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Supplementary methods

Supplementary Figure 1. Characterization of 23 PDAC cell lines.

Supplementary Figure 3. NVP-AUY922 toxicity in vivo and effect of gemcitabine treatment in ARID1A knock-out PDAC models in vitro and in vivo.

Comparison of IC50 values based on the gene mutation status

Blood test and serial transplantation of the tumors at the end of the 30 days of each treatment.

Only the mice treated by MQ+SN-38 revealed no apparent signs of tumor regrowth.

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSCs remains promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSCs and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an antimalarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug. Endolysosomal RAB5/7 and LAMP1/2 mediated parkin-dependent mitochondrial clearance and modulated mitophagy through lysosomal dynamics. In a patient-derived xenograft (PDX) model of colon cancer, treatment with mefloquine resulted in suppression of mitophagic PINK1/PARKIN and increased mitochondrial disorder and mitochondria-induced apoptosis without apparent side effects. These results suggest that the combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs.Significance:These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.

Supplementary Figure 2. Knocking out ARID1A does not impair viability in PDAC cell lines.

Cellular dedifferentiation is a key mechanism driving cancer progression. Acquisition of mesenchymal features has been associated with drug resistance, poor prognosis, and disease relapse in many tumor types. Therefore, successful targeting of tumors harboring these characteristics is a priority in oncology practice. The SWItch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex has also emerged as a critical player in tumor progression, leading to the identification of several SWI/SNF complex genes as potential disease biomarkers and targets of anticancer therapies. AT-rich interaction domain-containing protein 1A (ARID1A) is a component of SWI/SNF, and mutations in ARID1A represent one of the most frequent molecular alterations in human cancers. ARID1A mutations occur in approximately 10% of pancreatic ductal adenocarcinomas (PDAC), but whether these mutations confer a therapeutic opportunity remains unclear. Here, we demonstrate that loss of ARID1A promotes an epithelial–mesenchymal transition (EMT) phenotype and sensitizes PDAC cells to a clinical inhibitor of HSP90, NVP-AUY922, both in vitro and in vivo. Although loss of ARID1A alone did not significantly affect proliferative potential or rate of apoptosis, ARID1A-deficient cells were sensitized to HSP90 inhibition, potentially by promoting the degradation of intermediate filaments driving EMT, resulting in cell death. Our results describe a mechanistic link between ARID1A defects and a quasi-mesenchymal phenotype, suggesting that deleterious mutations in ARID1A associated with protein loss exhibit potential as a biomarker for patients with PDAC who may benefit by HSP90-targeting drugs treatment.Significance:This study identifies ARID1A loss as a promising biomarker for the identification of PDAC tumors that are potentially responsive to treatment with proteotoxic agents.

Cellular dedifferentiation is a key mechanism driving cancer progression. Acquisition of mesenchymal features has been associated with drug resistance, poor prognosis, and disease relapse in many tumor types. Therefore, successful targeting of tumors harboring these characteristics is a priority in oncology practice. The SWItch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex has also emerged as a critical player in tumor progression, leading to the identification of several SWI/SNF complex genes as potential disease biomarkers and targets of anticancer therapies. AT-rich interaction domain-containing protein 1A (ARID1A) is a component of SWI/SNF, and mutations in ARID1A represent one of the most frequent molecular alterations in human cancers. ARID1A mutations occur in approximately 10% of pancreatic ductal adenocarcinomas (PDAC), but whether these mutations confer a therapeutic opportunity remains unclear. Here, we demonstrate that loss of ARID1A promotes an epithelial–mesenchymal transition (EMT) phenotype and sensitizes PDAC cells to a clinical inhibitor of HSP90, NVP-AUY922, both in vitro and in vivo. Although loss of ARID1A alone did not significantly affect proliferative potential or rate of apoptosis, ARID1A-deficient cells were sensitized to HSP90 inhibition, potentially by promoting the degradation of intermediate filaments driving EMT, resulting in cell death. Our results describe a mechanistic link between ARID1A defects and a quasi-mesenchymal phenotype, suggesting that deleterious mutations in ARID1A associated with protein loss exhibit potential as a biomarker for patients with PDAC who may benefit by HSP90-targeting drugs treatment. Significance: This study identifies ARID1A loss as a promising biomarker for the identification of PDAC tumors that are potentially responsive to treatment with proteotoxic agents.

Anticancer drugs generate excessive reactive oxygen species (ROS), which can cause cell death. Cancer cells can resist this oxidative stress, but the mechanism of resistance and associations with chemoresistance are unclear. Here, we focused on Sirtuin 3 (SIRT3), a deacetylating mitochondrial enzyme, in oxidative stress resistance in colorectal cancer (CRC). To evaluate SIRT3-related changes in mitochondrial function, ROS (mtROS) induction, and apoptosis, we used the human CRC cell lines HT29 and HCT116 transfected with short-hairpin RNA targeting SIRT3 and small interfering RNAs targeting superoxide dismutase 2 mitochondrial (SOD2) and peroxisome proliferator–activated receptor γ coactivator-1 (PGC-1α). In 142 clinical specimens from patients with CRC, we also assessed the association of SIRT3 protein levels (high/low) and prognosis. SIRT3 expression correlated with mtROS generation and apoptosis induction in cells treated with anticancer agents. Suppressing SIRT3 increased mtROS levels and cell sensitivity to anticancer agents. SIRT3 knockdown decreased SOD2 expression and activity, and suppressing SOD2 also improved sensitivity to anticancer drugs. In addition, SIRT3 was recruited with PGC-1α under oxidative stress, and suppressing SIRT3 decreased PGC-1α expression and mitochondrial function. PGC-1α knockdown decreased mitochondrial activity and increased apoptosis in cells treated with anticancer drugs. In resected CRC specimens, high vs low SIRT3 protein levels were associated with significantly reduced cancer-specific survival. SIRT3 expression affected CRC cell chemoresistance through SOD2 and PGC-1α regulation and was an independent prognostic factor in CRC. SIRT3 may be a novel target for CRC therapies and a predictive marker of sensitivity to chemotherapy.

Surgeons are increasingly being faced with the challenge of treating elderly patients with colon cancer. The present study therefore aimed to compare the short-term outcomes of single-port laparoscopic surgery (SILS) for elderly patients with colon cancer (≥70 years) with those in younger patients (41–69 years; control group). Among 100 patients with colorectal cancer who had been treated with single-port laparoscopic surgery between January 2011 and December 2014, 56 (56.0%) were ≥70 years of age. The results of treatment and short-term outcomes in the elderly group (n=56) were retrospectively compared with the younger patients in the control group (n=44). The sex distribution, body mass index, history of prior surgery and the American Society of Anesthesiologists physical status classification were similar between the groups. Onodera's prognostic nutritional index demonstrated significant differences between the elderly and control groups (38.3 vs. 49.8; P

The frequency of multiple synchronous colorectal cancers is reported to be 2% to 7%. The surgical resection of 2 lesions and having 2 anastomotic sites are rare. According to previous studies, even if there are 2 anastomotic sites, the rate of complications associated with laparotomy will not increase. However, the number of studies confined to cases of laparoscopic surgery is limited. This study investigated effective methods for laparoscopic colorectal resection and their short-term results in cases of multiple synchronous colorectal cancers with 2 anastomotic sites. The safety of these methods were also evaluated. The study was comprised of 4 patients with multiple synchronous colorectal cancers who underwent resection using laparoscopy between January 2011 and March 2015. We retrospectively examined patients with 2 anastomosis sites. A total of 3 patients underwent multiport laparoscopic surgery (5-port) and 1 patient underwent single-port laparoscopic surgery. Complications due to the conversion to laparotomy or intraoperative or postoperative complications were not observed in any patient. Laparoscopic colorectal resection, resulting in 2 anastomosis sites, was performed safely. Compared to open colorectal resection with 2 anastomotic sites, laparoscopic resection was a smaller incision and minimally invasive. Therefore, laparoscopic colorectal resection with 2 anastomotic sites is regarded as a feasible and safe option for multiple synchronous colorectal cancers when tumors are located distantly from each other.

Urinary tract resection is the only procedure that can cure colorectal cancer that directly invades the ureter. In these cases, open surgery is commonly used. Here, we describe our experience of a case of sigmoidectomy following Boari flap construction with single-incision laparoscopic surgery (SILS) for advanced colon cancer with ureteric invasion. A 68-year-old woman was referred to our hospital with left flank pain. Left hydroureteronephrosis was detected on ultrasonography. Computed tomography revealed a solid mass in the sigmoid colon and hydroureteronephrosis due to swelling of a mesenteric lymph node. Computed tomography detected no signs of distant metastasis. Colonoscopy revealed an ulcerated, bleeding, and stricturing lesion in the sigmoid colon, which was identified as an adenocarcinoma with a moderate degree of differentiation at histological examination. Under general anesthesia, the patient was placed in the Trendelenburg semi-right lateral position. An umbilical incision was made for the insertion of a single multichannel port for SILS. Sigmoidectomy and Boari flap reconstruction were performed. There were no perioperative complications. The total operating time was 572 minutes (including Boari flap procedure of 174 minutes), and estimated blood loss was 200 mL. Single-incision laparoscopic sigmoidectomy with Boari flap construction is technically feasible with sigmoid cancer and ureteral invasion.

Patient: Female, 41 Final Diagnosis: Graft thrombosis Symptoms: None Medication: — Clinical Procedure: Doppler ultrasound Specialty: Transplantology Objective: Unusual clinical course Background: Graft thrombosis is the main cause of early graft loss after transplantation. In Japan, pancreases available for transplantation are frequently from marginal donors due to diverse backgrounds in the population. However, marginal tissues increase the risk of early thrombosis in the graft. Case Report: Here, we describe a 41-year-old woman with type 1 diabetes mellitus who underwent a simultaneous pancreas-kidney transplantation. The pancreas was retrieved from a 34-year-old man who had experienced severe hemodynamic instability. The pancreaticoduodenal graft was implanted in the recipient iliac fossa with enteric drainage. Although the patient had not shown any physical signs or alterations in substances that might indicate functional loss of the pancreas graft, a Doppler ultrasound analysis detected a major thrombus in the pancreas graft on day 7 after surgery. A thrombectomy was performed with a radiological emergent intervention. After percutaneous direct thrombolysis, the patient received adjuvant thrombolytic therapy. Thereafter, the postoperative course was uneventful and the pancreas graft remained functional. Conclusions: Early detection and treatment of thromboses are required to avoid graft failure and graft pancreatectomy. This case study demonstrates that early detection of severe thrombus with Doppler ultrasound in a grafted pancreas did not increase the risk of graft failure.

The safety of single-incision laparoscopic surgery (SLS) in elderly patients with colorectal cancer has not been established. The aim of the current study was to compare the outcomes of SLS and multi-port laparoscopic surgery (MLS) and to assess the feasibility of SLS in colorectal cancer patients aged ≥70 years. A retrospective case-control study of colon cancer patients undergoing elective surgical intervention between 2011 and 2014 was conducted. A total of 129 patients with colon cancer underwent surgery and were included in the analysis. Data regarding patient demographics, surgical variables, oncological outcomes and short-term outcomes were evaluated for statistical significance to compare MLS (n=79) and SLS (n=50) in colon cancer patients. No significant differences were observed in patient characteristics. No case required re-admission within 30 days post surgery. The mean surgery times were similar for the MLS and SLS groups when cases with left and right hemicolectomies were combined (207.7 and 215.9 min, respectively; P=0.47). In addition, overall perioperative outcomes, including blood loss, number of lymph nodes harvested, size of the surgical margin and complications, were similar between these groups. Thus, we suggest that SLS can be performed safely in elderly patients with colon cancer.

Purpose High-output syndrome (HOS) is a complication of ileostomy, which can affect quality of life significantly; however, its exact cause remains unknown. The aim of this study was to establish the frequency, as well as the preoperative and intraoperative factors predictive of HOS. Methods The subjects of this study were 164 consecutive patients who underwent colorectal cancer surgery with ileostomy construction at our institute between January, 2011 and August, 2018. Thirteen patients with postoperative complications reported as causes of HOS, including intraperitoneal abscess, paralytic ileus, and outlet obstruction, were excluded. We used a logistic regression analysis to identify the factors predictive of HOS. Results HOS developed in 36 of the 151 patients (23.8%). There were significantly more diabetic patients in the HOS group (P = 0.03), but other patient factors such as age, gender, body mass index, and use of daily laxatives were not significantly different between the groups. The HOS group had significantly more cases of total proctocolectomy (P = 0.04), but other surgical factors such as operative time, and blood transfusion were not significantly different between the two groups. Conclusions These results indicate that diabetes and total proctocolectomy are preoperative predictors of HOS, allowing for the possibility of early intervention via post-surgical treatment.

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSCs remains promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSCs and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an antimalarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug. Endolysosomal RAB5/7 and LAMP1/2 mediated parkin-dependent mitochondrial clearance and modulated mitophagy through lysosomal dynamics. In a patient-derived xenograft (PDX) model of colon cancer, treatment with mefloquine resulted in suppression of mitophagic PINK1/PARKIN and increased mitochondrial disorder and mitochondria-induced apoptosis without apparent side effects. These results suggest that the combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs. Significance: These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.

We prove the safety and feasibility of single-incision plus 1 port (SILS+1) laparoscopic total mesorectal excision (TME) + lateral pelvic lymph node dissection (LPLD) via a medial umbilical approach for rectal cancer. Only a few reports have been published about single-incision multiport laparoscopic low anterior resection with LPLD. Recently, minimally invasive surgery such as single-incision plus 1 port (SILS + 1) for advanced rectal cancer has been reported as safe and feasible. To our knowledge, this is the first reported case of SILS + 1 used for LPLD. A wound protector was inserted through a 30-mm transumbilical incision. Next, a single-port access device was mounted to the wound protector and 3 ports (5 mm each) were placed. A 12-mm port was inserted in the right lower quadrant. Super-low anterior resection of the rectum and bilateral LPLD and temporary ileostomy were performed with SILS + 1, with a blood loss of 50 mL and a total surgical time of 525 minutes. The time for right lateral dissection was 74 minutes; the time for left lateral dissection was 118 minutes. The total number of dissected lymph nodes was 57 and the number of lateral lymph nodes dissected was 21 (8 left pelvic lymph nodes, 13 right pelvic lymph nodes). No postoperative anastomotic insufficiency or voiding dysfunction was observed. We have documented the safety and feasibility of SILS + 1-TME + LPLD via a medial umbilical approach for rectal cancer.

With regard to laparoscopic and robotic abdominoperineal resection (APR) for primary rectal malignancies, limited data have been published in the literature. Single-incision laparoscopic surgery (SLS) has been successfully introduced for treating colorectal cancer. Here we describe our experience of APR with SLS plus one port (SLS + 1) for treating advanced rectal cancer. A 65-year-old man underwent the procedure, which involved a 35-mm incision in the left side of the umbilicus for the insertion of a single multichannel port as well as the insertion of a 5-mm port into the right lower quadrant. The sigmoid colon and rectum were mobilized from the pelvic floor using a medial and lateral approach. After the rectum with the mesorectum was completely mobilized according to the total mesorectal excision, the sigmoid colon was intracorporeally transected. The specimen was removed through the perineal wound. Terminal colostomy was fashioned at the left lower trocar site. Lateral pelvic lymph node dissection was bilaterally performed. There were no perioperative complications. The total operating time was 592 minutes, and the estimated blood loss was 180 mL. To our knowledge, this is the first reported case of SLS + 1 APR with lateral pelvic lymph node dissection for treating rectal cancer. We conclude that SLS + 1 APR is a technically promising alternative method for treating selected patients with advanced rectal cancer.

Unresectable advanced esophageal cancer is often treated with chemotherapy or chemoradiotherapy(CRT). Nutritional disorders caused by dysphagia may lead to a poor prognosis. Placing a PEG before starting CRT for advanced esophageal cancer may maintain better nutritional status.The purpose of this study is to evaluate the clinical significance of placing a PEG before starting CRT for advanced esophageal cancer.Fifty-one cases were evaluated, 22 PEG (+) and 29 PEG (-). The rate of a CRT was better in PEG (+) than PEG (-) cases (91% vs 79%). Infection around the PEG was the only type of complication, affecting 5%.PEG feeding during CRT is important in the development of effective treatments for unresectable advanced esophageal cancer.

A 78-year-old-man visited a nearby doctor for treatment of hepatitis C and high blood pressure.He was diagnosed with right hydronephrosis by abdominal echography conducted in follow-up of hepatitis C treatment in November 2011; he was then introduced to our hospital for close inspection and medical treatment.We observed wall hyperplasia and narrowing of the lumen in the central sigmoid part by contrast-enhanced computed tomography (CT).The right ureter at the L4/5 level showed wall hyperplasia and a deep color, and the right ureter, renal pelvis, and calix were expanded on the head side. By examination for CF, we observed a type 2 lesion in the sigmoid colon, and a biopsy showed well-differentiated adenocarcinoma. Based upon these findings, he was diagnosed with synchronous sigmoid colon cancer (cT4aN0M0, cStage II) and ureter cancer (cT2N0M0, cStage II); we performed laparotomy sigmoidectomy(D3 dissection)and full extraction of the right kidney urinary tract (lymph node dissection in front of the vena cava, the latter outside and between the aorta and vena cava). The postoperative course was particularly uneventful, and the patient was discharged from the hospital on day 38 after the operation. More than 2 years after the surgery, the patient exhibits no sign of sigmoid colon cancer or ureter cancer recurrence.

Single-incision laparoscopic colectomy (SLC) is touted as an improved approach to minimally invasive surgery, although no data currently exist regarding the acquisition of this technique. The aim of this study was to evaluate resident performance and outcomes in patients undergoing SLC performed by residents vs. staff colorectal surgeons. A retrospective case-control study was conducted, including 220 patients who underwent elective surgical intervention with multiport laparoscopic colectomy (MLC, n=141) or SLC (n=79) for colon cancer over a 24-month period at Yao Municipal Hospital (Yao, Japan). Data on patient demographics, operative data, oncological outcomes and short-term outcomes were evaluated for statistical significance. To investigate issues regarding the surgical procedures, the entire operation was recorded on video for all patients and was divided into 6 procedures, with each procedure measured in seconds. Senior-level residents were able to safely perform MLC under appropriate experienced supervision. For SLC, 1 case required conversion to an open procedure. No case required additional trocar placement. The mean operative times were similar for the staff and resident groups for total colon cancer (192.5 and 217.5 min, respectively; P=0.88), whereas the operative times of the staff group for right-sided colon cancer were significantly longer, and the operative times of the resident group for left-sided colon cancer were significantly longer. In addition, the overall perioperative outcomes, including blood loss, number of harvested lymph nodes, length of the surgical margin and complications, were similar between the two groups. When video recordings were evaluated by dividing the surgical process for the right colon into 4 procedures and that for the left colon into 6 procedures, the results demonstrated that the residents required more time to close the mesenteric margin for the left colon compared with the staff performing the same procedure (3,470.1±1,258.5 vs. 5,218.6±2,341.2 sec; P=0.01). Therefore, senior-level residents were able to safely perform SLC under appropriate experienced supervision. For the left colon, the main challenge for the residents appeared to be the closure of the mesenteric margin. Our data support that it is possible to train senior residents to complete a SLC safely and with the same efficacy as staff surgeons.

A man in his 30s visited our hospital after a local doctor diagnosed him with a rectal submucosal tumor. Colonoscopy and fine needle biopsy revealed a lower rectal gastrointestinal tumor (GIST). Pelvic MRI examination revealed apparent tumor invasion of the left levator ani muscle. Curative abdominoperineal resection( APR) of the tumor was required. Our strategy involved the initiation of neoadjuvant imatinib therapy to facilitate subsequent sphincter-preserving resection. Neoadjuvant chemotherapy for 11 months reduced the tumor size and permitted the R0 laparoscopic sphincter-preserving resection. He was discharged without any postoperative complications. The pathological findings revealed semi-curative effects and pR0 resection. Thus, neoadjuvant chemotherapy for advanced rectal GIST was a useful strategy for this function- preserving operation.

A 75-year-old man with a complaint of right hypochondrial pain consulted our hospital, and was diagnosed as having acute cholecystitis. We performed percutaneous transhepatic gallbladder drainage (PTGBD), and the cholecystitis resolved. However, obstructive jaundice occurred 2 weeks later. Thus, we performed an in-depth investigation and detected duodenal papilla cancer (cT3N1M0, Stage III). Pancreatoduodenectomy was performed. As postoperative histological diagnosis yielded positive and strongly positive immunostaining for synaptophysin and Ki-67, respectively, we diagnosed the patient as having neuroendocrine carcinoma (NEC) of the duodenal papilla. Three months after surgery, computed tomography (CT) scan showed multiple liver metastases and lymph node metastasis. Chemotherapy with carboplatin and etoposide was administered, but severe neutropenia developed, and therefore, the chemotherapy was discontinued. Subsequently, we decided on a policy of best supportive care (BSC). The patient died 11 months after surgery. NEC of the duodenal papilla is reported to be a rare and rapidly progressing disease and is associated with a very poor prognosis. Herein, we report a case of a patient in whom NEC of the duodenal papilla was resected.

We report a case of undifferentiated carcinoma of the duodenum. A 40-year-old man was referred to our hospital as he experienced upper abdominal pain that had persisted for half a year. Gastrointestinal endoscopy revealed a semicircular tumor in the duodenum. Enhanced computed tomography( CT) revealed that the tumor had not invaded the adjacent tissues, and lymph node metastases were not detected. Biopsy indicated a diagnosis of Group V cancer. Because the tumor was diagnosed as primary duodenal cancer, pancreatoduodenectomy and lymphadenectomy were performed. Histopathological examination revealed the presence of variant cells with irregular cores; we then diagnosed the tumor as undifferentiated cancer of the duodenum. No lymph node metastasis was detected microscopically. This patient has remained well without recurrence for 17 months since the operation. Undifferentiated carcinoma of the duodenum is rare, as only 9 cases have been reported in the Japanese literature.

Chemotherapy followed by surgery for Stage IV gastric cancer with passage obstruction poses a problem in terms of poor postoperative nutritional status. By maintaining an adequate postoperative nutrition status with jejunostomy catheter feeding, chemotherapy may possibly be continued. We treated 40 cases of Stage IV gastric cancer with passage obstruction from January 2008 to December 2011. In every case, jejunostomy catheter feeding tubes were placed during gastric cancer surgery. We performed 13 total gastrectomies, 20 distal gastrectomies, and 7 gastrojejunal bypass surgeries. Tube obstruction in 4 cases( 10%) and tube deviation in 1 case( 2.5%) occurred during the tube feeding period. Chemotherapy could be resumed in 37 cases( 92.5%), and the duration of chemotherapy was 330 days( range, 41-721). In cases of Stage IV gastric cancer, patients are obliged to start postoperative chemotherapy at an unstable period. By starting jejunal catheter feeding at an early stage after surgery, improved results could be expected in terms of shortening of the hospital stay or continuation of chemotherapy.

The patient was a 50-year-old woman who had undergone pancreaticoduodenectomy for bile duct carcinoma in April 2010. In August 2011, abdominal computed tomography (CT) revealed a solitary tumor (30×17 mm in diameter) behind the anastomosis of gastrojejunostomy. Gastrointestinal endoscopy revealed gastrojejunal ulceration (biopsy: Group V adenocarcinoma). Positron emission tomography (PET)-CT revealed a solitary tumor without any recurrence. We diagnosed the patient as having solitary recurrence of peritoneal dissemination of bile duct carcinoma. In September 2011, we performed resection of the peritoneal dissemination. The patient was discharged from the hospital 12 days after the operation and had a good postoperative course. Histologically, the tumor was diagnosed as peritoneal dissemination of bile duct carcinoma. Subsequently, the patient received postoperative chemotherapy. The patient remains alive with recurrence of peritoneal dissemination 37 months after pancreaticoduodenectomy and 20 months after resection of the peritoneal dissemination.

A 57-year-old woman was discovered to have a cystic tumor, 8 cm in diameter, at the pancreas tail, during routine screening with ultrasonography. The patient did not complain of tenderness, and no abdominal mass was palpable at physical examination. Enhanced computed tomography(CT) revealed that the tumor had mural nodules in the cyst wall, and we suspected it to be a malignant tumor that had occurred in the mucinous cystic neoplasm(MCN). Therefore, surgical resection was attempted, upon which the tumor was found to be hard and the surrounding tissue adhered widely to the stomach. We separated it carefully from the stomach and then performed a distal pancreatectomy. The cut surface revealed that the posterior wall of the cystic tumor was partly thickened, and microscopic examination revealed it to be invasive ductal carcinoma. No ovarian-like stroma was involved and some degree of dysplasia(PanIN 1-3) was found in the neighboring tissues. Therefore, we re-diagnosed it to be invasive ductal carcinoma of the pancreas derived from intraductal papillary mucinous tumor(IPMT), not from MCN. The patient received adjuvant chemotherapy, although 5 months later multiple lung metastases had appeared. The international consensus guidelines for management of IPMN and MCN of the pancreas suggest that they can usually be distinguished preoperatively, if there is a complete understanding of their clinical and imaging features. However, we sometimes find it difficult to distinguish the 2, because some IPMN or MCN cases have shared preoperative features. Herein, we report the case of invasive ductal carcinoma of the pancreas derived from IPMT that was originally misdiagnosed as a MCN.

Our patient was a 67-year-old man, with a chief complaint of brown urine. He subsequently underwent medical examination in June. Because the results of his blood examination revealed liver dysfunction, he was admitted to our hospital for further careful examination. An abdominal computed tomography(CT) scan showed the presence of a pancreas tumor, with a diameter of 2 cm, at the pancreas head, as well as common biliary duct dilatation and main pancreatic duct dilation from the head to the tail of the pancreas. The patient was diagnosed with pancreatic cancer[cT3( CH+, DU+), cN0, cM0, cStage III], with obstructive jaundice. After biliary drainage, we performed laparotomy in August. During the operation, other than the tumor on the pancreas head, identified at the preoperative diagnosis, we found 2 white nodules on the pancreas surface. One nodule was located at the body of the pancreas and the other, at its tail. On intraoperative pathological examination of the nodules, they were found to be invasive ductal carcinomas. On the basis of these findings, we suspected multiple cancers or overall pancreatic cancer; therefore, we performed total pancreatectomy, not pancreaticoduodenectomy (PD). We choose pancreatectomy over PD because it was impossible to confirm the cancerous area. Pathological examination of the resected specimen did not reveal any malignant lesion. Thus, if we had not performed pancreatectomy, assuming that the pancreas body or tail had no cancer lesion, based on the pathological examination result, the cancer would have persisted. Further, careful examination involving inspection and palpation is considered to be essential before resection of the pancreas tumor.