonal symptoms derived from advanced GEP-NENs by efficient minimal intervention, constructing a hormonal tumor map of liver metastases. METHODS: Between 2013 and 2019, we treated 12 insulinoma or gastrinoma patients with liver metastases. Liver segments containing hormone-producing tumors were identified by injecting calcium gluconate via the hepatic arteries and monitoring the change in serum hormone concentration in the three hepatic veins. A greater-than-twofold increase in hormone concentration indicated a tumor-feeding vessel. RESULTS: Cases included eight insulinomas and four gastrinomas. Primary lesions were functional in three patients and nonfunctional in 9. Nine patients showed hormonal step-up indicating the presence of functional lesions; eight showed step-up in tumor-bearing liver segments, while one with synchronous liver metastases showed step-up only in the pancreatic region. Five patients underwent surgery. Serum hormone concentration decreased markedly after removing the culprit lesions in 3; immediate improvement in hormonal symptoms was achieved in all patients. Three patients with previous surgical treatment who showed step-up underwent transcatheter arterial embolization, achieving temporary improvement of hormonal symptoms. Four patients showed unclear localization of the hormone-producing tumors; treatment options were limited, resulting in poor outcomes. CONCLUSION: Hormonal tumor mapping demonstrated heterogeneity in hormone production among primary and metastatic tumors of GEP-NENs. Minimally invasive treatment based on hormonal mapping may be a viable alternative to conventional cytoreduction.

Surgical approaches for minimally invasive distal pancreatectomy: A systematic review.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) was initially performed for benign tumors, but recently its indications have steadily broadened to encompass other conditions including pancreatic malignancies. Thorough anatomical knowledge is mandatory for precise surgery in the era of minimally invasive surgery. However, expert consensus regarding anatomical landmarks to facilitate the safe performance of MIDP is still lacking. METHODS: A systematic literature search was performed using keywords to identify articles regarding the vascular anatomy and surgical approaches/techniques for MIDP. RESULTS: All of the systematic reviews revealed that MIDP was not associated with an increase in postoperative complications. Moreover, most showed that MIDP resulted in less blood loss than open surgery. Regarding surgical approaches for MIDP, a standardized stepwise procedure improved surgical outcomes, including blood loss, operative time, and major complications. There are two approaches to the splenic vessels, superior and inferior; however, no study has ever directly compared them with respect to clinical outcomes. The morphology of the splenic artery affects the difficulty of approaching the artery's root. To select an appropriate dissecting layer when performing posterior resection, thorough knowledge of the anatomy of the fascia, left renal vein/artery, and left adrenal gland is needed. CONCLUSIONS: In MIDP, a standardized approach and precise knowledge of anatomy facilitates safe surgery and has the advantage of a shorter learning curve. Anatomical features and landmarks are particularly important in cases of radical MIDP and splenic vessel preserving MIDP.

Surgery after sunitinib administration to improve survival of patients with advanced pancreatic neuroendocrine neoplasms.

BACKGROUND: Little research is available regarding the treatments combining surgical resection with systemic chemotherapy for advanced pancreatic neuroendocrine neoplasm patients. We retrospectively elucidated whether sunitinib administration before surgery in advanced pancreatic neuroendocrine neoplasm (Pan-NEN) patients increases survival. METHODS: This study included 106 of 326 Pan-NEN patients with distant metastases and/or unresectable locally advanced tumors who visited our department to receive sunitinib for more than 1 mo during April 2002 to December 2019. Risk factors for overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: The median duration of preoperative sunitinib administration and observation time after sunitinib were 6 and 26.5 mo, respectively. Of 106 patients, 31 (29.2%) underwent surgery following sunitinib administration. Hepatectomy, synchronous hepatopancreatectomy, pancreatectomy, and lymphadenectomy were performed for 13, 12, 5, and 1 patient, respectively. The 5-y OS rates in the resected and nonresected groups were 88.9% and 14.1%, respectively (P < .001). In the multivariate analysis, the absence of surgical resection following sunitinib (hazard ratio [HR], 13.1; P = .001), poor differentiation (HR, 5.5; P = .007), and bilateral liver metastases (HR, 3.7; P = .048) were independent risk factors for OS, although large liver tumor volumes were more evident in the nonresected group, as patient characteristics. The median DFS was 16.1 mo in 22 patients who underwent R0/1 resections, and risk factors for postoperative recurrence were Ki-67 index >7.8% (HR, 7.4; P = .02) and R1 resection (HR, 4.4; P = .04). CONCLUSION: Surgical resection after sunitinib administration improved OS in advanced Pan-NENs.

Inhibitor library screening identifies ispinesib as a new potential chemotherapeutic agent for pancreatic cancers.

Screening custom-made libraries of inhibitors may reveal novel drugs for treating pancreatic cancer. In this manner, we identified ispinesib as a candidate and attempted to determine its clinical efficacy and the biological significance of its functional target Eg5 in pancreatic cancer. One hundred compounds in our library were screened for candidate drugs using cell cytotoxicity assays. Ispinesib was found to mediate effective antitumor effects in pancreatic cancer. The clinical significance of the expression of the ispinesib target Eg5 was investigated in 165 pancreatic cancer patients by immunohistochemical staining and in Eg5-positive pancreatic cancer patient-derived xenograft (PDX) mouse models. Patients with Eg5-positive tumors experienced significantly poorer clinical outcomes than those not expressing Eg5 (overall survival; P < .01, recurrence-free survival; P < .01). Ispinesib or Eg5 inhibition with specific siRNA significantly suppressed cell proliferation and induced apoptosis in pancreatic cancer cell lines. Mechanistically, ispinesib acted by inducing incomplete mitosis with nuclear disruption, resulting in multinucleated monoastral spindle cells. In the PDX mouse model, ispinesib dramatically reduced tumor growth relative to vehicle control (652.2 mm3 vs 18.1 mm3 in mean tumor volume, P < .01 by ANOVA; 545 mg vs 28 mg in tumor weight, P < .01, by ANOVA). Ispinesib, identified by inhibitor library screening, could be a promising novel therapeutic agent for pancreatic cancer. The expression of its target Eg5 is associated with poorer postoperative prognosis and is important for the clinical efficacy of ispinesib in pancreatic cancer.

C646 inhibits G2/M cell cycle-related proteins and potentiates anti-tumor effects in pancreatic cancer.

The activity of histone acetyltransferases (HATs) plays a central role in an epigenetic modification in cooperation with HDACs (histone deacetyl transferases). It is likely that malfunction of this enzymatic machinery controlling epigenetic modification is relevant to carcinogenesis and tumor progression. However, in pancreatic cancer, the clinical relevance of HAT activity and histone acetylation has remained unclear. We identified that H3 acetylation was expressed in all pancreatic cancer patients, indicating that H3 acetylation may be essential in pancreatic cancer cells. We also found that the HAT inhibitor C646 augmented anti-tumor effects in vitro by inhibiting cell proliferation and cell cycle progression concomitantly with suppression of acetylated H3K9 and H3K27 expression. C646 or p300 and CBP (CREB-binding protein)-specific siRNA treatment inhibited the transcription of the G2/M cell cycle regulatory proteins cyclin B1 and CDK1 (cyclin-dependent kinase 1). C646 treatment also inhibited tumor growth in vivo in a xenograft mouse model. C646 could be an effective therapeutic agent for pancreatic cancer. The epigenetic status of pancreatic cancers based on their level of histone H3 acetylation may influence patient survival. Epigenetic stratification according to H3K27 acetylation could be useful for predicting disease prognosis as well as the therapeutic efficacy of C646 in pancreatic cancer.

Successful conversion surgery of distal pancreatectomy with celiac axis resection (DP-CAR) with double arterial reconstruction using saphenous vein grafting for locally advanced pancreatic cancer: a case report.

BACKGROUND: Pancreatic cancer is a disease with a poor prognosis, requiring multidisciplinary treatment combining chemotherapy and surgery for effective management. Distal pancreatectomy with celiac axis resection (DP-CAR) is a surgical intervention performed for locally advanced pancreatic cancer, but the benefit of arterial reconstruction in DP-CAR is unclear. CASE PRESENTATION: A 49-year-old man with pancreatic cancer was referred to our hospital. Imaging revealed a 54-mm tumor mainly in the pancreatic body, but with arterial infiltration including into the celiac, common hepatic, left gastric, splenic and gastroduodenal arteries. Distant metastases were not detected. The patient was diagnosed with unresectable locally advanced pancreatic cancer and chemoradiotherapy was planned. Three cycles of gemcitabine (1000 mg/m2) plus nab-paclitaxel (125 mg/m2) every 4 weeks were followed by irradiation (2 Gy/day, total 50 Gy over 25 days) together with S-1 administration (80 mg/m2/day). A partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) was achieved, so surgical intervention was considered. Because the tumor had invaded the root of the gastroduodenal artery, we performed DP-CAR with resection of the gastroduodenal artery, followed by arterial reconstruction of the proper hepatic and left gastric arteries, anastomosed with the abdominal aorta using a great saphenous vein graft in the shape of a "Y". Histopathology showed that 60% of tumor cells were destroyed by the chemoradiotherapy, defined as grade IIb in the Evans classification. No malignancy was detected at the surgical margin, including the celiac artery, gastroduodenal artery or pancreatic stump; thus R0 surgery was successful. S-1 (80 mg/day) was administered as adjuvant chemotherapy for 6 months. The patient is now doing well without recurrence for > 2 years after the initial treatment (more than 16 months after surgery). CONCLUSION: For locally advanced pancreatic cancer, multidisciplinary treatment combining gemcitabine/nab-paclitaxel-based chemoradiotherapy and then DP-CAR surgery with gastroduodenal artery resection and arterial reconstruction using saphenous vein grafting enabled R0 resection in this patient and led to a favorable long-term prognosis.

[A Case Report of Gastric Cancer Excised after Neoadjuvant Chemotherapy and Long-Term Survival Achieved after NivolumabAdministration for Peritoneal Dissemination].

The patient was a 64-year-old man with Type 3 advanced cancer in the upper body of the stomach. The preoperative tumor marker value of CA19-9 was abnormally high, but there was no proof of distant metastasis or peritoneal dissemination. The first operation was an exploratory laparotomy due to direct tumor invasion to the pancreas. Systemic chemotherapy was performed for tumor reduction. First, S-1 plus cisplatin therapy was administered for 4 courses but discontinued because of renal dysfunction and thrombocytopenia. In the second-line therapy, ramucirumabplus paclitaxel therapy was administered for 7 courses. Since the tumor invasion to the pancreas turned to be clear based on a CT scan, total gastrectomy with regional lymphadenectomy was performed. However, 5 months after surgery, a single nodule appeared in the upper abdomen that was suspected to be peritoneal dissemination. Nivolumab therapy was administered for 16 months without tumor enlargement or any adverse effect. Recently, there has been a marked development in chemotherapy for gastric cancer. Unresectable cases became operable after the administration of appropriate chemotherapy. In our case, nivolumab therapy had no adverse effect. However, serious adverse effects have been reported by several authors which suggests that regular examinations for interstitial pneumonia, hypothyroidism, and other adverse effects are important.

In Vitro Evolution of Unmodified 16S rRNA for Simple Ribosome Reconstitution.

One of the largest challenges in the synthesis of artificial cells that can reproduce is in vitro assembly of ribosomes from in vitro synthesized rRNAs and proteins. In this study, to circumvent the post-transcriptional modification of 16S rRNA for reconstitution of the fully active 30S subunit, we performed artificial evolution of 16S rRNA, which forms the functional 30S subunit without post-transcriptional modifications. We first established an in vitro selection scheme by combining the integrated synthesis, assembly, and translation (iSAT) system with the liposome sorting technique. After 15 rounds of selection cycles, we found one point mutation (U1495C) near the 3' terminus that significantly enhanced the reconstitution activity of the functional 30S subunit from unmodified 16S rRNA to approximately 57% of that from native-modified 16S rRNA. The effect of the mutation did not depend on the reconstitution scheme, anti-SD sequences, or the target genes to be translated. The mutation we found in this study enabled reconstitution of the active 30S subunit without rRNA modification, and thus would be a useful tool for simple construction of self-reproducing ribosomes.

[A Case Report of Gastric Cancer with Positive Peritoneal Lavage Cytology and Metachronous Schnitzler's Metastasis Treated with Multimodality Therapy].

A69 -year-old male patient with type 3 gastric cancer in pyloric antrum underwent distal gastrectomy with regional lymphadenectomy. Serosal infiltration of cancer tissue was found in the anterior wall of antrum, and the evaluation of peritoneal lavage cytology were positive. Pathological analysis showed the tumor was mainly consist of moderately tubular adenocarcinoma and strongly positive for HER2 stain. Postoperatively, combined therapy of capecitabine and trastuzumab was carried out, but cisplatin was excluded because of the patient's rejection. However, nine months after drug withdrawal, singular tumor located at left anterior side of rectum was detected by abdominal CT scan. Colonoscopy revealed its mucosal invasion and the result of biopsy was metastasis of gastric cancer, also known as Schnitzler's metastasis. Local radiation therapy aimed at the tumor was performed, followed by capecitabine and oxaliplatin therapy for 18 months. After the therapy, Schnitzler's metastatic lesion was disappeared and biopsy from colonic mucosa revealed there was no tumor tissue left. The patient has been in good health 5 years after surgery. This case suggests that multimodality therapy including radiation and chemotherapy might improve survival of gastric cancer patient with positive peritoneal lavage cytology and metachronous metastasis.

[Recurrence of a Giant Retroperitoneal Leiomyosarcoma Six Years after the Initial Surgery].

A 51-year-old man came to our department because of a large abdominal mass. CT, MRI, and sonography revealed a large tumor adjacent to the retroperitoneal area. A resection was performed, and histologically we confirmed the diagnosis as a leiomyosarcoma originating from the retroperitoneum. Six years after the initial surgery, the patient came to our outpatient department with a complaint of nausea. A relatively large tumor was seen on a CT scan that was causing obstruction of the duodenum. Another surgery was performed with the final diagnosis as a recurrence of the leiomyosarcoma. After 3 courses of adjuvant chemotherapy with eribulin, the patient presented with abdominal distension. CT revealed a very large tumor with massive invasion to the ileum and colon. This time, we considered the tumor unresectable, and administered chemotherapy with a combination of doxorubicin and ifosfamide. However, after 1 course, the patient's condition worsened and he died of the disease 3 months after the chemotherapy.