The survival in octogenarians undergoing surgery for pancreatic cancer and its association with the nutritional status.

PURPOSES: This study explored the association between the nutritional status and survival outcomes after pancreatic cancer surgery and reconsidered surgical indications in octogenarians. METHODS: Three hundred and ninety-three consecutive pancreatic cancer patients who underwent resection were analyzed and grouped according to age (< 70 years old; septuagenarians [70-79 years old], and octogenarians [80-89 years old]). The Charlson age comorbidity index and nutritional parameters were recorded. Survival outcomes and their association with nutritional parameters and prognostic factors were examined. RESULTS: The overall survival was worse in the octogenarians than in other patients. The median overall survivals in the < 70 years old group, septuagenarians, and octogenarians were 27.2, 26.4, and 15.3 months, respectively (P = 0.0828). DUPAN-2 ≥ 150 U/mL, borderline resectable/unresectable tumors, blood loss volume ≥ 500 mL, and blood transfusion were predictors of the overall survival among octogenarians. Nutritional parameter values were worse in the octogenarians than in other patients. The octogenarian age group was not an independent predictor of postoperative complications in a univariate analysis. CONCLUSIONS: Survival outcomes were poor in octogenarians. However, an age ≥ 80 years old alone should not be considered a contraindication for pancreatic cancer surgery. The maintenance of perioperative nutritional status is an important factor associated with the survival.

Learning curve of robotic rectal surgery using risk-adjusted cumulative summation: a 5-year institutional experience.

PURPOSE: Outline learning phases of robot-assisted laparoscopic surgery for rectal cancer and compare surgical and clinical outcomes between each phase of robot-assisted laparoscopic surgery and the mastery phase of conventional laparoscopic surgery. METHODS: From 2015 to 2020, 210 patients underwent rectal cancer surgery at Sendai Medical Center. We performed conventional laparoscopic surgery in 110 patients and, laparoscopic surgery in 100 patients. The learning curve was evaluated using the cumulative summation method, risk-adjusted cumulative summation method, and logistic regression analysis. RESULTS: The risk-adjusted cumulative summation learning curve was divided into three phases: phase 1 (cases 1-48), phase 2 (cases 49-80), and phase 3 (cases 81-100). Duration of hospital stay (13.1 days vs. 18.0 days, respectively; p = 0.016) and surgery (209.1 min vs. 249.5 min, respectively; p = 0.045) were significantly shorter in phase 3 of the robot-assisted laparoscopic surgery group than in the conventional laparoscopic surgery group. Blood loss volume was significantly lower in phase 1 of the robot-assisted laparoscopic surgery group than in the conventional laparoscopic surgery group (17.7 ml vs. 79.7 ml, respectively; p = 0.036). The International Prostate Symptom Score was significantly lower in the robot-assisted laparoscopic surgery group (p = 0.0131). CONCLUSIONS: Robot-assisted laparoscopic surgery for rectal cancer was safe and demonstrated better surgical and clinical outcomes, including a shorter hospital stay, less blood loss, and a shorter surgical duration, than conventional laparoscopic surgery. After experience with at least 80 cases, tactile familiarity can be acquired from visual information only (visual haptic feedback). CLINICAL TRIAL REGISTRATION: UMIN reference no. UMIN000019857.

Potential urinary function benefits of initial robotic surgery for rectal cancer in the introductory phase.

We aimed to evaluate the advantages and disadvantages of initial robotic surgery for rectal cancer in the introduction phase. This study retrospectively evaluated patients who underwent initial robotic surgery (n = 36) vs. patients who underwent conventional laparoscopic surgery (n = 95) for rectal cancer. We compared the clinical and pathological characteristics of patients using a propensity score analysis and clarified short-term outcomes, urinary function, and sexual function at the time of robotic surgery introduction. The mean surgical duration was longer in the robot-assisted laparoscopy group compared with the conventional laparoscopy group (288.4 vs. 245.2 min, respectively; p = 0.051). With lateral pelvic lymph node dissection, no significant difference was observed in surgical duration (508.0 min for robot-assisted laparoscopy vs. 480.4 min for conventional laparoscopy; p = 0.595). The length of postoperative hospital stay was significantly shorter in the robot-assisted laparoscopy group compared with the conventional laparoscopy group (15 days vs. 13.0 days, respectively; p = 0.026). Conversion to open surgery was not necessary in either group. The International Prostate Symptom Score was significantly lower in the robot-assisted laparoscopy group compared with the conventional laparoscopy group. Moderate-to-severe symptoms were more frequently observed in the conventional laparoscopy group compared with the robot-assisted laparoscopy group (p = 0.051). Robotic surgery is safe and could improve functional disorder after rectal cancer surgery in the introduction phase. This may depend on the surgeon's experience in performing robotic surgery and strictly confined criteria in Japan.

Transanal total mesorectal excision and transabdominal robotic surgery for rectal cancer: A retrospective study.

BACKGROUND: Transabdominal robotic surgery and transanal total mesorectal excision (TaTME) are newly introduced strategies for rectal cancer. These procedures might have many advantages in rectal cancer treatment in terms of improving oncological and functional outcomes, especially in cases involving advanced cancer or technical difficulty. In the present study, we aimed to clarify the advantages and disadvantages of transabdominal robotic surgery and laparoscopic TaTME as a hybrid surgery for rectal cancer. MATERIALS AND METHODS: We retrospectively evaluated six patients who underwent hybrid surgery for rectal cancer from August 2018 to April 2020. Both clinical and pathological outcomes were assessed. RESULTS: Two patients showed circumferential margin involvement both before and after neoadjuvant therapy. Three patients were planned to undergo hybrid surgery with intersphincteric resection because of a narrow pelvis. One patient was planned to undergo hybrid surgery for a giant tumor of >10 cm. The median length of hospitalization was 17 days. No patients required conversion to an open procedure. All patients underwent formation of defunctioning ileostomies. Two patients had a stapled anastomosis and four had a hand-sewn coloanal anastomosis. Complications included one case of anastomotic leakage, which was managed conservatively with ultrasound- and computed tomography-guided drainage and antibiotics. Histological analysis revealed that all specimens had a negative radial margin and distal margin. The median number of lymph nodes harvested was 17.5. Two patients showed extensive lymph node metastases, including lateral node metastasis. CONCLUSION: Hybrid surgery was performed safely and may improve oncological outcomes for rectal cancer. This technique has many potential benefits and would be alternative option in multimodal strategies for rectal cancer.

Controlling the arterial supply into the pancreatic head region as a whole peripancreatic arterial arcade via a mesenteric approach during isolated pancreatoduodenectomy.

PURPOSE: The peripancreatic arterial system forms various arterial arcades and collateral branches; therefore, it stands to reason that the arterial supply into the pancreatic head region should be controlled as a whole peripancreatic arterial arcade rather than as the three major supplying arteries during isolated pancreatoduodenectomy (PD). We investigated the clinical importance of early control of the whole peripancreatic arterial arcade during PD. METHODS: The subjects of this retrospective study were 63 consecutive patients who underwent PD via a mesenteric approach at our hospital between October, 2014 and February, 2017. The patients were divided into an early control group (n = 27) and a late control group (n = 36) for comparative analysis. RESULTS: The peripancreatic arterial arcades and collateral branches were seen on preoperative multidetector row computed tomography (CT) images and during PD in all 63 patients. The early control group had significantly less intraoperative blood loss than the late control group. Early control of the whole peripancreatic arterial arcade was an independent factor associated with lower intraoperative blood loss in the multivariable analysis (P = 0.012). CONCLUSION: The arterial supply into the pancreatic head region should be controlled as a whole peripancreatic arterial arcade rather than as the three major supplying arteries during isolated PD.

Transanal total mesorectal excision of giant villous tumor of the lower rectum with McKittrick-Wheelock syndrome: a case report of a novel surgical approach.

BACKGROUND: McKittrick-Wheelock syndrome (MKWS) is caused by a villous tumor of the rectosigmoid colon with hypersecretion of mucus containing electrolytes. Complete resection of the tumor is needed to cure this disease. Transanal total mesorectal excision (TaTME) is currently a promising treatment for lower rectal tumor because of the reliability of its resection margin especially in bulky tumor. We present this first case report of a TaTME for MKWS with a lower rectal tumor. CASE PRESENTATION: An 81-year-old woman was admitted to our hospital with diarrhea and acute renal failure. Computed tomography and magnetic resonance imaging examinations revealed an 80-mm-sized enhanced tumor located in her lower rectum without lymph node swelling and distant metastasis. A giant villous tumor secreting mucus was seen in the lower rectum to the anal canal during colonoscopy. The result of tumor biopsy was adenocarcinoma. To preserve the anal function and ensure distal margin, we chose TaTME for curative resection. After improving the electrolyte imbalance, TaTME was performed successfully and R0 resection was achieved. There was no sign of recurrence or electrolyte depletion for 1 year after the surgery. CONCLUSION: TaTME could be a promising surgical approach for giant villous tumor with MKWS in the lower rectum.

Early ligation of the dorsal pancreatic artery with a mesenteric approach reduces intraoperative blood loss during pancreatoduodenectomy.

BACKGROUND: Early ligation of the inferior pancreatoduodenal artery has been advocated to reduce blood loss during pancreatoduodenectomy. However, the impact of early ligation of the dorsal pancreatic artery (DPA) remains unclear. This study was performed to investigate the clinical implications of early ligation of the DPA. METHODS: From October 2014 to April 2017, 34 consecutive patients underwent pancreatoduodenectomy using a mesenteric approach. The patients were divided into the early DPA ligation group (n = 15) and late DPA ligation group (n = 19). The clinical features were retrospectively compared between the two groups (H29-044). RESULTS: Preoperative multidetector row computed tomography and intraoperative findings revealed that the right branch of the DPA supplied the pancreatic head region in all cases. Intraoperative blood loss was significantly lower in the early than late ligation group (median 609 ml [range 94-1,013 ml] vs. 764 ml [range 367-1,828 ml], respectively; P = 0.008). Multivariable analysis revealed that early DPA ligation was independently associated with blood loss (P = 0.023). The DPAs arising from the superior mesenteric artery underwent early ligation at a significantly higher rate. CONCLUSIONS: Early ligation of the DPA during pancreaticoduodenectomy with a mesenteric approach could reduce intraoperative blood loss.

Gastric venous congestion and bleeding in association with total pancreatectomy.

BACKGROUND: Gastric venous congestion and bleeding in association with total pancreatectomy (TP) were evaluated. METHODS: Thirty-eight patients of TP were retrospectively analyzed. TP was classified as TP with distal gastrectomy (TPDG), pylorus-preserving TP (PPTP), subtotal stomach-preserving TP (SSPTP), and TP with segmental duodenectomy (TPSD). RESULTS: Portal vein or superior mesenteric vein resection and reconstruction was performed in 24 patients (62.2%). Gastric bleeding occurred immediately after tumor resection in one of eight patients who underwent SSPTP, and urgent anastomosis between the right gastroepiploic and left ovarian vein stopped the bleeding. Another case of gastric bleeding was observed a few hours after TP in one of nine patients who underwent PPTP, and hemostasis was achieved after conservative therapy. Gastric bleeding was not observed in 16 patients who underwent TPDG and five who underwent TPSD. Some patients underwent preservation of gastric drainage veins (left gastric vein, right gastric vein, or right gastroepiploic vein). Neither patient with bleeding underwent preservation of a gastric drainage vein. CONCLUSIONS: To preserve the subtotal or whole stomach when performing TP, one of the gastric drainage veins should undergo preservation or reconstruction, and anastomosis between the right gastroepiploic vein and left ovarian vein may be beneficial.

Splenic vein reconstruction is unnecessary in pancreatoduodenectomy combined with resection of the superior mesenteric vein-portal vein confluence according to short-term outcomes.

BACKGROUND: Superior mesenteric vein-portal vein confluence resection combined with pancreatoduodenectomy (SMPVrPD) is occasionally required for resection of pancreatic head tumors. It remains unclear whether such situations require splenic vein (SV) reconstruction for decompression of left-sided portal hypertension (LSPH). METHODS: The data from 93 of 104 patients who underwent pancreatoduodenectomy (PD) for pancreatic head malignancies were reviewed. Surgical outcomes in three groups-standard PD (control group), PD combined with vascular resection and SV preservation (SVp group), and SMPVrPD with SV resection (SVr group)-were compared. The influence of division and preservation of the two natural confluences (left gastric vein-portal vein and/or inferior mesenteric vein-SV confluences) on portal hemodynamics were evaluated using three-dimensional computed tomographic portography. RESULTS: No mortality occurred. The morbidity rates were not significantly different among the three groups (18/43, 8/21, and 7/29, respectively; p = 0.306). In the SVr group, three patients had gastric remnant venous congestion, and three had esophageal varices without hemorrhagic potential. No patients had splenomegaly, or severe or prolonged thrombocytopenia. These LSPH-associated findings were less frequently observed when the two confluences were preserved. CONCLUSIONS: SMPVrPD without SV reconstruction can be safely conducted. Additionally, preservation of these two confluences may reduce the risk of LSPH.

Lapatinib sensitivities of two novel trastuzumab-resistant HER2 gene-amplified gastric cancer cell lines.

BACKGROUND: Trastuzumab (Tmab) resistance is a major clinical problem to be resolved in patients with HER2-positive gastric cancers. However, in contrast to the situation for HER2-positive breast cancer lines, the Tmab-resistant gastric cancer preclinical models that are needed to develop a new therapy to overcome this problem are not yet available. METHODS: We developed three new cell lines from HER2 gene-amplified gastric cancer cell lines (GLM-1, GLM-4, NCI N-87) by a new in vivo selection method consisting of the repeated culture of small residual peritoneal metastasis but not subcutaneous tumor after Tmab treatment. We then evaluated the anti-tumor efficacy of lapatinib for these Tmab-resistant cells. RESULTS: We successfully isolated two Tmab-resistant cell lines (GLM1-HerR2(3), GLM4-HerR2) among the three tested cell lines. These resistant cells differed from the parental cells in their flat morphology and rapid growth in vitro, but HER2, P95HER2 expression, and Tmab binding were essentially the same for the parental and resistant cells. MUC4 expression was up- or downregulated depending on the cell line. These resistant cells were still sensitive to lapatinib, similar to the parental cells, in vitro. This growth inhibition of the Tmab-resistant cells by lapatinib was due to both G1 cell-cycle arrest and apoptosis induction via effective blockade of the PI3K/Akt and MAPK pathways. A preclinical study confirmed that the Tmab-resistant tumors are significantly susceptible to lapatinib. CONCLUSION: These results suggest that lapatinib has antitumor activity against the Tmab-resistant gastric cancer cell lines, and that these cell lines are useful for understanding the mechanism of Tmab resistance and for developing a new molecular therapy for Tmab-resistant HER2-positive gastric cancers.

A HIC-5- and KLF4-dependent mechanism transactivates p21(Cip1) in response to anchorage loss.

Anchorage loss elicits a set of responses in cells, such as transcriptional changes, in order to prevent inappropriate cell growth in ectopic environments. However, the mechanisms underlying these responses are poorly understood. In this study, we investigated the transcriptional up-regulation of cyclin-dependent kinase inhibitor p21(Cip1) during anchorage loss, which is important for cell cycle arrest of nonadherent cells in the G1 phase. Up-regulation was mediated by an upstream element, designated as the detachment-responsive element (DRE), that contained Kruppel-like factor 4 (KLF4) and runt-related transcription factor 1 (RUNX1) recognition sites; both of these together were necessary for transactivation, as individually they were insufficient. RNAi experiments revealed that KLF4 and a multidomain adaptor protein, hydrogen peroxide-inducible clone 5 (HIC-5), were critically involved in DRE transactivation. The role of HIC-5 in this mechanism was to tether KLF4 to DNA sites in response to cellular detachment. In addition, further analysis suggested that oligomerization and subsequent nuclear matrix localization of HIC-5, which was accelerated spontaneously in cells during anchorage loss, was assumed to potentiate the scaffolding function of HIC-5 in the nucleus and consequently regulate p21(Cip1) transcription in a manner responding to anchorage loss. At the RUNX1 site, a LIM-only protein, CRP2, imposed negative regulation on transcription, which appeared to be removed by anchorage loss and contributed to increased transcriptional activity of DRE together with regulation at the KLF4 sites. In conclusion, this study revealed a novel transcriptional mechanism that regulated gene expression in a detachment-dependent manner, thereby contributing to anchorage-dependent cell growth.

[A questionnaire survey about hair loss after chemotherapy for breast cancer].

Hair loss is one of the most common side effects of chemotherapies such as FEC and taxane, and it greatly affects quality of life. We conducted a questionnaire survey of breast cancer patients who were treated with adjuvant chemotherapy about their hair loss. Eighty-five patients participated. They all had lost their hair and suffered from persistent changes in their hair condition, ranging from thinning to curly. More than 80% of patients had worn wigs until their hair had grown back. Furthermore, a few patients did not remove their wigs for 2 years after treatment. Unfortunately, there is no prevention or medication to combat hair loss due to chemotherapy at present, so cumulative examinations are awaited. We must provide appropriate information and support to the patient.

Competitive nuclear export of cyclin D1 and Hic-5 regulates anchorage dependence of cell growth and survival.

Anchorage dependence of cell growth and survival is a critical trait that distinguishes nontransformed cells from transformed cells. We demonstrate that anchorage dependence is determined by anchorage-dependent nuclear retention of cyclin D1, which is regulated by the focal adhesion protein, Hic-5, whose CRM1-dependent nuclear export counteracts that of cyclin D1. An adaptor protein, PINCH, interacts with cyclin D1 and Hic-5 and potentially serves as an interface for the competition between cyclin D1 and Hic-5 for CRM1. In nonadherent cells, the nuclear export of Hic-5, which is redox-sensitive, was interrupted due to elevated production of reactive oxygen species, and cyclin D1 was exported from the nucleus. When an Hic-5 mutant that was continuously exported in a reactive oxygen species-insensitive manner was introduced into the cells, cyclin D1 was retained in the nucleus under nonadherent conditions, and a significant population of cells escaped from growth arrest or apoptosis. Interestingly, activated ras achieved predominant cyclin D1 nuclear localization and thus, growth in nonadherent cells. We report a failsafe system for anchorage dependence of cell growth and survival.

Glycosylation of bisphenol A by tobacco BY-2 cells.

Tobacco BY-2 cells in suspension culture absorbed and transformed bisphenol A dissolved in the culture medium. Major products were bisphenol A mono-O-beta D-gentiobioside and the trisaccharide bisphenol A mono-O-beta-D-glucopyranosyl-(1-->4)-[beta-D-glucopyranosyl-(1 --> 6)] beta-D-glucopyranoside. Also produced were the mono- and di- O-beta-D-glucopyranosides. As glycosides of bisphenol A lack the estrogenic activity of the parent compound, these findings enhance the possibilities of phytoremediation of natural waters contaminated by bisphenol A. .

Synthesis and estrogenic activity of bisphenol a mono- and di-beta-D-glucopyranosides, plant metabolites of bisphenol A.

The syntheses and characterization of bisphenol A mono- and di-beta-D-glucopyranosides were undertaken to confirm that these compounds are major plant metabolities of bisphenol A (BPA) and to allow an assessment of their estrogenicity. Synthesis involved the glucosidation of unprotected BPA with glucose penta-acetate with phosphorus oxychloride as catalyst. The estrogenic activity of BPA and its mono- and di-beta-D-glucopyranosides were measured with an enzyme-linked immunosorbent assay (ELISA)-based estrogen receptor competitive binding assay and with a yeast two-hybrid assay adapted to a chemiluminescent reporter gene (for beta-galactosidase). Both methods showed that the estrogenicity of BPA was eliminated by formation of the di-glucoside, but whereas the ELISA-based method indicated that reduced activity remained in the monoglucoside, the yeast two-hybrid method showed the monoglucoside to be inactive. Presumably these results reflect the more complex interactions of test compound and cellular components required to demonstrate estrogenicity in the yeast two-hybrid assay. As these processes parallel those in mammalian cells, the yeast two-hybrid method is likely to be the more realistic assay. The uptake and metabolism of BPA by plants offers the possibility of phytoremediation of contaminated water, but also provides an additional route for the compound to enter the human food chain.