Output-limiting symptoms induced by radiofrequency hyperthermia. Are they predictable?

BACKGROUND: During radiofrequency (RF) hyperthermia treatment, hot-spot phenomena may occur and prevent treatment continuation if the output is not lowered. We previously reported a significant correlation between the initial energy output at which output-limiting symptoms occurred and patient status. Patients with a complete clinical response had significantly increased temperature, while some patients with partial clinical response and stable disease had increased temperature, depending on the occurrence of output-limiting symptoms. To predict the initial energy output at which output-limiting symptoms occur, we performed multiple regression analysis with the parameters of patients' physical status. MATERIALS AND METHODS: Hyperthermia alone or concomitant with chemotherapy and/or radiotherapy was applied in 62 patients with malignant disease for a total of 310 treatments with a Thermotron RF-8 between December 2011 and April 2014. RESULTS: No output-limiting symptoms were shown in 65.5% of 310 treatments. Pain (29.7%), micturition desire (1.9%), skin discomfort (0.6%), subcutaneous induration (1.6%), cold sensation (0.6%), and nausea (0.3%) were reported in the 310 treatments. A good predictive equation for initial energy output at which output-limiting symptoms occur was determined with two parameters, initial time of an output-limiting symptom onset, and thickness of the fat of the abdominal wall. Multiple regression analysis showed an adjusted R(2 )= 0.99 and variance inflation factor < 2. CONCLUSIONS: We present a good predictive equation for initial energy output at which output-limiting symptoms occur. It is critical to prevent RF hyperthermia-induced output-limiting symptoms and establish new prevention strategies.

Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients.

BACKGROUND: Imatinib mesylate, a small-molecule tyrosine kinase inhibitor, is currently used for adjuvant therapy of patients who have undergone resection of high-risk gastrointestinal stromal tumors (GISTs). There are no data concerning the efficacy and safety of postoperative adjuvant therapy with imatinib for Japanese or East Asian patients with GIST. METHODS: A single-arm, open-label, multicenter trial was conducted in 17 hospitals in Japan. The eligibility criteria included histologically proven primary high-risk GISTs with macroscopic complete resection. Patients were treated with imatinib at a dose of 400 mg/day for 1 year after surgery. The primary endpoint was recurrence-free survival as assessed by Kaplan-Meier analysis. The secondary endpoints were overall survival and safety. This study was registered with ClinicalTrials.gov, number NCT00171977. RESULTS: A total of 64 patients were enrolled between September 2004 and July 2006. The median age of the patients was 59.5 years. Forty-nine (76.6%) patients completed the 1-year treatment, whereas 15 (23.4%) patients did not complete the treatment owing to recurrence, toxicities, and consent withdrawal. At the median follow-up period of 109 weeks, 20 patients had recurrence. The 3-year recurrence rate was 42.7% (95% confidence interval 29.2-56.3%), which exceeded the expected recurrence rate in this trial. The recurrence-free and overall survival rates at 2 years were 71.1 and 93.7%, respectively. The most frequent adverse drug reaction of any grade was eyelid edema (48.4%), followed by neutropenia (40.6%), leukopenia (39.1%), nausea (39.1%), rash (37.5%), and peripheral edema (37.5%), most of which were mild and manageable. CONCLUSIONS: Adjuvant therapy with imatinib at 400 mg/day for 1 year is well tolerated by Japanese patients and possibly reduces the risk of early recurrence of high-risk GISTs.

An annular pancreas associated with carcinoma of the papilla of Vater: report of a case.

An annular pancreas is an uncommon congenital anomaly that usually presents early in childhood. Malignancy in the setting of an annular pancreas is unusual. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 59-year-old man presented with epigastric discomfort and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla of Vater. Preoperative imaging showed the pancreatic parenchyma encircling the descending duodenum and a tumor at the papilla of Vater. A pancreaticoduodenectomy was performed for the annular pancreas and the ampullary tumor. Histological examination confirmed a complete annular pancreas and carcinoma in situ of the papilla of Vater. We also provide a review of the reported cases of an annular pancreas with periampullary neoplasms and discuss the clinical characteristics of this anomaly.

Prognostic significance of morphological distribution of metastatic foci in lymph nodes with gastric cancer.

BACKGROUND/AIMS: The morphological distribution of tumor cells in metastatic lymph nodes has been investigated in positive sentinel lymph nodes in several solid cancers. The aim of this study was to clarify the effect of the distribution of metastatic foci in lymph nodes on the prognosis in gastric cancer. METHODS: The distribution of metastatic foci in the 100 node-positive patients who had undergone curative gastrectomy were classified into two groups: (1) massive type, in which the tumor occupied the entire lymph node, and (2) non-massive type, in which the tumor did not occupy the entire lymph node. RESULTS: There were 38 patients in the massive type group and 62 patients in the non-massive type group. The 10-year survival rate was significantly poorer in the massive type group (p = 0.001). Multivariate analysis showed that distributional type and nodal status were independent prognostic factors. UICC N stage was subcategorized by distributional type, and survival was shown to be significantly worse in the massive type in the N1 group (p = 0.035). CONCLUSION: It seems necessary to take the morphological distribution of metastatic foci into consideration when dealing with node-positive patients who had received curative resection for gastric cancer.

Nonfunctioning pancreatic endocrine tumor with extension into the main pancreatic duct: report of a case.

Pancreatic endocrine tumors (PETs) rarely involve the main pancreatic duct. We report a case of malignant nonfunctioning pancreatic endocrine tumor (NFPET) with prevalent intraductal growth. A 47-year-old woman was referred to us after ultrasonography at a routine health check showed diffuse swelling of the pancreas. Preoperative imaging showed a solid mass in the tail of the pancreas and a bulging intraductal mass in the main pancreatic duct. We performed total pancreatectomy because the tumor occupied almost the entire lumen of the main pancreatic duct. Histological examination confirmed well-differentiated endocrine carcinoma. We review reported cases of the intraductal growth of NFPETs and discuss the pathogenesis of these unusual tumors.

Endoscopic balloon dilation for obstructive colorectal cancer: a basic study on morphologic and pathologic features associated with perforation.

BACKGROUND: The use of endoscopic dilation and a self-expandable stent for colorectal cancer (CRC) presenting with a stricture or obstruction, either prior to surgery or as a palliative measure (an alternative to colostomy), causes perforation with relative high incidence (1%-17%). OBJECTIVE: To experimentally investigate risk factors associated with perforation in excised CRC specimens. DESIGN: Experimental study. SETTING: Ex vivo experiment on freshly excised human colon cancer specimens at an academic hospital. PATIENTS: This study involved 47 patients with strictured CRCs of <15 mm in internal diameter as assessed by a preoperative contrast enema. INTERVENTION: Immediately after surgical resection, a balloon with a diameter of 18 mm was placed in the stricture. The balloon was inflated slowly with hydrostatic pressure over 1 minute and kept at the maximum diameter for 1 minute. MAIN OUTCOME MEASUREMENTS: Correlations between macroscopic perforation and 20 items, including morphological and histopathological characteristics. RESULTS: Perforation occurred in 8 of 47 (17.0%) CRC specimens. Four items showed statistically significant (P < .05) correlations with perforation: peritumoral proliferation of collagen fibers (relative area > or =23.9% in the visual field), annularity of the tumor, severe stricture (<7.9 mm), and fewer residual smooth muscle cells in the muscularis propria, reflecting tumor encroachment. The best predictor of perforation was a combination of severe stricture and pronounced peritumoral proliferation of collagen fibers. LIMITATIONS: An uncontrolled study with a small number of patients. CONCLUSION: Histopathological and morphological items associated with a decrease in elastic compliance were more important as predictors of perforation than dilation procedure parameters, such as balloon pressure.

Impact of difference in the definition of extranodal spread on the outcome of node-positive patients with gastric cancer.

PURPOSE: Previous studies have reported that extranodal spread is a prognostic factor in patients with several solid cancers. However, the definition of extranodal spread varies with the reporting investigator and has not been standardized yet. Therefore, we selected several widely used definitions from previous reports and comparatively assessed the clinicopathologic significance of these definitions. METHODS: Extranodal spread in the 103 node-positive patients who had received curative resections for gastric cancer was classified into two groups, viz., (a) capsule rupture, where cancer cells infiltrated into the perinodal fatty tissue beyond the capsule of the involved lymph node, and (b) no capsule rupture, where nests of cancer cells were detected demonstrable in adjacent tissues around the metastatic lymph node without rupture of the capsule. RESULTS: Sixty-five (63.1%) of the 103 patients showed extranodal spread. Of the 65 patients, 50 patients showed the capsule rupture type and 15 showed the no capsule rupture type of extranodal spread. The 5-year survival rate was significantly poorer in the capsule rupture group as compared with that in the no capsule rupture group and extranodal spread-negative group (P < 0.05 and P < 0.01, respectively). In regard to the mode of recurrence, the rate of peritoneal recurrence was significantly higher in the capsule rupture group (P < 0.01). CONCLUSIONS: In the assessment of patients with extranodal spread, it is considered important to classify the patients based on the status of extranodal spread into the capsule rupture group and no capsule rupture group.

Subclassification of extranodal involvement in gastric cancer patients.

BACKGROUND/AIMS: Extranodal involvement (Ex) has been shown as a negative prognostic factor in several cancers. We classified Ex using 3 methods for gastric cancer and evaluated its influence on patient outcome. METHODOLOGY: The status of Ex in the 103 node-positive patients with curative resection was classified according to: 1) the number of lymph nodes with Ex, 2) the lymph node grouping system, as specified by the Japanese Classification of Gastric Carcinoma, into Ex confined to compartment 1 lymph nodes and Ex detected in compartment 2 and 3 lymph nodes, and 3) the histological type of tumor cells detected in extranodal metastatic sites. RESULTS: Ex was observed in 65 of the 103 patients. An increase in the number of lymph nodes with Ex was associated with a significantly poorer outcome. Patients with Ex detected in compartment 2 and 3 lymph nodes had a significantly poorer outcome. The survival rate of patients with two or more histological types was significantly poorer. Multivariate analysis showed that the method 1) and 2) were independent prognostic factors. CONCLUSIONS: The degree of Ex was shown to be important for determining the prognosis of node-positive gastric cancer patients with curative resection.

Endoscopy-assisted gastric resection: a safe and reliable procedure for tumor clearance during laparoscopic high distal or proximal gastrectomy.

BACKGROUND: Preoperative endoscopic tattooing or clipping is generally used to delineate the tumor-free margin in surgery for early gastric cancer. However, it is sometimes difficult to identify the line of resection during laparoscopic gastrectomy. METHODS: Between June 2003 and February 2008, we performed a total of 12 endoscopy-assisted gastric resections during laparoscopic gastrectomy for cancer, including four cases of high distal gastrectomy and eight cases of proximal gastrectomy. In the laparoscopic high distal gastrectomy cases, a surgeon performed transduodenal endoscopy to identify the clips before gastric resection. For totally laparoscopic proximal gastrectomy, an endoscopist performed transoral endoscopy to identify the clips placed in the distal margin of the lesion and to facilitate intracorporeal anastomosis. RESULTS: In all cases, we were able to observe clips as well as the primary lesion. Gastric resection was successfully performed with no positive margin. In the high distal gastrectomy group (n = 4), proximal and distal margins were 19.5 +/- 2.1 (range, 10-35) mm and 1,185 +/- 190.9 (range, 850-1,320) mm, respectively. In the proximal gastrectomy group (n = 8), proximal and distal margins were 21.3 +/- 7.1 (range, 5-38) mm and 47.5 +/- 3.5 (range, 15-75) mm, respectively. The intracorporeal side-to-side anastomosis during proximal gastrectomy was successfully performed using an endolinear stapler. CONCLUSIONS: Endoscopy-assisted gastric resection is a safe and reliable procedure for tumor clearance during laparoscopic high distal or proximal gastrectomy.

Laparoscopy-assisted combined resection for synchronous gastric and colorectal cancer: report of three cases.

In gastric cancer patients, the most common form of synchronous cancer is colorectal cancer. To reduce the invasiveness of the resection, a laparoscopy-assisted combined resection was performed in three patients with synchronous gastric and colorectal cancer. Although all gastric lesions were in the early stages, two colorectal lesions were advanced cases. In all cases, the laparoscopic gastric resection and reconstruction was performed first, followed by the colorectal resection. In the case of right-side colon cancer in addition to gastric cancer, it was relatively easy to perform the combined resection with lymph node dissection sharing the same ports used for the gastrectomy, although we needed an additional port. In one case, in which rectal cancer was present in addition to gastric cancer located in the upper portion of the stomach, a totally laparoscopic proximal gastrectomy was combined with a laparoscopy-assisted low anterior resection, leaving only a lower abdominal minilaparotomy wound. All patients quickly returned to normal activity without remarkable complications, with the exception of a wound infection in one patient. With a mean follow-up of 30.7 months, all patients survived without any sign of recurrence. This procedure represents a feasible option for minimally invasive treatment of synchronous gastric and colorectal cancer.

Clinical outcome of jejunal pouch double-tract reconstruction after total gastrectomy.

BACKGROUND/AIMS: The importance of the duodenal passage and the need for pouch reconstruction after total gastrectomy are matters of controversy. METHODOLOGY: Twenty consecutive patients with early gastric cancer were studied 20who underwent jejunal pouch double-tract (JPD) reconstruction after total gastrectomy. Nutritional variables were examined for > or =10 years postoperatively. RESULTS: The mean operation time was 204 minutes. There was no anastomotic leakage and no hospital mortality. Anastomotic stenosis between the esophagus and a jejunal pouch developed in 2 patients (10%), and reflux esophagitis was observed in 4 (20%). Symptoms were controlled by conserva tive treatment within 3 years after surgery. Body mass indices in all patients were significantly decreased from 1 month (p<0.05) to 10 years (p<0.005) after the operation. The mean body weight decrease occurring during the first to the tenth postoperative year was 12.7% overall, but 17.8% and 9.1% in patients aged > or =60 years and <60 years, respectively. The body weight decreases from 3 (p<0.05) to 6 (p<0.01), and at 9 years (p<0.01) were significantly lower before 60 years of age than after. CONCLUSIONS: JPD reconstruction facilitates long-term recovery of body weight after total gastrectomy and should be considered before the aged of 60.

The first thermic treatment predicts following chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer.

The present study aimed to evaluate whether the neoadjuvant chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer can be predicted following the first thermic treatment. Eighty patients with primary rectal adenocarcinoma (≤12 cm from the anal verge) were included in this study. Fifty-four received surgery and pathological response was evaluated. Intensity-modulated radiotherapy was administered conventionally once daily 5 times/week. Neoadjuvant radiotherapy consisted of 50 Gy delivered to the planning target volume in 25 fractions. Concurrent neoadjuvant chemotherapy was delivered in 5-day courses. Capecitabine was administered orally at 1,700 mg/m2/day for 5 days/week. Thermic treatment was performed using the Thermotron-RF 8 and administered once/week for 5 weeks with 50 min irradiation. Patients with a gross tumor volume (GTV) ≤32 cm3 and a radiofrequency (RF) output difference (RO difference) ≥77 Watt/min exhibited pathological complete response (pCR) and CR rates of 50 and 75%, respectively. Those with a GTV ≥80 cm3 and a RO difference ≥77 Watt/min exhibited pCR and CR rates of 42.9 and 42.9%, respectively. The changes in the skin temperature during RF treatment in patients with pCR with a RO difference ≥77 Watt/min increased significantly compared with those of other outcomes, and progressive disease. These data suggest a strategy for predicting which patients will respond best following the first thermic treatment. The results identified that the group of patients with a GTV ≤32 cm3 and a RO difference ≥77 Watt/min (outputable/heatable patients) may respond best.

SUVmax-based Parameters of FDG-PET/CT Reliably Predict Pathologic Complete Response After Preoperative Hyperthermo-chemoradiotherapy in Rectal Cancer.

BACKGROUND/AIM: To determine the most reliable predictor for pathologic complete response (pCR) in patients who underwent preoperative chemoradiotherapy and regional hyperthermia (HCRT) for rectal cancer. PATIENTS AND METHODS: Thirty-six patients were enrolled. The local control status of the patients was assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), magnetic resonance imaging (MRI), and colonoscopy before and after HCRT. The relationships between various parameters of these clinical examinations and pCR were analyzed. RESULTS: Ten (28%) patients achieved pCR. The accuracies of predicting pCR using FDG-PET/CT, MRI, and colonoscopy were 78%, 61%, and 75%, respectively. FDG-PET/CT was the only independent predictive modality for pCR (p=0.021). The maximum standardized uptake value (SUVmax) and SUVmax normalized to liver uptake (SLR) after HCRT showed the highest sensitivity (90%) and the decreasing rate of SUVmax and SLR demonstrated the highest specificity (89%) for pCR. CONCLUSION: SUVmax-based parameters of FDG-PET/CT after HCRT were the most reliable predictors for pCR.

New method of jejunal pouch reconstruction after selective vagotomy and antrectomy.

Selective vagotomy and antrectomy (SV-A) is performed as a surgical treatment in patients with pyloric stenosis due to peptic ulcer. Since this method shows that the incidence of postoperative complaints is not low, various reconstruction methods have been evaluated to prevent the sequelae. However, there have been no definitely useful methods. A jejunal pouch reconstruction used for gastric cancer surgery has been performed to compensate for the disadvantages of SV-A in 7 patients with complicated gastric, duodenal ulcers at this study. A 10- to 15-cm-long pouch is interposed between the remnant stomach and the duodenum. The pouch is anastomosed to the duodenum using the double tract method. The median postoperative follow-up period was 61 months. No patients showed gastric stasis, ulcer recurrence, residual gastritis. We demonstrated the method of jejunal pouch double tract reconstruction after SV-A. This method was useful for preventing the sequelae after SV-A.

Chemoradiotherapy and concurrent radiofrequency thermal therapy to treat primary rectal cancer and prediction of treatment responses.

The present study aimed to evaluate a previously reported predictive formula of output-limiting symptoms induced by radiofrequency (RF) to determine the efficacy of this neoadjuvant chemoradiation (NACR) and concurrent RF thermal therapy. The present study included 81 consecutive patients with confirmed diagnoses of rectal adenocarcinoma that was localized in the mid-low rectum (up to 12 cm from the anal verge) who received NACR [intensity-modulated radiotherapy (IMRT), 50 Gy/25 fractions, capecitabine 1,700 mg/m2/day for 5 days/week)] with concurrent thermal therapy (Thermotron-RF8, once a week for 5 weeks with 50 min irradiation). Patients with progressive disease (PD) did not receive RF outputs higher than the predicted value. Some patients who were predicted to receive more output in fact received more than the predicted output. In patients who were predicted to receive moderately higher outputs, 37.5% of the patients experienced pathological complete responses, which was the highest rate, while in those who did not receive more than the predicted output, 66.7% of the patients experienced PD, which was the highest rate in the present study. We speculate that RF thermal therapy may offset the chemoradiation effects in some patients. Adding thermal therapy as a multimodality therapy to NACR potentially affects patients with lower predicted outputs and actual observed outputs slightly higher than the predictive value. Our predictive equation for initial energy output, in which output­limiting symptoms can be used to predict treatment efficacy, consequently, can be used to decide whether to continue this treatment modality.

Influence of aging, gastric mucosal atrophy and dietary habits on gastric secretion.

BACKGROUND/AIMS: Studies in Japan have reported on the association between gastric secretion and age with consideration given to gastric mucosal atrophy but not pepsin secretion. Though recent reports have shown enhanced gastric secretion in the Japanese, attributed to dietary westernization, the association between diet and gastric secretion is not clear. In this study, the association between gastric secretion and mucosal atrophy, age, and dietary habits was evaluated. METHODOLOGY: The subjects were 47 preoperative patients without upper gastrointestinal disorders. Acid secretion, pepsin secretion, serum pepsinogen level, and serum Helicobacter pylori antibody titer were measured. Dietary habits were investigated by questionnaire. RESULTS: Gastric secretion did not differ among the young, middle, and elderly age groups. Compared with the group without atrophy (pepsinogen I/II > 3.0, 32 subjects), the group with atrophy (I/II < or = 2.5, 11 subjects) showed significantly decreased gastric secretion and a significantly high Helicobacter pyloriseropositive rate. In the group without atrophy, acid and pepsin secretion was significantly correlated with energy intake, pepsin secretion was significantly correlated with glucose intake, and gastric secretion tended to increase with age. CONCLUSIONS: In the absence of gastric mucosal atrophy, gastric secretion does not decrease with age, and is related to dietary habits.

Did the histologic diversity of the primary tumor affect the patient's outcome in gastric cancer?

The objective of this study was to evaluate the clinical significance of the histologic diversity of primary lesions in the gastric cancer patient. This study included 165 patients with node-negative gastric cancer who underwent curative gastrectomy. Grade of histologic diversity in primary lesion was classified as 1, 2, 3, and 4 histologic types by the number of the composing histologic types, regardless of the predominant histologic type. The relationships between the number of histologic types and the clinicopathological parameters were studied. There was no progressive increase in the number of kinds of histologic types with increasing depth of invasion of the tumor. Analysis of survival rates by number of histologic types showed that the increasing number of composing histologic types was not associated with a poorer prognosis. We were not able to predict the prognosis by studying the number of histologic types composing the primary lesions in node-negative gastric cancer.

Radiofrequency thermal treatment with chemoradiotherapy for advanced rectal cancer.

We previously reported that patients with a clinical complete response (CR) following radiofrequency thermal treatment exhibit significantly increased body temperature compared with other groups, whereas patients with a clinical partial response or stable disease depended on the absence or presence of output limiting symptoms. The aim of this study was to evaluate the correlation among treatment response, Hidaka radiofrequency (RF) output classification (HROC: termed by us) and changes in body temperature. From December 2011 to January 2014, 51 consecutive rectal cancer cases were included in this study. All patients underwent 5 RF thermal treatments with concurrent chemoradiation. Patients were classified into three groups based on HROC: with ≤9, 10-16, and ≥17 points, calculated as the sum total points of five treatments. Thirty-three patients received surgery 8 weeks after treatment, and among them, 32 resected specimens were evaluated for histological response. Eighteen patients did not undergo surgery, five because of progressive disease (PD) and 13 refused because of permanent colostomy. We demonstrated that good local control (ypCR + CR + CRPD) was observed in 32.7% of cases in this study. Pathological complete response (ypCR) was observed in 15.7% of the total 51 patients and in 24.2% of the 33 patients who underwent surgery. All ypCR cases had ≥10 points in the HROC, but there were no patients with ypCR among those with ≤9 points in the HROC. Standardization of RF thermal treatment was performed safely, and two types of patients were identified: those without or with increased temperatures, who consequently showed no or some benefit, respectively, for similar RF output thermal treatment. We propose that the HROC is beneficial for evaluating the efficacy of RF thermal treatment with chemoradiation for rectal cancer, and the thermoregulation control mechanism in individual patients may be pivotal in predicting the response to RF thermal treatment.

A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study.

The safety of weekly regional hyperthermia performed with 8 MHz radiofrequency (RF) capacitive heating equipment has been established in rectal cancer. We aimed to standardize hyperthermia treatment for scientific evaluation and for assessing local tumor response to RF hyperthermia in rectal cancer. Forty-nine patients diagnosed with rectal adenocarcinoma were included in the study. All patients received chemoradiation with intensity-modulated radiation therapy 5 days/week (dose, 50 Gy/25 times) concomitant with 5 days/week for five times of capecitabine (1700 mg/m(2) per day) and once a week for five times of 50 min irradiations by an 8 MHz RF capacitive heating device. Thirty-three patients underwent surgery 8 weeks after treatment. Three patients did not undergo surgery because of progressive disease (PD) and 13 refused. Eight (16.3%) patients had a pathological complete response (ypCR) after surgery. Among patients without surgery, 3 (6.1%) had clinical complete response (CR) and 3 (6.1%) had local CR but distant PD (CRPD). Ninety percent of ypCR + CR patients were shown in 6.21 W min(-1) m(-2) /treatment or higher group of average total accumulated irradiation output with 429°C min(-1) m(-2) or higher group of total accumulated thermal output. However, a patient with CRPD was in the higher total accumulated thermal output group. We propose a new quantitative parameter for the hyperthermia and demonstrated that patients can benefit from mild irradiation with mild temperature. Using these parameters, the exact output, optimal thermal treatment, and contraindications or indications of this modality could be determined in a multi-institutional, future study.