[Locally Advanced Sigmoid Colon Cancer in an Elderly Patient Treated with Curative Resection after Successful Panitumumab Treatment].

An 84-year-old woman had locally advanced sigmoid colon cancer that was unresectable because of deep invasion in the left pelvic wall. Transverse double-barrel colostomy was performed owing to stenosis in the sigmoid colon. The patient's performance status score was 2, and it was difficult to administer cytotoxic chemotherapy. Single-agent panitumumab chemotherapy was initiated. In addition, although S-1 was administered for 4 days in the fourth cycle, it was discontinued owing to drug intolerance. Panitumumab was administered seven times. The tumor size markedly reduced, and sigmoid colectomy was performed. Thus, single-agent panitumumab chemotherapy is a possible treatment option for advanced colorectal cancer in elderly patients.

[A Case of Long-Term Survival of a Patient with Gastric Cancer with Synchronous Liver Metastasis and Portal Vein Thrombus after Multidisciplinary Treatment].

A 77-year-old man was diagnosed with gastric cancer with synchronous single liver metastasis and portal vein thrombus. His HER2 immunohistochemistry tumor score was 3+; therefore, we administered trastuzumab plus capecitabine plus cisplatin. After 2 courses of chemotherapy, we observed disappearance of the portal vein thrombus and tumor reduction as a partial response, according to the RECIST guidelines. We performed distal gastrectomy and right lobectomy; the therapeutic grades of the primary and metastatic tumors were 1a and 2, respectively. We administered postoperative chemotherapy, and no recurrent lesions have appeared 2 years after surgery. Multidisciplinary treatment for gastric cancer with liver metastasis might be a feasible and useful strategy.

Long-Term Outcomes of Self-Expandable Metallic Stents as a Bridge to Surgery for Obstructive and Symptomatic Primary Tumors of Stage IV Colorectal Cancer: A Propensity-Score Analysis.

Background: Self-expandable metallic stent (SEMS) was introduced for the treatment of obstructive colorectal cancer (CRC) a few decades ago. However, its long-term outcomes remain controversial, especially for stage IV CRC. The aim of this study was to clarify the outcomes of SEMS as a "bridge to surgery" (BTS) for obstructive and symptomatic primary tumors in stage IV CRC by one-to-one propensity-score matching. Materials and Methods: This retrospective cohort study was conducted at a single center from January 2007 to December 2017. Patients with obstructive and symptomatic primary tumors of stage IV CRC underwent primary resection (PR) or placement of a SEMS as a BTS. They were divided into SEMS and PR groups, and their short- and long-term outcomes were compared. Results: In total, 52 patients were reviewed (SEMS group, 21; PR group, 31). Sixteen patients in both groups were matched using propensity scores. Patients in the SEMS group more frequently underwent laparoscopic surgery than those in the PR group (75% versus 19%, P = .004). The two groups showed no significant differences in perioperative and pathological outcomes. The 5-year overall survival was not significantly different between groups (29% versus 20%, P = .53). Conclusions: As a BTS, the use of SEMS for obstructive and symptomatic primary tumors in CRC stage IV can be a comparable option to PR in terms of short- and long-term outcomes, and would be less invasive with respect to surgical procedures.

How do magnetic resonance cholangiopancreatography findings predict conversion from laparoscopic cholecystectomy for acute cholecystitis to bailout procedures?

BACKGROUND: Acute cholecystitis is one of the most prevalent surgical abdominal conditions. The Tokyo Guidelines describe the management of acute cholecystitis and recommend bailout procedures for "difficult" cholecystitis cases. This study aimed to identify risk factors for conversion from laparoscopic cholecystectomy to bailout procedures in patients with acute cholecystitis. METHODS: This retrospective cohort study was conducted at a single center between January 2017 and December 2021. Patients who underwent laparoscopic cholecystectomy for acute cholecystitis were enrolled and classified into bailout and non-bailout groups. The patients' characteristics and perioperative data were compared between the 2 groups. RESULTS: In total, 161 patients who underwent laparoscopic cholecystectomy for acute cholecystitis were reviewed. Fourteen were excluded because of a lack of preoperative magnetic resonance cholangiopancreatography; thus, 147 patients were enrolled (bailout group, 21; non-bailout group, 126). Age (74 vs 67 years old; P = .048), days from onset to surgery (3 vs 2 days; P = .02), or defect of cystic duct in magnetic resonance cholangiopancreatography (57% vs 29%; P = .02) were significantly associated with conversion to bailout procedures. In the logistic regression analysis, a defect of the cystic duct in magnetic resonance cholangiopancreatography was an independent predictor for bailout procedures (odds ratio, 2.793; P = .04). CONCLUSION: In this study, defect of the cystic duct in the magnetic resonance cholangiopancreatography can predict conversion to bailout procedures. To the best of our knowledge, this is the first report to describe magnetic resonance cholangiopancreatography finding of the cystic duct as a predictor of surgical difficulty in patients with acute cholecystitis.

Anatomical challenge: a rare coexistence of caecal cancer and isolated duodenal malrotation.

Intestinal malrotation is a congenital anomaly, treated mostly during childhood. A small number of cases are incidentally found in adulthood, during operation for other abdominal diseases, such as colon cancer.Here, we present a case of caecal cancer with isolated duodenal malrotation, a subtype of intestinal malrotation, discovered incidentally during the operation for the cancer. Although the anatomical abnormality made the operation more complicated, laparoscopic resection was safely performed with oncologically adequate lymphadenectomy, owing to intraoperative confirmation of anatomy and careful dissection.

Ptf1a inactivation in adult pancreatic acinar cells causes apoptosis through activation of the endoplasmic reticulum stress pathway.

Pancreas transcription factor 1 subunit alpha (PTF1A) is one of the key regulators in pancreatogenesis. In adults, it transcribes digestive enzymes, but its other functions remain largely unknown. Recent conditional knockout studies using Ptf1aCreER/floxed heterozygous mouse models have found PTF1A contributes to the identity maintenance of acinar cells and prevents tumorigenesis caused by the oncogenic gene Kras. However, Ptf1a heterozygote is known to behave differently from homozygote. To elucidate the effects of Ptf1a homozygous loss, we prepared Elastase-CreERTM; Ptf1afloxed/floxed mice and found that homozygous Ptf1a deletion in adult acinar cells causes severe apoptosis. Electron microscopy revealed endoplasmic reticulum (ER) stress, a known cause of unfolded protein responses (UPR). We confirmed that UPR was upregulated by the activating transcription factor 6 (ATF6) and protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) pathways, but not the inositol requiring enzyme 1 (IRE1) pathway. Furthermore, we detected the expression of CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP), a pro-apoptotic factor, indicating the apoptosis was induced through UPR. Our homozygous model helps clarify the role PTF1A has on the homeostasis and pathogenesis of exocrine pancreas in mice.

Liver-specific Prox1 inactivation causes hepatic injury and glucose intolerance in mice.

Previous reports have revealed that Prospero-related homeobox 1 (Prox1) is required for the migration and differentiation of hepatoblasts during embryonic liver formation. However, the role of Prox1 in adults remains to be elucidated. We created liver-specific Prox1 knockout mice to verify the role of Prox1 in adult hepatocytes. The mutant mice exhibit hepatic injury and a nonobese, insulin-resistant diabetic phenotype in vivo. Hepatocyte injury is observed predominantly in the perivenous region and is characterized by the formation of vacuoles and emergence of round-shaped mitochondria, suggesting that the effect of Prox1 on the maintenance of adult hepatocytes is region dependent. Furthermore, glycolysis is suppressed, and both oxidative phosphorylation and autophagy are upregulated in the livers of Prox1 knockout mice, indicating that Prox1 has a role in regulating energy homeostasis in hepatocytes.

Impact of Sox9 dosage and Hes1-mediated Notch signaling in controlling the plasticity of adult pancreatic duct cells in mice.

In the adult pancreas, there has been a long-standing dispute as to whether stem/precursor populations that retain plasticity to differentiate into endocrine or acinar cell types exist in ducts. We previously reported that adult Sox9-expressing duct cells are sufficiently plastic to supply new acinar cells in Sox9-IRES-CreERT2 knock-in mice. In the present study, using Sox9-IRES-CreERT2 knock-in mice as a model, we aimed to analyze how plasticity is controlled in adult ducts. Adult duct cells in these mice express less Sox9 than do wild-type mice but Hes1 equally. Acinar cell differentiation was accelerated by Hes1 inactivation, but suppressed by NICD induction in adult Sox9-expressing cells. Quantitative analyses showed that Sox9 expression increased with the induction of NICD but did not change with Hes1 inactivation, suggesting that Notch regulates Hes1 and Sox9 in parallel. Taken together, these findings suggest that Hes1-mediated Notch activity determines the plasticity of adult pancreatic duct cells and that there may exist a dosage requirement of Sox9 for keeping the duct cell identity in the adult pancreas. In contrast to the extended capability of acinar cell differentiation by Hes1 inactivation, we obtained no evidence of islet neogenesis from Hes1-depleted duct cells in physiological or PDL-induced injured conditions.