Prognostic Relevance of Primary Tumor Sidedness in Early-stage Colorectal Cancer: An Integrated Analysis of 4 Randomized Controlled Trials (JCOG2003A).

OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.

Risk factors for anastomotic leakage after low anterior resection for obese patients with rectal cancer.

PURPOSE: We aimed to analyze the risk factors for anastomotic leakage (AL) after low anterior resection (LAR) in obese patients (body mass index [BMI] ≥ 25 kg/m2) with rectal cancer. METHODS: Data were collected from four hundred two obese patients who underwent LAR for rectal cancer in 51 institutions. RESULTS: Forty-six (11.4%) patients had clinical AL. The median BMI (27 kg/m2) did not differ between the AL and non-AL groups. In the AL group, comorbid respiratory disease was more common (p = 0.025), and the median tumor size was larger (p = 0.002). The incidence of AL was 11.5% in the open surgery subgroup and 11.4% in the laparoscopic surgery subgroup. Among the patients who underwent open surgery, the AL group showed a male predominance (p = 0.04) in the univariate analysis, but it was not statistically significant in the multivariate analysis. Among the patients who underwent laparoscopic surgery, the AL group included a higher proportion of patients with comorbid respiratory disease (p = 0.003) and larger tumors (p = 0.007). CONCLUSION: Comorbid respiratory disease and tumor size were risk factors for AL in obese patients with rectal cancer. Careful perioperative respiratory management and appropriate selection of surgical procedures are required for obese rectal cancer patients with respiratory diseases.

Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910.

Large-scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted-capture sequencing of 171 potentially colorectal cancer-associated genes was performed, and somatic single-nucleotide variants and insertion-deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra-mutated tumors with POLE mutations. Genes with alterations associated with relapse-free survival were analyzed using multivariable Cox regression models. In all patients (184 right-sided, 350 left-sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%; 14.1% right-sided, 1.4% left-sided). Modest associations were observed: poorer relapse-free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse-free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse-free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse-free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer.

The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial.

OBJECTIVE: This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. BACKGROUND: No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. METHODS: This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3-4, N0-2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. RESULTS: Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%-81.0%] and 76.2% (95% CI 71.9%-80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800- 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. CONCLUSION: The present study failed to confirm the superiority of the no touch.

Risk factors for postoperative pneumonia in elderly patients with colorectal cancer: a sub-analysis of a large, multicenter, case-control study in Japan.

PURPOSE: Postoperative pneumonia affects the length of stay and mortality after surgery in elderly patients with colorectal cancer (CRC). We aimed to determine the risk factors of postoperative pneumonia in elderly patients with CRC, and to evaluate the impact of laparoscopic surgery on elderly patients with CRC. METHODS: We retrospectively investigated 1473 patients ≥ 80 years of age who underwent surgery for stage 0-III CRC between 2003 and 2007. Using a multivariate analysis, we determined the risk factors for pneumonia occurrence from each baseline characteristic. RESULTS: Among all included patients, 26 (1.8%) experienced postoperative pneumonia, and restrictive respiratory impairment, obstructive respiratory impairment, history of cerebrovascular events, and open surgery were determined as risk factors (odds ratio [95% confidence interval], 2.78 [1.22-6.20], 2.71 [1.22-6.30], 3.60 [1.37-8.55], and 3.57 [1.22-15.2], respectively). Furthermore, postoperative pneumonia was more frequently accompanied by increasing cumulative numbers of these risk factors (area under the receiver operating characteristic curve = 0.763). CONCLUSIONS: Laparoscopic surgery may be safely performed in elderly CRC patients, even those with respiratory impairment and a history of cerebrovascular events.

Postoperative Chemoradiotherapy After Local Resection for High-Risk T1 to T2 Low Rectal Cancer: Results of a Single-Arm, Multi-Institutional, Phase II Clinical Trial.

BACKGROUND: After treatment with local excision for TNM stage I low rectal cancer, the risk of local recurrence is not only high for T2 lesions but also for T1 lesions with features of massive invasion to the submucosal layer and/or lymphovascular invasion. OBJECTIVE: The purpose of this study was to determine the efficacy of chemoradiotherapy combined with local excision in the treatment of T1 to T2 low rectal cancer. DESIGN: We conducted a prospective, single-arm, phase II trial. SETTINGS: This was a multicenter study. PATIENTS: From April 2003 to October 2010, 57 patients were treated with local excision after additional external beam irradiation (45 Gy) plus continuous 5-week intravenous injection of 5-fluorouracil (250 mg/m per day) at 10 domestic hospitals. Fifty-three patients had clinical T1N0 lesions, and 4 had T2N0 lesions in the low rectum, located below the peritoneal reflection. MAIN OUTCOMES MEASURES: The primary end point was disease-free survival at 5 years. RESULTS: The completion rate for full-dose chemoradiotherapy was 86% (49/57). Serious, nontransient treatment-related complications were not reported. With a median follow-up of 7.3 years after local excision, the 5-year disease-free survival rate was 94% for the 53 patients with T1 lesions and 75% for the 4 patients with T2 lesions. There were 2 local recurrences during the entire observation period. Anal function after local excision and chemoradiation were kept at almost the same levels as observed before treatment. LIMITATIONS: The study was limited by the small number of registered T2 rectal cancers, retrospective evaluations of quality of life, and the exclusion of poorly differentiated adenocarcinoma (a high-risk feature of T1 lesions). CONCLUSIONS: The addition of chemoradiotherapy to local excision of T1 rectal adenocarcinomas with poor prognostic features including deep submucosal invasion and lymphovascular invasion could improve on less favorable historic oncologic outcomes of local excision alone in this high-risk group for lymph node metastasis. See Video Abstract at http://links.lww.com/DCR/A421.

Incidence of metachronous gastric cancer in the remnant stomach after synchronous multiple cancer surgery.

BACKGROUND: In the preoperative evaluation for gastric cancer, high-resolution endoscopic technologies allow us to detect small accessory lesions. However, it is not known if the gastric remnant after partial gastrectomy for synchronous multiple gastric cancers has a greater risk for metachronous cancer. The purpose of this study was to determine the incidence of metachronous cancer in this patient subset compared with that after solitary cancer surgery. METHODS: Data on a consecutive series of 1,281 patients gastrectomized for early gastric cancer from 1991 to 2007 were analyzed retrospectively. The 715 gastric remnants after distal gastrectomy were periodically surveyed by endoscopic examination in Shikoku Cancer Center. Among those surveyed cases, 642 patients were pathologically diagnosed with solitary lesion (SO group) and 73 patients with synchronous multiple lesions (MU group) at the time of the initial surgery. RESULTS: In the follow-up period, 15 patients in the SO group and 3 patients in the MU group were diagnosed as having metachronous cancer in the gastric remnant. The cumulative 4-year incidence rate was 1.9 % in the SO group and 5.5 % in the MU group. The difference did not reach the significant level by the log-rank test. CONCLUSIONS: The incidence of metachronous cancer is higher after multiple cancer surgery; however, the difference is not statistically significant.

Hand-sewn anastomotic technique after esophageal cancer resection.

BACKGROUND/AIMS: Mechanical stapled anastomosis can be performed easily and quickly in esophagogastrostomy after esophageal cancer resection. However, we have performed cervical hand-sewn anastomosis in the esophagogastrostomy. Here we introduce the surgical technique and report the outcomes after the anastomosis. METHODOLOGY: The gastric tube is pulled up via the posterior mediastinal route. A single layer of Gambee sutures is used to approximate the cervical esophagus and the posterior wall of the gastric tube in end-to-side fashion. After the anastomosis, the redundant part in the gastric tube apex is removed. We analyzed 152 consecutive patients who underwent this anastomosis in our institute from 1999 to 2012. RESULTS: There was no postoperative mortality. We experienced anastomotic leakage in 7 patients (5%) and anastomotic stenosis in 5 patients (3%). CONCLUSIONS: The anastomotic complication rates in the hand-sewn anastomosis were comparable to those of the mechanical stapled anastomosis in the previous reports.

Long-term outcome after proximal gastrectomy with jejunal interposition for gastric cancer compared with total gastrectomy.

BACKGROUND: Proximal gastrectomy (PG) has been widely accepted as treatment for early gastric cancer located in the upper third of the stomach. Reconstruction by jejunal interposition has been known to reduce reflux esophagitis for PG patients. The aim of this study was to compare the long-term outcomes of patients who underwent PG with jejunal interposition with those treated by total gastrectomy (TG). METHODS: Data on 102 cases of PG with jejunal interposition and 49 cases of TG with Roux-Y reconstruction for gastric cancer were analyzed retrospectively in terms of overall survival, weight maintenance, anemia and nutritional status, and endoscopic findings. RESULTS: Median follow-up time was 59 months in the both groups. There was no significant difference in the overall 5-year survival rate between the PG group (94%) and the TG group (84%). The PG group showed significantly better body weight maintenance at the first year. The laboratory blood tests showed that the PG group had a significantly better red blood cell count and hemoglobin and hematocrit levels at the second and third year. However, postoperative endoscopic surveillance detected reflux esophagitis (3%), peptic ulcer (9%), and metachronous gastric cancer (5%) in the PG group. CONCLUSIONS: Proximal gastrectomy maintains comparable oncological radicality to TG and is preferred over TG in terms of preventing postoperative anemia. However, periodic endoscopic follow-up is necessary to monitor the upper gastrointestinal tract.

[A case of reversible encephalopathy syndrome caused by hyponatremia during neoadjuvant 5-FU+CDDP therapy for esophageal cancer].

We present a case of reversible encephalopathy syndrome caused by hyponatremia during neoadjuvant chemotherapy with 5-FU+CDDP for esophageal cancer. A 52-year-old woman visited another hospital with the complaint of discomfort during swallowing. Upper gastrointestinal endoscopy revealed an ulcerated lesion in the lower thoracic esophagus, which was pathologically diagnosed as squamous cell carcinoma. She was admitted to our institution, and the diagnosis of esophageal cancer Mt-Lt, type 2, cT2N1M0, stage II was made. We obtained informed consent for her treatment with both CRT and surgery, and she selected surgery. Therefore, she was administered neoadjuvant chemotherapy with 5-FU+CDDP therapy. On day 4, abnormalities of the central nerve, such as unconsciousness, difficulty in speaking, and muscle cramps were, observed. After the examinations she was diagnosed with encephalopathy. It should be noted that hyponatremia induced by renal sodium wasting syndrome(RSWS)was considerd to be the cause, and we report our case with the literature cited.

Surgical resection of a retroperitoneal liposarcoma producing insulin-like growth factor II: a case report.

BACKGROUND: Tumor-produced high molecular weight insulin-like growth factor-II (big insulin-like growth factor-II) is considered to cause non-islet cell tumor hypoglycemia. This paper presents a case of surgically resected retroperitoneal liposarcoma that produced big insulin-like growth factor-II. CASE PRESENTATION: Here, we report the case of a 62-year-old woman who presented with an abdominal mass and hypoglycemia. Non-islet cell tumor hypoglycemia due to retroperitoneal liposarcoma was suspected. After complete resection of the tumor, the patient's hypoglycemia improved and big insulin-like growth factor-II disappeared in the molecular weight analysis of serum insulin-like growth factor-II by western blotting. The patient had no tumor recurrence or reappearance of hypoglycemia 16 months after the operation without any adjuvant therapy. CONCLUSIONS: Although insulin-like growth factor-II-producing tumors are generally large and difficult to operate on, surgical resection is currently the most effective and only treatment; thus, it is essential to attempt resection aggressively.

Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial.

PURPOSE: Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS: In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS: Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided P = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration. CONCLUSION: DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.

Risk factors for surgical site infection and association of surgical site infection with survival of lower rectal cancer patients without clinical lateral pelvic lymph node metastasis (clinical Stage II/III): Analysis of data from JCOG0212.

This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 [95% Confidence interval: 0.36-0.93] for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 [1.03-4.86] for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 [1.03-2.68]). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.

Rare squamous cell carcinoma arising from a presacral epidermoid cyst: A case report.

INTRODUCTION: Presacral epidermoid cysts are uncommon, usually benign cysts caused by developmental abnormalities in the fetal period. We present a rare case of squamous cell carcinoma arising from a presacral epidermoid cyst. PRESENTATION OF CASE: A 59-year-old woman complained of tenesmus and discomfort in the buttocks. Computed tomography revealed a 50-mm well-defined cystic mass in the presacrum and a 70-mm solid mass extending from the cyst into the rectum, vagina, and left sciatic spine. On T1-weighted magnetic resonance images, the cyst was unilocular and the mass was marginated with low intensity. On T2-weighted images, the mass had high intensity. A malignant presacral developmental cyst was diagnosed, without obvious metastasis. Using abdominal and parasacral approaches, Hartmann's operation was performed with multiorgan resection, including the sacrum, coccyx, left sciatic spine, internal obturator muscle, rectum, and uterine appendage. Histopathology of the excised specimen revealed a squamous cell carcinoma originating from the presacral epidermoid cyst. DISCUSSION: Reports of malignant transformation of epidermoid cysts in the presacral space, as in the present case, are extremely rare. Because of their unusual location and slow growth, epidermoid cysts tend to remain asymptomatic. Because the patient had a malignant tumor with suspected invasion of adjacent organs, combination surgery was selected. CONCLUSION: Although further research is required, presacral epidermoid cysts are extremely rare and may be malignant. Thorough preoperative image evaluation is crucial for complete resection.

Primary extranodal non-Hodgkin's lymphoma of the common bile duct manifesting as obstructive jaundice: report of a case.

Primary non-Hodgkin's lymphoma (NHL) of the common bile duct (CBD) manifesting as obstructive jaundice is extremely rare: to our knowledge, only 22 cases of primary NHL arising from the CBD have been reported. The patient in this case report was a 63-year-old man who presented with obstructive jaundice. Abdominal sonography, positron emission tomography, and computed tomography showed a mass with abnormal 18-fluorodeoxyglucose uptake in pancreatic head. Magnetic resonance cholangiopancreatography demonstrated a strictured segment of the CBD with proximal bile duct dilatation. We performed pancreaticoduodenectomy for a presumptive diagnosis of pancreatic head carcinoma or cholangiocarcinoma of the CBD. However, the histological diagnosis was a primary, diffuse, large B-cell lymphoma of the CBD. He received three courses of combination chemotherapy, including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The patient remains well, without evidence of tumor recurrence, 8 months after surgery. In summary, primary NHL of the CBD, despite its rarity, should be considered in the differential diagnosis of obstructive jaundice. An accurate histopathologic diagnosis and complete surgical resection, followed by combination chemotherapy plus rituximab may be effective.

Randomized phase III trial comparing surgery alone to UFT + PSK for stage II rectal cancer (JFMC38 trial).

BACKGROUND: We conducted a randomized phase III trial comparing tegafur/uracil (UFT) and Polysaccharide-K (PSK) to surgery alone in curatively resected stage II rectal cancer patients. METHODS: Patients were randomly assigned to receive either UFT and PSK or surgery alone in a 1:1 ratio with a minimization method to balance the treatment allocation. The primary end point of this study was the disease-free survival (DFS). The secondary end point was the overall survival (OS). RESULTS: From October 2011 to February 2013, 111 patients were registered from 62 institutions. The study was prematurely closed due to poor accrual after reaching 20% of its goal. The patients' characteristics were similar between the UFT and PSK group and the surgery-alone group. The DFS rate was 76.0% at 3 years and 65.1% at 5 years in the UFT and PSK arm and 84.0% at 3 years and 77.2% at 5 years in the surgery-alone arm. The DFS was slightly worse in the UFT + PSK arm than in the surgery-alone arm, but the difference did not reach statistical significance (log rank p = 0.102). The OS rate was 100% at 3 years and 97.9% at 5 years in the UFT + PSK arm, while that was 100% at 3 years and 93.4% at 5 years in the surgery-alone arm. The OS was similar in the UFT + PSK arm and surgery-alone arm (p = 0.533). CONCLUSION: The present study suggests that UFT and PSK are not attractive candidates to advance to the next phase III study because the DFS was slightly worse in the UFT and PSK arm than in the surgery-alone arm.

Local control of sphincter-preserving procedures and abdominoperineal resection for locally advanced low rectal cancer: Propensity score matched analysis.

Sphincter-preserving procedures (SPPs) for surgical treatment of low-lying rectal tumors have advanced considerably. However, their oncological safety for locally advanced low rectal cancer compared with abdominoperineal resection (APR) is contentious. We retrospectively analyzed cohort data of 1500 consecutive patients who underwent elective resection for stage II-III rectal cancer between 2010 and 2011. Patients with tumors 2-5 cm from the anal verge and clinical stage T3-4 were eligible. Primary outcome was 3-year local recurrence rate, and confounding effects were minimized by propensity score matching. The study involved 794 patients (456 SPPs and 338 APR). Before matching, candidates for APR were more likely to have lower and advanced lesions, whereas SPPs were carried out more often following preoperative treatment, by laparoscopic approach, and at institutions with higher case volume. After matching, 398 patients (199 each for SPPs and APR) were included in the analysis sample. Postoperative morbidity was similar between the SPPs and APR groups (38% vs 39%; RR 0.98, 95% CI 0.77-1.27). Margin involvement was present in eight patients in the SPPs group (one and seven at the distal and radial margins, respectively) and in 12 patients in the APR group. No difference in 3-year local recurrence rate was noted between the two groups (11% vs 14%; HR 0.77, 95% CI 0.42-1.41). In this observational study, comparability was ensured by adjusting for possible confounding factors. Our results suggest that SPPs and APR for locally advanced low rectal cancer have demonstrably equivalent oncological local control.

[First report of malignant hyperthermia which occurred during laparoscopic surgery in Japan in a patient with typical family history].

We experienced a case of fulminant malignant hyperthermia during laparoscopic surgery, which is the first reported case of this kind. A 69-year-old man, weighing 69 kg, underwent laparoscopic colectomy for cecal colon cancer. He had a remarkable familial history of malignant hyperthermia (MH). His uncle had MH from enflurane. In addition, 6 male relatives died at operation, exercise or drinking. However, he hid it intentionally because of social concern about inheriting abnormal genes and of inadequate explanation from medical personnel. Anesthesia was induced with fentanyl 100 microg, propofol 60 mg and vecuronium 9 mg intravenousely and maintained with nitrous oxide, oxygen and sevoflurane. About 120 min after the induction of anesthesia (50 min after pneumoperitoneum), PETCO2 increased to 54 mmHg. Thirty min later, body temperature (BT), heart rate (HR), PETCO2 and airway pressure (Paw) increased rapidly to 37.5 degrees C, 92 beats x min(-1), 62 mmHg and 3/33 cmH2O, respectively. The diagnosis of MH was made. The inspiratory gas was changed to 100% O2, and a bolus of 100 mg dantrolene was given. He had BT of 39.7 degrees C, HR of 152 beats x min(-1), PETCO2 of 123 mmHg, Paw of 3/40 cmH2O at the worst point. Rise in Paw and arrhythmia turned up frequently as complications of laparoscopic surgery, but they are very similar to the first symptoms of malignant hyperthermia. The decrease in BT with CO2 pneumoperitoneum can mask symptoms of MH. Awareness of this fact is important not to delay the diagnosis.

Port site recurrence diagnosed by positron emission tomography after laparoscopic surgery for colon cancer.

Port site recurrence after laparoscopic surgery for colorectal cancer patients is a rare complication. We report a case of port site recurrence in a 46-year-old woman that was detected by positron emission tomography (PET) using 18[F]-fluoro-deoxyglucose (FDG). Surgical treatment consisted of laparoscopic ileo-cecal resection and lymph node dissection. At her nine months postoperative follow-up examination, her serum carcinoembryonic antigen (CEA) levels had raised to 15.8ng/mL. Although computed tomography and colonoscopic examination were performed, lung, liver and local recurrence in the colon were not detected. FDG-PET was then performed and detected a higher concentration of FDG at the port site in the abdominal wall. Port site recurrence was diagnosed clinically and surgical resection of tumor at the port site was performed. Pathology revealed a moderately differentiated adenocarcinoma diagnosed as port site recurrence. This case suggests that FDG-PET is an important examination for the detection of port site recurrence when serum CEA levels are rising and routinely radiographic examinations are unable to detect the site of recurrence.

Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas.

The p57KIP2 gene belongs to the Cip/Kip family of CDK inhibitors and has been demonstrated to be a tumor suppressor gene, being inactivated in various types of human cancers. We analyzed the methylation and expression status of p57KIP2 in lung and breast cancers, and in malignant mesotheliomas (MMs). The promoter region of p57KIP2 was determined by methylation-specific PCR (MSP) in samples of lung and breast cancer, and of MM. The expression of the gene in the cell lines was determined by RT-PCR and correlated with the methylation status. Aberrant methylation was detected by MSP in 9 of 27 (33%) and 25 of 78 (32%) lung cancer cell lines and tumors, respectively, 11 of 18 (61%) and 17 of 38 (45%) breast cancer cell lines and tumors, respectively, and 1 of 25 (4%) MM tumors. DNA methylation was detected but rarely in the corresponding non-malignant tissues. In addition, the gene expression was restored in the methylated cell lines following 5-aza-2'-deoxycytidine treatment, confirming that the methylation was indeed responsible for the gene down-regulation. We also examined the relationship between the p57KIP2 methylation status and the clinicopathological features of the primary tumors, and found that there was no relationship between the p57KIP2 methylation status and any of the examined clinicopathological features. In summary, our results demonstrate that p57KIP2 methylation associated with the gene down-regulation is frequently present in lung and breast cancers and plays an important role at the molecular level in the pathogenesis of these cancers.