Prognosis of Pancreatic Cancer Based on Resectability: A Single Center Experience.

Although conversion surgery has increasingly been performed for initially unresectable advanced pancreatic ductal adenocarcinoma (PDAC), the rate of conversion, including that for patients who do not undergo resection, remains unclear. Patients with PDAC who were treated between January 2013 and December 2018 were classified into three groups: resectable (R), borderline resectable (BR), and unresectable (UR). We analyzed patient outcomes, including the rate of surgical resection and survival, in each of these groups. In total, 211 patients (R, 118; BR, 22; UR, 81) were selected. Among them, 117 (99%), 18 (82%), and 15 (19%) patients in the R, BR, and UR groups, respectively, underwent surgical resection. R0 resection rates were 88, 78, and 67%, whereas median overall survival (OS) from treatment initiation were 31, 18, and 11 months (p < 0.0001) in the R, BR, and UR groups, respectively. In patients who underwent surgical resection, relapse-free survival (RFS) and OS were similar among the three groups (R vs. BR vs. UR; median RFS (months), 17 vs. 13 vs. 11, p = 0.249; median OS (months), 31 vs. 26 vs. 32, p = 0.742). Lymph node metastases and incomplete adjuvant chemotherapy were identified as independent prognostic factors for OS. Although the surgical resection rate was low, particularly in the BR and UR groups, the prognosis of patients who underwent surgical resection was similar irrespective of the initial resectability status.

Primary Tumor Histology Affects Oncological Outcomes Independently of the Anatomical Extent of Disease in Colorectal Liver Metastasis.

INTRODUCTION: Growing evidence indicates the prognostic importance of the crosstalk between cancer cells and stroma through the induction of epithelial-mesenchymal transition (EMT). This study aimed to clarify the prognostic value of evaluating primary tumor histology with the anatomical extent of disease in patients with colorectal liver metastasis (CRLM). METHODS: Prognostic analyses were performed in 411 CRLM patients who underwent hepatectomy at two institutions. Tumors were graded into one of three histological categories based on integrated assessment of EMT-associated histology (HistologyEMT) in primary tumors, i.e., poorly differentiated clusters (PDCs) and desmoplastic reaction (DR). RESULTS: A prognostic grouping system for the anatomical extent of disease (N stage, liver metastasis number and size, and extrahepatic disease; Gradeanatomical) stratified patients into three groups with different five-year relapse-free survival (RFS) rates after hepatectomy: A, 31% (191 patients); B, 15% (124 patients); and C, 6% (96 patients; P < 0.0001). HistologyEMT (A, G1 PDC and mature-type DR; C, G3 PDC and immature-type DR; and B, others) identified 49, 120, and 242 patients with 46%, 5%, and 22% five-year RFS, respectively (P < 0.0001). Among prognostic factors, the Akaike information criterion was most favorable in Gradeanatomical, followed by HistologyEMT. Multivariate analysis demonstrated that these two factors independently impacted RFS; two-year RFS after hepatectomy in different patient groups had a wide range (10%-76%). CONCLUSIONS: Histological assessment of dedifferentiation and the stromal environment of primary tumors contributed to effective risk stratification of early relapse after hepatectomy, which could be useful to determine clinical management for CRLM patients.

Prognostic Impact of Budding Grade in Patients With Residual Liver Recurrence of Colorectal Cancer After Initial Hepatectomy.

BACKGROUND: Many patients undergoing hepatectomy for colorectal liver metastases (CRLM) experience recurrence. However, no criteria for screening candidates to undergo repeat hepatectomy (RH) for CRLM have been established. Budding, one form by which colorectal carcinoma malignancies are expressed, is a new pathologic index. This study aimed to analyze prognostic factors, including budding, and to provide criteria for screening candidates to undergo RH for recurrent CRLM. METHODS: Data of 186 consecutive patients who underwent hepatectomy for CRLM between April 2008 and December 2015 were collected. Survival was calculated using the Kaplan-Meier method. Uni- and multivariate analyses were performed to determine factors significantly affecting mortality. RESULTS: Of 186 patients, 131 experienced recurrence after hepatectomy, with 83 of the 131 patients showing recurrence in the liver, and 52 of these 83 patients undergoing primary surgery at the authors' institution and having information on budding grade. In the univariate analysis, preoperative chemotherapy, budding grade, extrahepatic metastases, and number of liver metastases at the time of recurrence were associated with overall survival (OS) for the 52 patients. In the multivariate analysis, budding grade and number of liver metastases at the time of recurrence were associated with OS. CONCLUSION: The study examined simple prognostic factors that could help to screen patients better for RH. Repeat hepatectomy improved the prognosis for patients with recurrent CRLM. The independent prognostic factors for OS were number of liver metastases at recurrence as a conventional factor and budding grade as a new pathologic factor. With budding used as an index, patients who could benefit from hepatectomy can be screened more precisely.

Prognostic significance of regional lymph node metastasis according to station in ampullary carcinoma.

BACKGROUND: The TNM (Tumor, Node, Metastasis) classification of the 8th Union for International Cancer Control and the 6th Japanese classification of biliary tract cancer were made on the premise that the prognostic effect of each regional lymph node station is similar. However, some studies have reported different effects of lymph node metastasis location on post-resection prognosis. This study aimed to investigate outcome following radical resection of ampullary carcinoma according to station of lymph node metastasis. METHODS: Patients who underwent surgical resection for ampullary carcinoma between January 2007 and December 2017 at two separate Japanese institutions were included. Regional lymph nodes were subclassified as follows: Pancreatoduodenal lymph nodes (PD) and others (OT). RESULTS: Of the 101 patients analyzed, 34 had regional lymph node metastasis. OT metastasis was found in eight patients. Significant differences were found in relapse-free survival (RFS) and overall survival (OS) between the three study groups (no nodal metastasis, only PD metastasis and OT metastasis; P < .001 for both). OT metastasis was an independent prognostic factor in the multivariate analysis for RFS (hazard ratio [HR] 17.14; 95% confidence interval [CI], 6.33-43.93) and OS (HR 11.06; 95% CI, 3.7-32.99). CONCLUSION: The poor prognosis of ampullary carcinoma patients with OT metastasis suggests that regional lymph nodes should not be categorized equally into one group.

A patient with a pancreatic neuroendocrine tumor and multiple liver metastases achieved a long-term partial response to third-line streptozocin treatment.

The Japanese guideline for gastroenteropancreatic neuroendocrine tumor treatment recommends everolimus or sunitinib as first-line treatment for unresectable pancreatic neuroendocrine tumors (PNETs). Streptozocin (STZ) is recommended as an alternative. We encountered a patient with PNET who had multiple liver metastases and who showed a remarkable response to third-line STZ. The patient was a 50-year-old man with a pancreatic head tumor 32 mm in diameter. We planned to perform subtotal stomach-preserving pancreaticoduodenectomy, but abandoned resecting the pancreas during the surgery upon discovering a small liver tumor 3 mm in diameter, examination of frozen sections of which revealed a poorly differentiated adenocarcinoma. However, the final pathological examination revealed that the liver nodule was a PNET; hence, we completed the subtotal stomach-preserving pancreaticoduodenectomy 5 weeks after the first laparotomy. The patient received no adjuvant chemotherapy after surgery. Twenty-one months later, we discovered 20 scattered liver metastases via computed tomography; these were considered unresectable. Therefore, we administered everolimus for 7 months, but the patient developed interstitial pneumonia and experienced metastatic progression. Subsequent sunitinib administration for 6 months was ineffective. Finally, we chose STZ (1000 mg/m2, weekly) as a third-line treatment, which produced a partial response for 10 months. The patient remains alive 38 months after the detection of recurrence. As the order in which anti-cancer drugs should be administered to treat PNET has not been determined, additional predictors of their therapeutic efficacy should be investigated.

Stapler sizes optimized for pancreatic thickness can reduce pancreatic fistula incidence after distal pancreatectomy.

PURPOSE: The purpose of this paper was to identify the optimum-sized stapler cartridges for reducing the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: The authors retrospectively analyzed 101 patients who underwent DP with a triple-row stapler to identify the clinicopathological factors that strongly influence POPF after DP. The height difference (HD) was defined as the difference between the pancreatic thickness and the height of the closed stapler. RESULTS: POPF occurred in 58 (57%) patients. A multivariate analysis identified HD and pancreatic thickness as independent risk factors for the occurrence of POPF after DP. Akaike's information criterion for identifying the risk factors was more favorable for HD (115.18) than for pancreatic thickness (118.02). The incidence of POPF was significantly lower (29%) in patients with an HD between 6 and 12 mm than in the other two groups (< 6-mm group: 100%, P = 0.008; ≥ 12-mm group: 84%, P < 0.001). CONCLUSIONS: A too-thick or too-narrow pancreas carries a risk of developing POPF after DP when using a triple-row stapler. Selecting staplers to achieve an HD of 6-12 mm may reduce the incidence of POPF following DP.

Nutritional benefit of laparoscopic jejunostomy during neoadjuvant chemotherapy for obstructing esophageal cancer.

Neoadjuvant chemotherapy (NAC) confers a survival benefit in esophageal carcinoma, but it is difficult to perform in patients who cannot receive enteral feeding due to an esophageal obstruction. In the current study, the nutritional benefit of laparoscopic jejunostomy (Lap-J) was evaluated in patients with NAC for obstructing esophageal cancer. A total of 91 patients with esophageal cancer who received NAC between 2009 and 2017 were included in the present study. Lap-J was performed prior to NAC in 15 patients (16.5%) with an obstructing tumor. Patients with NAC without Lap-J were used as the control group (n=76). Nutritional parameters and surgical outcomes of the two groups were compared retrospectively. In the patients with Lap-J, 14 of the 15 patients (93.3%) did not experience any procedure-associated complications. No mortalities were associated with Lap-J. Significant decreases in total serum protein, albumin, hemoglobin concentrations and prognostic nutritional index (PNI) occurred following NAC in the control but not in the Lap-J group. Serum albumin and the improved modified Glasgow prognostic score increased significantly after NAC in the Lap-J group but not in the control group. In conclusion, perioperative nutritional support with Lap-J was safe and effective in patients with NAC for obstructing esophageal cancer.

Successful resection of a granulocyte colony-stimulating factor-producing carcinoma of the pancreas: A case report.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation of precursor cells in the bone marrow and their maturation into fully differentiated neutrophils. G-CSF-producing cancers rarely occur in the digestive system, particularly the pancreas. Herein we report the rare case of a G-CSF-producing pancreatic carcinoma associated with severe anemia due to bleeding in the duodenum, which was successfully treated with surgery. A 79 year-old man presented with epigastralgia and anemia at our institution. Esophagogastroduodenoscopy revealed a duodenal tumor, which was diagnosed as a poorly differentiated adenocarcinoma. To control breeding, subtotal stomach-preserving pancreaticoduodenectomy was performed. The excised tumor measured 86×55×54 mm. It was primarily located in the pancreas and compressed the pancreatic parenchyma and main bile duct. It comprised poorly differentiated adenocarcinoma, and prominent neutrophil infiltration was noted around the tumor. Immunohistochemical examination revelaed that the tumor was positive for G-CSF expression. Based on these results, a final diagnosis of G-CSF-producing primary pancreatic cancer was made. At 18 months following surgery, the patient was alive without recurrence.

Laparoscopic fenestration for a large ruptured splenic cyst combined with an elevated serum carbohydrate antigen 19-9 level: a case report.

BACKGROUND: Non-parasitic splenic cysts are associated with elevated serum carbohydrate antigen (CA) 19-9 levels. We report a case in which a 23-year-old female exhibited a large ruptured splenic cyst and an elevated serum CA19-9 level. CASE PRESENTATION: The patient, who experienced postprandial abdominal pain and vomiting, was transferred to our hospital and was found to have a large splenic cyst during an abdominal computed tomography (CT) scan. On physical examination, her vital signs were stable, and she demonstrated rebound tenderness in the epigastric region. An abdominal CT scan revealed abdominal fluid and a low-density region (12 × 12 × 8 cm) with enhanced margins in the spleen. The patient's serum levels of CA19-9 and CA125 were elevated to 17,580 U/mL and 909 U/mL, respectively. A cytological examination of the ascitic fluid resulted in it being categorized as class II. Finally, we made a diagnosis of a ruptured splenic epidermoid cyst and performed laparoscopic splenic fenestration. The patient's postoperative course was uneventful, and she was discharged on postoperative day 5. The cystic lesion was histopathologically diagnosed as a true cyst, and the epithelial cells were positive for CA19-9. Follow-up laboratory tests performed at 4 postoperative months showed normal CA19-9 (24.6 U/L) and CA125 (26.8 U/L) levels. No recurrence of the splenic cyst was detected during the 6 months after surgery. CONCLUSION: Laparoscopic fenestration of a ruptured splenic cyst was performed to preserve the spleen, after the results of abdominal fluid cytology and MRI were negative for malignancy.

Restoration of Dehiscent Pancreaticojejunostomy Causing a Major Postoperative Pancreatic Fistula by Reinsertion of a Pancreatic Duct Tube Using the Rendezvous Technique.

INTRODUCTION: A postoperative clinically relevant pancreatic fistula can cause severe sequelae. We aimed to describe our minimally invasive procedure (rendezvous technique) for the treatment of a pancreatic fistula resulting from pancreaticojejunal anastomosis dehiscence involving a dislodged main pancreatic duct tube. METHODS: In our rendezvous technique, a guidewire is advanced into the jejunal lumen from the access site of the drainage tube and is caught by a snare catheter, which is used to replace the dislodged main pancreatic duct tube. Then, the guidewire is passed from the access site of the drainage tube to the site of the dislodged main pancreatic duct tube. A sheath is inserted along the route of the dislodged main pancreatic duct tube and is placed across the pancreaticojejunal anastomosis over the guidewire. Another guidewire is advanced into the main pancreatic duct via the sheath, and a new main pancreatic duct tube is inserted into the main pancreatic duct over the second wire. This technique was performed in two patients with a pancreatic fistula. RESULTS: Our rendezvous technique was successfully performed in a 73-year-old man with an intractable clinically relevant pancreatic fistula and large discharge from the drain and a 74-year-old woman with a pancreatic fistula and fluid collection between the elevated jejunum and remnant pancreas. Discharge from the drain and fluid collection decreased after the procedure. CONCLUSION: Our rendezvous technique is an effective minimally invasive approach for a pancreatic fistula resulting from pancreaticojejunal anastomosis dehiscence.

Prognostic significance of histological categorization of desmoplastic reaction in colorectal liver metastases.

Desmoplastic reaction (DR) involves the growth of fibrous or connective tissues around a tumor and has recently attracted attention as an indicator of malignant potential. Previous studies have confirmed that histological categorization of DR in the primary tumor is an independent prognostic factor in patients with colorectal liver metastases (CRLM). However, it remains unclear whether the DR status of the metastatic liver lesion (DRliver) is a useful prognostic factor. This pathological review evaluated records from 204 patients who underwent hepatectomy for CRLM at the National Defense Medical College Hospital in Japan. Each case's DRliver was classified as mature, intermediate, or immature based on the presence of keloid-like collagen and myxoid stroma in the metastatic liver lesion. This resulted in 12 cases of mature DRliver, 101 cases of intermediate DRliver, and 91 cases of immature DRliver. There was a significant correlation between the DR statuses of the primary tumor and the metastatic liver lesion (Spearman's rho = 0.3, P = 0.0001). The 5-year relapse-free survival rates after hepatectomy were 33.8% for mature/intermediate DRliver and 16.7% for immature DRliver (P = 0.0021). The 5-year overall survival rate after hepatectomy was higher in the mature/intermediate DRliver group (64.8%) than in the immature DRliver group (35.0%; P = 0.0012). The multivariate analysis confirmed that DRliver categorization could independently predict relapse-free survival and overall survival. In conclusion, DRliver categorization may be valuable for predicting prognosis after hepatectomy among patients with CRLM.

Long-term outcome following sentinel node navigation surgery for cT1 gastric cancer.

Sentinel node navigation surgery (SNNS) has become a standard procedure for early-stage melanoma and breast cancer. However, very few studies have evaluated the long-term clinical outcomes following SNNS for gastric cancer. The present study analyzed 51 patients with cT1 gastric cancer who underwent SNNS at our hospital. Sentinel nodes (SNs) were identified using the dual tracer method. Patients underwent limited gastrectomy with SN station dissection when the SNs were reported as pathologically negative during surgery. When SNs were pathologically positive, standard gastrectomy with D2 lymphadenectomy was performed. Out of the 51 cases, 42 cases (82%) were pathologically diagnosed as SN-negative using a frozen section. The surgical procedures included segmental gastrectomy (n=33) and local resection (n=9). A total of 9 patients (18%) had lymph node metastasis in SNs. The mean observation period was 3,125±167 days, and the 5-year overall survival rate was 98%. There was no recurrence, and body weight loss was minimal following the SNNS. Remnant gastric cancer developed in 4 (8%) of the 50 patients except total gastrectomy. Thus, SNNS was a useful procedure for cT1 gastric cancer from the long-term clinical outcomes, though metachronous gastric cancer should paid further attention to.

Pathomorphological features of metastatic lymph nodes as predictors of postoperative prognosis in pancreatic cancer.

To investigate the pathological features of metastatic lymph nodes (LN) in pancreatic ductal adenocarcinoma (PDAC) and to determine factors with prognostic implications.Metastatic LN status is a proven significant factor for predicting postoperative prognosis in pancreatic cancer patients. However, the effective prognostic criteria regarding metastatic LNs for such disease remain unknown.We retrospectively reviewed 98 patients with R0/1 resection for PDAC. All metastatic LNs were evaluated for the pathomorphological features of metastasis and analyzed in terms of postoperative outcomes. Various morphological patterns of metastasis were assessed in 440 positive LNs and then classified into 4 groups: common type, direct type (continuously invaded by the main tumor), scatter type (multiple tumor clusters among the normal LN tissues), and isolated tumor cell (ITC).The pathological stage was defined as stage IIA in 10% and IIB in 90% patients. Common-type metastasis was noted in 55% positive LNs of 75% node-positive patients; direct type in 36% LNs of 69% patients; scatter type in 5% LNs of 14% patients; and ITCs in 5% LNs of 18% patients. Significant difference was noted only in recurrence-free survival (RFS) but not in overall survival (OS) in the common-type; only in OS but not in RFS for the scatter type; and neither in RFS nor OS for both direct type and ITC. Multivariate analysis revealed that only LN ratio and curability were independent predictive factors of poor.The tumor distribution patterns in metastatic LNs are the postoperative prognostic factors in pancreatic cancer.

A case of intrahepatic cholangiocarcinoma that was difficult to diagnose prior to surgery: A case report.

The present study reports a case of mass-forming intrahepatic cholangiocarcinoma (ICC), which mimicked cholangiocellular carcinoma (CoCC) during imaging and a needle biopsy examination. A 51-year-old female with no relevant medical history was referred to the National Defense Medical College hospital with an intrahepatic tumor. Computed tomography demonstrated non-homogeneous enhancement in the early arterial phase and persistent enhancement in the portal and equilibrium phases, together with notable swelling of the para-aortic lymph nodes. Gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging revealed low signal intensity in the hepatobiliary phase. The liver tumor and lymph nodes exhibited increased radiotracer uptake (maximum standardized uptake value=14.0) with positron emission tomography. A histological examination of a percutaneous needle biopsy specimen of the liver tumor indicated a diagnosis of CoCC. The patient underwent left hepatectomy and lymphadenectomy. The surgical specimen contained a poorly differentiated adenocarcinoma with anaplastic changes, which was immunohistochemically positive for epithelial membrane antigen (at the luminal membrane), cytokeratins 7 and 19, and negative for α-fetoprotein, hepatocyte-specific antigen, cluster of differentiation 56 and KIT. Based on these histopathological and immunohistochemical findings, the patient was diagnosed with ICC.

Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis.

Surgical injury can be a life-threatening complication, not only due to the injury itself, but also due to immune responses to the injury and subsequent development of infections, which readily result in sepsis. Sepsis remains the leading cause of death in most intensive care units. Unfavorable outcomes of several high-profile trials in the treatment of sepsis have led researchers to state that sepsis studies need a new direction. The immune response that occurs during sepsis is characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immunosuppressive phase. Therefore, therapies that improve host immunity might increase the survival of patients with sepsis. Many mechanisms are responsible for sepsis-induced immunosuppression, including apoptosis of immune cells, increased regulatory T cells and expression of programmed cell death 1 on CD4+ T cells, and cellular exhaustion. Immunomodulatory molecules that were recently identified include interleukin-7, interleukin-15, and anti-programmed cell death 1. Recent studies suggest that immunoadjuvant therapy is the next major advance in sepsis treatment.

Prognostic Value of Preoperative Systemic Immunoinflammatory Measures in Patients with Esophageal Cancer.

BACKGROUND: It is reported that several systemic immunoinflammatory measures, including systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and C-reactive protein (CRP)-to-albumin ratio (CAR), are associated with survival in patients with various types of cancer. OBJECTIVE: The aim of the present study was to clear which systemic immunoinflammatory measures had the greatest prognostic values. In addition, we examined which component had the greatest prognostic power in patients with esophageal cancer. METHODS: Preoperative systemic immunoinflammatory measures were evaluated in 143 patients undergoing esophageal resection for esophageal cancer from 2009 to 2014. Univariate and multivariate analyses were performed to determine the prognostic significance of these markers. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curves (AUROCs) were compared to verify the accuracy of each measure in predicting overall survival (OS). RESULTS: In univariate analysis, preoperative SII, NLR, and CAR were the predictors of OS in patients who underwent esophagectomy for esophageal cancer (p < 0.05, respectively), whereas in multivariate analysis, CAR and pathological tumor depth were the significant predictors of OS (hazard ratio [HR] 1.994, p = 0.03 vs. HR 1.967, p = 0.02, respectively). According to AUROC, the CRP (0.66) and albumin levels (0.66) were more important systemic immunoinflammatory measures than neutrophil (0.58), lymphocyte (0.63), and platelet (0.56) levels. CONCLUSION: Among systemic immunoinflammatory measures, CAR was the most significant predictor of OS in patients with esophageal cancer. CRP and albumin levels were more important components of systemic immunoinflammatory measures.

Impact of angiotensin-converting enzyme 2 levels on postoperative pneumonia after esophagectomy.

BACKGROUND: Pulmonary complications after esophagectomy are often fatal. The prediction of postoperative pulmonary complications remains a challenge. Accumulating evidence demonstrates a physiological and pathological role for angiotensin-converting enzyme 2 (ACE2) in the respiratory system. The purpose of this study was to evaluate the predictive value of ACE2 levels for the development of postoperative pneumonia. METHODS: To evaluate the association between serum ACE2 levels and pneumonia after esophagectomy, we retrospectively reviewed the medical records of 80 patients who underwent thoracoscopic esophagectomy for esophageal cancer from 2009 to 2014. RESULTS: Nineteen patients (23.8%) developed pneumonia after esophagectomy. Patients with pneumonia had significantly higher levels of ACE2 from the preoperative day to postoperative day (POD) 3, white blood cell count (POD7), and C-reactive protein (POD3, POD5, and POD7) than patients without pneumonia. Patients with postoperative pneumonia had higher serum ACE2 levels on POD3 than patients without pneumonia. CONCLUSIONS: The elevation of ACE2 levels on POD3 may predict the incidence of pneumonia.

Hepatic portal venous gas related to appendicitis.

BACKGROUND: Hepatic portal venous gas (HPVG) is rare with high mortality. There are few reports on HPVG's association with appendicitis. Here we report a case of HPVG associated with appendicitis. Case presentation: A 79-year-old man presented with acute abdominal pain. Physical examination suggested peritoneal irritation. Blood tests indicated acute inflammation, metabolic acidosis, renal dysfunction and disseminated intravascular coagulation. Contrast-enhanced abdominal computed tomography revealed HPVG, a contrast defect in the small intestine, and minor ascites around the intestine. Urgent laparotomy was performed as intestinal ischemia was suspected. There were no findings of intestinal ischemia, but the appendix was discolored with wall thickening. We confirmed a clinical diagnosis of peritonitis caused by gangrenous appendicitis. We performed appendectomy and abdominal drainage. After surgery, the patient needed intensive care for septic shock. He left the ICU 7 days after the surgery and was discharged 10 days later. Conclusion: Thus, appendicitis may cause HPVG.

Vitamin A-coupled liposome system targeting free cholesterol accumulation in hepatic stellate cells offers a beneficial therapeutic strategy for liver fibrosis.

AIM: Liver fibrosis is a life-threatening disorder for which no approved therapy is available. Recently, we reported that mouse hepatic stellate cell (HSC) activation increased free cholesterol (FC) accumulation, partly by enhancing signaling through sterol regulatory element-binding protein 2 (SREBP2) and microRNA-33a (miR-33a), which resulted in HSC sensitization to transforming growth factor-ß (TGFß)-induced activation in a "vicious cycle" of liver fibrosis. METHODS: Human HSCs were isolated from surgical liver specimens from control patients and patients with liver fibrosis. C57BL/6 mice were treated with carbon tetrachloride for 4 weeks and concurrently given SREBP2-siRNA- or anti-miR-33a-bearing vitamin A-coupled liposomes. RESULTS: In human activated HSCs obtained from patients with liver fibrosis, FC accumulation was enhanced independently of serum cholesterol levels through increased signaling by both SREBP2 and miR-33a. This increased FC accumulation enhanced Toll-like receptor 4 (TLR4) protein levels and lowered the TGFß-pseudoreceptor Bambi (bone morphogenetic protein and activin membrane-bound inhibitor) mRNA levels in HSCs. Notably, in a mouse liver fibrosis model, reduction of FC accumulation, specifically in activated HSCs by suppression of SREBP2 or miR-33a expression using SREBP2-siRNA- or anti-miR-33a-bearing vitamin A-coupled liposomes, downregulated TLR4 signaling, increased Bambi expression, and consequently ameliorated liver fibrosis. CONCLUSIONS: Our results suggest that FC accumulation in HSCs, as an intracellular mediator promoting HSC activation, contributes to a vicious cycle of HSC activation in human and mouse liver fibrosis independent of serum cholesterol levels. Targeting FC accumulation-related molecules in HSCs through a vitamin A-coupled liposomal system represents a favorable therapeutic strategy for liver fibrosis.

A case of pneumatosis intestinalis during neoadjuvant chemotherapy with cisplatin and 5-fluorouracil for esophageal cancer†.

Pneumatosis intestinalis (PI) is a relatively rare disease. A 70-year-old man with stage II squamous cell carcinoma of the middle thoracic esophagus was administered cisplatin plus 5-fluorouracil (CF) therapy as neoadjuvant chemotherapy. On Day 14 of the first course of CF therapy, he complained of acute abdominal pain. Computed tomography (CT) revealed PI of the entire colon and a small air bubble in the mesentery. A colonoscopy revealed that there was no finding suggestive of ischemia. Because there was no sign of peritoneal irritation, conservative treatment was selected. On Day 7 after PI diagnosis, CT indicated the disappearance of PI. The patient underwent a radical esophagectomy. Intraoperative laparoscopic findings showed the serosa of the colon to be intact. The patient was discharged without any complications. It is important to take into account that CF therapy may cause PI and that PI can be treated conservatively.